Incidence of Long COVID-19 at 12-18 Months Following Delta Wave of Coronavirus Disease 2019: Hospital-based Prospective Registry.

BACKGROUND AND OBJECTIVE: Long coronavirus disease 2019 (COVID-19) has emerged as an important consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify its incidence 12-18 months following hospitalization in patients with COVID-19, we performed a prospective study. METHODS: Virologically confirmed successive patients with moderate-to-severe COVID-19, hospitalized during the delta wave in India, were recruited. Data on clinical features, investigations, and outcomes were obtained. Long COVID-19 was diagnosed using the European quality of life questionnaire (EQ-5D) and Birmingham symptom burden questionnaire (SBQ) at 12-18-month follow-up. RESULTS: During the study period (January-July 2021), we evaluated 8,680 suspected COVID-19 patients, of whom 1,641 were confirmed virologically and 388 were hospitalized. Men accounted for 64.4%, individuals aged >60 years for 41.5%, hypertension for 42.8%, diabetes for 38.4%, and cardiovascular disease for 17.3%. At admission, there was a high prevalence of cough (71.1%), fever (86.6%), and oxygen requirement (38.6%). Proning was deployed in 89.2% of cases, nasal cannula in 36.3%, nonrebreather masks in 15.7%, noninvasive ventilation in 14.4%, and invasive ventilation in 16.2%. In-hospital deaths totaled 75 (19.3%), with 310 discharged for home care and eligible for follow-up. At a median follow-up of 15 months, 9 patients had died, 40 were lost to follow-up, and 264 were evaluated. The incidence of Long COVID-19 was 45 [17.0%, 95% confidence of interval (CI) 12.6-21.9%]. The median EQ-5D score was 5.0, with >5 observed in only 11 patients (0.6%). Using the SBQ, new-onset dyspnea on exertion was noted in 13 (4.9%), rest dyspnea in 7 (2.6%), fatigue in 31 (11.7%), feverishness in 18 (6.8%), and low energy in 16 (6.1%). Long COVID-19 was significantly more prevalent in women and older individuals. In Long COVID-19 compared to controls, the mean duration of oxygen requirement (5.46 ± 9.8 vs 2.46 ± 4.5 days, p = 0.002), use of nonrebreather masks (17.8 vs 7.3%, p = 0.026), noninvasive ventilation (11.1 vs 3.2%, p = 0.020), and duration of intensive care unit (ICU) stay (13.5, 8.7-17.3 vs 8.0, 5.0-11.0 days, p = 0.028) were significantly higher. CONCLUSION: The incidence of Long COVID-19 at 12-18 months follow-up is 17.0%. It is significantly higher in women, older age groups, and patients requiring longer oxygenation, nonrebreather oxygen masks, noninvasive respiratory support, and extended stays in the ICU.

Complementary Strategies for Installation of Thioimidates into Peptide Backbones.

Thioimidates are a precursor and synthetic branch point to access either thioamide or amidine isosteres of the native amide (peptide bond). Previous syntheses of thioimidate-containing peptides were prone to side reactivity and required slow, cumbersome steps that were difficult to monitor. We describe a more efficient approach to directly couple thioimidates onto the growing peptide chain. This work also outlines optimal conditions for thioimidate formation on solid support and identifies potential off-target sites for alkylation that impact the choice of protecting group.

Toxicodynamics of cadmium in the green mussel Perna viridis (Linnaeus, 1758) using bioenergetic and physiological biomarkers.

This study evaluated the toxicity of cadmium (Cd) on the green mussel Perna viridis, aiming to identify toxicological endpoints and investigate its responses across physiological, bioenergetic, and biochemical parameters. The 96-hour LC50 value for Cd in P. viridis was 3.03 ± 0.12 mg L-1, with a 95% confidence interval of 2.35-3.91 mg L-1. Chronic toxicity tests revealed a No Observable Effect Concentration (NOEC), Lowest Observable Effect Concentration (LOEC), and chronic toxicity values of 0.20, 0.37, and 0.29 mg L-1, respectively. Cadmium accumulation in treated mussels increased 46- to 215-fold compared to the control group. Superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase levels in exposed mussels exhibited a significant increase compared to the control group. The redox index ratio, acetylcholinesterase activity, and lysosomal membrane stability decreased with increasing exposure concentrations. Levels of reduced and oxidized glutathione, glutathione reductase, lipid peroxidation, and metallothionein-like proteins increased in exposed mussels. Clearance rate, respiration rate, and excretion rate decreased in a dose-dependent manner. Protein, carbohydrate, and lipid levels decreased with increasing exposure concentration (p < 0.001). Mitochondrial electron transport system activity increased, while cellular energy allocation (p < 0.001) and scope for growth decreased in a dose-dependent manner (p < 0.01). The significant increase in antioxidants suggests heightened oxidative stress in mussels under Cd exposure. The physiological activities of the mussels were severely affected, ultimately leading to a reduced scope for growth. The toxicological data generated in this study contribute to the development of seawater quality criteria for the metal Cd.

