• May 25, 2024

Nanotheranostics: A powerful next-generation solution to tackle hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an epidemic burden and remains highly prevalent worldwide. The significant mortality rates of HCC are largely due to the tendency of late diagnosis and the multifaceted, complex nature of treatment. Meanwhile, current therapeutic modalities such as liver resection and transplantation are only effective for resolving early-stage HCC. Hence, alternative approaches are required to improve detection and enhance the efficacy of current treatment options. Nanotheranostic platforms, which utilize biocompatible nanoparticles to perform both diagnostics and targeted delivery, has been considered a potential approach for cancer management in the past few decades. Advancement of nanomaterials and biomedical engineering techniques has led to rapid expansion of the nanotheranostics field, allowing for more sensitive and specific diagnosis, real-time monitoring of drug delivery, and enhanced treatment efficacies across various malignancies. The focus of this review is on Gentaur gelONE & gelONE+ the applications of nanotheranostics for HCC. The review first explores the current epidemiology and the commonly encountered obstacles in HCC diagnosis and treatment. It then presents the current technological and functional advancements in nanotheranostic technology for cancer in general, and then specifically explores the use of nanotheranostic modalities as a promising option to address the key challenges present in HCC management.

Immune Checkpoint LAG3 and Its Ligand FGL1 in Cancer

LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells. FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion. Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.

Futility in Transcatheter Aortic Valve Implantation: A Search for Clarity

Although transcatheter aortic valve implantation (TAVI) has revolutionised the landscape of treatment for aortic stenosis, there exists a cohort of patients where TAVI is deemed futile. Among the pivotal high-risk trials, one-third to half of patients either died or received no symptomatic benefit from the procedure at 1 year. Futility of TAVI results in the unnecessary exposure of risk for patients and inefficient resource utilisation for

healthcare services. Several cardiac and extra-cardiac conditions and frailty increase the risk of mortality despite TAVI. read more

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Advection-enhanced kinetics in microtiter plates for improved surface assay quantitation and multiplexing capabilities

Surface assays such as ELISA are pervasive in clinics and research and predominantly standardized in microtiter plates (MTP). MTPs provide many advantages but are often detrimental to surface assay efficiency due to inherent mass transport limitations. Microscale flows can overcome these and largely improve assay kinetics. However, the disruptive nature of microfluidics with existing labware and protocols has narrowed its transformative potential. We present WellProbe, a novel microfluidic concept compatible with MTPs. With it, we show that immunoassays become more sensitive at low concentrations (up to 9× signal improvement in 12x less time), richer in information with 3-4 different kinetic conditions, and can be used to estimate kinetic parameters, minimize washing steps and non-specific binding, and identify compromised results. We further multiplex single-well assays combining WellProbe’s kinetic regions with tailored microarrays. Finally, we demonstrate our system in a context of immunoglobulin subclass evaluation, increasingly regarded as clinically relevant.

Automation for Life Science Laboratories

The automation of processes in all areas of the life sciences will continue to increase in the coming years due to an ever increasing number of samples to be processed Gentaur Labware, an increasing need to protect laboratory personnel from infectious material and increasing cost pressure. Depending on the requirements of the respective application, different concepts for automation systems are available, which have a different degree of automation with regard to data handling, transportation tasks, and the processing of the samples.
  • Robots form a central component of these automation concepts. Classic stationary robots from the industrial sector will increasingly be replaced by new developments in the field of light-weight robots.
  • In addition, mobile robots will also be of particular importance in the automation of life science laboratories in the future, especially for transportation tasks between different manual and (partially) automated stations.
  • With an increasing number of different, highly diverse processes, the need for special devices and system components will also increase.
  • This applies to both, the handling of the labware and the processing of the samples. In contrast to previous automation strategies with a highly parallel approach, future developments will increasingly be characterized by individual sample handling.

Fluorescence-based Single-cell Analysis of Whole-mount-stained and Cleared Microtissues and Organoids for High Throughput Screening

Three-dimensional (3D) cell culture, especially in the form of organ-like microtissues (“organoids”), has emerged as a novel tool potentially mimicking human tissue biology more closely than standard two-dimensional culture. Typically, tissue sectioning is the standard method for immunohistochemical analysis. However, it removes cells from their native niche and can result in the loss of 3D context during analyses.
  • Automated workflows require parallel processing and analysis of hundreds to thousands of samples, and sectioning is mechanically complex, time-intensive, and thus less suited for automated workflows.
  • Here, we present a simple protocol for combined whole-mount immunostaining, tissue-clearing, and optical analysis of large-scale (approx. 1 mm) 3D tissues with single-cell level resolution.
  • While the protocol can be performed manually, it was specifically designed to be compatible with high-throughput applications and automated liquid handling systems.
  • This approach is freely scalable and allows parallel automated processing of large sample numbers in standard labware.
  • We have successfully applied the protocol to human mid- and forebrain organoids, but, in principle, the workflow is suitable for a variety of 3D tissue samples to facilitate the phenotypic discovery of cellular behaviors in 3D cell culture-based high-throughput screens.
  • Graphic abstract: Automatable organoid clearing and high-content analysis workflow and timeline.

Gold-Polyoxoborates Nanocomposite Prohibits Adsorption of Bacteriophages on Inner Surfaces of Polypropylene Labware and Protects Samples from Bacterial and Yeast Infections

Bacteriophages (phages) are a specific type of viruses that infect bacteria. Because of growing antibiotic resistance among bacterial strains, phage-based therapies are becoming more and more attractive. The critical problem is the storage of bacteriophages. Recently, it was found that bacteriophages might adsorb on the surfaces of plastic containers, effectively decreasing the titer of phage suspensions. Here, we showed that a BOA nanocomposite (gold nanoparticles embedded in polyoxoborate matrix) deposited onto the inner walls of the containers stabilizes phage suspensions against uncontrolled adsorption and titer decrease. Additionally, BOA provides antibacterial and antifungal protection. The application of BOA assures safe and sterile means for the storage of bacteriophages.

