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1.
Adv Sci (Weinh) ; : e2405251, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958496

ABSTRACT

The pursuit of advanced brain-inspired electronic devices and memory technologies has led to explore novel materials by processing multimodal and multilevel tailored conductive properties as the next generation of semiconductor platforms, due to von Neumann architecture limits. Among such materials, antimony sulfide (Sb2S3) thin films exhibit outstanding optical and electronic properties, and therefore, they are ideal for applications such as thin-film solar cells and nonvolatile memory systems. This study investigates the conduction modulation and memory functionalities of Sb2S3 thin films deposited via the vapor transport deposition technique. Experimental results indicate that the Ag/Sb2S3/Pt device possesses properties suitable for memory applications, including low operational voltages, robust endurance, and reliable switching behavior. Further, the reproducibility and stability of these properties across different device batches validate the reliability of these devices for practical implementation. Moreover, Sb2S3-based memristors exhibit artificial neuroplasticity with prolonged stability, promising considerable advancements in neuromorphic computing. Leveraging the photosensitivity of Sb2S3 enables the Ag/Sb2S3/Pt device to exhibit significant low operating potential and conductivity modulation under optical stimulation for memory applications. This research highlights the potential applications of Sb2S3 in future memory devices and optoelectronics and in shaping electronics with versatility.

2.
Polymers (Basel) ; 16(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891440

ABSTRACT

The frontal polymerization (FP) of carbon/epoxy (C/Ep) composites is investigated, considering FP as a viable route for the additive manufacturing (AM) of thermoset composites. Neat epoxy (Ep) resin-, short carbon fiber (SCF)-, and continuous carbon fiber (CCF)-reinforced composites are considered in this study. The evolution of the exothermic reaction temperature, polymerization frontal velocity, degree of cure, microstructures, effects of fiber concentration, fracture surface, and thermal and mechanical properties are investigated. The results show that exothermic reaction temperatures range between 110 °C and 153 °C, while the initial excitation temperatures range from 150 °C to 270 °C. It is observed that a higher fiber content increases cure time and decreases average frontal velocity, particularly in low SCF concentrations. This occurs because resin content, which predominantly drives the exothermic reaction, decreases with increased fiber content. The FP velocities of neat Ep resin- and SCF-reinforced composites are seen to be 0.58 and 0.50 mm/s, respectively. The maximum FP velocity (0.64 mm/s) is observed in CCF/Ep composites. The degree of cure (αc) is observed to be in the range of 70% to 85% in FP-processed composites. Such a range of αc is significantly low in comparison to traditional composites processed through a long cure cycle. The glass transition temperature (Tg) of neat epoxy resin is seen to be approximately 154 °C, and it reduces slightly to a lower value (149 °C) for SCF-reinforced composites. The microstructures show significantly high void contents (12%) and large internal cracks. These internal cracks are initiated due to high thermal residual stress developed during curing for non-uniform temperature distribution. The tensile properties of FP-cured samples are seen to be inferior in comparison to autoclave-processed neat epoxy. This occurs mostly due to the presence of large void contents, internal cracks, and a poor degree of cure. Finally, a highly efficient and controlled FP method is desirable to achieve a defect-free microstructure with improved mechanical and thermal properties.

3.
ACS Appl Mater Interfaces ; 16(23): 30010-30019, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38814930

ABSTRACT

The present study demonstrates that precursor passivation is an effective approach for improving the crystallization process and controlling the detrimental defect density in high-efficiency Cu2ZnSn(S,Se)4 (CZTSSe) thin films. It is achieved by applying the atomic layer deposition (ALD) of the tin oxide (ALD-SnO2) capping layer onto the precursor (Cu-Zn-Sn) thin films. The ALD-SnO2 capping layer was observed to facilitate the homogeneous growth of crystalline grains and mitigate defects prior to sulfo-selenization in CZTSSe thin films. Particularly, the CuZn and SnZn defects and deep defects associated with Sn were effectively mitigated due to the reduction of Sn2+ and the increase in Sn4+ levels in the kesterite CZTSSe film after introducing ALD-SnO2 on the precursor films. Subsequently, devices integrating the ALD-SnO2 layer exhibited significantly reduced recombination and efficient charge transport at the heterojunction interface and within the bulk CZTSSe absorber bulk properties. Finally, the CZTSSe device showed improved power conversion efficiency (PCE) from 8.46% to 10.1%. The incorporation of ALD-SnO2 revealed reduced defect sites, grain boundaries, and surface roughness, improving the performance. This study offers a systematic examination of the correlation between the incorporation of the ALD-SnO2 layer and the improved PCE of CZTSSe thin film solar cells (TFSCs), in addition to innovative approaches for improving absorber quality and defect control to advance the performance of kesterite CZTSSe devices.

