Hybrid Polymer Salogels for Reversible Entrapment of Salt-Hydrate-Based Thermal Energy Storage Materials.

One of the challenges preventing wide use of inorganic salt hydrate phase change materials (PCMs) is their low viscosity above their melting point, leading to leakage, phase segregation, and separation from heat exchanger surfaces in thermal management applications. The development of a broad strategy for using polymers that provide tunable, temperature-reversible shape stabilization of a variety of salt hydrates by using the lowest possible polymer concentrations is hindered by differences in solubility and gelation behavior of polymers with change in the type of ion. This work addressed the challenge of creating robust, temperature-responsive shape-stabilizing polymer gels (i.e., salogels) using a low cost PCM, calcium chloride hexahydrate (CaCl2·6H2O, CCH). Due to the extremely high (9 M) concentration of chloride ions and the tendency to salting-out polymer chains, the previous strategy of using single-polymer salogels was not successful. Thus, this work introduced a strategy of using two polymers, poly(vinyl alcohol) and ultrahigh molecular weight polyacrylamide (PVA and PAAm, respectively), along with borax as a cross-linker to achieve temperature-reversible, shape-stable salogels. This system resulted in robust salogels whose gel-to-sol transition temperature (Tgel) was tunable within an application-relevant range of gelation temperature (30-80 °C). This behavior was enabled by a synergistic combination of dynamic covalent cross-links between PVA units and entanglements of PAAm chains which were combined into a single hybrid network. The hybrid salogels had <5 wt % polymer content, maintaining ∼95% of the heat of fusion of the pure PCM. Importantly, the noncovalent nature of gelation supported thermo-reversibility of gelation, shape stability, and retention of thermal properties over 50 melting/crystallization cycles.

Increasing SARS-CoV2 cases, hospitalizations and deaths among the vaccinated elderly populations during the Omicron (B.1.1.529) variant surge in UK.

BACKGROUNDThere were increased SARS-CoV2 hospitalizations and deaths noted during Omicron (B.1.1.529) variant surge in the UK despite decreased cases, and the reasons are unclear. METHODSIn this retrospective observational study, we analyzed reported SARS-CoV2 cases, hospitalizations, and deaths during the COVID-19 pandemic in the UK. We also analyzed variables that affect the outcomes (including ethnicity, deprivation score, vaccination disparities, and pre-existing conditions). We also analyzed the vaccine effectiveness among those [≥]18 years of age (from August 16, 2021 to March 27, 2022). RESULTSOf the total cases (n= 22,072,550), hospitalizations (n=848,911), and deaths (n=175,070) due to COVID-19 in the UK; 51.3% of cases (n=11,315,793), 28.8% of hospitalizations (n=244,708), and 16.4% of deaths (n=28,659) occurred during the Omicron variant surge as of May 1, 2022. During the latter part of the Omicron variant surge (February 28 - May 1, 2022 period), we observed a significant increase in the proportion of cases (23.7% vs 40.3%; RR1.70 [1.70-1.71]; p<0.001) and hospitalizations (39.3% vs 50.3%; RR1.28 [1.27-1.30]; p<0.001) among [≥]50 years of age, and deaths (67.89% vs 80.07%; RR1.18 [1.16-1.20]; p<0.001) among [≥]75 years of age compared to the earlier period (December 6, 2021-February 27, 2022) during the Omicron variant surge. Using the available data from vaccine surveillance reports, we compared the Omicron variant surge (December 27, 2021-March 20, 2022) with the Delta variant surge (August 16-December 5, 2021). Our comparative analysis shows a significant decline in case fatality rate (all ages [0.21% vs 0.39%; RR 0.54 (0.52-0.55); p<0.001], over 18 years of age [0.25% vs 0.58%; RR 0.44 (0.43-0.45); p<0.001], and over 50 years of age [0.72% vs 1.57%; RR 0.46 (0.45-0.47); P<0.001]) and the risk of hospitalizations (all ages [0.62% vs 0.99%; RR 0.63 (0.62-0.64); p<0.001], over 18 years of age [0.67% vs 1.38%; RR 0.484 (0.476-0.492); p<0.001], and over 50 years of age [1.45% vs 2.81%; RR 0.52 (0.51-0.53); p<0.001]). Both the unvaccinated (0.41% vs 0.77%; RR 0.54 (0.51-0.57); p<0.001) and vaccinated (0.25% vs 0.59%; RR 0.43 (0.42-0.44); p<0.001) populations of over 18 years of age showed a significant decline in the case fatality rate during the Omicron variant surge when compared to the Delta variant surge. In summary, a significant decline in the risk of hospitalizations was observed both among the unvaccinated (1.27% vs 2.92%; RR 0.44 (0.42-0.45); p<0.001) and vaccinated (0.65% vs 1.19%; RR 0.54 (0.53-0.55); p<0.001) populations of over 18 years of age during the same period. We observed negative vaccine effectiveness (VE) for the third dose since December 20, 2021, with a significantly increased proportion of SARS-CoV2 cases hospitalizations, and deaths among the vaccinated; and a decreased proportion of cases, hospitalizations, and deaths among the unvaccinated. The pre-existing conditions were present in 95.6% of all COVID-19 deaths. We also observed various ethnicity, deprivation score, and vaccination rate disparities that can adversely affect hospitalizations and deaths among the compared groups based on vaccination status. CONCLUSIONSThere is no discernable optimal vaccine effectiveness among [≥]18 years of age and vaccinated third dose population since the beginning (December 20, 2021) of the Omicron variant surge. Other data including pre-existing conditions, ethnicity, deprivation score, and vaccination rate disparities need to be adjusted by developing validated models for evaluating VE against hospitalizations and deaths. Both the vaccinated and unvaccinated populations showed favorable outcomes with a significant decline in case fatality rate and risk of hospitalizations during the Omicron variant surge. The suboptimal vaccine effectiveness with an increased proportion of cases among the vaccinated population was associated with a significantly increased proportion of hospitalizations and deaths during the Omicron variant surge. This underscores the need to prevent infections, especially in the elderly vaccinated population irrespective of vaccination status by employing uniform screening protocols and protective measures.