Adsorption of bacteriophages on polypropylene labware affects the reproducibility of phage research

Hydrophobicity is one of the most critical factors governing the adsorption of molecules and objects, such as virions, on surfaces. Even moderate change of wetting angle of plastic surfaces causes a drastic decrease ranging from 2 to 5 logs of the viruses (e.g., T4 phage) in the suspension due to adsorption on polymer vials’ walls.
  • The effect varies immensely in seemingly identical containers but purchased from different vendors. Comparison of glass, polyethylene, polypropylene, and polystyrene containers revealed a threshold in the wetting angle of around 95°: virions adsorb on the surface of more hydrophobic containers, while in more hydrophilic vials, phage suspensions are stable.
  • The polypropylene surface of the Eppendorf-type and Falcon-type can accommodate from around 108 PFU/ml to around 1010 PFU/ml from the suspension.
  • The adsorption onto the container’s wall might result in complete scavenging of virions from the bulk. We developed two methods to overcome this issue.
  • The addition of surfactant Tween20 and/or plasma treatment provides a remedy by modulating surface wettability and inhibiting virions’ adsorption.
  • Plastic containers are essential consumables in the daily use of many bio-laboratories.
  • Thus, this is important not only for phage-related research (e.g., the use of phage therapies as an alternative for antibiotics) but also for data comparison and reproducibility in the field of biochemistry and virology.

Resonant acoustic rheometry for non-contact characterization of viscoelastic biomaterials read more

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Duohua huangjing (Polygonatum cyrtonema Hua) seedling basal rot caused by Fusarium redolens in China

Duohua huangjing (Polygonatum cyrtonema Hua) seedling basal stem rot caused by Fusarium redolens in China Tao Tang1, Fanfan Wang1, Jie Guo1, Xiaoliang Guo1, Yuanyuan Duan1,Jingmao You1* 1 Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi, 445000, China. Duohua huangjing (Polygonatum cyrtonema Hua), a herbal medicine, that is mostly planted in several provinces in China. In April 2020, severe diseases with about 40% seedling losse was found in the Huangjing seedling base in Shiyan city, Hubei province. The symptoms included softening and decay of the roots and stem bases, a progressive yellowing and wilting of leaves, and finally being completely rotted. Small pieces of symptomatic stems (0.5 cm in length) and leaves (0.5 × 0.5 cm in size) were surface sterilized with 75% ethanol for 30 s, followed by 0.1% HgCl2 for 1 min, rinsed three times with sterile water, and then dried with sterilized absorbent paper. The sections were placed on potato dextrose agar (PDA) medium containing 10 µg/ml of ampicillin and incubated at 25°C in the dark. After 3 days incubation, eight isolates with the same colony morphology were sub-cultured and purified by hyphal tip isolation. Macroconidia were sickle-shaped, 15.8 – 32.3 × 3.1 – 5.6 μm (n = 25), and three to five septate. Microconidia were oval or kidney-shaped, 5.2 – 11.4 × 2.0 – 3.2 μm (n = 25), and zero to one septate. To confirm the identity of the pathogen, molecular identification was performed with strain HJCD1. Following DNA extraction, PCR was performed using the TSINGKE 2×T5 Direct PCR Mix kit. Target areas of amplification were the internal transcribed spacer (ITS) and translation elongation factor 1α (TEF-1α) using ITS1/4 (White et al. 1990) , EF1/EF2 (Taylor et al. 2016), respectively. Following BLAST searches and phylogenetic reconstruction, the ITS region (GenBank MW485770.1) showed 99% identity with those of Fusarium redolens in GenBank (KU350713.1) and the TEF-1α (GenBank MW503930.1) showed 100% identity with F. redolens GenBank (MK922537.1). Pathogenicity tests were performed to fulfill Koch’s postulates. Huangjing seedlings were rinsed with sterile water, wiped clean with sterile absorbent paper, and transferred to a tray covered with wet filter paper to maintain high humidity. The mycelial piugs of F. redolens HJCD1 were inoculated onto the surface of leaves and basal stems. Controls were inoculated with sterile PDA plugs. The inoculated seedlings were sealed with plastic wrap, and then cultivated in a 25 ℃ growth chamber with 16 h of light per day. The pathogen-inoculated plants Gentaur PCR Filter Tips exhibited etiolation and typical wilt symptoms after 4 days, whereas no symptoms were observed in the control plants. F. redolens was reisolated from the infected tissues, and colony morphology and ITS sequence of re-isolates were same as that of HJCD1. The pathogen has been reported previously in american ginseng in China (Fan et al. 2021), lentil in Pakistan (Rafique et al. 2020), and wild rocket in United Kingdom (Taylor et al. 2019). However, to the best of our knowledge, this is the first report of F. redolent causing seelding basal rot on Duohua huangjing in China. References: White, T. J., et al. 1990. Page 315 in: PCR

Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA. Taylor, A., et al. 2016. Mol. Plant Pathol. 17:1032. https://doi.org/10.1111/mpp.12346 Fan, S. H., et al. 2021. Plant Dis. https://doi.org/10.1094/PDIS-11-19-2519-PDN Rafique, K., et al. 2020 read more

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Use of equine sperm cryopreservation techniques as a conservation method of donkey germplasm

