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The endoplasmic reticulum (ER) regulates protein folding and maintains proteostasis in cells. We observed that the ER transcriptome is impaired during chronic reductive stress (RS) in cardiomyocytes. Here, we hypothesized that a prolonged moderate treadmill exercise mitigates the RS-induced ER dysfunction and cardiac remodeling in cardiac-specific constitutively active Nrf2 mice (CaNrf2-TG). RNA sequencing showed notable alterations in the ER transcriptome of TG hearts at 4, 12, and 24 weeks (16, 28, and 35 genes, respectively). Notably, the downregulation of ER genes was significant at 12 weeks, and further pronounced at 24 weeks, at which the cardiac pathology is evident. We also observed increased levels of ubiquitinated proteins in CaNrf2-TG hearts across all ages, along with VCP, a marker of ERAD function, at 24 weeks. These findings indicate that constitutive Nrf2 activation and RS impair protein-folding activity and augments ERAD function over time. Exercise intervention for 20 weeks (beginning at 6 weeks of age), reduced cardiomyocyte hypertrophy (from 448 μm2 to 280 μm2) in TG mice, through adaptive remodeling, and preserved the cardiac function. However, while exercise did not influence antioxidants or ER stress protein levels, it significantly improved ERAD function and autophagy flux (LC-I to LC-II) in the TG-EXE hearts. Collectively, our findings underscore the prophylactic potential of exercise in mitigating RS-associated pathology, highlighting its essential role in maintaining cellular proteostasis through ER-independent mechanisms.

A product of microorganisms, crop plants, and animal-based oil, biodiesel holds excellent promise as a sustainable energy resource and a solution to the world's rising energy issues. Biofuel resembles the qualities of fossil diesel, while it is also proven to be a greener fuel and viable alternative. To enhance the properties of biodiesel, the additives, mainly antioxidants, were added to the 20 % blend of safflower biodiesel (B20) at various injection pressures (190, 200, and 210 bar). At a concentration of 1000 ppm, the antioxidants, namely BHA (butylated hydroxy anisole) and BHT (butylated hydroxytoluene), were added to the B20 blend of higher IP. Investigation on the effects of antioxidants with biodiesel on the performance and emission characteristics were tested in CI diesel engines at different injection pressures (IP). The findings from this study indicate that antioxidants added to biodiesel significantly improved the engine's performance. Higher IP resulted in higher BTE (1.6 %) with lesser emissions of CO (33.33 %), HC (10 %) and smoke (19.5 %) than diesel. But it emits higher NOx emissions (2.5 %). The addition of the antioxidant BHA showed a decrease in NOx emissions by 5 % to higher IP. Thus, the safflower biodiesel B20 added with antioxidant BHA will likely be a tremendous alternate fuel for the CI engine.

The effects of gamma irradiation on Cadmium-doped PbS (Cd-PbS) nanoparticles are thoroughly examined in this lattice study. The study sheds light on the changes in structural, morphological, and electrical properties brought about by Cd doping and gamma irradiation by employing a variety of methods such as X-ray diffraction, FESEM imaging, EDAX analysis, Raman spectroscopy, photoluminescence (PL) spectra, and Hall effect measurements. The Cd-doped PbS shows a fluctuating crystallite size as the average size first increases by ∼3 nm and then decreases by ∼3 nm with Cd concentration. This is due to the induced strain by the Cd dopant, which has a smaller ionic radius compared to Pb ions. With Cd substitution, the bandgap of PbS first decreases from 2.29 eV to 2.19 eV and then increases with mild fluctuations. Meanwhile, gamma irradiation causes these changes, decreasing the bandgap from 2.19 eV to 2.03 eV for lower Cd concentrations (x = 0.005) and increasing it to 2.41 eV for higher concentrations (x=0.01). The Hall data shows a wide range shift in electrical characteristics between the cadmium doped gamma-irradiated sample, and the pure sample, PS0. The electrical mobility increases from 6.05 V − 1s−1 for PS0 to 4.95×102 V − 1s−1 for GPS3 (higher cadmium concentration of x = 0.02), indicating a significant enhancement in which charge carriers can move through the material post-irradiation. Electrical resistivity shows a drastic increase from 4.42×101 Ωcm in PS0 to 9.41×102 Ωcm in GPS3, suggesting a marked increase in electrical conductivity post-irradiation. The findings demonstrate considerable changes in crystal characteristics, morphological transformations, increased crystallinity, and changed electrical properties, showing the promise of gamma-irradiated Cd-doped PbS in advanced optoelectronic device applications.

The present work focused on molecular structure and various spectroscopic studies of 2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy] acetic acid is also called as Ethacrynic acid (EA). The B3LYP/6-311G(d,p) level of theory was adopted to compute the molecular geometry (monomer and dimer) for EA molecule, the computed geometrical parameters are well coincided with related XRD data. The Natural Bond Orbital (NBO) was calculated to find donor-acceptor interaction. The vibrational modes of EA molecule was computed by B3LYP/6-311G(d,p) method and assignments were carried out by finding Potential Energy Distribution (PED) using VEDA software. The deviation in wavenumber of O-H vibrations (in COOH) group evident the intermolecular hydrogen bond interaction is possible between nearby molecules. The Gauge Independent Atomic Orbital (GIAO) method is used to find 1H and 13C NMR chemical shift and correlated with recorded NMR spectrum. The Time-Dependent density functional theory (TD-DFT) is used to determine the various electronic parameters. The intra, inter molecular and non covalent interactions of the EA molecule are examined by Atoms in Molecules (AIM), ELF, LOL and RDG analysis. From AIM analysis the EA molecule form C-H…...Cl hydrogen bond of energies 1.2863 and 1.1922 Kcal/mol in both monomer and dimer were determined. Mulliken atomic charge analysis is used find the electronegativity equalization and charge transfer in the molecular system. Fukui function carried out to identify electrophilic and nucleophilic attack in the EA molecule. Thermal (DTA) and thermogravimetric (TG) analyzes adopted to determine the thermal behavior of compound which denote the compound dissociate around 122.5 °C. The thermodynamic parameters for different temperature were also calculated by B3LYP/6-311G(d,p) method. The EA compound was monitor to the antibacterial activity by agar well diffusion method. Molecular docking analysis carried out using Autodock software with protein inhibit thyroid and breast cancer show binding energies of -4.79 and -3.99 Kcal/mol.