Importance of Dyslipidemias in Very Premature Coronary Artery Disease in India: A Registry-based Study.

BACKGROUND AND OBJECTIVE: Premature coronary artery disease (CAD) is an important cause of death in India. To identify risk factors in patients with premature CAD, we performed a registry-based study. METHODS: Consecutive patients admitted for percutaneous coronary intervention (PCI) from October 2020 to June 2021 were recruited. The patients were classified into three groups-group I (very premature CAD < 40 years), group II (premature CAD 40-59 years), and group III (nonpremature CAD > 60 years). Major risk factors were determined, and intergroup comparison was performed. RESULTS: A total of 627 patients were enrolled (men 541, women 86). Group I had 79 (12.4%), group II had 420 (66.9%), and group III had 128 (20.4%) patients. The prevalence of risk factors in groups I, II, and III, respectively, were-CAD family history in 45.1, 41.1, and 26.6% (p = 0.005), current smoking/tobacco use in 29.1, 21.0, and 10.2% (p = 0.002), hypertension in 31.6, 43.6, and 59.4% (p < 0.001), and diabetes in 22.8, 34.3, and 46.1% (p < 0.001). High total cholesterol (>170 mg/dL) was present in 50.0, 38.0, and 29.9% (p = 0.005), nonhigh-density lipoprotein (HDL) cholesterol (>100 mg/dL) in 76.9, 64.4, and 54.5% (p = 0.001), low-density lipoprotein (LDL) cholesterol (>70 mg/dL) in 85.9, 76.8, and 76.4% (p = 0.167), triglycerides (>150 mg/dL) in 56.4, 45.3, and 33.1% (p = 0.001), and very low density lipoprotein (VLDL) cholesterol (>30 mg/dL) in 24.4, 10.4, and 9.4% (p = 0.005). Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) for smoking/tobacco use in groups I and II compared to group III, respectively, were 3.17 (1.60-6.27) and 2.59 (1.51-4.46); high total cholesterol 2.39 (1.29-4.13) and 1.42 (0.92-2.17); high non-HDL cholesterol 2.70 (1.45-5.03) and 1.48 (0.99-2.20); and high triglycerides 2.57 (1.44-4.58) and 1.64 (1.08-2.49). CONCLUSION: Important coronary risk factors in very premature and premature CAD in India are a family history of CAD, any tobacco use, and dyslipidemias (raised total, LDL, non-HDL, and VLDL cholesterol and triglycerides).

Feasibility and Methodology of a Pilot Free Blood Pressure Monitoring and Follow-Up Program at Two Free Clinics.

BACKGROUND: Hypertension affects approximately 1 in 2 adults in the US. Home blood pressure (BP) monitoring programs are effective in the diagnosis and management of hypertension. Free clinics serve as an integral safety net for millions of uninsured and economically disadvantaged patients in the US. The feasibility and effects of a free home BP monitoring and follow-up program in a free clinic setting is not well characterized. METHODS: This was a prospective study of the implementation of a pilot BP monitoring and follow-up program between March 2021 and August 2023 at 2 free clinics in the San Francisco Bay Area. A total of 78 hypertensive patients were enrolled in the program and given a free BP monitor. We surveyed via telephone the change in systolic and diastolic BPs and BP monitor use and comfort at 3 weeks. Volunteers in clinic roles involved in the BP monitoring program were surveyed to assess their time spent and perceptions of the program. RESULTS: Of the 78 patients, 37 provided responses to the 3-week survey. A total of 36 of 37 (97%) patients reported using their BP monitor. A total of 35 patients reported using it at least once a week (95%), with the majority reporting at least four uses a week (68%). A total of 36 patients (97%) planned on continuing to use their BP monitor. At 3 weeks, the mean systolic and diastolic BP changed by -6.40 mmHg (95% CI, -10.8 to -2.01 mmHg; P = .00577) and -2.72 mmHg (95% CI, -5.62 to 0.188 mmHg; P = .0657), respectively. The time commitment for this program ranged from 130 ± 51 min for program leaders to 16 ± 14 min per week for patient-facing roles. All volunteer roles (patient-facing, phone follow-up, program leaders) expressed that they had a clear understanding of their responsibilities in the program (median 4 on Likert scale, IQR 3-5). CONCLUSION: Home BP monitoring and follow-up is feasible to implement in free clinics, resulting in high rates of patient engagement among respondents. Our findings suggest that home BP monitoring and follow-up programs may be beneficial in vulnerable patient populations.