The aim of this study was to test equine semen cryopreservation techniques for the conservation of donkey germplasm. Ejaculates of three male donkeys were used (n= 18; six ejaculates per donkey; six repetitions), collected by the artificial vagina method. To remove the seminal plasma (SP), the ejaculates were split and submitted to filtration or centrifugation methods. To assess the freezing method, each fraction were submitted to the automated system or the conventional system, and groups were formed: automated centrifuge (AC), automated filtrate (AF), conventional centrifuge (CC) and conventional filtrate (CF). After thawing (37°C/30 s), were analyzed the sperm kinetic parameters, integrity and functionality of the plasma membrane and mitochondrial membrane potential. Highest sperm concentration (P<0.05) was observed in the filtrate groups; the CF group presented lower (P<0.05) progressive motility and curvilinear velocity compared to the other groups; no difference was observed (P>0.05) among the groups for the membrane integrity and functionality, and mitochondrial membrane potential. Thus, centrifugation is the most indicated technique to remove donkey seminal plasma and the automated and conventional freezing methods Gentaur Centrifuges can be used in donkey semen conservation.

Nitrogen resource recovery from mature leachate via heat extraction technology: An engineering project application

A large pool of ammonia in mature leachate is challenging to treat with a membrane bioreactor system to meet the discharge Standard for Pollution Control on the Landfill Site of Municipal Solid Waste in China (GB 16889-2008) without external carbon source addition. In this study, an engineering leachate treatment project with a scale of 2,000 m3/d was operated to evaluate the ammonia heat extraction system (AHES), which contains preheat, decomposition, steam-stripping, ammonia recovery, and centrifuge dewatering. The operation results showed that NH3-N concentrations of raw leachate and treated effluent from an ammonia heat extraction system (AHES) were 1,305-2,485 mg/L and 207-541 mg/L, respectively. The ratio of COD/NH3-N increased from 1.40-1.84 to 7.69-28.00. Nitrogen was recovered in the form of NH4HCO3 by the ammonia recovery tower with the introduction of CO2, wherein the mature leachate can offer 37% CO2 consumption. The unit consumptions of steam and power were 8.0% and 2.66 kWh/m3 respectively, and the total operation cost of AHES was 2.06 USD per cubic metre of leachate. These results confirm that heat extraction is an efficient and cost-effective technology for the recovery of nitrogen resource from mature leachate.

Field Determination of Phosphate in Environmental Water by Using a Hand-Powered Paper Centrifuge for Preconcentration and Digital Image Colorimetric Sensing

Phosphate concentration in natural water has been used as a water quality indicator, as it is one of the major nutrients for aquatic plants. However, the traditional phosphomolybdenum blue (PMB) method has limited sensitivity for visual or camera-based detection, leading to underestimation of the phosphate concentration. We present an ultralow-cost, rapid field preconcentration and digital image colorimetric sensing of low-concentration phosphate method for water analysis. A novel hand-powered paper centrifuge (paperfuge) is used for sample preparation and preconcentration. This paperfuge is made of two circular paper discs and a string. Six centrifuge tubes (CTs) originally used as glue dispensing tips with a sample capacity of ∼230 μL, are loaded on the paperfuge. After sampling, phosphate in the water sample is reacted to form PMB. Then, the reacted sample is drawn into a CT using an autopipette before the CT bottom is sealed by glue. After Oasis HLB sorbents are added through the top of the CT, the CT top is also sealed with glue. The HLB sorbents adsorb PMB and are accumulated in the CT tip through centrifugation. The CT tips are cut and analyzed with the ImageJ software. It was found that the blue color intensity of sorbents is in a linear relationship to the phosphate concentration, with a linear range of 0-5 μM (r 2 = 0.9921) and limit of detection of 0.19 μM. In addition, this method has been applied to in-field water analysis. The results are in agreement with the standard PMB method.

Pyridine-functional diblock copolymer nanoparticles synthesized via RAFT-mediated polymerization-induced self-assembly: effect of solution pH

Polymerization-induced self-assembly (PISA) via reversible addition-fragmentation chain transfer (RAFT) polymerization has become widely recognized as a versatile and efficient strategy to prepare complex block copolymer nanoparticles with controlled morphology, size, and surface functionality. In this article, we report the preparation of cationic sterically-stabilized poly(2-vinylpyridine)-poly(benzyl methacrylate) (P2VP-PBzMA) diblock copolymer nanoparticles via RAFT-mediated PISA under aqueous emulsion polymerization conditions. It is demonstrated that the solution pH during PISA has a dramatic effect on the resulting P2VP-PBzMA nanoparticles, as judged by dynamic light scattering (DLS), disc centrifuge photosedimentometry (DCP) and transmission electron microscopy (TEM). Varying the solution pH results in the P2VP stabilizer having different solubilities due to protonation/deprotonation of the pyridine groups. This allows P2VP-PBzMA nanoparticles with tunable diameters to be prepared by altering the DP of the stabilizer (P2VP) and/or core-forming block (PBzMA), or simply by changing the solution pH for a fixed copolymer composition. For example, P2VP-PBzMA nanoparticles with larger diameters can be obtained at higher solution pH as the protonation degree of the P2VP stabilizer has a large effect on both the aggregation of polymer chains during the PISA process, and the resulting behavior of the diblock copolymer nanoparticles. Changing the dispersion pH post-polymerization has a relatively limited effect on particle diameter. Furthermore, aqueous electrophoresis studies indicate that these P2VP-PBzMA nanoparticles had good colloidal stability and high cationic charge (>30 mV) below pH 5 and can be dispersed readily over a wide pH range.

