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The release of metal-based nanoparticles (MNPs) and nanoplastic debris (NPDs) has become ubiquitous in the natural ecosystem. Interaction between MNPs and NPDs may alter their fate and transport in the sub-surface environment and have not been addressed so far. Therefore, the present study has explored the role of NPDs on the stability and mobility of extensively used MNPs, i.e., CuO nanoparticles (NPs) under varying soil solutions (SS) chemistry. In the absence of NPDs, a very high aggregation of CuO NPs observed in SS extracted from black, lateritic, and red soils, which can be correlated with ionic strength (IS) and type of ionic species. The sedimentation rate (k

Methylene Blue (MB) is a brain-penetrating drug with putative neuroprotective, antioxidant and metabolic enhancing effects. In vitro studies suggest that MB enhances mitochondrial complexes activity. However, no study has directly assessed the haemodynamic and metabolic effects of MB in the human brain.We used in vivo neuroimaging to measure the effect of MB on cerebral blood flow (CBF) and brain metabolism in humans and in rats. Two doses of MB (0.5 and 1 mg/kg in humans; 2 and 4 mg/kg in rats; iv) induced reductions in global cerebral blood flow (CBF) in humans (F(1.74, 12.17)5.82, p=0.02) and rats (F(1,5)26.04, p=0.0038). Human cerebral metabolic rate of oxygen (CMRO2) was also significantly reduced (F(1.26, 8.84)8.01, p=0.016), as was the rat cerebral metabolic rate of glucose (CMRglu) (t=2.6(16) p=0.018).This was contrary to our hypothesis that MB will increase CBF and energy metrics. Nevertheless, our results were reproducible across species and dose dependent. One possible explanation is that the concentrations used, although clinically relevant, reflect MB’s hormetic effects, i.e., higher concentrations produce inhibitory rather than augmentation effects on metabolism. Additionally, here we used healthy volunteers and healthy rats with normal cerebral metabolism where MB’s ability to enhance cerebral metabolism might be limited.

40K is one of the main isotopes responsible for the radiogenic heating of the mantle in Earth-like exoplanets [1] and hence, plays a very important role in the internal geophysical dynamics of a planet. The abundance of 40K in the mantle and the core of such planets is not always possible to be determined by astrophysical observations, although constraining the nuclear reaction rates of 40K during stellar evolution can also lead to constraining the present amount of 40K in these planets, which will improve our understanding on the habitability potential of Earth-like exoplanets. This study aims to constrain the 40K(n,α)37Cl reaction rate, one of the two major destruction paths of 40K in stellar nucleosynthesis,by measuring the reverse reaction 37Cl(α,n)40K and applying the principle of detailed balance as we have done before for the 40K (40K(n,p)40Ar reaction rate) [2]. During the first set of measurements we performed differential cross-section measurements of the 37Cl(α,n1γ)40K, 37Cl(α,n2γ)40K and 37Cl(α,n3γ)40K reaction channels, for six different center of mass energies in the range between 5.1 and 5.4 MeV. The experiment took place at the Edwards Accelerator Laboratory of Ohio University. The gamma rays from the reaction channels mentioned above were detected by two LaBr3 scintillators. Using the swinger facility to change the angle of the beam-target system with respect to the detection system, we were able to take measurements for the differential cross-section at six different angles between 20° and 120° in the lab system.

Background The epidural analgesia technique is effective for labor analgesia and combinations of various local anesthetics with lipophilic opioids like fentanyl are used. However, fentanyl can cause an increased incidence of pruritus, urinary retention, nausea, vomiting, giddiness, shivering, and respiratory depression. Dexmedetomidine and clonidine are selective alpha 2 agonists with analgesic properties and have been used via the neuraxial route with local anesthetics for the same without the side effects of fentanyl. Thus, the primary objective was to assess and compare the analgesic efficacy of the two-drug combinations by the visual analog scale (VAS) score. Methods Fifty-four primigravida women were randomly allocated in two groups of 27 each and were given an initial bolus of 10 mL of 0.125% levobupivacaine with dexmedetomidine 0.5 ug/kg in Group A and with clonidine 1 μg/kg in Group B. Subsequently, each patient received a background infusion rate of 10 mL/h, a bolus dose of 5 ml, and a lock-out interval of 10 min via a patient-controlled-analgesia (PCA) pump. The blood pressure, heart rate, and severity of pain using VAS were assessed. Durations of the stages of labor, rate of instrumental delivery, and cesarean section, side effects, maternal sedation, and neonatal Apgar scores were also recorded. Results VAS scores in both the groups progressively decreased to