4.
Chemosphere ; 351: 141244, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38242515

ABSTRACT

Amines, which are classified as volatile organic compounds (VOCs), serve a variety of purposes in the fields of environmental monitoring, food safety, and healthcare diagnosis. The present technique for detecting amine levels involves sophisticated setups and bulky equipment. Here. In this study, a chemoresistive gas sensor is developed that is cost-effective and easy to operate at room temperature (RT). The sensor is designed specifically for the detection of Ammonia, dimethylamine (DMA), trimethylamine (TMA), and total volatile basic nitrogen (TVB-N). Using biphenyl-reduced graphene oxide (B-rGO) composite gas sensors effectively addresses the issues of low sensitivity-selectivity and long-term instability commonly observed in conventional amine sensors. B-rGO sensor produced sensitivity of ∼3500 and selectivity above 30 for TVB-N sensing. The sensor is stable for temperature fluctuations below 50 °C and shows stable sensing response for period of over 3 months. A Chemoresistive B-rGO sensor was developed using an ultrasonic spray deposition system with optimized flow rate of 50 mL/h. Rapid evaporation of solvent using hot plate has resulted in unique morphology for B-rGO film sensors. The highest sensitivity, ∼836, is obtained for 100 ppm of ammonia with ammonia > DMA > TMA as a sensitivity order. B-rGO showed almost seven times higher amine sensitivity than rGO which highlights the importance of biphenyl in the B-rGO composite. Sensor calibration curve has been presented in the study to understand change in the sensitivity of sensor with increasing analyte gas concentration. The calibration curve has an average R-squared value of 0.98.


Subject(s)
Amines , Ammonia , Biphenyl Compounds , Dimethylamines , Graphite , Methylamines , Temperature , Nitrogen
5.
Dalton Trans ; 52(33): 11481-11488, 2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37534542

ABSTRACT

The successful deployment of sodium-ion batteries (SIBs) requires high-performance sustainable and cost-effective anode materials having a high current density. In this regard, sodium disulphide (NiS2) has been prepared as a composite with activated carbon (C) using a facile hydrothermal synthesis route in the past. The X-ray diffraction pattern of the as-prepared NiS2/C composite material shows well-defined diffraction peaks of NiS2. Most carbonaceous materials are amorphous, and the Brunauer-Emmett-Teller (BET) study shows that the surface area is close to 148 m2 g-1. At a current density of 50 mA g-1, the NiS2/C composite exhibits a high capacity of 480 mA h g-1 during the initial cycle, which subsequently decreases to 333 mA h g-1 after the completion of the 100th cycle. The NiS2/C composite electrode provides an exceptional rate capability by delivering a capacity of 270 mA h g-1 at a high current density of 2000 mA g-1, suggesting the suitability of the NiS2/C composite for SIBs. Ex situ X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses at the Ni K-edge have been used to examine the type of chemical bonding present in the anode and also how it changes during electrochemical redox cycling. The understanding of the sodium storage mechanism is improved by the favorable results, which also offer insights for developing high-performance electrode materials for rechargeable SIBs.

6.
Environ Res ; 236(Pt 2): 116793, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37532212

ABSTRACT

Herein, we present the gas-dependent electrical properties of a reduced graphene oxide nanocomposite. The reduced graphene oxide (rGO) was synthesized by reducing GO with sodium borohydride (NaBH4). As-synthesized rGO was dispersed in DI water containing 1, 2, 3, 4, and 5 wt% polyethylene glycol (PEG) to prepare PEG-rGO supramolecular assemblies. The successful preparation of supramolecular assemblies was verified by their characterization using XRD, FESEM, EDS, TEM, FTIR, and Raman spectroscopy. At room temperature, the gas-dependent electrical properties of these supramolecular assemblies were investigated. The results showed that sensors composed of PEG-rGO supramolecular assemblies performed better against benzene and methanol at 3% and 4% PEG, respectively. However, high selectivity and a wide range of activation energies (∼1.64-1.91 eV) were observed for H2 gas for 4% PEG-modified supramolecular assemblies. The PEG-rGO supramolecular assemblies may be an excellent candidate for constructing ultrahigh-performance gas sensors for a variety of applications due to their high sensitivity and selectivity.