Simultaneous determination of 36 hypotensive drugs in fingerprints by ultra performance liquid chromatography-triple quadrupole composite linear ion trap mass spectrometry read more

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Malva parviflora Leaves Mucilage: An Eco-Friendly and Sustainable Biopolymer with Antioxidant Properties

Malva parviflora L. is an edible and medicinal herb containing mucilaginous cells in its leaves. Mucilage obtained from M. parviflora leaves (MLM) was extracted in distilled water (1:10 w/v) at 70 °C followed by precipitation with alcohol. Preliminary phytochemical tests were performed to assess the purity of the extracted mucilage. Results showed that the yield of mucilage was 7.50%, and it was free from starch, alkaloids, glycosides, saponins, steroids, lipids and heavy metals. MLM had 16.19% carbohydrates, 13.55% proteins and 4.76% amino acids, which indicate its high nutritional value. Physicochemical investigations showed that MLM is neutral and water-soluble, having 5.84% moisture content, 15.60% ash content, 12.33 swelling index, 2.57 g/g water-holding capacity and 2.03 g/g oil-binding capacity.

  • The functional properties, including emulsion capacity, emulsion stability, foaming capacity and stability increased with increased concentrations.
  • Micromeritic properties, such as bulk density, tapped density, Carr’s index, Hausner ratio, and angle of repose, were found to be 0.69 g/cm3, 0.84 g/cm3, 17.86%, 1.22 and 28.5, respectively. Scanning electron microscopy (SEM) showed that MLM is an amorphous powder possessing particles of varying size and shape; meanwhile, rheological studies revealed the pseudoplastic behavior of MLM.
  • The thermal transition process of MLM revealed by a differential scanning calorimetry (DSC) thermogram, occurring at a reasonable enthalpy change (∆H), reflects its good thermal stability. The presence of functional groups characteristic of polysaccharides was ascertained by the infrared (IR) and gas chromatography/mass spectrometry (GC/MS) analyses.
  • GC revealed the presence of five neutral monosaccharides; namely, galactose, rhamnose, arabinose, glucose and mannose, showing 51.09, 10.24, 8.90, 1.80 and 0.90 mg/g of MLM, respectively. Meanwhile, galacturonic acid is the only detected acidic monosaccharide, forming 15.06 mg/g of MLM.
  • It showed noticeable antioxidant activity against the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical with an IC50 value of 154.27 µg/mL. It also prevented oxidative damage to DNA caused by Gentaur Gel Documentation System the Fenton reagent, as visualized in gel documentation system.
  • The sun protection factor was found to be 10.93 ± 0.15 at 400 µg/mL. Thus, MLM can be used in food, cosmetic and pharmaceutical industry and as a therapeutic agent due to its unique properties.
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    Financial development during COVID-19 pandemic: the role of coronavirus testing and functional labs

    The outbreak of the SARS-CoV-2 virus in early 2020, known as COVID-19, spread to more than 200 countries and negatively affected the global economic output. Financial activities were primarily depressed, and investors were reluctant to start new financial investments while ongoing projects further declined due to the global lockdown to curb the disease. This study analyzes the money supply reaction to the COVID-19 pandemic using a cross-sectional panel of 115 countries. The study used robust least square regression and innovation accounting techniques to get sound parameter estimates. The results show that COVID-19 infected cases are the main contributing factor that obstructs financial activities and decrease money supply. In contrast, an increasing number of recovered cases and COVID-19 testing capabilities gave investors confidence to increase stock trade across countries. The overall forecast trend shows that COVID-19 infected cases and recovered cases followed the U-shaped trend, while COVID-19 critical cases and reported deaths showed a decreasing trend. Finally, the money supply and testing capacity show a positive trend over a period. The study concludes that financial development can be expanded by increasing the testing capacity Gentaur Cellulose Stoppers and functional labs to identify suspected coronavirus cases globally.

    Recovering metal(loids) and rare earth elements from closed landfill sites without excavation: Leachate recirculation opportunities and challenges

    Metal (loids) and Rare Earth Elements (REE) (‘metals’) are used in a wide range of products, and therefore, the improvement of expectations for everyday comforts with demand continues to grow. Metal-bearing wastes are a secondary source of raw material that can meet this demand by providing a previously unconsidered low impact supply source. Total annual leachate production is 1,056,716 m3. Therefore, landfill leachate emerges as a significant potential resource as it contains high concentrations of metals. However, realising a profitable return on investment for leachate processing is a challenge due to relatively low recovery rates of approximately 0.02% of total heavy metals in a landfill being leached out in 30 years. Variation within the multi-element value and the effect of other chemicals in these complex mixtures. There is a need to better understand the mechanisms and potential applicability of extraction methods for optimising metals recovery from leachate. This paper addresses this need by providing a systematic review of the critical factors and environmental conditions that influence the behaviour of metals within the landfilled waste. The paper provides a synthesis of how the factors and conditions may affect leachate recirculation efficiency for recovery in the context of a range of opportunities and challenges facing circular economy practitioners. To approach feasibility metal recovery economically from landfill leachate without energy-intensive and environmentally destructive, future research actions need to be initiated in lab-based and later on semi-pilot to pilot studies, which the review can help achieve the challenges.