Oxidative stress underlies the pathology of many human diseases, including the doxorubicin-induced off-target cardiotoxicity in cancer chemotherapies. Since current diagnostic procedures are only capable of monitoring cardiac function, a noninvasive means of detecting biochemical changes in redox status prior to irreversible functional changes is highly desirable for both early diagnosis and prognosis. We designed a novel 18F-labeled molecular probe, 18F-FPBT, for the direct detection of superoxide in vivo using positron emission tomography (PET). 18F-FPBT was radiosynthesized in one step by nucleophilic radiofluorination. In vitro, 18F-FPBT showed rapid and selective oxidation by superoxide (around 60% in 5 min) compared to other physiological ROS. In healthy mice and rats, 18F-FBPT is distributed to all major organs in the first few minutes post injection and is rapidly cleared via both renal and hepatobiliary routes with minimal background retention in the heart. In a rat model of doxorubicin-induced cardiotoxicity, 18F-FBPT showed significantly higher (P < 0.05) uptake in the hearts of treated animals compared to healthy controls. These results warrant further optimization of 18F-FBPT for clinical translation.

We studied the nature of excitons in the transition metal dichalcogenide alloy Mo

Developing eco-friendly formulations using waste cooking oil as renewable biomass is of great interest and commercial importance in the fuels and lubricant industry. This manuscript reports novel study on preparing a biolubricant formulations as WCO-1, WCO-2 and WCO-3 by blending the curcumin extracted soybean waste cooking oil in three different compositions viz 10%, 20%, 30% v/v with the mineral base oil N-150. Curcumin was extracted as a natural antioxidant in 0.5 wt% waste cooking oil to inhibit thermal oxidation. This study comprises a detailed analysis in terms of tribological, rheological and thermophysical characteristics such as viscosity, viscosity index, pour point and flash point parameters of the biolubricant by standard ASTM methods. Further, tribological and rheological analysis was done by the four-ball wear tester and Anton Paar, MCR-72, respectively. The thermophysical evaluation of WCO formulated biolubricant has shown excellent properties. The viscosity index of the formulated biolubricant increases with an increase in the concentration of waste cooking oil. In contrast, the pour point has also been depressing at lower temperature conditions. Thus, WCO based biolubricant was found to be more effective at extreme temperature conditions than the mineral base oil (N-150). Rheological studies have indicated the non-Newtonian behaviour of the biolubricant with an increase in shear rate. Whereas, tribological analysis demonstrates that wear scar diameter has significantly reduced from 0.685 to 0.573 mm, and the coefficient of friction decreased from 0.117 to 0.080 with respect to the mineral base oil. Thus, a straightforward green approach has been discovered by directly utilizing waste cooking oil for biolubricant formulation.

The neutron inelastic scattering of carbon-12, populating the Hoyle state, is a reaction of interest 17 for the triple-alpha process. The inverse process (neutron upscattering) can enhance the Hoyle state’s decay rate to the bound states of 12 18 C, effectively increasing the overall triple-alpha reaction rate. 19 The cross section of this reaction is impossible to measure experimentally but has been determined 20 here at astrophysically-relevant energies for the first time using detailed balance. This cross section 21 will inform astrophysical models on the importance of neutron upscattering in neutron-rich stellar 22 environments. 23 Using a highly-collimated monoenergetic beam of neutrons incident on the Texas Active Target 24 Time Projection Chamber (TexAT TPC) filled with CO2 gas, the 3α-particles (arising from the decay 25 of the Hoyle state following inelastic scattering) were measured and a cross section was extracted 26 between En = 8.15 MeV and En = 10.0 MeV. The cross section above the threshold was dominated by a few resonances in 13 27 C around Ex = 13.5 MeV. This has a significant effect on the contribution 28 of neutron upscattering in stellar environments. 29 The neutron-upscattering enhancement is observed to be much smaller than previously expected. 30 For a temperature of 1 GK, the total enhancement factor, from upscattering to the ground state and 31 first-excited state, was seen to be 5, rising to around 46 at 10 GK thereby exceeding the contribution 32 from proton enhancement. The importance of the neutron-upscattering enhancement may therefore 33 not be significant aside from in very particular astrophysical sites (e.g. neutron star mergers).

The bioprocessing of lignocellulosic biomass to produce bio-based products under biorefinery setup is gaining global attention. The economic viability of this biorefinery would be inclined by the efficient bioconversion of all three major constituents of lignocellulosic biomass i.e. cellulose, hemicellulose, and lignin for value-added biochemicals and biofuels production. Although the lignocellulosic biorefinery setup has a clear value proposition, the commercial success at the industrial scale is still inadequate. This can be attributed mainly to irregular biomass supply chain, market uncertainties, and scale-up challenges. Global research efforts are underway by public and private sectors to get deeper market penetration. A comprehensive account of important factors, limitations, and propositions are worth consideration for the commercial success of lignocellulosic biorefineries. In this article, the importance of integration of lignocellulosic biorefineries with existing petrochemical refineries, the technical challenges of industrialization, SWOT analysis, and future directions have been reviewed.

