Perindopril and losartan attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike protein.

Thrombotic events are highly prevalent in coronavirus disease 2019 (COVID-19), especially in patients presenting with risk factors of adverse outcomes such as obesity. Recently, the associations between the angiotensin converting enzyme 2 (ACE2) pathway and thrombosis have been reported. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used cardiovascular pharmacologic agents that upregulate ACE2 levels. An observation of the alterations in pro-coagulation factors after exposure to ACEIs and ARBs may provide valuable insight into the thrombosis mechanism and how it may relate to ACE2. This study use adipose tissue harvested from an obese male donor was isolated and exposed to perindopril, losartan, and ACE2 recombinant as binding assay, following exposure with 10 nm of SARS-CoV-2 S1 spike protein. After 48 hours, tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) as pro-coagulation factors as well as ACE2 levels and binding evaluated. The results shows TF level was significantly reduced in Perindopril group compared to control (4.834; p=0.005), while a non-significant reduction was observed in Losartan group (5.624; p=0.111). However, Losartan group showed a better reduction of PAI-1 levels (2.633; p≤0.001) than Perindopril group (3.484; p=0.001). These findings were consistent with the observations in ACE2 recombinant group, suggesting that both drugs lowered the bindings of ACE2 and SARS-CoV-2 spike proteins. This study indicated that both perindopril and losartan may attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike proteins, and therefore showcased a potential role of ACE2 in the mechanism of COVID-19-related thrombosis. Further investigation in non-COVID-19 populations should commence and may be of value to expanding this potential in general cardiovascular diseases.

INFERIOR VENA CAVA FILTER PLACEMENT FOR PREVENTION OF PULMONARY THROMBOEMBOLISM: CASE SERIES FROM NORTHWESTERN NIGERIA.

Background: Inferior vena cava (IVC) filter placement is an image-guided procedure aimed at primarily preventing pulmonary thromboembolism in patients with lower limb venous thromboembolic (VTE) disease. In Northern Nigeria with a relatively high incidence of thromboembolic disease such as Deep vein thrombosis, reports on IVC filter placement are largely low. We report the feasibility of IVC filter placement on eight patients for the first time in a typical low-resource setting in Northern Nigeria. Case Presentations: We had an equal number of males and females of the eight patients. Their ages ranged from 20 to 80 years. Five patients presented with bilateral lower limbs Deep vein thrombosis (DVT) of which one had a pulmonary embolism. Two other patients had extensive left femoral DVT and one had extensive IVC, iliac, femoral, and popliteal veins thrombosis. The medical records of seven patients, who had IVC filter placement in our department, were reviewed. The IVC filter was deployed with the aid of a C-arm fluoroscopic unit. In a single case, access was secured via an indwelling dialysis catheter. Conclusions: All the patients had successful deployment with satisfactory postprocedure conditions. The intended benefit of pulmonary embolism prevention was achieved in the series of procedures that were performed. Indicating the value of IVC filter even in resource-poor settings and effort should be made towards exploring such intervention.

Multi-component T2∗ relaxation modelling in human Achilles tendon: Quantifying chemical shift information in ultra-short echo time imaging.

PURPOSE: To examine multi-component relaxation modelling for quantification of on- and off-resonance relaxation signals in multi-echo ultra-short echo time (UTE) data of human Achilles tendon (AT) and compare bias and dispersion errors of model parameters to that of the bi-component model. THEORY AND METHODS: Multi-component modelling is demonstrated for quantitative multi-echo UTE analysis of AT and supported using a novel method for determining number of MR-visible off-resonance components, UTE data from six healthy volunteers, and analysis of proton NMR measurements from ex vivo bovine AT. Cramer-Rao lower bound expressions are presented for multi- and bi-component models and parameter estimate variances are compared. Bias error in bi-component estimates is characterized numerically. RESULTS: Two off-resonance components were consistently detected in all six volunteers and in bovine AT data. Multi-component model exhibited superior quality of fit, with a marginal increase in estimate variance, when compared to the bi-component model. Bi-component estimates exhibited notable bias particularly in R2,1∗ in the presence of off-resonance components. CONCLUSION: Multi-component modelling more reliably quantifies tendon matrix water components while also providing quantitation of additional non-water matrix constituents. Further work is needed to interpret the origin of the observed off-resonance signals with preliminary assignments made to chemical groups in lipids and proteoglycans.

Soliton mode-locked pulse generation with a bulk structured MXene Ti3AlC2 deposited onto a D-shaped fiber.