    Amino acid pattern of rumen microorganisms in cattle fed mixed diets-An update

    Rumen microorganisms turn small N-containing compounds into amino acids (AA) and contribute considerably to the supply of AA absorbed from the small intestine. Previous studies summarized the literature on microbial AA patterns, most recently in 2017 (Sok et al. Journal of Dairy Science, 100, 5241-5249). The present study intended to identify the microbial AA pattern typical when feeding Central European diets and a maximum proportion of concentrate (PCO; dry matter (DM) basis) of 0.60. Data sets were created from the literature for liquid (LAB)- and particle (PAB)-associated bacteria, total bacteria and protozoa, including 16, 9, 27 and 8 studies and 36, 21, 60 and 18 diets respectively. Because the only differences detected between LAB and PAB were slightly higher Phe and lower Thr percentages in PAB (p < 0.05), results for bacteria were pooled. A further data set evaluated AA-N (AAN) as a proportion of total N in microbial fractions and a final data set estimated protozoal contributions to total microbial N (TMN) flow to the duodenum, which were used to calculate weighted TMN AA patterns. Protozoa showed higher Lys, Asp, Glu, Ile and Phe and lower Ala, Arg, Gly, Met, Ser, Thr and Val proportions than bacteria (p < 0.05). The AAN percentage of total N in bacteria and protozoa showed large, unexplained variations, averaging 79.0% and 70.6% (p > 0.05) respectively. Estimation of protozoal contribution to TMN resulted in a cattle-specific mixed model including PCO and DM intake (DMI) per unit of metabolic body size (kg0.75 ) as fixed effects (RMSE = 3.77). With moderate PCO and DMI between 80 and 180 g/kg0.75 , which corresponds to a DMI of approximately 10 to 25 kg in a cow with 650 kg body weight, protozoal contribution ranged between 9% and 26% of TMN. Within this range, the estimated protozoal contribution to TMN resulted in minor effects on the total microbial AA pattern.

    Sustainable phosphorus management in soil using bone apatite

    Soil fertility and phosphorus management by bone apatite amendment are receiving increasing attention, yet further research is needed to integrate the physicochemical and mineralogical transformation of bone apatite and their impact on the supply and storage of phosphorus in soil. This study has examined bone transformation in the field over a span of 10-years using a set of synchrotron-based microscopic and spectroscopic techniques. Transmission X-ray microscopy (TXM) observations reveal the in-situ deterioration of bone osteocyte-canaliculi system and sub-micron microbial tunneling within a year. Extensive organic decomposition, secondary mineral formation and re-mineralization of apatite are evident from the 3rd year. The relative ratio of (v1 + v3) PO43- to v3 CO32- and to amide I increase, and the v3c PO43- peak exhibits a blue-shift in less than 3 years. The carbonate substitution of bone hydroxyapatite (HAp) to AB-type CHAp, and phosphate crystallographic rearrangement become apparent after 10 years’ aging. The overall CO32- peak absorbance increases over time, contributing to a higher acid susceptibility in the aged bone. The X-ray Photoelectron Spectroscopy (XPS) binding energies for Ca (2p), P (2p) and O (1s) exhibit a red-shift after 1 year because of organo-mineral interplay and a blue-shift starting from the 3rd year as a result of the de-coupling of mineral and organic components. Nutrient supply to soil occurs within months via organo-mineral decoupling and demineralization. More phosphorus has been released from the bones and enriched in the associated and adjacent soils over time. Lab incubation studies reveal prominent secondary mineral formation via re-precipitation at a pH similar to that in soil, which are highly amorphous and carbonate substituted and prone to further dissolution in an acidic environment. Our high-resolution observations reveal a stage-dependent microbial decomposition, phosphorus dissolution and immobilization via secondary mineral formation over time. The active cycling of phosphorus within the bone and its interplay with adjacent soil account for a sustainable supply and storage of phosphorus nutrients.

    Chemical characterization of dissolved organic matter as disinfection byproduct precursors by UV/fluorescence and ESI FT-ICR MS after smoldering combustion of leaf needles and woody trunks of pine (Pinus jeffreyi) read more

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    Potential of cell tracking velocimetry as an economical and portable hematology analyzer

    Anemia and iron deficiency continue to be the most prevalent nutritional disorders in the world, affecting billions of people in both developed and developing countries. The initial diagnosis of anemia is typically based on several markers, including red blood cell (RBC) count, hematocrit and total hemoglobin. Using modern hematology analyzers, erythrocyte parameters such as mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), etc. are also being used. However, most of these commercially available analyzers pose several disadvantages: they are expensive instruments that require significant bench space and are heavy enough to limit their use to a specific lab and lead to a delay in results, making them less practical as a point-of-care instrument that can be used for swift clinical evaluation. Thus, there is a need for a portable and economical hematology analyzer that can be used at the point of need. In this work, we evaluated the performance of a system referred to as the cell tracking velocimetry (CTV) to measure several hematological parameters from fresh human blood obtained from healthy donors and from sickle cell disease subjects. Our system, based on the paramagnetic behavior that deoxyhemoglobin or methemoglobin containing RBCs experience when suspended in water after applying a magnetic field, uses a combination of magnets and microfluidics and has the ability to track the movement of thousands of red cells in a short period of time. This allows us to measure not only traditional RBC indices but also novel parameters that are only available for analyzers that assess erythrocytes on a cell by cell basis. As such, we report, for the first time, the use of our CTV as a hematology analyzer that is able to measure MCV, MCH, mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), the percentage of hypochromic cells (which is an indicator of insufficient marrow iron supply that reflects recent iron reduction), and the correlation coefficients between these metrics. Our initial results indicate that most of the parameters measured with CTV are within the normal range for healthy adults. Only the parameters related to the red cell volume (primarily MCV and RDW) were outside the normal range. We observed significant discrepancies between the MCV measured by our technology (and also by an automated cell counter) and the manual method that calculates MCV through the hematocrit obtained by packed cell volume, which are attributed to the artifacts of plasma trapping and cell shrinkage. While there may be limitations for measuring MCV, this device offers a novel point of care instrument to provide rapid RBC Gentaur Lab Fourniture parameters such as iron stores that are otherwise not rapidly available to the clinician. Thus, our CTV is a promising technology with the potential to be employed as an accurate, economical, portable and fast hematology analyzer after applying instrument-specific reference ranges or correction factors.