The parasites of the genus Leishmania survive and proliferate in the host phagocytic cells by taking control over their microbicidal functions. The parasite also promotes differentiation of antigen-specific anti-inflammatory cytokines producing effector T cells, which eventually results in disease pathogenesis. The mechanisms that parasites employ to dominate host adaptive immunity are largely unknown. For the first time, we report that L. donovani, which causes visceral leishmaniasis in the Indian subcontinent, upregulates the expression of an immune inhibitory receptor i.e., CD300a on antigen presenting and phagocytic cells to dampen their effector functions. The blocking of CD300a signals in leishmania antigens activated macrophages and dendritic cells enhanced the production of nitric oxide, pro-inflammatory cytokines along with MHCI/II genes expression, and reduced parasitic uptake. Further, the abrogation of CD300a signals in Leishmania infected mice benefited antigen-experienced, i.e., CD4+CD44+ and CD8+CD44+ T cells to acquire more pro-inflammatory cytokines producing phenotypes and helped in the early clearance of parasites from their visceral organs. The CD300a receptor blocking also enhanced the conversion of CD4+ T effectors cells to their memory phenotypes i.e., CCR7high CD62Lhigh up to 1.6 and 1.9 fold after 14 and 21 days post-infection, respectively. These findings implicate that CD300a is an important determinant of host phagocytic cells functions and T cells differentiation against Leishmania antigens.

Despite the massive accumulation of nanoplastics (NPs) in the freshwater system, research so far has highly focused on the marine environment. NPs interaction with mineral surfaces can influence their fate in freshwater, which will further impact their bioavailability and transport to the oceans. Current work focuses on understanding NPs interaction with weathering sequence of minerals in freshwater under varying geochemical conditions. Primary mineral feldspar and weathering originated secondary minerals, i.e., kaolinite and gibbsite, were investigated for interaction with NPs under batch mode under relevant environmental conditions. Minerals-NPs interaction was also investigated in natural water samples. Results showed that the amorphous nature, small particle size, and positive surface charge of gibbsite resulted in multi-fold sorption of NPs (108.1 mg/g) compared to feldspar (7.7 mg/g) and kaolinite (11.9 mg/g). FTIR spectroscopy revealed hydrogen bonding and complexation as major players in gibbsite-NPs interaction suggesting the possibility of their co-precipitation. The continuous adsorption-desorption and limited sorption capacity of feldspar and kaolinite can be attributed to their negative surface charge, larger size, crystalline nature, and physical sorption. Therefore, both minerals can co-transport and enhance the mobility of NPs.

To compare the diagnostic accuracy of single test (HPV DNA) with double tests (HPV DNA and VIA/VILI) for cervical cancer screening. This hospital-based cross-sectional study was carried out on 256 women aged between 30 and 65 years. All women underwent HPV DNA test followed by VIA/VILI test and colposcopy. Colposcopic-guided biopsy was performed in 35 women with Reids score 3 and above. Diagnostic accuracy of HPV, VIA and VILI tests was calculated taking colposcopy and HPE reports as gold standard. The diagnostic tests included sensitivity, specificity, PPV and NPV, and kappa statistics was applied to find agreement levels among various tests. Pre-invasive lesions were significantly more common in lower socioeconomic group of women. HPV DNA test was positive in 8.5%, VIA in 19.5% and VILI in 15.2% of women. The agreement level was fair between HPV and VIA (k = 0.34), moderate between HPV and VILI (k = 0.51) and good between VIA and VILI (k = 0.79). HPV DNA test had significantly high specificity while VIA/VILI was more sensitive tests. There was no statistically significant difference in diagnostic accuracy of HPV test alone or with VIA/VILI. Addition of VIA and VILI does not increase the diagnostic accuracy of HPV DNA test for cervical cancer screening.

Amyotrophic lateral sclerosis and frontotemporal dementia are overlapping diseases in which MRI reveals brain structural changes in advance of symptom onset. Recapitulating these changes in preclinical models would help to improve our understanding of the molecular causes underlying regionally selective brain atrophy in early disease. We therefore investigated the translational potential of the TDP-43Q331K knock-in mouse model of amyotrophic lateral sclerosis-frontotemporal dementia using MRI. We performed in vivo MRI of TDP-43Q331K knock-in mice. Regions of significant volume change were chosen for post-mortem brain tissue analyses. Ex vivo computed tomography was performed to investigate skull shape. Parvalbumin neuron density was quantified in post-mortem amyotrophic lateral sclerosis frontal cortex. Adult mutants demonstrated parenchymal volume reductions affecting the frontal lobe and entorhinal cortex in a manner reminiscent of amyotrophic lateral sclerosis-frontotemporal dementia. Subcortical, cerebellar and brain stem regions were also affected in line with observations in pre-symptomatic carriers of mutations in C9orf72, the commonest genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Volume loss was also observed in the dentate gyrus of the hippocampus, along with ventricular enlargement. Immunohistochemistry revealed reduced parvalbumin interneurons as a potential cellular correlate of MRI changes in mutant mice. By contrast, microglia was in a disease activated state even in the absence of brain volume loss. A reduction in immature neurons was found in the dentate gyrus, indicative of impaired adult neurogenesis, while a paucity of parvalbumin interneurons in P14 mutant mice suggests that TDP-43Q331K disrupts neurodevelopment. Computerized tomography imaging showed altered skull morphology in mutants, further suggesting a role for TDP-43Q331K in development. Finally, analysis of human post-mortem brains confirmed a paucity of parvalbumin interneurons in the prefrontal cortex in sporadic amyotrophic lateral sclerosis and amyotrophic lateral sclerosis linked to C9orf72 mutations. Regional brain MRI changes seen in human amyotrophic lateral sclerosis-frontotemporal dementia are recapitulated in TDP-43Q331K knock-in mice. By marrying in vivo imaging with targeted histology, we can unravel cellular and molecular processes underlying selective brain vulnerability in human disease. As well as helping to understand the earliest causes of disease, our MRI and histological markers will be valuable in assessing the efficacy of putative therapeutics in TDP-43Q331K knock-in mice., Graphical Abstract Graphical Abstract