We propose a bulk structured MXene, Ti3AlC2 deposited onto D-shaped fiber for soliton generation in an erbium-doped fiber laser (EDFL) cavity. Our saturable absorber (SA) device, based on MAX phase, was prepared by using stirring and ultrasonic vibration, which offer easier sample preparation compared with its 2D counterparts. By means of the polishing wheel technique, we fabricated a D-shaped fiber with a controlled polishing depth and incorporated the MAX phase Ti3AlC2 solution onto its polishing region. We obtained a mode-locked soliton pulse with the proposed MAX phase D-shaped (MAX-DS) SA in EDFL cavity. The pulse width, repetition rate, and central wavelength of the pulse train are 2.21 ps, 1.89 MHz, and 1557.63 nm, respectively. The polarization-insensitive EDFL cavity initiated a soliton operation with superior stability as the pump power tuned from 21 to 131 mW; further, the ML laser exhibits an average power of 15.3 mW, peak power of 3.8 kW, and pump efficiency of 12.5%. The MAX-DS SA incorporated inside the EDFL reveals efficient output performance, with a pulse energy of 8.14 nJ, the highest ever reported, to our best knowledge, among D-shaped fiber-based SA.

Synergistic Antibacterial Efficacy of Biogenic Synthesized Silver Nanoparticles using Ajuga bractosa with Standard Antibiotics: A Study Against Bacterial Pathogens.

BACKGROUND: Multi-drug resistance in bacterial pathogens is a major concern of today. Green synthesis technology is being used to cure infectious diseases. OBJECTIVES: The aim of the current research was to analyze the antibacterial, antioxidant, and phytochemical screening of green synthesized silver nanoparticles using Ajuga bracteosa. METHODS: Extract of A. bracteosa was prepared by maceration technique. Silver nanoparticles were synthesized using A. bracteosa extract and were confirmed by UV-Vis spectrophotometer, Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, TLC-Bioautography, TLC-Spot screening, antioxidant, and phytochemical screening were also investigated. RESULTS: UV-Vis spectrum and Scanning electron microscopy confirmed the synthesis of green nanoparticles at 400 nm with tube-like structures. FTIR spectrum showed that functional groups of nanoparticles have a role in capping and stability of AgNP. Agar well diffusion assay represented the maximum antibacterial effect of ABAgNPs against Escherichia coli, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Pseudomonas aeruginosa at 0.10 g/mL concentration compared to ABaqu. Two types of interactions among nanoparticles, aqueous extract, and antibiotics (Synergistic and additive) were recorded against tested pathogens. Crystal violet, MTT, TLC-bio-autography, and spot screening supported the findings of the antibacterial assay. Highest antioxidant potential effect in ABaqu was 14.62% (DPPH) and 13.64% (ABTS) while 4.85% (DPPH) and 4.86% (ABTS) was recorded in ABAgNPs. Presence of phytochemical constituents showed pharmacological importance. CONCLUSION: It was concluded that green synthesis is an innovative technology in which natural products are conjugated with metallic particles and are used against infectious pathogens. The current research showed the significant use of green nanoparticles against etiological agents.

Q-switched ytterbium-doped fiber laser based on evanescent field interaction with lutetium oxide.

We demonstrated lutetium oxide (${\textrm{Lu}_2}{\textrm{O}_3}$Lu2O3) deposited onto D-shaped fiber producing Q-switched ytterbium-doped fiber laser (YDFL) with an operating wavelength of 1037 nm. D-shaped fiber ${\textrm{Lu}_2}{\textrm{O}_3}$Lu2O3 as a saturable absorber (SA) was prepared using a polishing-wheel technique by polishing 2 times to establish an excellent evanescent field interaction between material and light on the surface of the polished region. The SA was deployed into a YDFL to generate Q-switching. The proposed D-shaped fiber ${\textrm{Lu}_2}{\textrm{O}_3}$Lu2O3 initiated pulses as short as 3.6 µs, with the highest repetition rate of 65.8 kHz. Stability of the SA is proven, as it produced stable pulses within the pump power of 99 to 133 mW with an SNR of 62.13 dB. Q-switched YDFL generates pulses with an output power of 0.93 to 1.99 mW and pulse energy of 17 to 30 nJ. We obtained a laser cavity with the optical-to-optical efficiency of 3.33%, which was the highest among D-shaped fiber-deposited SA materials in YDFL. Therefore, ${\textrm{Lu}_2}{\textrm{O}_3}$Lu2O3 deposited onto D-shaped fiber can be deployed as an SA in YDFL for a portable Q-switched laser source.

Genetic Basis Underlying Correlations Among Growth Duration and Yield Traits Revealed by GWAS in Rice (Oryza sativa L.).

Avoidance of disadvantageous genetic correlations among growth duration and yield traits is critical in developing crop varieties that efficiently use light and energy resources and produce high yields. To understand the genetic basis underlying the correlations among heading date and three major yield traits in rice, we investigated the four traits in a diverse and representative core collection of 266 cultivated rice accessions in both long-day and short-day environments, and conducted the genome-wide association study using 4.6 million single nucleotide polymorphisms (SNPs). There were clear positive correlation between heading date and grain number per panicle, and negative correlation between grain number per panicle and panicle number, as well as different degrees of correlations among other traits in different subspecies and environments. We detected 47 pleiotropic genes in 15 pleiotropic quantitative trait loci (pQTLs), 18 pleiotropic genes containing 37 pleiotropic SNPs in 8 pQTLs, 27 pQTLs with r2 of linkage disequilibrium higher than 0.2, and 39 pairs of interactive genes from 8 metabolic pathways that may contribute to the above phenotypic correlations, but these genetic bases were different for correlations among different traits. Distributions of haplotypes revealed that selection for pleiotropic genes or interactive genes controlling different traits focused on genotypes with weak effect or on those balancing two traits that maximized production but sometimes their utilization strategies depend on the traits and environment. Detection of pQTLs and interactive genes and associated molecular markers will provide an ability to overcome disadvantageous correlations and to utilize the advantageous correlations among traits through marker-assisted selection in breeding.