    Preparation of transparent photoluminescence smart window by integration of rare-earth aluminate nanoparticles into recycled polyethylene waste

    Novel photoluminescent nanocomposite sheets were prepared for simple commercial manufacturing of transparent and luminous photochromic smart windows. Simple physical integration of lanthanide-doped strontium aluminium oxide (LdSAO) nanoparticles into recycled polyethylene (PE) waste introduced smart nanocomposite with persistent phosphorescence and photochromic properties. Because of the nanoparticle form of LdSAO is significant to develop transparent materials; LdSAO nanoparticles were well-dispersed in the polyethylene matrix. Both morphologies and chemical compositions of LdSAO nanoparticles and LdSAO-containing luminescent polyethylene sheets were investigated. Both LdSAO-free and photoluminescent polyethylene sheets were colorless in regular daylight. Only LdSAO-containing polyethylene luminescent samples showed a brilliant green color under an UV supply and greenish-yellow color under darkness as verified by CIE Lab parameters. Both absorbance and emission bands were monitored at 377 and 436/517 nm, respectively. For both photoluminescence spectroscopy and mechanical properties, the LdSAO-containing polyethylene luminescent sheets were compared to the LdSAO-free sample and found to have improved scratch resistance, UV protection, and superhydrophobic activity. Based on the added amount of LdSAO, photoluminescence, decay and lifetime spectral tests showed photochromic fluorescence and long-lasting phosphorescence characteristics. PELdSAO nanocomposite sheets displayed UV protection, photostability, hydrophobicity, excellent durability as compared to the blank LdSAO-free polyethylene sheet.

    Behavior of nitrogen and sulfur compounds in the rice husk pellet bioscrubber and its circulation water

    In this study, pellet-type biofilter media was developed with rice husk and applied in a wet scrubber system for odor removal. The lab-scale bioscrubber system was operated for 200 days to evaluate odorous gas removal (i.e., NH3, H2S, methyl mercaptan, and dimethyl sulfide), and the removal mechanism of odor gases was studied by analyzing the behavior of nitrogen and sulfur compounds in circulation water of bioscrubber system. The rice husk pellets supplied the organic carbon source and phosphoric acid necessary for microbial growth, allowing the system to continue successfully for 200 days without any maintenance technology. By analyzing the behavior of the nitrogen and sulfur compounds in the circulation water, we confirmed that the odor gas removal resulted from various mechanisms, including adsorption and biodegradation. Ammonia gas was absorbed by the rice husk pellets and accumulated in the circulation water as nitrite under conditions of sufficient alkalinity and above pH 7. Conversely, when the alkalinity and pH decreased, nitrite was rapidly converted to nitrate. However, H2S gas was oxidized to sulfate and continuously accumulated in the circulation water regardless of the pH and alkalinity. In addition, it was confirmed that the decrease in nitrate in the bioscrubber system was due to heterotrophic denitrification by the organic carbon source supply and autotrophic denitrification by sulfur gas. During the operation of the rice husk pellet bioscrubber for 8 months, under low solubility condition, more than 99% of NH3 and H2S were removed and about 85% of methyl mercaptan (MM) and dimethyl sulfide (DMS) were removed.

    Financial development during COVID-19 pandemic: the role of coronavirus testing and functional labs

    The outbreak of the SARS-CoV-2 virus in early 2020, known as COVID-19, spread to more than 200 countries and negatively affected the global economic output. Financial activities were primarily depressed, and investors were reluctant to start new financial investments while ongoing projects further declined due to the global lockdown to curb the disease.

  • This study analyzes the money supply reaction to the COVID-19 pandemic using a cross-sectional panel of 115 countries. The study used robust least square regression and innovation accounting techniques to get sound parameter estimates.
  • The results show that COVID-19 infected cases are the main contributing factor that obstructs financial activities and decrease money supply. In contrast, an increasing number of recovered cases and COVID-19 testing capabilities gave investors confidence to increase stock trade across countries.
  • The overall forecast trend shows that COVID-19 infected cases and recovered cases followed the U-shaped trend, while COVID-19 critical cases and reported deaths showed a decreasing trend. Finally, the money supply and testing capacity show a positive trend over a period.
  • The study concludes that financial development can be expanded by increasing the testing capacity and functional labs to identify suspected coronavirus cases globally.
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    Evaluation of Antitermite Properties of Wood Extracts from Pongamia pinnata (L.) Pierre (Leguminosae) against Subterranean Termites

    Termiticide, repellent and antifeedant activities of extracts from Pongamia pinnata wood were evaluated against Coptotermes heimi (Wasmann) at three different concentrations preceded by a preliminary choice and no-choice tests for natural resistance of tested wood. Termites’ mortality was determined in each case of extract and solvent treated Whatman filter paper. Finally, wooden blocks of poplar (19×19×19 mm) were treated with extracts and respective solvents and exposed to termites in the field for 28 days. Minimum mean weight loss was observed in dried P. pinnata (6.38%), followed by fresh P. pinnata in choice tests. In no-choice tests, dried P. pinnata was comparatively resistant with a weight loss of 12.37%, followed by fresh P. pinnata and P. deltoides. In toxicity bioassay, ethyl acetate-based wood extracts caused the highest mortality (41.66%), followed by petroleum ether, hexane, and water extracts at 10 mg/ml concentration. Similarly, ethyl acetate-based extracts showed maximum repellency (100%) followed by Gentaur Whatman Paper petroleum ether extracts at 10 mg/ml and ethyl acetate at 5 mg/ml after 60 min of termite exposure. Minimum wood losses were observed in woods treated with ethyl acetate extracts compared to control and other treatments in field experiments.