Subject(s)
Graphite , Polyethylene Glycols , Polyethylene Glycols/chemistry , Temperature , Graphite/chemistry
7.
Indian Pediatr ; 60(9): 709-713, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37260063

ABSTRACT

The diagnosis and management of encephalitis were previously largely based on clinical grounds and minimal laboratory investigations. Japanese encephalitis (JE) gets considered as the probable diagnosis in most encephalitis cases. However, reports of JE in adults and the elderly are increasing after the JE vaccine introduction among children in 2006. The Nipah virus (NiV) emerged in 2002 and continues to afflict humans in new geographic areas. Many other infections cause encephalitis, including Chandipura, chikungunya, dengue, and West Nile. Significant advances in diagnostic testing like multiplex testing panels and metagenomic approaches along with sequencing have helped in the detection of new etiologies. Recent years have witnessed an increase in climate-sensitive zoonotic diseases with encephalitis. This highlights the importance of the One Health approach in studying the impact of climate change-associated infectious diseases on human health. The government of India's efforts to develop health research infrastructure would help future responses to emerging infectious disease epidemics.


Subject(s)
Acute Febrile Encephalopathy , Communicable Diseases , Encephalitis, Japanese , Encephalitis , Child , Adult , Humans , Aged , Acute Febrile Encephalopathy/diagnosis , Acute Febrile Encephalopathy/epidemiology , Acute Febrile Encephalopathy/etiology , Encephalitis, Japanese/diagnosis , Encephalitis, Japanese/epidemiology , Encephalitis/diagnosis , Encephalitis/epidemiology , India/epidemiology
8.
J Epidemiol Glob Health ; 13(2): 173-179, 2023 06.
Article in English | MEDLINE | ID: mdl-37162636

ABSTRACT

BACKGROUND: We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE vaccine. METHODS: We implemented enhanced surveillance of AES and JE hospitalizations in endemic districts in Maharashtra and Telangana States during 2015-2016 and 2018-2020. We estimated incidence and compared differences in the incidence of JE and AES between two states, and vaccinated and unvaccinated districts during two study periods. We also considered secondary data from public health services to understand long-term trends from 2007 to 2020. RESULTS: The annual AES incidence rate of 2.25 cases per 100,000 children in Maharashtra during 2018-2020 was significantly lower than 3.36 cases per 100,000 children during 2015-2016. The six JE-vaccinated districts in Maharashtra had significantly lower incidence rates during 2018-2020 (2.03, 95% CI 1.73-2.37) than in 2015-16 (3.26, 2.86-3.70). In addition, the incidence of both JE and AES in two unvaccinated districts was higher than in the vaccinated districts in Maharashtra. Telangana had a lower incidence of both JE and AES than Maharashtra. The AES incidence rate of 0.95 (0.77-1.17) during 2018-2020 in Telangana was significantly lower than 1.67 (1.41-1.97) during 2015-2016. CONCLUSIONS: The annual incidence rate of Japanese encephalitis was < 1 case per 100,000 children. It indicated accelerated control of Japanese encephalitis after routine immunization. However, the annual incidence of acute encephalitis syndrome was still > 1 case per 100,000 children. It highlights the need for improving surveillance and evaluating the impacts of vaccination.


Subject(s)
Acute Febrile Encephalopathy , Encephalitis, Japanese , Child , Humans , Encephalitis, Japanese/epidemiology , Encephalitis, Japanese/prevention & control , Incidence , Acute Febrile Encephalopathy/epidemiology , India/epidemiology , Hospitalization
9.
J Med Virol ; 95(1): e28399, 2023 01.
Article in English | MEDLINE | ID: mdl-36512338

ABSTRACT

Japanese encephalitis (JE) disease among children continues in central India despite vaccination implemented in the routine immunization program. Therefore, we planned to estimate the JE vaccination effectiveness among children by undertaking a 1:2 individually-matched population-based case-control study from August 2018 to October 2020. The laboratory-confirmed JE cases aged 1-15 years were enrolled along with neighborhood controls without fever and encephalitis matched on the residence area, age and sex. The JE vaccination history was enquired from parents and verified independently from the vaccination cards available at home and records at health facilities. We enrolled 35 JE cases and 70 matched controls. The vaccination effectiveness of 86.7% (95% confidence interval [CI]: 30.8-94.7) was estimated on the per-protocol analysis of 31 case-control sets. The screening method provided an effectiveness of 89.5% (CI: 78.9-94.7) on using the population vaccination coverage of 90% reported earlier in the same area. In conclusion, JE vaccination offered a moderate level of protection among children in JE medium-endemic central India, similar to reports from high-endemic areas in India. The operational aspects of vaccination program implementation need to be evaluated to assess the impact of vaccination on the disease burden of JE in medium-endemic regions of India.