Stem cells exhibit pluripotency and self-renewal abilities. Adipose-derived mesenchymal stem cells can potentially be used to reconstruct various tissues. They possess significant versatility and alleviate various aging-related diseases. Unfortunately, aging leads to senescence, apoptosis, and a decline in regenerative capacity in adipose-derived mesenchymal stem cells. These changes necessitate a strategy to mitigate the effects of aging on stem cells. Ohwia caudata (O. caudata) has therapeutic effects against several illnesses. However, studies on whether O. caudata has therapeutic effects against aging are lacking. In this study, we aimed to identify potential therapeutic anti-aging effects in the crude aqueous extract of O. caudata on adipose-derived mesenchymal stem cells. Using 0.1 μM doxorubicin, we induced aging in human adipose-derived mesenchymal stem cells (hADMSCs) and evaluated whether various concentrations of O. caudata aqueous extract exhibit anti-aging effects on them. The O. caudata extract exhibited significant antioxidant effects on hADMSCs without any toxicity. Furthermore, after treatment with the O. caudata aqueous extract, the levels of mitochondrial superoxide, DNA double-strand breaks, and telomere shortening were reduced in the hADMSCs subjected to doxorubicin-induced aging. The extract also suppressed doxorubicin-induced aging by upregulating klotho and downregulating p21 in hADMSCs. These findings indicated that the O. caudata extract exhibited anti-aging properties that modulated hADMSC homeostasis. Therefore, it could be a potential candidate for restoring the self-renewal ability and multipotency of aging hADMSCs.

In this work, vanadium pentoxide (V2O5) and titanium-modified V2O5 thin films were synthesized using the sol-gel spin coating route. The effect of Ti-doping concentration on the electrochromic optical properties and atomic/electronic structures of V2O5 smart thin films is examined. As the doping concentration of Ti increases, the surface roughness of the films is reduced. The structure of the films is analyzed using X-ray diffraction (XRD) and Raman spectroscopy, while the electrochromic modulation of atomic and electronic structures is elucidated through Raman and X-ray absorption spectroscopy (XAS) conducted during lithiation and delithiation. The XRD patterns demonstrate that an increase in Ti concentration leads to a more amorphous structure of the films and a shift of the main diffraction peak to a lower angle, attributable to the enlarged spacing between the stacking layers resulting from the incorporation of Ti ions. Soft X-ray absorption spectroscopy (XAS) and in situ hard XAS of the V L-edge, the O K-edge, and the V K-edge revealed a reduction in the charge state of V and local atomic structural symmetry modification upon lithated coloration and delithiated bleaching process. The critical insights provided by in situ XAS provides reveal that a small amount of Ti has the ability to modify the interlayer distance and local atomic structure of V2O5, thereby improving its electrochromic switching rate and stability when utilized in smart windows.

Summary: Background: Dengue shows high geographic heterogeneity within and across endemic countries. In the context of increasing burden and predicted outbreaks due to climate change, understanding the heterogeneity will enable us to develop region specific targeted interventions, including vaccination. World Health Organisation (WHO) suggests standard methodologies to study the burden and heterogeneity at national and subnational levels. Regional studies with robust and standard methodology to capture heterogeneity are scarce. We estimated the seroprevalence of dengue in children aged 9–12 years and the force of infection in Kerala, India, from where Zika cases also have been reported recently. Methods: We conducted a school-based cross-sectional survey in 38 clusters; selected by stratified random sampling, representing rural, urban, high burden and low-burden administrative units. Validation of Indirect IgG ELISA was done by Plaque Reduction Neutralization Test (PRNT90) using the local isolates of all four serotypes. Force of infection (FOI) was estimated using the WHO-FOI calculator. We conducted a follow-up survey among a subsample of seronegative children, to estimate the rate of sero-conversion. Results: Among 5236 children tested, 1521 were positive for anti-dengue IgG antibody. The overall seroprevalence in the state was 29% (95% CI 24.1–33.9). The validity corrected seroprevalence was 30.9% in the overall sample, 46.9% in Thiruvananthapuram, 26.9% in Kozhikkode and 24.9% in Kollam. Age-specific seroprevalence increased with age; 25.7% at 9 years, 29.5% at 10 years, 30.9% at 11 years and 33.9% at 12 years. Seroprevalence varied widely across clusters (16.1%–71.4%). The estimated force of infection was 3.3/100 person-years and the seroconversion rate was 4.8/100 person-years. 90% of children who tested positive were not aware of dengue infection. All the four serotypes were identified in PRNT and 40% of positive samples had antibodies against multiple serotypes. Interpretation: The study validates the WHO methodology for dengue serosurveys and confirms its feasibility in a community setting. The overall seroprevalence in the 9–12 year age group is low to moderate in Kerala; there are regional variations; high burden and low burden clusters co-exist in the same districts. The actual burden of dengue exceeds the reported numbers. Heterogeneity in prevalence, the high proportion of inapparent dengue and the hyperendemic situation suggest the need for region-specific and targeted interventions, including vaccination. Funding: World Health Organization.

Summary: Background: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18–45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April–May 2021. Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18–45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p

Summary: Adeno-associated virus (AAV) is a member of the genus Dependoparvovirus, which infects a wide range of vertebrate species. Here, we observe that, unlike most primate AAV isolates, avian AAV is transcriptionally silenced in human cells. By swapping the VP1 N terminus from primate AAVs (e.g., AAV8) onto non-mammalian isolates (e.g., avian AAV), we identify a minimal component of the AAV capsid that controls viral transcription and unlocks robust transduction in both human cells and mouse tissue. This effect is accompanied by increased AAV genome chromatin accessibility and altered histone methylation. Proximity ligation analysis reveals that host factors are selectively recruited by the VP1 N terminus of AAV8 but not avian AAV. Notably, these include AAV essential factors implicated in the nuclear factor κB pathway, chromatin condensation, and histone methylation. We postulate that the AAV capsid has evolved mechanisms to recruit host factors to its genome, allowing transcriptional activation in a species-specific manner.