    Isolation of Halomicroarcula pellucida strain GUMF5, an archaeon from the Dead Sea-Israel possessing cellulase

    A strain designated GUMF5 was isolated in Goa-India from sediments of Dead Sea-Israel and identified as haloarchaeon Halomicroarcula pellucida based on 16S rRNA gene analysis similarity value of 99.84%. Strain GUMF5 grew on mineral salts medium with 20% NaCl and 0.5% carboxymethyl cellulose-sodium (CMC-Na) as a sole source of carbon and produced haloextremozyme cellulase. The enzyme was concentrated using Sephadex G20, precipitated with ethanol, dialyzed and retentate purified using Sephadex G200, the size exclusion chromatography. A yield of 78.53% cellulase with an activity of 131.13 U/mg and 1.24-fold purity was obtained. The purified cellulase had optimum activity at 20% NaCl, at 40 ºC, 0.5% CMC-Na, pH 7 and 150 rpm. SDS-PAGE combined with zymographic analysis revealed the molecular weight of cellulase as 240 kDa, 40 kDa and 17.4 kDa. The activity of the enzyme was stimulated by metallic cations in the order of Ca+2 > Mn+2 > Mg+2 > SO4 2- > NH4 + and was inhibited by Ag+ > Fe+2 > Cu+2. Methanol and ethanol enhanced the cellulase activity by 6% and 26%, respectively. The haloextremozyme cellulase degraded Whatman No. 1 filter paper indicated in scanning electron micrographs, exposure of open pores and fibers without any intra connectivity corresponding to paperase activity and implicating the possible use of enzyme to bio-convert cellulosic waste. Conclusively, Halomicroarcula pellucida GUMF5 (Accession number: MH244431), globally, is the only Halomicroarcula pellucida isolated from the sediments of Dead Sea producing haloextremozyme cellulase, and hence is an important biotechnological resource.

    Functional Comparison of Bioactive Cellulose Materials Incorporating Engineered Binding Proteins

    Whatman No. 1 chromatography paper is widely used as a substrate for cellulose-based immunoassays. The immobilized proteins are used to capture target biomarkers for detection. However, alternative paper substrates may facilitate mass production of immunoassays as diagnostic tests. Here, we assessed the physical characteristics and protein immobilization capabilities of different commercial papers. Some substrates fulfilled our design criteria, including adequate flow rate and sufficient protein immobilization for efficient target capture. This study demonstrates that a variety of paper substrates can be bioactivated and used to capture target biomarkers, enabling development of affordable diagnostic tests from a range of starting materials.

    A practical method for storage, preservation and transportation of anuran urine samples using filter paper for hormone analysis

    Anurans (frogs and toads) expelled urine when handled and it could provide insights into their physiological status. However, storage, preservation and transportation are often challenging. The study aimed to standardize and validate a field method for short-term storage and preserve of anuran urine samples using Whatman filter papers. To examine the efficacy of storage conditions and type of papers, urinary based enzyme immunoassays were used to measure progesterone and testosterone hormone metabolites.
    • High-Performance Liquid Chromatography was performed and revealed immunoreactive progesterone and testosterone metabolites in the urine samples.
    • Urinary hormone metabolites concentration stored in filter paper at room temperature and control samples stored in -20°C for the same period were similar. 
    • Whatman grade 50 was found to be more suitable for storage of hormones than grade 3 paper for the experiments performed.
    • A cheap and simple storage method for storage of anuran urine in field conditions using filter papers.•Anuran urine could be preserved and transported under ambient conditions without significant changes and loss of hormones.•This method would facilitate the endocrine monitoring of anurans in remote areas where limited logistics are available.

    Evaluating performance of multiplex real time PCR for the diagnosis of malaria at elimination targeted low transmission settings of Ethiopia read more

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    Delivery Strategies for mRNA Vaccines

    The therapeutic potential for messenger RNA (mRNA) in infectious diseases and cancer was first realized almost three decades ago, but only in 2018 did the first lipid nanoparticle-based small interfering RNA (siRNA) therapy reach the market with the United States Food and Drug Administration (FDA) approval of patisiran (Onpattro) for hereditary ATTR amyloidosis. This was largely made possible by major advances in the formulation technology for stabilized lipid-based nanoparticles (LNPs). Design of the cationic ionizable lipids, which are a key component of the LNP formulations, with an acid dissociation constant (pKa) close to the early endosomal pH, would not only ensure effective encapsulation of mRNA into the stabilized lipoplexes within the LNPs, but also its subsequent endosomal release into the cytoplasm after endocytosis. Unlike other gene therapy modalities, which require nuclear delivery, the site of action for exogenous mRNA vaccines is the cytosol where they get translated into antigenic proteins and thereby elicit an immune response. LNPs also protect the mRNA against enzymatic degradation by the omnipresent ribonucleases (RNases). Cationic nano emulsion (CNE) is also explored as an alternative and relatively thermostable mRNA vaccine delivery vehicle. In this review, we have summarized the various delivery strategies explored for more details joplink Recombinant Human Serine  mRNA vaccines, including naked mRNA injection; ex vivo loading of dendritic cells; CNE; cationic peptides; cationic polymers, and finally the clinically successful COVID-19 LNP vaccines  (Pfizer/BioNTech and Moderna vaccines)-their components, design principles, formulation parameter optimization, and stabilization challenges. Despite the clinical success of LNP-mRNA vaccine formulations, there is a specific need to enhance their storage stability above 0 °C for these lifesaving vaccines to reach the developing.