The treatment of multiple gingival recessions (GRs) is often challenging for clinicians, mainly due to a larger avascular surface, limited blood supply, differences in recession depth, and residual keratinized tissue. Considering these factors, it may be prudent to take advantage of one surgical technique and overcome its limitations by combining it with another technique in certain clinical situations. The present clinical report describes the treatment of multiple GRs of different depths with a combination of the tunnel technique (TUN) and pedicle flap (PED) - double papilla flap (DPF) or coronally positioned flap (CPF) - in conjunction with deepithelialized connective tissue grafts in two patients. The TUN was considered as it allows faster wound healing and improved esthetics due to the avoidance of visible incisions on the surface. However, to achieve complete coverage of the exposed root surface in the deep recession of the terminal tooth, the DPF or CPF were performed. Healing was uneventful, and no postoperative complications were observed. Complete root coverage was achieved in the treated teeth of both patients at the 12-month follow-up. The combination techniques described in this article can be utilized when there is a deep recession on one of the terminal teeth and the remaining teeth exhibit shallow to moderate recession depths. Clinicians should consider the amalgamation of surgical techniques to achieve the goals of complete root coverage in order to meet patients' esthetic and functional demands while at the same time minimizing postsurgical morbidity.

Hippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine-system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABAA and NMDA receptors in MAM-treated rats and to elucidate the receptor mechanisms underlying the promising effects of peripubertal diazepam exposure. Quantitative receptor autoradiography was used to measure receptor density in the dorsal hippocampus CA1, ventral hippocampus CA1, and ventral subiculum. Specifically, [3H]-Ro15-4513 was used to quantify the density of α5GABAA receptors (α5GABAAR), [3H]-flumazenil to quantify α1-3;5GABAAR, and [3H]-MK801 to quantify NMDA receptors. MAM rats exhibited anxiety and schizophrenia-relevant behaviors as measured by elevated plus maze and amphetamine-induced hyperlocomotion (AIH), although diazepam only partially rescued these behaviors. α5GABAAR density was reduced in MAM-treated rats in all hippocampal sub-regions, and negatively correlated with AIH. Ventral hippocampus CA1 α5GABAAR density was positively correlated with anxiety-like behavior. Dorsal hippocampus CA1 NMDA receptor density was increased in MAM-treated rats, and positively correlated with AIH. [3H]-flumazenil revealed no significant effects. Finally, we found no significant effect of diazepam treatment on receptor densities, potentially related to the only partial rescue of schizophrenia-relevant phenotypes. Overall, our findings provide first evidence of α5GABAAR and NMDA receptor abnormalities in the MAM model, suggesting that more selective pharmacological agents may become a novel therapeutic mechanism in schizophrenia.

Background COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44–45 weeks) between the first and second dose, and response to a third dose as a booster given 28–38 weeks after the second dose. Methods In this substudy, volunteers aged 18–55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44–45 weeks after first dose) or a third dose of the vaccine (28–38 weeks after second dose). Data from volunteers aged 18–55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. Findings Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44–45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83–91·08] vs 1·75 EUs [1·60–1·93]). 32 participants received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525–1764] with an 8–12 week interval; 1860 EUs [917–4934] with a 15–25 week interval; and 3738 EUs [1824–6625] with a 44–45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047–6420]) than 28 days after a second dose (median 1792 EUs [IQR 899–4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127–389] immediately before the third dose to 399 SFUs per milion PBMCs [314–662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. Interpretation An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. Funding UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome.

Diversity, equity and inclusion (DEI) are three words that we hear and see in our practice and in all areas of workplace and media development, particularly in the Global North. While each of us will have our own context and definitions of these words and how they impact our practice, what do they mean when we shift our attention to the global agendas of maternal and reproductive health?

Background Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. Methods Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. Findings Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. Interpretation Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. Funding UK Vaccine Task Force and National Institute for Health Research.