Subject(s)
Encephalitis, Japanese , Child , Humans , Encephalitis, Japanese/epidemiology , Encephalitis, Japanese/prevention & control , Case-Control Studies , Vaccination , Immunization Programs , India/epidemiology
10.
J Biomol Struct Dyn ; 41(10): 4696-4710, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35532095

ABSTRACT

Targeting kinases with oncogenic driver mutations in malignancies with allosteric kinase inhibitors is a promising new treatment technique. EGFR inhibitors targeting the L858R/T790M/C797S mutation bearing thiazolidine-4-one scaffold were discovered, optimized, synthesized, and biologically evaluated. According to in silico and in vitro studies, compounds 6a and 6b resulted to be highly potent with IC50 values of 120 nM and 134 nM and good selectivity. Compound 6a displayed significant antioxidant activity, with a DPPH radical scavenging value of 92.15%. The potency of compounds was also compared with ADMET and molecular dynamics simulations study. A comparative simulation of model protein and protein-ligand complex in presence and absence of compound 6a has been carried out.Communicated by Ramaswamy H. Sarma.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Molecular Dynamics Simulation , ErbB Receptors/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Protein Kinase Inhibitors/chemistry , Mutation
11.
Nanomaterials (Basel) ; 12(23)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36500786

ABSTRACT

The current need to accelerate the adoption of photovoltaic (PV) systems has increased the need to explore new nanomaterials that can harvest and convert solar energy into electricity. Transition metal dichalcogenides (TMDCs) are good candidates because of their tunable physical and chemical properties. CuCrS2 has shown good electrical and thermoelectrical properties; however, its optical and photoconductivity properties remain unexplored. In this study, we synthesized CuCrS2 nanosheets with average dimensions of 43.6 ± 6.7 nm in length and 25.6 ± 4.1 nm in width using a heat-up synthesis approach and fabricated films by the spray-coating method to probe their photoresponse. This method yielded CuCrS2 nanosheets with an optical bandgap of ~1.21 eV. The fabricated film had an average thickness of ~570 nm, exhibiting a net current conversion efficiency of ~11.3%. These results demonstrate the potential use of CuCrS2 as an absorber layer in solar cells.

12.
Nanomaterials (Basel) ; 12(19)2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36234507

ABSTRACT

Herein, aqueous ammonium sensing characteristics of polyvinylpyrrolidone (PVP) capped silver nanoparticles (Ag-NPs) coated optical fiber-based sensors are presented. The PVP-capped Ag-NPs were prepared using cold and modified polyol synthesis methods. Aqueous ammonium detection was carried out by the surface plasmon resonance (SPR) effect observed in the Ag-NPs coated optical fiber system. The effect of cold and modified polyol synthesis methods on optical sensing performance was studied. The optical fiber cladding was modified with PVP-capped Ag-NPs according to the standard protocol for sensing investigation. The probe sensing response was analyzed for varying concentrations of ammonium ions on red, green, and blue LEDs. The sensor characteristics, viz., sensing response, repeatability, calibration curve, and ambient light effect, were investigated for PVP capped Ag-NPs coated optical fiber-based sensor. The PVP capped Ag-NPs synthesized via the polyol synthesis method showed a detection limit of 48.9 mM, 1.33 mV/M sensitivity, and an excellent linear relationship (R2 = 0.9992) between voltage and ammonium ion concentration in the range of 0.054-13.4 M concentration. On the other hand, PVP capped Ag-NPs synthesized using the cold synthesis method showed a detection limit of 159.4 mM, a sensitivity of 0.06 mV/M, and a poor linear relationship (R2 = 0.4588) between voltage and ammonium ion concentration in the range of 0.054-13.4 M concentration. The results indicate that the PVP-capped Ag-NPs synthesized using the polyol synthesis method exhibit enhanced ammonium ion sensing compared to the cold synthesis method.