Genetic Architecture and Candidate Genes for Deep-Sowing Tolerance in Rice Revealed by Non-syn GWAS.

Dry direct-seeding of rice is rapidly increasing in China, but variable planting depth associated with machine sowing can lead to low seedling emergence rates. Phenotype analysis of 621 rice accessions showed that mesocotyl length (ML) was induced by deep soil covering and was important in deep-sowing tolerance in the field. Here, we performed and compared GWAS using three types of SNPs (non-synonymous SNP, non-synonymous SNPs and SNPs within promoters and 3 million randomly selected SNPs from the entire set of SNPs) and found that Non-Syn GWAS (GWAS using non-synonyomous SNP) decreased computation time and eliminated confounding by other loci relative to GWAS using randomly selected SNPs. Thirteen QTLs were finally detected, and two new major-effect genes, named OsML1 and OsML2, were identified by an integrated analysis. There were 2 and 7 non-synonymous SNPs in OsML1 and OsML2, respectively, from which 3 and 4 haplotypes were detected in cultivated rice. Combinations of superior haplotypes of OsML1 and OsML2 increased ML by up to 4 cm, representing high emergence rate (85%) in the field with 10 cm of soil cover. The studies provide key loci and naturally occurring alleles of ML that can be used in improving tolerance to dry direct-seeding.

In vitro Studies on Cytotoxic, DNA Protecting, Antibiofilm and Antibacterial Effects of Biogenic Silver Nanoparticles Prepared with Bergenia ciliata Rhizome Extract.

BACKGROUND: Many health hazardous diseases are caused by clinical pathogens. Drugresistant microbes are one of the major health problems in the world. To overcome the effect of infectious diseases new antimicrobial agent from nature has been explored which is environmentally friendly, less costly and more effective for the development of next-generation drugs. Bergenia ciliata and silver nitrate both have medicinal properties. OBJECTIVES: The aim of the current research was to evaluate the cytotoxic, and antibacterial effect of green synthesized nanoparticles using Bergenia ciliata rhizome against clinical bacterial pathogens. METHODS: Extract of Bergenia ciliata was prepared by maceration technique. Silver nanoparticles were synthesized using Bergenia ciliata rhizome extract. Synthesized silver nanoparticles were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, DNA protection, brine shrimp lethality effects of synthesized nanoparticles were investigated. RESULTS: UV-vis spectrophotometer indicated the prelaminar synthesis of silver nanoparticles at 400 nm. The spherical shape of synthesized nanoparticles with 35 nm size was confirmed using SEM. Greatest zone of inhibition (6.0 ± 0.0 mm to 8.3 ± 0.57 mm) was recorded against all tested pathogens compared with the B. ciliata aqueous extract. Anti-biofilm analysis and MTT assay supported the results of the antibacterial activity. Silver nanoparticles protect the DNA degradation. CONCLUSION: Green synthesized nanoparticles had potent antibacterial activity and may provide a basis for the development of the new antibacterial drug.

Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.

Homozygous mutations in GNPTAB and GNPTG are classically associated with mucolipidosis II (ML II) alpha/beta and mucolipidosis III (ML III) alpha/beta/gamma, which are rare lysosomal storage disorders characterized by multiple pathologies. Recently, variants in GNPTAB, GNPTG, and the functionally related NAGPA gene have been associated with non-syndromic persistent stuttering. In a worldwide sample of 1013 unrelated individuals with non-syndromic persistent stuttering we found 164 individuals who carried a rare non-synonymous coding variant in one of these three genes. We compared the frequency of these variants with those in population-matched controls and genomic databases, and their location with those reported in mucolipidosis. Stuttering subjects displayed an excess of non-synonymous coding variants compared to controls and individuals in the 1000 Genomes and Exome Sequencing Project databases. We identified a total of 81 different variants in our stuttering cases. Virtually all of these were missense substitutions, only one of which has been previously reported in mucolipidosis, a disease frequently associated with complete loss-of-function mutations. We hypothesize that rare non-synonymous coding variants in GNPTAB, GNPTG, and NAGPA may account for as much as 16% of persistent stuttering cases, and that variants in GNPTAB and GNPTG are at different sites and may in general, cause less severe effects on protein function than those in ML II alpha/beta and ML III alpha/beta/gamma.