Activation of adenylyl cyclases (ACs) by G-protein Gαs catalyzes the production of cyclic adenosine monophosphate (cAMP), a key second messenger that regulates diverse physiological responses. There are 10 AC isoforms present in humans, with AC5 and AC6 proposed to play vital roles in cardiac function. We have previously shown that under hypoxic conditions, AC6 is amenable to post-translational modification by nitrosylation, resulting in decreased AC catalytic activity. Using a computational model of the AC6-Gαs complex, we predicted key nitrosylation-amenable cysteine residues involved in the interaction of AC6 with Gαs and pursued a structure-function analysis of these cysteine residues in both AC6 and Gαs. Our results based on site-directed mutagenesis of AC6 and Gαs, a constitutively active Gαs, AC activity, and live cell intracellular cAMP assays suggest that Cys1004 in AC6 (subunit C2) and Cys237 in Gαs are present at the AC-Gαs interface and are important for the activation of AC6 by Gαs. We further provide mechanistic evidence to show that mutating Cys 1004 in the second catalytic domain of AC6 makes it amenable to inhibition by Gαi, which may account for decreased functional activity of AC6 when this residue is unavailable.

Pigeonpea (Cajanus cajan) is an important crop in semi-arid regions and a significant source of dietary proteins in India. The plant is sensitive to salinity stress, which adversely affects its productivity. Based on the dosage-dependent influence of salinity stress on the growth and ion contents in the young seedlings of pigeonpea, a comparative proteome analysis of control and salt stressed (150 mM NaCl) plants was conducted using 7 days-old seedlings. Among various amino acids, serine, aspartate and asparagine were the amino acids that showed increment in the root, whereas serine, aspartate and phenylalanine showed an upward trend in shoots under salt stress. Furthermore, a label-free and gel-free comparative Q-Tof, Liquid Chromatography-Mass spectrometry (LC–MS) revealed total of 118 differentially abundant proteins in roots and shoots with and without salt stress conditions. Proteins related to DNA-binding with one finger (Dof) transcription factor family and glycine betaine (GB) biosynthesis were differentially expressed in the shoot and root of the salinity-stressed seedlings. Exogenous application of choline on GB accumulation under salt stress showed the increase of GB pathway in C. cajan. Gene expression analysis for differentially abundant proteins revealed the higher induction of ethanolamine kinase (CcEthKin), choline-phosphate cytidylyltransferase 1-like (CcChoPh), serine hydroxymethyltransferase (CcSHMT) and Dof protein (CcDof29). The results indicate the importance of, choline precursor, serine biosynthetic pathways and glycine betaine synthesis in salinity stress tolerance. The glycine betaine protects plant from cellular damages and acts as osmoticum under stress condition. Protein interaction network (PIN) analysis demonstrated that 61% of the differentially expressed proteins exhibited positive interactions and 10% of them formed the center of the PIN. Further, The PIN analysis also highlighted the potential roles of the cytochrome c oxidases in sensing and signaling cascades governing salinity stress responses in pigeonpea. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01116-w.

Background: A comparative analysis of Automatic Generation Control (AGC) of two-area electric power systems interconnected by AC and AC-DC links under deregulated environment is conducted. Each area has Thermal-Thermal (TT), Thermal-Hydro (TH) and/or Hydro-Hydro (HH) multiple power sources. A maiden attempt is made to study the demeanour of HH power system under restructured mode. Methods: The state space models of the power systems have been developed to simulate all market transactions probable in a deregulated power environment and optimal proportional integral structured controller is applied to improve the dynamic performance. The concept of DISCO participation matrix is harnessed to simulate the transactions. Results: Eigenvalue analysis is carried out to assess the comparative stability analysis of the power systems with/without AC-DC links. Further, the dynamic responses of TT, TH and HH power systems are contrasted in the presence of AC link and AC-DC links. The inclusion of AC-DC links improves the dynamic performance of all the systems remarkably, however, the responses of HH system are sluggish/poor with large undershoots in comparison to TT and TH systems. Also, TH system exhibits degraded dynamic performance compared to TT system. Conclusion: Moreover, optimal controller is found competent to demonstrate the matching of generation with power demand under different market transactions.

Morphological changes in insect-induced galls in flowers and fruits of Alstonia scholaris (L.) R. Br. (Apocynaceae) were recorded. The insect Pauropsylla tuberculata Crawford (Homoptera: Psyllidae) penetrates the thalamus of young flowers inducing hypertrophy and hyperplasia in the parenchymatous tissue resulting in the formations of green galls of various sizes and shapes. The reproductive organs, stamens, and pistil of galled flowers are sterile. Pollen sterility was associated with abnormal behaviour of endothecium and the tapetum. In young anthers of severely infested flowers, the sporogenous tissue and tapetum degenerate. In anthers of some infested flowers, the callose wall surrounding pollen mother cells was thick although tapetal cells showed normal signs of degeneration. In anthers of a few infested flowers, the microspores were formed but they degenerated along with tapetal cells. Anthers of some diseased flowers contained thick-walled vacuolated and sterile microspores surrounded by degenerated tapetum layer and radially elongated endothecial cells which lacked the usual fibrous thickenings. The size of gynoecium and the size and number of ovules were reduced in galled flowers. Ovules failed to differentiate and represented by a globular undifferentiated mass of cells. A large number of green, conical galls are formed on fruits by hypertrophy and hyperplasia in the parenchymatous pericarp. Size of severely infested fruits was reduced, and they became thick, circular and seedless. As a consequence, sexual reproduction of the host tree was completely inhibited.