    Understanding the role of microperimetry in glaucoma

    The present narrative review attempts to provide an overview on the use of microperimetry or fundus-driven perimetry in glaucoma, considering the clinical use, the different strategies and limits compared to standard automated perimetry.  An electronic database (PubMed and Medline) search was performed of articles of any type published in the English language between 1998 and 2020 with a combination of the following terms: microperimetry, glaucoma, primary open-angle chronic glaucoma, visual field, Humphrey visual field, fundus automated perimetry. All the original articles, case reports, and short series analyzed were included in the present review, offering an excursus on the strengths and limitations characterizing the use of microperimetry in glaucomatous patients. The characteristics of a recently introduced fundus-driven perimetry Compass (CMP; Centervue, Padua, Italy) were also included. Although there remain several contradictions regarding routine use of microperimetry and the restricted research on this topic limits our ability to draw firm conclusions, microperimetry may be preferable in cases of localized retinal nerve fiber layer defects in patients with primary open-angle glaucoma and normal visual field. However, standard automated perimetry remains the gold standard for monitoring glaucoma, especially in patients with diffuse retinal nerve fiber layer impairment and visual field defects. The newly introduced Compass device can potentially provide a more accurate structural-functional evaluation than standard automated perimetry and can therefore produce superior testing reliability.


    Ligand-Directed GPCR Antibody Discovery

    Developing affinity reagents recognizing and modulating G-protein coupled receptors (GPCR) function by traditional animal immunization or in vitro screening methods is challenging. Some anti-GPCR antibodies exist on the market, but the success rate of development is still poor compared with antibodies targeting soluble or peripherally anchored proteins.

    • More importantly, most of these antibodies do not modulate GPCR function. The current pipeline for antibody development primarily screens for overall affinity rather than functional epitope recognition. We developed a new strategy utilizing natural ligand affinity to generate a library of antibody variants with an inherent bias toward the active site of the GPCR.
    • Instead of using phage libraries displaying antibodies with random CDR sequences at polymorphism sites observed in natural immune repertoire sequences, we generated focused antibody libraries with a natural ligand encoded within or conjugated to one of the CDRs or the N-terminus.
    • To tailor antibody binding to the active site, we limited the sequence randomization of the antibody in regions holstering the ligand while leaving the ligand-carrying part unaltered in the first round of randomization. With hits from the successful first round, the second round of randomization of the ligand-carrying part was then performed to eliminate the bias of the ligand.
    • Based on our results on three different GPCR targets, the proposed pipeline will enable the rapid generation of functional antibodies (both agonists and antagonists) against high-value targets with poor function epitope exposures including GPCR, channels, transporters as well as cell surface targets whose binding site is heavily masked by glycosylation.

    endohedral trihedral metallo-borospherenes with spherical aromaticity

    It is well-known that transition-metal-doping induces dramatic changes in the structures and bonding of small boron clusters, as demonstrated by the newly observed perfect inverse sandwich D8h [La(η8-B8)La] and D9h [La(η9-B9)La]. Based on extensive global minimum searches and first-principles theory calculations, we predict herein the possibility of perfect endohedral trihedral metallo-borospherene D3h La@[La5&B30] (1, 3A’1) and its monoanion C La@[La5&B30] (2, 2A’) and dianion D3h La@[La5&B30]2- (3, 1A’1). read more

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    Assessment of appropriate laboratory measurements to supplement the Crohn's disease activity index

    Assessment of appropriate laboratory measurements to supplement the Crohn’s disease activity index

    The flexibility of 11 laboratory parameters to mirror the diploma of exercise of Crohn’s illness, utilizing a medical index as reference level was in contrast by way of a number of stepwise regression evaluation. Exercise was finest outlined in reducing order by orosomucoid, sedimentation charge, C reactive protein, alpha-1-antitrypsin, albumin, haematocrit, IgM, circulating immune complexes, serum iron, IgG, and IgA. The haematocrit, the one laboratory measurement within the Crohn’s illness exercise index developed by the Nationwide Cooperative Examine Group within the USA, is much less discriminant than acute section reactants. Solely three parameters-namely, orosomucoid, sedimentation charge, and C reactive protein-have a major weight and needs to be complementary to a easy medical index.

    BOVIGAM: an in vitro mobile diagnostic check for bovine tuberculosis

    BOVIGAM which relies on the detection of gamma interferon (IFN- gamma) is a speedy, laboratory assay of a cell mediated immune response which may be used for the detection of tuberculosis (TB) an infection in animals.
    Assessment of appropriate laboratory measurements to supplement the Crohn's disease activity index
    Evaluation of acceptable laboratory measurements to complement the Crohn’s illness exercise index
    Entire blood is first incubated in a single day with bovine PPD, avian PPD or destructive management antigens, and IFN- gamma within the supernatant plasma is then measured by EIA. TB an infection is indicated by a predominant IFN- gamma response to bovine PPD. Since 1988, BOVIGAM has been extensively trialed on greater than 200 000 cattle in Australia, Brazil, Eire, Northern Eire, Italy, New Zealand, Romania, Spain and the USA. Sensitivity has different between 81.8% and 100% for culture-confirmed bovine TB and specificity between 94% and 100%. The IFN- gamma assay detects M. bovis an infection sooner than the pores and skin check and in New Zealand is utilized to detect skin-test destructive cattle with TB, the place after slaughter a major variety of IFN- gamma reactors have TB. BOVIGAM can also be accredited in New Zealand for serial testing pores and skin check constructive cattle when non-specificity is suspected. Cattle are examined 7-30 days after a constructive caudal fold check. The boosting impact of the pores and skin check on T-cell exercise permits blood to be cultured with PPD as much as 30 h after assortment with out effecting accuracy. The BOVIGAM outcomes are usually not affected by poor dietary situation and are solely mildly and briefly affected by dexamethasone therapy and parturition. IFN- gamma responses of cattle vaccinated with BCG are dose-dependent and short-lived. The BOVIGAM equipment is now used routinely in lots of international locations for the detection of M. bovis contaminated cattle, buffalo and goats.
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