Assessment of obstructive airway disease in the multicenter SWORD survey India.

BACKGROUND AND OBJECTIVES: The study aimed to assess the control of asthma and the severity of chronic obstructive pulmonary disease (COPD) and evaluate the adequacy of treatment in patients presenting to the outpatient department (OPD) across India. The secondary aim was to assess the risk factors associated with poorly controlled asthma and severe COPD. MATERIALS AND METHODS: This is the analysis of Phase IV of the multicenter questionnaire-based point prevalence SWORD survey, conducted in May 2018, and designed to capture details on disease control and treatment as per the global initiative for asthma and the global initiative for chronic obstructive lung disease guidelines. RESULTS: Of the 5,311 respiratory disease patients presenting to the OPD, there were 1,419 and 412 patients with asthma and COPD, respectively, across 290 sites in India. There were 1,022 (72%) patients having well-controlled asthma, 293 (20.6%) patients with partly controlled asthma, and 104 (7.4%) patients with poorly controlled asthma. Of the 412 patients with COPD, there were 307 (74.5%) in A, 54 (13.1%) in B, and 51 (12.4%) in the E category. In spite of poor control or severe disease, 34.8% of asthmatic and 25.7% of patients in the B and E categories of COPD were not using any medicine. Risk factors for partly and poorly controlled asthma included rain wetting (adjusted odds ratio [AOR]: 1.59, 95% confidence interval [CI]: 1.02-2.47) and gastroesophageal reflux disease (AOR: 1.50, 95%CI: 1.08-2.10). CONCLUSION: This study identifies a gap in the treatment of both poorly controlled asthma and severe COPD. A substantial number of patients had poorly controlled asthma and severe COPD, and many were either not taking treatment or taking it inappropriately.

Leveraging integrative toxicogenomic approach towards development of stressor-centric adverse outcome pathway networks for plastic additives.

Plastics are widespread pollutants found in atmospheric, terrestrial and aquatic ecosystems due to their extensive usage and environmental persistence. Plastic additives, that are intentionally added to achieve specific functionality in plastics, leach into the environment upon plastic degradation and pose considerable risk to ecological and human health. Limited knowledge concerning the presence of plastic additives throughout plastic life cycle has hindered their effective regulation, thereby posing risks to product safety. In this study, we leveraged the adverse outcome pathway (AOP) framework to understand the mechanisms underlying plastic additives-induced toxicities. We first identified an exhaustive list of 6470 plastic additives from chemicals documented in plastics. Next, we leveraged heterogenous toxicogenomics and biological endpoints data from five exposome-relevant resources, and identified associations between 1287 plastic additives and 322 complete and high quality AOPs within AOP-Wiki. Based on these plastic additive-AOP associations, we constructed a stressor-centric AOP network, wherein the stressors are categorized into ten priority use sectors and AOPs are linked to 27 disease categories. We visualized the plastic additives-AOP network for each of the 1287 plastic additives and made them available in a dedicated website: https://cb.imsc.res.in/saopadditives/ . Finally, we showed the utility of the constructed plastic additives-AOP network by identifying highly relevant AOPs associated with benzo[a]pyrene (B[a]P), bisphenol A (BPA), and bis(2-ethylhexyl) phthalate (DEHP) and thereafter, explored the associated toxicity pathways in humans and aquatic species. Overall, the constructed plastic additives-AOP network will assist regulatory risk assessment of plastic additives, thereby contributing towards a toxic-free circular economy for plastics.

Gut colonization with antibiotic-resistant Escherichia coli pathobionts leads to disease severity in ulcerative colitis.

BACKGROUND: Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored until now. METHODS: Human gut microbiota composition and meta-gut resistome were evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to gain insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. RESULTS: In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy controls (HC) [518]. The metagenome study revealed a higher prevalence of AMR genes in the rural population (378 in HC; 607 in UC) compared to the urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant (MDR), with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and inflammatory mediator (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. CONCLUSIONS: In addition to the conventional culturomics method, a multi-omics strategy provides deeper insights into the disease etiology, emergence of MDR pathobionts, and their roles in the disruption of the healthy gut environment in UC patients.