Calcium (Ca2+) and inositol 1,4,5-trisphosphate (IP3) is critically important actors for a vast array of cellular processes. The most significant of the functions is One of the main functions is communication in all parts of the body which is achieved through cell signaling. Abnormalities in Ca2+signaling have been implicated in clinically important conditions such as heart failure and cardiac arrhythmias. We propose a mathematical model which systematically investigates complex Ca2+and IP3dynamics in cardiac myocyte. This two dimensional model is based on calcium-induced calcium release via inositol 1,4,5-trisphosphate receptors and includes calcium modulation of IP3levels through feedback regulation of degradation and production. Forward-Time Centered-Space method has been used to solve the coupled equations. We were able to reproduce the observed oscillatory patterns in Ca2+as well as IP3signals. The model predicts that calcium-dependent production and degradation of IP3is a key mechanism for complex calcium oscillations in cardiac myocyte. The impact and sensitivity of source, leak, diffusion coefficients on both Ca2+and IP3dynamics have been investigated. The results show that the relationship between Ca2+and IP3dynamics is nonlinear.

Bitter sensation is mediated by various bitter taste receptors (T2Rs), thus T2R antagonists are actively explored. Our objective was to look for novel T2R blockers in hen protein hydrolysate (HPH). We screened the least bitter HPH fractions using electronic tongue, and analyzed their peptide sequences and calcium mobilization in HEK293T cells expressing T2Rs. The results showed that the HPH fractions with higher bitterness intensity had higher hydrophobicity, more hydrophobic amino acids, and more positively charged peptides, but fewer known umami peptides. The peptide fractions from the least bitter HPH fraction significantly inhibited quinine bitterness (P 0.05), and also significantly inhibited quinine- or diphenhydramine-dependent calcium mobilization of HEK293T cells expressing human T2R4, T2R7, or T2R14 (P 0.05). Among them, the first eluted (least bitter) peptide fraction showed the strongest bitter-inhibitory effect. In conclusion, HPH peptides are the blockers of T2R4, T2R7, and T2R14.

In this study, we report synthesis of pure rutile phase titanium oxide (TiO2) nanoparticles (NPs) at a considerably low temperature with particle size ca. 20 nm (from TEM). The sample showed mesoporous nature as per Brunauer- Emmett- Teller (BET) method with a surface area of 211.7 m2 g−1and band gap 2.94 eV stretching into the visible portion of the electromagnetic spectrum. Two Indium tin oxide (ITO)/TiO2 (rutile and commercial)/Aluminium (Al) based heterojunctions were fabricated and carrier transport properties evaluated with the help of space charge limited current (SCLC) theory. The values of mobility and transit time for rutile were 7.44 × 10−7 m2V−1s−1and 9.52 × 10−5 s respectively and were found to be enhanced on illumination in comparison to commercial TiO2. Rutile exhibited a higher photosensitivity of 5.48 which predict photo-switching nano device applicability. Impedance analysis showed stable and enhanced photocurrent response. The degradation ability of rutile for malachite green oxalate (MG), a hazardous dye, was also checked and found to be 97.54% in 3 h being comparable to commercial TiO2 when irradiated with a definite dose of ultraviolet (Uv) radiation (1.035 × 10−15 Jsm2). The Langmuir- Hinshelwood model was delineated to calculate the reaction rate which was higher for rutile (0.0183 min−1). Lower electron hole pair (EHP) recombination was proved for rutile by photoluminescence (PL) measurements.

Nanoplastics (NPs) are one of the most dangerous fractions of plastics because of their possible eco-toxicological impacts. NP stability and transport are highly influenced by various environmental factors, which warrants the necessity to understand their fate in ambient water systems. This study investigates the polystyrene (PS) NP stability under the effect of varying ionic strength, temperature, dissolved organic matter (DOM), inorganic soil colloids and heavy metal salts using the dynamic light scattering technique. Controlled studies were used to examine the aggregation of NPs in the presence of natural river water (RW), groundwater (GW), and seawater (SW). Results highlight that, at all studied temperatures, divalent cations had a greater influence on the aggregation rate of NPs as compared to monovalent cations whereas for the same salt, a drop in temperature tended to increase the stability. A rise in critical coagulation concentration (CCC) by 1.6 and 2.4 times for NaCl and CaCl2 was observed, respectively, at 15 °C as compared to 35 °C. Steric repulsion produced by DOM stabilizes NPs shifting the CCC value to a higher salt concentration for NaCl. However, faster aggregation with CaCl2 due to complexation was notable. The clay colloids participate in heteroaggregation with NPs under the influence of salts; this was confirmed using cryo-TEM. Heavy metal salts such as ZnCl2 and CdCl2 had interactions with PS NPs similar to that presented by CaCl2 but showed independent behaviour in the presence of HgCl2, due to metal speciation under different redox conditions. The concentration of salts and organic substances in the complex matrix of natural water results in the least stable NPs in SW > RW > GW. The results of this study contribute to the fundamental understanding of the fate of NPs in complex aquatic environments.