Changing dynamics of SARS-CoV2 B.1.617.2 (Delta variant) outbreak in the United Kingdom: Shifting of SARS-CoV2 infections from younger to elderly populations with increasing hospitalizations and mortality among elderly.

BackgroundTo assess the comprehensive dynamics of outcomes during the SARS-CoV2 B.1.617.2 (Delta variant) compared to the Alpha variant outbreak in the United Kingdom. MethodsIn this observational study of the cases reported by Public Health England for confirmed (sequencing and genotyping), SARS-CoV2 cases Delta variant (n=592,692) and Alpha variant (n=150,934) were used. Outcomes were analyzed by age groups and compared with all reported weekly cases in the UK. ResultsThe Delta variant surge is associated with a significantly lower case fatality rate (0.43% vs 1.07; RR 0.39; 95% CI 0.37-0.42; P<0.0001); lower odds of hospitalization (2.1% vs 3.0%; RR 0.70; 95% CI 0.68-0.73; P<0.0001) than the Alpha variant. During the Delta variant surge there were significant increased cases (11.3% to 21.1%, RR 1.87; 95% CI 1.84-1.89; P<0.0001), hospitalizations (40.2% to 56.5%; RR 1.40, 95% CI 1.3-1.46; P<0.0001) among confirmed Delta variant cases in the [≥]50 years age group during the August 3-September 12, 2021 period compared to earlier reported cases. There was also a significant increase in total weekly COVID-19 deaths noted among [≥]70 years old age group (71.4% to 75.1%; RR 1.05; 95% CI 1.01-1.08; P=0.0028) during August 6-October 8, 2021 compared to June 4-July 30, 2021 period. ConclusionsThe Delta variant surge is associated with significantly lower mortality and hospitalizations than the Alpha variant. As the Delta variant surge progressed, [≥]50 years old had a significant increased percentage of cases, hospitalizations and a significant increased COVID-19 deaths occurred among [≥]70 years old age group.

A machine learning-based approach to determine infection status in recipients of BBV152 whole virion inactivated SARS-CoV-2 vaccine for serological surveys

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the effectiveness of interventions. Asymptomatic breakthrough infections have been a major problem during the ongoing surge of Delta variant globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines used in the higher-income regions. Here, we show for the first time how statistical and machine learning (ML) approaches can discriminate SARS-CoV-2 infection from immune response to an inactivated whole virion vaccine (BBV152, Covaxin, India), thereby permitting real-world vaccine effectiveness assessments from cohort-based serosurveys in Asia and Africa where such vaccines are commonly used. Briefly, we accessed serial data on Anti-S and Anti-NC antibody concentration values, along with age, sex, number of doses, and number of days since the last vaccine dose for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine (SVM) model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, 724 were classified as infected. Since the vaccine contains wild-type virus and the antibodies induced will neutralize wild type much better than Delta variant, we determined the relative ability of a random subset of such samples to neutralize Delta versus wild type strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, Delta variant, was neutralized more effectively than the wild type, which cannot happen without infection. The fraction rose to 71.8% (28 of 39) in subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period.

Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2.

Immunization is expected to confer protection against infection and severe disease for vaccinees, while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies, we show that during a severe SARS-CoV2 Delta-variant outbreak in Delhi, 25.3% (95% CI 16.9 - 35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare-workers (HCW) were infected within a period of less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, IQR 374) or not (342 U/ml, IQR 497), as was induction of neutralization activity to wildtype. Most infections were unrecognized. The Delta-variant thus causes frequent unrecognized breakthrough infections in adequately immunized subjects, reducing any herd-effect of immunity, and requiring reinstatement of preventive measures such as masking.

Drug-induced modifications and modulations of microRNAs and long non-coding RNAs for future therapy against Glioblastoma Multiforme.

Non-coding RNAs are known to participate in cancer initiation, progression, and metastasis by regulating the status of chromatin epigenetics and gene expression. Although these non-coding RNAs do not possess defined protein-coding potential, they are involved in the expression and stability of messenger RNA (mRNA). The length of microRNAs (miRs) ranges between 20 and 22 nt, whereas, long non-coding RNAs (lncRNAs) length ranges between 200 nt to 1 Kb. In the case of circular RNAs (circRNAs), the size varies depending upon the length of the exon from where they were derived. Epigenetic regulations of miR and lncRNA genes will influence the gene expression by modulating histone acetylation and methylation patterns. Especially, lncRNAs will act as a scaffold for various epigenetic proteins, such as EZH2 and LSD1, and influence the chromatin epigenetic state at various genomic loci involved at silencing. Thus investigations on the expression of lncRNAs and designing drugs to modulate the expression of these genes will have a profound impact on future therapeutics against cancers such as Glioblastoma Multiforme (GBM) and also against various other diseases. With the recent advancements in genome-wide transcriptomic studies, scientists are focused on the non-coding RNAs and their regulations on various cellular processes involved in GBM and on other types of cancer as well as trying to understand possible epigenetic modulations that help in generating promising therapeutics for the future generations. In this review, the involvement of epigenetic proteins, enzymes that change chromatin architecture and epigenetic landscape and new roles of lncRNAs that are involved in GBM progression are elaborately discussed.

Levan production from sucrose using chicken feather peptone as a low cost supplemental nutrient source.

Chicken feather peptone (CFP) derived from poultry waste is a rich source of essential minerals and amino acids. This, along with suitable carbon source, can be used as a low cost complex supplemental nutrient source for microbial fermentation. In the present work, CFP blended with sucrose was evaluated for the production of levan using Bacillus subtilis MTCC 441. Amount of CFP added to the medium significantly influenced levan production and it was found that at a concentration 2 g/L, maximum levan yield of 0.26 ±â€¯0.04 g/g sucrose was obtained. The levan yield obtained with CFP as a low cost supplemental nutrient source was comparable with that obtained from commercial medium (0.31 ±â€¯0.02 g/g sucrose). Levan produced using CFP was tested on primary cell lines at various concentrations (100-1000 µM) and found to be non-toxic and bio-compatible in nature. This indicates that CFP could be used as low cost nutrient source for levan production.

In-silico and in-vitro analysis of endocan interaction with statins.

Endocan known as a cardiovascular inflammatory biomarker, found to be elevated in atherosclerosis. However, the 3D structure and the stimulatory effect of endocan on macrophages are unknown. Hence, we predicted the three-dimensional structure of human endocan and calculated the binding efficiency of statins towards endocan and determined their inhibition potential. Molecular docking studies of simvastatin (-9.64 kcal/mol) showed that binding is stabilized by the hydrogen bonds with Cys60, Cys54 residues, and several hydrophobic interactions. Moreover, MD simulations and pull-down assay results confirmed that simvastatin binding is stable with human endocan. In-silico results obtained in the present study were validated under in-vitro condition by analysing the effect of endocan under simvastatin treatment. Western blot results have shown that simvastatin could reduce endocan expression in LPS-treated endothelial cells. Further, endocan treatment in RAW 264.7 macrophages stimulates NO, ROS production and increases iNOS, CRP expression. However, endocan and simvastatin combination treatment could suppress NO, ROS production and iNOS, CRP activation. The present study results suggest that endocan could induce vascular inflammation in macrophages. In addition, the results showed that simvastatin could interact with endocan and thereby suppress the stimuli-induced effect. Thus, endocan may play a role in atherogenesis by activating macrophages.

Corrigendum to "Studies on solvent precipitation of levan synthesized using Bacillus subtilis MTCC 441" [Heliyon 5 (9) (September 2019) e02414].