Escalating concern over global warming, which is mostly associated with deforestation, has led to the development of new classes of materials that can replace wood and better utilise natural resources. Presently, waste is a significant factor in recycling. In this regard, one of the leading contributors to waste is agricultural waste, which includes dried branches, leaves of trees, plants, and other organic materials. In the current study, waste from corn agriculture was utilised as a potential reinforcement for the fabrication of corn stalk-low density polyethylene (CS-LDPE) composites via an injection moulding technique at 170 °C. The different parameters were assessed to develop composites using CS, including physico-chemical, macromolecular, mineralogical, elemental, and morphological analysis. The amount of corn stalk (CS) was varied from 10 to 50 wt% with respect to the polymer. The mechanical, physical and thermal performance of the composites was examined. The density and water absorption of the composites were found to remain within the ranges of 1.00–1.11 g/cm3 and 0.22–1.01 %, respectively, whereas these parameters increased as the proportion of CS increased. The thermal conductivity decreases with the addition of CS from 0.36964 ± 0.020 to 0.22388 ± 0.002 W/mK. It was observed that adding CS to the composites increased their tensile and flexural properties, but decreased their impact strength. The maximum flexural strength of 14.40 ± 1.558 MPa, flexural modulus of 752.53 ± 180.409 MPa, tensile strength of 10.49 ± 0.946 MPa and tensile modulus of 539.79 ± 91.044 MPa were observed with a 50 % CS content. The results suggest that these materials have considerable potential to serve as a cost-effective substitute for the conventional lignocellulosic fillers in the manufacturing of wood-plastic composites.

Objectives: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. Methods: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. Results: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. Conclusion: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.

Objective: To find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period. Methods: This was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke. Results: 410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) Conclusions: In this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher.

In this study we have reported sodium tartrate (ST) and Zn2+ as the potential mixed corrosion inhibitors for copper corrosion in drinking water, by using electrochemical impedance and polarization techniques. The results of potentio-dynamic polarization indicated that sodium tartrate could be used as mixed type inhibitor with Zn2+. ST was found to be 92% effective for slowing down both the anodic and cathodic reaction rates. It was additionally found that ST could coat the surface of copper to prevent it from conducting electricity. As the inhibitor concentration increased, the stability of the formed protective layer was also improved. The results obtained from studies like SEM, EDAX, AFM, and water contact angle clearly indicated the development of a barrier by inducing the lotus effect on copper surface. The water contact angle measurement results suggested that the coating formed in the presence of inhibitor was superhydrophobic, and the surface was homogeneous.

In this work, the mixture of trisodium cittrate and Zn2+ was used as binary (hetero type) inhibitor for corrosion inhibition of copper metal in potable water. The binary inhibitor system (Zn2+ and trisodium citrate) was used to form hydrophobic surfaces on copper submerged in potable water. Water contact angle (WCA) was found to be 155°4° when the inhibitor was present, whereas it was 84°2° when there was no inhibitor. These observations suggested the development of superhydrophobic layer on the surface of copper in drinkable water. Electrochemical impedance spectroscopy (EIS – AC mode), and potentiodynamic polarization (DC mode) experiments conveyed that the copper surface could be protected by utilizing the mixture of trisodium citrate and Zn2+ in potable water. The morphological studies including SEM (coupled with EDX), AFM, and WCA were evidenced the formulation of a hetero-type inhibitor for the corrosion inhibition of copper in potable water. In this study, the decline in the double-layer capacitance and the rise in the charge transfer resistance were due to the adsorption of inhibitor confirming the development of protective layer, which EIS, SEM, EDX, AFM, and WCA studies also supported. Thus, there was a synergism observed between TSC and Zn2+, and the formulation consisting of TSC and Zn2+ provided 83% of inhibition efficiency (IEp). So, it was suggested that the approach reported in this study could be a simple method for obtaining the superhydrophobic copper surface.

Summary: The amygdala, cholinergic basal forebrain, and higher-order auditory cortex (HO-AC) regulate brain-wide plasticity underlying auditory threat learning. Here, we perform multi-regional extracellular recordings and optical measurements of acetylcholine (ACh) release to characterize the development of discriminative plasticity within and between these brain regions as mice acquire and recall auditory threat memories. Spiking responses are potentiated for sounds paired with shock (CS+) in the lateral amygdala (LA) and optogenetically identified corticoamygdalar projection neurons, although not in neighboring HO-AC units. Spike- or optogenetically triggered local field potentials reveal enhanced corticofugal—but not corticopetal—functional coupling between HO-AC and LA during threat memory recall that is correlated with pupil-indexed memory strength. We also note robust sound-evoked ACh release that rapidly potentiates for the CS+ in LA but habituates across sessions in HO-AC. These findings highlight a distributed and cooperative plasticity in LA inputs as mice learn to reappraise neutral stimuli as possible threats.

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Objectives: Safety-net hospitals (SNHs) provide essential services to predominantly underserved patients regardless of their ability to pay. We hypothesized that patients who underwent coronary artery bypass grafting (CABG) would have inferior observed outcomes at SNHs compared with non-SNHs but that matched cohorts would have comparable outcomes. Methods: We queried the Nationwide Readmissions Database for patients who underwent isolated CABG from 2016 to 2018. We ranked hospitals by the percentage of all admissions in which the patient was uninsured or insured with Medicaid; hospitals in the top quartile were designated as SNHs. We used propensity-score matching to mitigate the effect of confounding factors and compare outcomes between SNHs and non-SNHs. Results: A total of 525,179 patients underwent CABG, including 96,133 (18.3%) at SNHs, who had a greater burden of baseline comorbidities (median Elixhauser score 8 vs 7; P = .04) and more frequently required urgent surgery (57.1% vs 52.8%; P

The growing demand for sustainable, lightweight yet rigid and cost-effective materials for airplane construction served as the impetus for this work. An E-glass fiber (400 GSM) is layered in a 6:2 ratio with natural basalt fiber and infused with graphene nanoparticles to produce a more appealing 40% lighter hybrid composite of 1.1 mm thickness for the aviation industry. Samples of hybrid composites with 1% and 2% graphene-to-fiber filler weight ratios are used. Then, using ASTM standard analysis tools, the damage that is caused on toughened laminates during low-velocity drop weight impact tests, tensile, 3-point bending, and Compression After Impact(CAI) is evaluated. The composites' tensile strength, flexural strength, low-velocity double impact, and compression impact strength all significantly improved at 2 wt% graphene, increasing by 37%, 55%, 56%, and 78%, respectively. Scanning Electron Microscope analysis of the damaged area demonstrated the presence of important toughening mechanisms, such as damage confinement through microcracks and improved fiber-matrix bonding. It has been established that adding an optimum blend of graphene and basalt to Glass Fiber Reinforced Polymer(GFRP) results in an unprecedented increase in effective strength with reduced weight.