Nanoparticles have shown great promise in improving cancer treatment efficacy by changing the intracellular calcium level through activation of intracellular mechanisms. One of the mechanisms of the killing of the cancerous cell by a nanoparticle is through elevation of the intracellular calcium level. Evidence accumulated over the past decade indicates a pivotal role for the IP3 receptor mediated Ca2+ release in the regulation of the cytosolic and the nuclear Ca2+ signals. There have been various studies done suggesting the role of IP3 receptors (IP3R) and IP3 production and degradation in cardiomyocytes. In the present work, we have proposed a three-dimensional unsteady-state mathematical model to describe the mechanism of cardiomyocytes which focuses on evaluation of various parameters that affect these coupled dynamics and elevate the cytosolic calcium concentration which can be helpful to search for novel therapies to cure these malignancies by targeting the complex calcium signaling process in cardiomyocytes. Our study suggests that there are other factors involved in this signaling which can increase the calcium level, which can help in finding treatment for cancer. The cytosolic calcium level may be controlled by IP3 signaling, leak, source influx of calcium (σ) and maximum production of IP3 (VP). We believe that the proposed model suggests new insight into finding treatment for cancer in cardiomyocytes through elevation of the cytosolic Ca2+ concentration by various parameters like leak, σ, VP and especially by other complex cell signaling dynamics, namely IP3 dynamics.

A new supportive signal namely Combined Derivative of Reactive Power and Bus Frequency (CDRPF) in SVS for alleviating torsional oscillations due to SSR is developed. The IEEE first benchmark model incorporating midpoint located SVS is considered as a test system. The effect of CDRPF-SVS supportive signal for restraining torsional oscillations due to SSR is illustrated. An analysis through eigenvalues of the linearized series compensated power system is demonstrated once incorporating the proposed supportive signal and once without any supportive signal. It is found that the unstable torsional modes are effectively eliminated with the proposed supportive signal. Also, the performance of the proposed supportive signal is assessed for the non-linear system model under large disturbance conditions. The concept of designing of proposed supportive signal has been implemented by using a detailed system model reflecting the system dynamics of various power system components accurately. Results of simulation demonstrate the effective damping of torsional oscillation due to subsynchronous resonance (SSR) under severe conditions and confirm the efficacy of the supportive input signal under consideration.

N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = −0.47, p = 0.04), depressive (rho = −0.67, p = 0.002), and general symptom severity (rho = −0.74, p

EGFR is deregulated, in several types of cancer, by three mechanisms: (1) activating gene mutations; (2) overexpression of the EGFR transmembrane form and (3) altered ligand expression. Selective EGFR inhibitors have been suggested as first-line therapy in lung cancer patients harboring EGFR mutations, tumors of the pancreas and certain histotypes of ovarian tumors. Carbohydrate antigen 125(CA125) and Human Epididymis 4 are being used routinely for detection and follow up of ovarian cancer globally. A comparative observational study, over a 40 samples was carried out using Pre-operative and Post-operative Measurement of CA125 and HE4 by chemiluminescence and sEGFR by ELISA (Bioassay Technology Laboratory, Cat. No.E0313Hu). Results were compared between the three markers in various histological types of ovarian tumor using Statistical analysis (SPSS version 21.0). A combined panel of serum sEGFR, CA125, and HE4 increases the specificity and efficiency in ovarian cancer diagnosis.

The extensive application of metal oxide nanoparticles (NPs) in various sectors has raised concern about their subsequent release and potentially harmful impacts on the soil system. The present study has addressed the interaction of CuO NPs with bentonite clay colloids (CC) under varying environmental parameters as a model to represent the soil pore water scenario. Based on CuO – CC interaction in model and natural soil solution extracts (SSE), the role of clay fraction and their stability on CuO retention in various types of soils have been evaluated. Results suggested that increasing ionic strength (IS) in the system caused aggregation of CuO NPs, and in the presence of CC, critical coagulation concentration decreased drastically from 27.8 and 17.3 mM to 10.7 and 0.33 mM for NaCl and CaCl2 respectively, due to heteroaggregation in the system. Interestingly, in the SSE, the dominating role of ionic valency, dissolved organic carbon (DOC), and CC was observed in colloidal stabilization over IS. No significant impact of temperature was observed on the stability of CuO NPs both in model and SSE. Further, stability studies in the SSE were correlated with NPs retention behavior in soils. Observations suggest that retention of CuO NPs in soils is a function of binding of the colloidal fraction to the soil, which in turn depends on the colloidal stability. The highest retention was observed in black and laterite soils, whereas lower binding of clay fraction in red soil caused the least retention. A decrease in K d values after a certain application concentration provided maximum sustainable application concentration of CuO NPs, which may vary with soil properties. Results suggest that the binding of clay and organic matter with a sandy matrix of soil plays a prime role in deciding the overall fate of CuO NPs in the soils.