13.
PLoS Pathog ; 18(10): e1010849, 2022 10.
Article in English | MEDLINE | ID: mdl-36227859

ABSTRACT

Reversible phosphorylation by protein kinases is one of the core mechanisms by which biological signals are propagated and processed. Mitogen-activated protein kinases, or MAPKs, are conserved throughout eukaryotes where they regulate cell cycle, development, and stress response. Here, we review advances in our understanding of the function and biochemistry of MAPK signaling in apicomplexan parasites. As expected for well-conserved signaling modules, MAPKs have been found to have multiple essential roles regulating both Toxoplasma tachyzoite replication and sexual differentiation in Plasmodium. However, apicomplexan MAPK signaling is notable for the lack of the canonical kinase cascade that normally regulates the networks, and therefore must be regulated by a distinct mechanism. We highlight what few regulatory relationships have been established to date, and discuss the challenges to the field in elucidating the complete MAPK signaling networks in these parasites.


Subject(s)
Mothers , Toxoplasma , Female , Humans , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation , Signal Transduction , Toxoplasma/metabolism
14.
J Med Virol ; 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36114690

ABSTRACT

BACKGROUND: We aimed to estimate the coverage of Japanese encephalitis (JE) vaccination in central India to help explain the continued occurrence of JE disease despite routine vaccination. METHODS: We implemented a 30-cluster survey for estimating the coverage of JE vaccination in the medium-endemic areas implemented with JE vaccination in central India. The parents were enquired about the uptake of the JE vaccine by their children aged 2 to 6 years, followed by verification of the immunization cards at home along with reasons for non-vaccination. Vaccination coverage was reported as a percentage with 95% confidence intervals. RESULTS: We estimated high coverage of live-attenuated SA 14-14-2 JE vaccination in Maharashtra (94.8%, 95% CI 92.7-96.3) and Telangana (92.8%, 90.0-94.9). The vaccination card retention was 90.3% in Maharashtra and 70.4% in Telangana state. There were no gender differences in coverage in both states. A similar level of JE vaccination coverage was observed during the year 2013 to 2021 in both states. In Maharashtra, the maximum age-wise coverage was 96.6% in the >60 months age category, whereas in Telangana it was in the <24 months age category (97.2%). The timeliness of JE vaccination was appropriate and similar in both states. We found very good agreement between JE and Measles-Rubella vaccinations administered simultaneously. The reasons for non-vaccination were the shortage of vaccines and the parental migration for work. CONCLUSIONS: The coverage of Japanese encephalitis vaccination was high in medium-endemic regions in central India. Vaccination effectiveness studies may help further explain the continued incidence of Japanese encephalitis. This article is protected by copyright. All rights reserved.

15.
Biochem J ; 479(17): 1877-1889, 2022 09 16.
Article in English | MEDLINE | ID: mdl-35938919

ABSTRACT

Apicomplexan parasites like Toxoplasma gondii grow and replicate within a specialized organelle called the parasitophorous vacuole. The vacuole is decorated with parasite proteins that integrate into the membrane after trafficking through the parasite secretory system as soluble, chaperoned complexes. A regulator of this process is an atypical protein kinase called WNG1. Phosphorylation by WNG1 appears to serve as a switch for membrane integration. However, like its substrates, WNG1 is secreted from the parasite dense granules, and its activity must, therefore, be tightly regulated until the correct membrane is encountered. Here, we demonstrate that, while another member of the WNG family can adopt multiple multimeric states, WNG1 is monomeric and therefore not regulated by multimerization. Instead, we identify two phosphosites on WNG1 that are required for its kinase activity. Using a combination of in vitro biochemistry and structural modeling, we identify basic residues that are also required for WNG1 activity and appear to recognize the activating phosphosites. Among these coordinating residues are the 'HRD' Arg, which recognizes activation loop phosphorylation in canonical kinases. WNG1, however, is not phosphorylated on its activation loop, but rather on atypical phosphosites on its C-lobe. We propose a simple model in which WNG1 is activated by increasing ATP concentration above a critical threshold once the kinase traffics to the parasitophorous vacuole.


Subject(s)
Protozoan Proteins , Toxoplasma , Adenosine Triphosphate/metabolism , Phosphorylation , Protein Kinases/metabolism , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Toxoplasma/physiology , Vacuoles/metabolism
16.
ACS Med Chem Lett ; 13(6): 943-948, 2022 Jun 09.
Article in English | MEDLINE | ID: mdl-35707160

ABSTRACT

Formyl peptide receptor 2 (FPR2) agonists have shown efficacy in inflammatory-driven animal disease models and have the potential to treat a range of diseases. Many reported synthetic agonists contain a phenylurea, which appears to be necessary for activity in the reported chemotypes. We set out to find isosteres for the phenylurea and focused our efforts on heteroaryl rings. The wide range of potencies with heterocyclic isosteres demonstrates how electronic effects of the heteroatom placement impact molecular recognition. Herein, we report our discovery of benzimidazole and aminophenyloxadiazole FPR2 agonists with low nanomolar activity.