Coronavirus disease 2019 (COVID-19) is a worldwide health threat that has long-term effects on the patients and there is currently no efficient cure prescribed for the treatment and the prolonging effects. Traditional Chinese medicines (TCMs) have been reported to exert therapeutic effect against COVID-19. In this study, the therapeutic effects of Jing Si herbal tea (JSHT) against COVID-19 infection and associated long-term effects were evaluated in different in vitro and in vivo models. The anti-inflammatory effects of JSHT were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in Omicron pseudotyped virus-induced acute lung injury model. The effect of JSHT on cellular stress was determined in HK-2 proximal tubular cells and H9c2 cardiomyoblasts. The therapeutic benefits of JSHT on anhedonia and depression symptoms associated with long COVID were evaluated in mice models for unpredictable chronic mild stress (UCMS). JSHT inhibited the NF-ƙB activities, and significantly reduced LPS-induced expression of TNFα, COX-2, NLRP3 inflammasome, and HMGB1. JSHT was also found to significantly suppress the production of NO by reducing iNOS expression in LPS-stimulated RAW 264.7 cells. Further, the protective effects of JSHT on lung tissue were confirmed based on mitigation of lung injury, repression in TMRRSS2 and HMGB-1 expression and reduction of cytokine storm in the Omicron pseudotyped virus-induced acute lung injury model. JSHT treatment in UCMS models also relieved chronic stress and combated depression symptoms. The results therefore show that JSHT attenuates the cytokine storm by repressing NF-κB cascades and provides the protective functions against symptoms associated with long COVID-19 infection.

Due to the inconsistency of rice variety, agricultural industry faces an important challenge of rice grading and classification by the traditional grading system. The existing grading system is manual, which introduces stress and strain to humans due to visual inspection. Automated rice grading system development has been proposed as a promising research area in computer vision. In this study, an accurate deep learning-based non-contact and cost-effective rice grading system was developed by rice appearance and characteristics. The proposed system provided real-time processing by using a NI-myRIO with a high-resolution camera and user interface. We firstly trained the network by a rice public dataset to extract rice discriminative features. Secondly, by using transfer learning, the pre-trained network was used to locate the region by extracting a feature map. The proposed deep learning model was tested using two public standard datasets and a prototype real-time scanning system. Using AlexNet architecture, we obtained an average accuracy of 98.2% with 97.6% sensitivity and 96.4% specificity. To validate the real-time performance of proposed rice grading classification system, various performance indices were calculated and compared with the existing classifier. Both simulation and real-time experiment evaluations confirmed the robustness and reliability of the proposed rice grading system.

Gamma irradiation at specific doses controls the material properties of thin films because of its high-ionization energy and high penetrating power. In the present work, the effects of gamma irradiation (γ-rays) on the structural, morphological, electrical, and optical properties of pulsed laser-deposited SnO2 thin films were examined. These films were exposed to γ-rays for doses of 0, 75, 100, 125, and 200 kGy. X-ray diffraction analysis reveals that the films are polycrystalline with a crystallite size of 49.27 nm and it increases with the gamma doses. While the dislocation density and the microstrain decrease, the band gap reduces from 3.8 eV to 3.4 eV with the increase in doses. Raman spectra show the presence of defects caused by gamma irradiation and the photo luminance spectra demonstrate a decrease in the peak intensities for thin films. The blue emission at 437 nm, is associated with oxygen-related defects produced during the phase formation. The Hall measurements confirm that these films are of n-type semiconductors. The I–V characteristics show a rise in conductivity linearly up to 125 kGy and a reduction at 200 kGy due to oxygen vacancies created at the higher gamma doses. The electrical conductivity of all the films increases as a function of temperature, and gamma doses as evident from the rectification behavior. This study infers that gamma rays can modify the material properties hence these films are useful as an electrode for sensing and radiation detection.

Summary: Epithelial cells of diverse tissues are characterized by the presence of a single apical domain. In the lung, electron microscopy studies have suggested that alveolar type-2 epithelial cells (AT2s) en face multiple alveolar sacs. However, apical and basolateral organization of the AT2s and their establishment during development and remodeling after injury repair remain unknown. Thick tissue imaging and electron microscopy revealed that a single AT2 can have multiple apical domains that enface multiple alveoli. AT2s gradually establish multi-apical domains post-natally, and they are maintained throughout life. Lineage tracing, live imaging, and selective cell ablation revealed that AT2s dynamically reorganize multi-apical domains during injury repair. Single-cell transcriptome signatures of residual AT2s revealed changes in cytoskeleton and cell migration. Significantly, cigarette smoke and oncogene activation lead to dysregulation of multi-apical domains. We propose that the multi-apical domains of AT2s enable them to be poised to support the regeneration of a large array of alveolar sacs.

Background: Emesis gravidarum is a common obstetrical problem affecting 50–80% of pregnant women during their first trimester which begins in the morning and frequently continues throughout the day; considered as one of the Vyakta Garbha Lakshana in Ayurveda. If it is not treated effectively in time; it may lead to complications in pregnancy affecting the quality of life and thus the pregnancy outcome. Objective: To evaluate the clinical effectiveness of Bilwa-Lajadi syrup in emesis gravidarum. Material and methods: A single arm open labeled clinical trial was conducted on 30 participants fulfilling the inclusion criteria from OPD and IPD of Prasuti Tantra Evam StreeRoga, Sri Dharmasthala Manjunatheshwara College of Ayurveda and Hospital, Hassan and administered with Bilwa-Lajadi Syrup 20 ml per day in two divided doses, empty stomach before food for 30 days with followed up every 15 days during treatment and 15 days after completion of trial period. Results: The drug showed statistically significant effect in reducing the frequency of vomiting per day, quantity of vomitus, aversion to smell, nausea and anorexia, altered content of vomitus, improved appetite, imparted lightness of body and increased haemoglobin gm%. Conclusion: Thus, early medication with Bilwa-Lajadi syrup and following dietetic regimen played a vital role in relieving the symptoms of emesis gravidarum.

Circular RNAs (circRNAs) are highly stable RNA molecules that are attractive templates for expression of therapeutic proteins and non-coding RNAs. In eukaryotes, circRNAs are primarily generated by the spliceosome through backsplicing. Here, we interrogate different molecular elements including intron type and length, Alu repeats, internal ribosome entry sites (IRESs), and exon length essential for circRNA formation and exploit this information to engineer robust backsplicing and circRNA expression. Specifically, we leverage the finding that the downstream intron can tolerate large inserts without affecting splicing to achieve tandem expression of backspliced circRNAs and tRNA intronic circRNAs from the same template. Further, truncation of selected intronic regions markedly increased circRNA formation in different cell types in vitro as well as AAV-mediated circRNA expression in cardiac and skeletal muscle tissue in vivo. We also observed that different IRES elements and exon length influenced circRNA expression and translation, revealing an exonic contribution to splicing, as evidenced by different RNA species produced. Taken together, these data provide new insight into improving the design and expression of synthetic circRNAs. When combined with AAV capsid and promoter technologies, the backsplicing introns and IRES elements constituting this modular platform significantly expand the gene expression toolkit.