[This corrects the article DOI: 10.1016/j.heliyon.2019.e02414.].

Studies on solvent precipitation of levan synthesized using Bacillus subtilis MTCC 441.

Levan is a water soluble biopolymer widely used in food, pharma, personal care and aquaculture industries. In this work, levan was synthesized by Bacillus subtilis MTCC 441 using sucrose as a sole carbon source. Effects of pH, sucrose concentration, nitrogen source, nitrogen concentration, inoculum size and agitation speed on levan production were studied. Yeast extract (YE) was found to be the best nitrogen source. Sucrose concentration - 100 g/L, pH - 7, YE concentration - 2 g/L, inoculum size 10% (v/v) and RPM - 150 were found to be optimal values for levan production. Effects of precipitation pH (3-12), choice of solvent (ethanol, isopropanol, acetone, and methanol) and supernatant to solvent ratio (1:1 to 1:6) on levan yield were also studied. Isopropanol resulted in maximum levan recovery among the four solvents considered. Optimal pH and supernatant to solvent ratio for levan precipitation were found to be 11 and 1:5, respectively. Corresponding levan yield was 0.395 g/g of sucrose supplied. The product obtained was characterized using FTIR, 1H-NMR, 13C-NMR, and GPC. The cytotoxicity of the precipitated levan was studied on EA.hy926 cell line using MTT assay and the compound was proven to be non-toxic to the cells.

Ex vivo Caprine Model to Study Virulence Factors in Keratitis.

PURPOSE: To develop an infectious keratitis model using caprine (goat) corneas and to investigate the expression of virulence factors during infection. METHODS: Goat eyes were surface-sterilized and dissected, and the corneas were placed on an agarose-gelatin solid support (0.5% in phosphate-buffered saline) in a 12-well culture plate containing 10% fetal bovine serum-supplemented culture medium for 3 weeks. Cell viability tests (trypan blue and MTT) were performed on the cultured corneas. Corneas were infected with Pseudomonas aeruginosa and Fusarium solani separately. Infection progression was observed via histological analysis and hematoxylin and eosin (H-E) staining. For Pseudomonas-infected corneas, expression of eight virulence genes (exoS, exoT, exoY, alpR, prpL, lasA, lasB, and algD) was determined via quantitative real-time PCR (qRT-PCR) at 48-h and 72-h time-points. For Fusarium-infected corneas, expression of five proteases (C7Z0E6, C7ZFW9, C7Z7U2, C7ZNV5, and C7YY94) was quantified via qRT-PCR at 2, 4, and 8 days after infection. Protease from infected corneas was detected via gelatin zymography. RESULTS: Goat corneas with a viable epithelium could be maintained for 15 days. Pseudomonas infection progressed rapidly, and complete corneal degradation was observed on day 4 after infection. Fusarium infection progressed more slowly. Histological analysis and H-E staining of Fusarium-infected cornea revealed mycelia penetrating all layers of the cornea. qRT-PCR revealed expression of all eight virulence factors, and statistically significant difference in expression of prpL and alpR in Pseudomonas-infected corneas. Expression of C7ZNV5 was highest in Fusarium-infected corneas. CONCLUSION: Goat corneas can be used to evaluate the expression of virulence factors involved in Pseudomonas and Fusarium infection.

Gold nanoparticles electroporation enhanced polyplex delivery to mammalian cells.

Nonviral methods have been explored as the replacement of viral systems for their low toxicity and immunogenicity. However, they have yet to reach levels competitive to their viral counterparts. In this paper, we combined physical and chemical methods to improve the performance of polyplex delivery of DNA and small interfering RNA. Specifically, gold nanoparticles (AuNPs) were used to carry polyplex (a chemical approach) while electroporation (a physical approach) was applied for fast and direct cytosolic delivery. In this hybrid approach, cationic polymer molecules condense and/or protect genetic probes as usual while AuNPs help fix polycations to reduce their cytotoxicity and promote the transfection efficiency of electroporation. AuNPs of various sizes were first coated with polyethylenimine, which were further conjugated with DNA plasmids or small interfering RNA molecules to form AuNPs-polyplex. The hybrid nanoparticles were then mixed with cells and introduced into cell cytosol by electroporation. The delivery efficiency was evaluated with both model anchor cells (i.e., NIH/3T3) and suspension cells (i.e., K562), together with their impact on cell viability. We found that AuNP-polyplex showed 1.5∼2 folds improvement on the transfection efficiency with no significant increase of toxicity when compared to free plasmid delivery by electroporation alone. Such a combination of physical and chemical delivery concept may stimulate further exploration in the delivery of various therapeutic materials for both in vitro and in vivo applications.