Tick-borne illnesses pose a serious concern to human and veterinary health and their prevalence is on the rise. The interactions between ticks and the pathogens they carry are largely undefined. However, the genus Anaplasma, a group of tick-borne bacteria, has been instrumental in uncovering novel paradigms in tick biology. The emergence of sophisticated technologies and the convergence of entomology with microbiology, immunology, metabolism and systems biology has brought tick–Anaplasma interactions to the forefront of vector biology with broader implications for the infectious disease community. Here, we discuss the use of Anaplasma as an instrument for the elucidation of novel principles in arthropod-microbe interactions. We offer an outlook of the primary areas of study, outstanding questions and future research directions.

"Nanoplastics- the emerging contaminants" and "agricultural waste to resource conversion" both are currently at the scientific frontiers and require solutions. This study aims to utilize sugarcane bagasse-derived biochar for the removal of nanoplastics (NPs) from aqueous environment. Three types of biochar were synthesized at three different pyrolysis temperatures, i.e. 350, 550, and 750 ℃ and evaluated for their potential in removing NPs. Effect of various environmental parameters, i.e., competing ions, pH, humic acid and complex aqueous matrices on NPs sorption was also studied. Results showed that attributing to decreased carbonyl functional groups, increased surface area and pore abundance, biochar prepared at 750 ℃ showed drastically higher NPs removal (99%), while BC-550 and BC-350 showed comparatively lower NPs sorption (39% and24%, respectively). Further sorption studies confirmed instantaneous NPs removal with equilibrium attainment within 5 min of interaction and efficient NPs sorption capacity, i.e. 44.9 mg/g for biochar prepared at 750 ℃. Non-linear-kinetic modeling suggested pseudo 1st order removal kinetics while isotherm and thermodynamic modeling confirmed- monolayer instantaneous sorption of NPs sorption. Enhanced electrostatic repulsion resulted in decrease in NPs sorption at alkaline conditions, whereas steric hindrance caused limited removal (25%) at higher humic acid concentrations.

Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. Humans express 25 T2Rs that are known to detect several bitter compounds including bacterial quorum sensing molecules (QSM). Primarily found to be key receptors for bitter sensation T2Rs are known to play an important role in mediating innate immune responses in oral and extraoral tissues. Several studies have led to identification of Gram-negative and Gram-positive bacterial QSMs as agonists for T2Rs in airway epithelial cells and immune cells. However, the pharmacological characterization for many of the QSM-T2R interactions remains poorly defined. In this chapter, we discuss the extraoral roles including localization of T2Rs in extracellular vesicles, molecular pharmacology of QSM-T2R interactions, role of T2Rs in mediating innate immune responses, and some of the challenges in understanding T2R pharmacology.

Host-pathogen interactions play an important role in defining the outcome of a disease. Recent studies have shown that the bacterial quorum sensing molecules (QSM) can interact with host cell membrane proteins, mainly G protein-coupled receptors (GPCRs), and induce innate immune responses. However, few studies have examined QSM-GPCR interactions and their influence on oral innate immune responses. In this study, we examined the role of bitter taste receptor T2R14 in sensing competence stimulating peptides (CSPs) secreted by cariogenic bacterium Streptococcus mutans and in mediating innate immune responses in gingival epithelial cells (GECs). Transcriptomic and western blot analyses identify T2R14 to be highly expressed in GECs. Our data show that only CSP-1 from S. mutans induces robust intracellular calcium mobilization compared to CSP-2 and CSP-3. By using CRISPR-Cas9, we demonstrate that CSP-1 induced calcium signaling and secretion of cytokines CXCL-8/IL-8, TNF-α, and IL-6 is mediated through T2R14 in GECs. Interestingly, the NF-kB signaling activated by CSP-1 in GECs was independent of T2R14. CSP-1-primed GECs attracted differentiated HL-60 immune cells (dHL-60) and this effect was abolished in T2R14 knock down GECs and also in cells primed with T2R14 antagonist 6-Methoxyflavone (6-MF). Our findings identify S. mutans CSP-1 as a peptide ligand for the T2R family. Our study establishes a novel host-pathogen interaction between cariogenic S. mutans CSP-1 and T2R14 in GECs leading to an innate immune response. Collectively, these findings suggest T2Rs as potential therapeutic targets to modulate innate immune responses upon oral bacterial infections.