Introduction: Insulin-like growth factor-I receptor (IGF1R) mediated survival signaling is a crucial mechanism for cellular endurance and a potential indicator of recuperation in deteriorating hearts. Objective: This study evaluates the impact of long-term exercise training in enhancing cardiac survival mechanism in D-galactose-induced toxicity associated aging rats. Methods: Forty-eight male SD-rats were segregated into 4 groups (n=9) and were named as control, exercise training groups, aging group and aging group with exercise training. Aging was induced by intraperitoneal (IP) D-galactose (150 mL/kg) injection for 8 weeks and for exercise training, the rats were left to swim in warm water for 60 min every day and 5 times/week. Western blotting of proteins from the left ventricles was performed to identify the modulations in the survival signaling. Tissue sections were analyzed to determine the extent of fibrosis and apoptosis. Results: Western-blot analysis performed on the excised left ventricles (LV) showed that proteins of the cardiac survival pathway including IGF1R and Akt and the pro-survival Bcl-2 showed significant decrease in the aging group, whereas the levels were restored in the aging rats subjected to exercise training. In addition, aging groups showed increased interstitial space and collagen accumulation. Further, TUNEL assay showed higher number of apoptotic cells in the LV of aging group, which was correlated with increase in the proteins involved in FAS-FADD-dependent apoptosis. However, these aging associated effects were ameliorated upon exercise training in the D-galactose-induced aging rats that showed elevated IGF1R/Akt signaling. Conclusion: The results suggest that IGFIR survival signaling cascadeis elevated in following long-term exercise training and thereby provide cardio-protective benefits in D-galactose induced aging rats.

Objective: Ovarian cancer is one of the most common cancers among Malaysian women with high recurrence. Patients with recurrence are prone to emotional distress and are forced to cope with poor prognosis. This study aimed to explore the coping strategies employed by women with recurrent ovarian cancer in Malaysia, a developing multicultural country in Asia. Methods: This was a qualitative study with patients diagnosed with recurrent ovarian cancer and receiving chemotherapy at a hospital gynecologic day-care unit. In-depth individual interviews were conducted with patients to explore how they coped with recurrence of ovarian cancer. Interviews were audio-recorded, transcribed verbatim, and analyzed thematically. Results: The participants' (n = 10) age range was 52–84 years, the three most common ethnic backgrounds were represented (Malay, Chinese, and Indian), and most of the patients were well educated. All patients were on chemotherapy. Six coping strategies were identified: (1) maintaining a mindset of hopefulness, (2) avoidance of information, (3) accepting their condition, (4) seeking spiritual help, (5) relying on family for support, and (6) coping with financial costs. Conclusions: Coping strategies employed during ovarian cancer recurrence in this setting were rarely based on the accurate information appraisal, but rather on the individual emotion and personal beliefs.

Delivery of therapeutic transgenes with adeno-associated viral (AAV) vectors for treatment of myopathies has yielded encouraging results in animal models and early clinical studies. Although certain AAV serotypes efficiently target muscle fibers, transduction of the muscle stem cells, also known as satellite cells, is less studied. Here, we used a Pax7nGFP;Ai9 dual reporter mouse to quantify AAV transduction events in satellite cells. We assessed a panel of AAV serotypes for satellite cell tropism in the mdx mouse model of Duchenne muscular dystrophy and observed the highest satellite cell labeling with AAV9 following local or systemic administration. Subsequently, we used AAV9 to interrogate CRISPR/Cas9-mediated gene editing of satellite cells in the Pax7nGFP;mdx mouse. We quantified the level of gene editing using a Tn5 transposon-based method for unbiased sequencing of editing outcomes at the Dmd locus. We also found that muscle-specific promoters can drive transgene expression and gene editing in satellite cells. Lastly, to demonstrate the functionality of satellite cells edited at the Dmd locus by CRISPR in vivo, we performed a transplantation experiment and observed increased dystrophin-positive fibers in the recipient mouse. Collectively, our results confirm that satellite cells are transduced by AAV and can undergo gene editing to restore the dystrophin reading frame in the mdx mouse.

Common characteristics of aging include reduced somatic stem cell number, susceptibility to cardiac injuries, metabolic imbalances and increased risk for oncogenesis. In this study, Pleiotropic anti-aging effects of a decoction Jing Si herbal drink (JS) containing eight Traditional Chinese Medicine based herbs, with known effects against aging related disorders was evaluated. Adipose derived mesenchymal stem cells (ADMSCs) from 16 week old adult and 24 month old aging WKY rats were evaluated for the age-related changes in stem cell homeostasis. Effects of JS on self-renewal, klotho and Telomerase Reverse Transcriptase expression DNA damage response were determined by immunofluorescence staining. The effects were confirmed in senescence induced human ADMSCs and in addition, the potential of JS to maintain telomere length was evaluated by qPCR analysis in ADMSCs challenged for long term with doxorubicin. Further, the effects of JS on doxorubicin-induced hypertrophic effect and DNA damage in H9c2 cardiac cells; MPP+-induced damages in SH-SY5Y neuron cells were investigated. In addition, effects of JS in maintaining metabolic regulation, in terms of blood glucose regulation in type-II diabetes mice model, and their potential to suppress malignancy in different cancer cells were ascertained. The results show that JS maintains stem cell homeostasis and provides cytoprotection. In addition JS regulates blood glucose metabolism, enhances autophagic clearances in neurons and suppresses cancer growth and migration. The results show that JS acts on multiple targets and provides a cumulative protective effect against various age-associated disorders and therefore it is a candidate pleiotropic agent for healthy aging.