17.
J Clin Virol ; 153: 105194, 2022 08.
Article in English | MEDLINE | ID: mdl-35687988

ABSTRACT

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.


Subject(s)
Acute Febrile Encephalopathy , Encephalitis Virus, Japanese , Encephalitis, Japanese , Leptospirosis , Typhoid Fever , Acute Febrile Encephalopathy/epidemiology , Acute Febrile Encephalopathy/etiology , Adult , Child , Encephalitis, Japanese/diagnosis , Encephalitis, Japanese/epidemiology , Hospitalization , Humans , India/epidemiology , Simplexvirus
18.
Sci Rep ; 12(1): 8744, 2022 05 24.
Article in English | MEDLINE | ID: mdl-35610240

ABSTRACT

The role of RORγ as a transcription factor for Th17 cell differentiation and thereby regulation of IL-17 levels is well known. Increased RORγ expression along with IL-17A levels was observed in animal models, immune cells and BAL fluid of COPD patients. Increased IL-17A levels in severe COPD patients are positively correlated with decreased lung functions and increased severity symptoms and emphysema, supporting an urgency to develop novel therapies modulating IL-17 or RORγ for COPD treatment. We identified a potent RORγ inhibitor, PCCR-1 using hit to lead identification followed by extensive lead optimization by structure-activity relationship. PCCR-1 resulted in RORγ inhibition with a high degree of specificity in a biochemical assay, with > 300-fold selectivity over other isoforms of ROR. Our data suggest promising potency for IL-17A inhibition in human and canine PBMCs and mouse splenocytes with no significant impact on Th1 and Th2 cytokines. In vivo, PCCR-1 exhibited significant efficacy in the acute CS model with dose-dependent inhibition of the PD biomarkers that correlated well with the drug concentration in lung and BAL fluid, demonstrating an acceptable safety profile. This inhibitor effectively inhibited IL-17A release in whole blood and BALf samples from COPD patients. Overall, we identified a selective inhibitor of RORγ to pursue further development of novel scaffolds for COPD treatment.


Subject(s)
Airway Obstruction , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Airway Obstruction/metabolism , Animals , Dogs , Humans , Interleukin-17/metabolism , Lung/metabolism , Mice , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Emphysema/metabolism , Th17 Cells
19.
J Org Chem ; 87(9): 6097-6104, 2022 05 06.
Article in English | MEDLINE | ID: mdl-35439411

ABSTRACT

Thermolysis of ω-iodoalkyl-ß-siloxyalkenenitriles in DMSO triggers an oxidative cyclization cascade that affords highly oxygenated hydrindanones, decalones, and undecanones. The cyclization cascade is highly unusual on three counts: the cyclization installs a contiguous array of tertiary-quaternary-tertiary centers, thermolysis equilibrates a quaternary center, and the enolsilyl ether crossed-aldol proceeds without a catalyst.


Subject(s)
Dimethyl Sulfoxide , Oxidative Stress , Catalysis , Cyclization , Stereoisomerism
20.
Semin Immunol ; 59: 101602, 2022 01.
Article in English | MEDLINE | ID: mdl-35277300

ABSTRACT

Formyl peptide receptor type 2 (FPR2) regulates the initiation and resolution phases of the inflammatory response. In the setting of heart injury and disease, dysregulated inflammation can potentiate maladaptive healing and pathological remodeling of the heart leading to cardiac dysfunction and failure. The potential to regulate and resolve adverse inflammation is postulated to improve outcome in the setting of heart disease. This review covers emerging concepts on the role of FPR2 in heart disease and strategies to activate pro-resolution processes to limit disease progression. We summarize key preclinical studies that support use of FPR2 agonists in heart disease. Finally, we briefly discuss the status of FPR2 agonists under evaluation in the clinic.


Subject(s)
Heart Diseases , Receptors, Formyl Peptide , Humans , Inflammation/pathology , Receptors, Formyl Peptide/agonists , Receptors, Formyl Peptide/physiology , Wound Healing
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