The rapid increase in the efficiency of perovskite solar cells (PSCs) in last few decades have made them very attractive to the photovoltaic (PV) community. However, the serious challenge is related to the stability under various conditions and toxicity issues. A huge number of articles have been published in PSCs in the recent years focusing these issues by employing different strategies in the synthesis of electron transport layer (ETL), active perovskite layer, hole transport layer (HTL) and back contact counter electrodes. This article tends to focus on the role and classification of different materials used as HTL in influencing long-term stability, in improving the photovoltaic parameters and thereby enhancing the device efficiency. Hole Transport Materials (HTMs) are categorized by dividing into three primary types, namely; organic, inorganic and carbonaceous HTMs. To analyze the role of HTM in detail, we further divide these primary type of HTMs into different subgroups. The organic-based HTMs are subdivided into three categories, namely; long polymer HTMs, small molecule HTMs and cross-linked polymers and the inorganic HTMs have been classified into nickel (Ni) derivatives and copper (Cu) derivatives based HTMs, p-type semiconductor based HTMs and transition metal based HTMs. We further analyze the dual role of carbonaceous materials as HTM and counter electrode in the perovskite devices. In addition, in this review, an overview of the preparation methods, and the influence of the thickness of the HTM layers on the performance and stability of the perovskite devices are also provided. We have carried out a detailed comparison about the various classification of HTMs based on their cost-effectiveness and considering their role on effective device performance. This review further discusses the critical challenges involved in the synthesis and device engineering of HTMs. This will provide the reader a better insight into the state of the art of perovskite solar devices. Keywords: Perovskite solar cells, Hole transporting materials, Organic HTMs, Inorganic HTMs, Carbonaceous HTMs, Photovoltaic parameters

Spray deposited Molybdenum trioxide (MoO3) thin film of thickness nearly 379 nm were irradiated with 200 MeV Ag15+ ion beam at different fluences (Ø) of 5 × 1011, 1 × 1012, 5 × 1012 and 1 × 1013 ions/cm2. The X-ray diffraction (XRD) pattern of the pristine film confirms orthorhombic structure and the crystallinity decreased after irradiation with the fluence of 5 × 1011 ions/cm2 due to irradiation induced defects and became amorphous at higher fluence. In pristine film, Raman modes at 665, 820, 996 cm−1 belong to Mo–O stretching, 286 cm−1 belong to Mo–O bending mode and those below 200 cm−1 are associated with lattice modes. Raman peak intensities decreased upon irradiation and vanished completely for the ion fluence of 5 × 1012 ions/cm2. The percentage of optical transmittance of pristine film was nearly 40%, while for irradiated films it decreased significantly. Red shift was observed for both the direct and indirect band gaps. The pristine film surface had densely packed rod like structures with relatively less porosity. Surface roughness decreased significantly after irradiation. The electrical transport properties were also studied for both the pristine and irradiated films by Hall effect. The results are discussed. Keywords: Ion beam technology, MoO3 thin films, Spray coatings, Optical materials and properties, Radiation damage

In the present study, the role of the Bound Magnetic Polaron (BMP) model is understood in Sm-doped ZnO nanoparticles synthesized via a facile co-precipitation method based on the experimental results from magnetic properties and electronic structures. Experimentally, these compounds exhibit a typical M vs H curve at room temperature depicting ferromagnetic (FM) ordering which decreases exponentially upon doping. Investigation using X-ray diffraction, Raman, and X-ray Photoelectron Spectroscopy (XPS) rule out the role of any impurity phases or micro-clusters of Sm, in the observed FM ordering. Further, O 1s XPS spectra reveal enhancement in the lattice O2− anions in Zn-O bond and reduction in oxygen vacancies (VO) resulting in the modification of oxygen defect structure. In the BMP model, the formation of Sm3+-VO-Sm3+, upon doping is assumed to be an important factor that mediates and stabilizes the FM ordering. By increasing the Sm concentration, the VO decreases, thus reducing the total number of BMPs to 1017cm−3, well below the percolation threshold of 1020 cm−3 resulting in reducing the FM component. This study shows that the BMP model explains the FM ordering in the ZnO host and is sensitive to the concentration of Sm ions and the induced oxygen vacancies play a vital role in stabilizing the FM behavior.

The total ionizing dose (TID) and non ionizing energy loss (NIEL) effects of 100 MeV phosphorous (P7+) and 80 MeV nitrogen (N6+) ions on 200 GHz silicon-germanium heterojunction bipolar transistors (SiGe HBTs) were examined in the total dose range from 1 to 100 Mrad(Si). The in-situ I–V characteristics like Gummel characteristics, excess base current (ΔIB), net oxide trapped charge (NOX), current gain (hFE), avalanche multiplication (M − 1), neutral base recombination (NBR) and output characteristics (IC-VCE) were analysed before and after irradiation. The significant degradation in device parameters was observed after 100 MeV P7+ and 80 MeV N6+ ion irradiation. The 100 MeV P7+ ions create more damage in the SiGe HBT structure and in turn degrade the electrical characteristics of SiGe HBTs more when compared to 80 MeV N6+. The SiGe HBTs irradiated up to 100 Mrad of total dose were annealed from 50 °C to 400 °C in different steps for 30 min duration in order to study the recovery of electrical characteristics. The recovery factors (RFs) are employed to analyse the contribution of room temperature and isochronal annealing in total recovery. Keywords: SiGe HBT, Ion irradiation, Gamma irradiation, Current gain degradation, Isochronal annealing, Recovery factors

Eye movement evaluation is vital for diagnosis of various ophthalmological and neurological disorders. The present study proposes a novel, noninvasive, wearable device to acquire the eye movement based on a Fiber Bragg Grating (FBG) Sensor. The proposed Fiber Bragg Grating Eye Tracker (FBGET) can capture the displacement of the eyeball during its movements in the form of strain variations on a cantilever. The muscular displacement generated by the eyeball over the lower eyelid, by its swiveling action while moving the gaze on a target object, is converted into strain variations on a cantilever. The developed FBGET is investigated for dynamic tracking of the eye-gaze movement for various actions of the eye such as fixations, saccades and main sequence. This approach was validated by recording the eye movement using the developed FBGET as well as conventional camera-based eye tracker methodology simultaneously. The experimental results demonstrate the feasibility and the real-time applicability of the proposed FBGET as an eye tracking device. In conclusion, the present study illustrates a novel methodology involving displacement of lower eyelid for eye tracking application along with the employment of FBG sensors to carry out the same. The proposed FBGET can be utilized in both clinical and hospital environment for diagnostic purposes owing to its advantages of wear-ability and ease of implementation making it a point of care device. Keywords: Fiber Bragg grating sensor, Eye tracker, Eye muscular movement detection

Fisetin, a naturally occurring flavonoid in fruits, nuts and vegetables possess antioxidant and anti-inflammatory properties. This study shows that fisetin exerts preventive and therapeutic effects on hypertension associated cardiac abnormalities in H9c2 cells and Spontaneously Hypertensive Rats (SHRs). For In vitro analysis, H9c2 cells were challenged with AngII and Fisetin (50 µM/mL) was administered either before 2 h or after 12 h of AngII challenge. For In vivo studies, SHRs received oral fisetin (10 mg/kg, twice a week for 6 weeks) and their cardiac function was analyzed by echocardiography. Histological studies and Western blotting were performed to assess the severity and the mechanism of the underlying cardiac abnormality. Fisetin effectively suppressed calcineurin-NFATC3 involved cellular hypertrophic effects as observed in H9c2 cells and in SHR hearts. Fisetin also enhanced cardiac function and restored cardiac morphology and therefore, fisetin is a potential agent against hypertension associated hypertrophy and cardiac deterioration.

Circular RNAs (circRNAs) are long-lived, covalently closed RNAs that are abundantly expressed and evolutionarily conserved across eukaryotes. Possible functions ranging from microRNA (miRNA) and RNA binding protein sponges to regulators of transcription and translation have been proposed. Here we describe the design and characterization of recombinant adeno-associated viral (AAV) vectors packaging transgene cassettes containing intronic sequences that promote backsplicing to generate circularized RNA transcripts. Using a split GFP transgene, we demonstrate the capacity of vectors containing different flanking intronic sequences to efficiently drive persistent circRNA formation in vitro. Further, translation from circRNA is efficiently driven by an internal ribosomal entry site (IRES). Upon injecting AAV vectors encoding circRNA in mice, we observed robust transgene expression in the heart, but low transduction in the liver for the intronic elements tested. Expression in the murine brain was restricted to astrocytes following systemic or intracranial administration, while intravitreal injection in the eye yielded robust transgene expression across multiple retinal cell layers. These results highlight the potential for exploiting AAV-based circRNA expression to study circRNA function and tissue-specific regulation in animal models, as well as development of therapeutic platforms using this approach. Keywords: adeno-associated virus, circular RNA, gene therapy

The recent global pandemic due to COVID-19 is caused by a type of coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite rigorous efforts worldwide to control the spread and human to human transmission of this virus, incidence and death due to COVID-19 continue to rise. Several drugs have been tested for treatment of COVID-19, including hydroxychloroquine. While a number of studies have shown that hydroxychloroquine can prolong QT interval, potentially increasing risk of ventricular arrhythmias and Torsade de Pointes, its effects on immune cell function have not been extensively examined. In the current review, an overview of coronaviruses, viral entry and pathogenicity, immunity upon coronavirus infection, and current therapy options for COVID-19 are briefly discussed. Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged/oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs. Therefore, it is likely that hydroxychloroquine treatment may in fact impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with co-morbidities. Further, this review provides a rationale for developing and selecting antiviral drugs and includes a brief review of traditional strategies combined with new drugs to combat COVID-19.

Redox homeostasis regulates key cellular signaling in both physiology and pathology. While perturbations result in shifting the redox homeostasis towards oxidative stress are well documented, the influence of reductive stress (RS) in neurodegenerative diseases and its mechanisms are unknown. Here, we postulate that a redox shift towards the reductive arm (through the activation of Nrf2 signaling) will damage neurons and impair neurogenesis. In proliferating and differentiating neuroblastoma (Neuro 2a/N2a) cells, sulforaphane-mediated Nrf2 activation resulted in increased transcription/translation of antioxidants and glutathione (GSH) production along with significantly declined ROS in a dose-dependent manner leading to a reductive-redox state (i.e. RS). Interestingly, this resulted in endoplasmic reticulum (ER) stress leading to subsequent protein aggregation/proteotoxicity in neuroblastoma cells. Under RS, we also observed elevated Tau/α-synuclein and their co-localization with other protein aggregates in these cells. Surprisingly, we noticed that acute RS impaired neurogenesis as evidenced from reduced neurite outgrowth/length. Furthermore, maintaining the cells in a sustained RS condition (for five consecutive generations) dramatically reduced their differentiation and prevented the formation of axons (p

Mosquito-borne diseases cause several deaths every year in tropical and subtropical climate countries. Control of vectors is an alarming problem in today’s world due to the resistance matters. In this study magnesium incorporated hydroxyapatite nanoparticles have been synthesized by microwave irradiation method. Magnesium chloride hexahydrate (MgCl2·6H2O) calcium nitrate tetra hydrate (Ca (NO3)2·6H2O) and disodium hydrogen phosphate (Na2HPO4) were used as magnesium, calcium and phosphorous sources to prepare hydroxyapatite nanoparticles. The FT-IR studies show the presence of hydroxyl and phosphate functional groups. The structural properties have been studied using X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FESEM) and Transmission Electron Microscope (HRTEM). The energy dispersive X-ray analysis (EDAX) revealed the presence of Ca, Mg, P and O in the prepared samples. The antibacterial activity of the as-synthesized nanoparticles was evaluated against two prokaryotic strains, the gram negative bacteria Escherichia coli for three different concentrations of as-synthesized nanoparticles and they showed excellent antibacterial activity. The as-synthesized Mg-HAp nanoparticles were tested against fourth instar larvae of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus and the nanoparticles exhibited significant mortality against the selected mosquitoes. The observed results suggest that the magnesium incorporated hydroxyapatite nanoparticles have the potential to be used as an effective mosquito larvae control agent against Ae. aegypti, An. stephensi, and Cx. quinquefasciatus. From the detailed literature review it has been observed that no work has been carried out so far on the larvicidal activity using hydroxyapatite (HAp) nanoparticles and magnesium substituted hydroxyapatite (Mg-HAp) nanoparticles. Keywords: Microwave irradiation method, Hydroxyapatite, Nanoparticles, Antibacterial activity, Prokaryotic strains, Larvicidal activity

Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2/Nrf2) is an inducible transcription factor that is essential for maintenance of redox signaling in response to stress. This suggests that if Nrf2 expression response could be enhanced for a defined physiological pro-oxidant stress then it would be protective. This has important implications for the therapeutic manipulation of the Keap1/Nrf2 signaling pathway which is now gaining a lot of attention. We tested this hypothesis through the generation of Nrf2 transgene expression mouse model with and without isoproterenol-induced cardiac stress. Cardiac-specific mouse Nrf2 transgenic (mNrf2-TG) and non-transgenic (NTG) mice were subjected to isoproterenol (ISO) treatment and assessed for myocardial structure, function (echocardiography and electrocardiography), and glutathione redox state. Myocardial infarction and fibrosis along with increased inflammation leading to myocardial dysfunction was noted in NTG mice exposed to ISO, while mNrf2-TG hearts were resistant to the ISO insult. Preservation of myocardial structure and function in the mNrf2-TG mice was associated with the enhanced Nrf2 expression displayed in these hearts with an increased basal and post-treatment expression of redox modulatory genes and an overall enhanced antioxidant status. Of note, myocardium of ISO-treated TG mice displayed significantly increased stabilization of the KEAP1-NRF2 complex and enhanced release of NRF2 to the nucleus resulting in overall decreased pro-oxidant markers. Taken together, we suggest that a basal enhanced Nrf2 expression in mouse heart results in maintenance of redox homeostasis and counteracts ISO-induced oxidative stress, and suppresses pathological remodeling. These data suggest that an alternative therapeutic approach to enhance the efficacy of the Keap1-Nrf2 system is to stimulate basal expression of Nrf2. Keywords: Nrf2, Isoproterenol, Antioxidants, Cardiac remodeling, Echocardiography

Summary: Quiescent neural stem cells (qNSCs) with radial morphology are the only proven source of new neurons in the adult mammalian brain. Our understanding of the roles of newly generated neurons depends on the ability to target and manipulate adult qNSCs. Although various strategies have been developed to target and manipulate adult hippocampal qNSCs, they often suffer from prolonged breeding, low recombination efficiency, and non-specific labeling. Therefore, developing a readily manufactured viral vector that allows flexible packaging and robust expression of various transgenes in qNSCs is a pressing need. Here, we report a recombinant adeno-associated virus serotype 4 (rAAV4)-based toolkit that preferentially targets hippocampal qNSCs and allows for lineage tracing, functional analyses, and activity manipulation of adult qNSCs. Importantly, targeting qNSCs in a non-Cre-dependent fashion opens the possibility for studying qNSCs in less genetically tractable animal species and may have translational impact in gene therapy by preferentially targeting qNSCs. : In this article, Song and colleagues report a recombinant adeno-associated virus serotype 4-based toolkit comprising several distinct rAAV4 vectors that preferentially target qNSCs within the hippocampus. They demonstrate that rAAV4-mediated transgene expression is robust in qNSCs and allows for lineage tracing, genetic manipulation using the Cre-Lox system, functional analyses using electrophysiology and calcium imaging, and activity manipulation using chemogenetics. Keywords: adult hippocampal neural stem cells, rAAV4, quiescence, radial, toolkit

Summary: Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids or viral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition. The optimized 10E8 antibody, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ∼10-fold increased potency. We propose surface-matrix screening as a general method to improve antibodies, with improved semi-specific interactions between antibody and antigen enabling increased potency without compromising breadth.

During eukaryotic translation initiation, eIF3 binds the solvent-accessible side of the 40S ribosome and recruits the gate-keeper protein eIF1 and eIF5 to the decoding center. This is largely mediated by the N-terminal domain (NTD) of eIF3c, which can be divided into three parts: 3c0, 3c1, and 3c2. The N-terminal part, 3c0, binds eIF5 strongly but only weakly to the ribosome-binding surface of eIF1, whereas 3c1 and 3c2 form a stoichiometric complex with eIF1. 3c1 contacts eIF1 through Arg-53 and Leu-96, while 3c2 faces 40S protein uS15/S13, to anchor eIF1 to the scanning pre-initiation complex (PIC). We propose that the 3c0:eIF1 interaction diminishes eIF1 binding to the 40S, whereas 3c0:eIF5 interaction stabilizes the scanning PIC by precluding this inhibitory interaction. Upon start codon recognition, interactions involving eIF5, and ultimately 3c0:eIF1 association, facilitate eIF1 release. Our results reveal intricate molecular interactions within the PIC, programmed for rapid scanning-arrest at the start codon.

Study region: The large semi-arid Aral Region in Central Asia and the smaller tropical Mahanadi River Basin (MRB) in India. Study focus: Few studies have so far evaluated the performance of the latest generation of global climate models on hydrological basin scales. We here investigate the performance and projections of the global climate models in the Coupled Model Intercomparison Project, Phase 5 (CMIP5) for freshwater fluxes and their changes in two regional hydrological basins, which are both irrigated but of different scale and with different climate. New hydrological insights for the region: For precipitation in both regions, model accuracy relative to observations has remained the same or decreased in successive climate model generations until and including CMIP5. No single climate model out-performs other models across all key freshwater variables in any of the investigated basins. Scale effects are not evident from global model application directly to freshwater assessment for the two basins of widely different size. Overall, model results are less accurate and more uncertain for freshwater fluxes than for temperature, and particularly so for model-implied water storage changes. Also, the monsoon-driven runoff seasonality in MRB is not accurately reproduced. Model projections agree on evapotranspiration increase in both regions until the climatic period 2070–2099. This increase is fed by precipitation increase in MRB and by runoff water (thereby decreasing runoff) in the Aral Region. Keywords: CMIP5 global climate models, Hydro-climate, Freshwater change, Central Asia, South Asia, Monsoon driven seasonality

Nonalcoholic fatty liver disease (NAFLD) is a common outcome of obesity characterized with the accumulation of triacylglycerols, increase in tissue apoptosis and fibrosis. This study was performed to determine the effect of a lipolysis stimulating peptide-VHVV to reduce the NAFLD related effects in mice liver induced by high fat diet (HFD). Five groups of mice (n = 8), control fed with standard chow; HFD-induced obese control and three treatment groups with high/moderate/low dose VHVV-treatment, were used to evaluate the effect of VHVV. HFD fed mice exhibited heavier body weight than those with control chow diet. However, the levels of triacylglycerol and low density lipoprotein-cholesterol were significantly reduced in mice administered with low, moderate and high doses of VHVV. VHVV-administration also suppressed the HFD-induced hepatic apoptosis and fibrosis related proteins. Our results indicate that VHVV attenuate hepatic lipid accumulation and ameliorate inflammation related events in HFD fed mice to suppress apoptosis and fibrosis.

Gene therapy using recombinant adeno-associated viral (AAV) vectors is emerging as a promising approach to treat central nervous system disorders such as Spinal muscular atrophy, Batten, Parkinson and Alzheimer disease amongst others. A critical remaining challenge for central nervous system-targeted gene therapy, silencing or gene editing is to limit potential vector dose-related toxicity in off-target cells and organs. Here, we characterize a lab-derived AAV chimeric (AAV2g9), which displays favorable central nervous system attributes derived from both parental counterparts, AAV2 and AAV9. This synthetic AAV strain displays preferential, robust, and widespread neuronal transduction within the brain and decreased glial tropism. Importantly, we observed minimal systemic leakage, decreased sequestration and gene transfer in off-target organs with AAV2g9, when administered into the cerebrospinal fluid. A single intracranial injection of AAV2g9 vectors encoding guide RNAs targeting the schizophrenia risk gene MIR137 (encoding MIR137) in CRISPR/Cas9 knockin mice resulted in brain-specific gene deletion with no detectable events in the liver. This engineered AAV vector is a promising platform for treating neurological disorders through gene therapy, silencing or editing modalities.