Proteome profiling, biochemical and histological analysis of diclofenac-induced liver toxicity in Yersinia enterocolitica and Lactobacillus fermentum fed rat model: a comparative analysis.

Diclofenac is a hepatotoxic non-steroidal anti-inflammatory drug (NSAID) that affects liver histology and its protein expression levels. Here, we studied the effect of diclofenac on rat liver when co-administrated with either Yersinia enterocolitica strain 8081 serotype O:8 biovar 1B (D*Y) or Lactobacillus fermentum strain 9338 (D*L). Spectroscopic analysis of stool samples showed biotransformation of diclofenac. When compared with each other, D*Y rats lack peaks at 1709 and 1198 cm-1, while D*L rats lack peaks at 1411 cm-1. However, when compared to control, both groups lack peaks at 1379 and 1170 cm-1. Assessment of serum biomarkers of hepatotoxicity indicated significantly altered activities of AST (D*Y: 185.65 ± 8.575 vs Control: 61.9 ± 2.607, D*L: 247.5 ± 5.717 vs Control: 61.9 ± 2.607), ALT (D*Y: 229.8 ± 6.920 vs Control: 70.7 ± 3.109, D*L: 123.75 ± 6.068 vs Control: 70.7 ± 3.109), and ALP (D*Y: 276.4 ± 18.154 vs Control: 320.6 ± 9.829, D*L: 298.5 ± 12.336 vs Control: 320.6 ± 9.829) in IU/L. The analysis of histological alterations showed hepatic sinusoidal dilation with vein congestion and cell infiltration exclusively in D*Y rats along with other histological changes that are common to both test groups, thereby suggesting more pronounced alterations in D*Y rats. Further, LC-MS/MS based label-free quantitation of proteins from liver tissues revealed 74.75% up-regulated, 25.25% down-regulated in D*Y rats and 51.16% up-regulated, 48.84% down-regulated in D*L experiments. The proteomics-identified proteins majorly belonged to metabolism, apoptosis, stress response and redox homeostasis, and detoxification and antioxidant defence that demonstrated the potential damage of rat liver, more pronounced in D*Y rats. Altogether the results are in favor that the administration of lactobacilli somewhat protected the rat hepatic cells against the diclofenac-induced toxicity.

Gut microbial metalloproteins and its role in xenobiotics degradation and ROS scavenging.

The gut microbial metalloenzymes play an important role in maintaining the balance between gut microbial ecosystem, human physiologically processes and immune system. The metals coordinated into active site contribute in various detoxification and defense strategies to avoid unfavourable environment and ensure bacterial survival in human gut. Metallo-ß-lactamase is a potent degrader of antibiotics present in periplasmic space of both commensals and pathogenic bacteria. The resistance to anti-microbial agents developed in this enzyme is one of the global threats for human health. The organophosphorus eliminator, organophosphorus hydrolases have evolved over a course of time to hydrolyze toxic organophosphorus compounds and decrease its effect on human health. Further, the redox stress responders namely superoxide dismutase and catalase are key metalloenzymes in reducing both endogenous and exogenous oxidative stress. They hold a great importance for pathogens as they contribute in pathogenesis in human gut along with reduction of oxidative stress. The in-silico study on these enzymes reveals the importance of point mutation for the evolution of these enzymes in order to enhance their enzyme activity and stability. Various mutation studies were conducted to investigate the catalytic activity of these enzymes. By using the "directed evolution" method, the enzymes involved in detoxification and defense system can be engineered to produce new variants with enhance catalytic features, which may be used to predict the severity due to multi-drug resistance and degradation pattern of organophosphorus compounds in human gut.

Declining Trend in Antimicrobial Sensitivity in Respiratory Tract Bacterial Pathogens against Commonly Used Drugs at a Tertiary Care Hospital.

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.

Foot-and-mouth disease-associated myocarditis is age dependent in suckling calves.

Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype "O". Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P < 0.001) in < 2 months old FMD-infected calves showing clinical signs suggestive of myocarditis (264.833 ± 4.16; 11.650 ± 0.34 and 1213.33 ± 29.06) than those without myocarditis (< 2 months old: 110.00 ± 0.00, 0.06 ± 0.00, 1050.00 ± 0.00; > 2 months < 4 months: 83.00 ± 3.00, 0.05 ± 0.02, 1159.00 ± 27.63) and healthy control groups (< 2 months old: 67.50 ± 3.10, 0.047 ± 0.01, 1120.00 ± 31.62; > 2 months < 4 months: 72.83 ± 2.09, 0.47 ± 0.00, 1160.00 ± 18.44). However, mean serum CK-MB did not differ significantly amongst the groups. Four calves under 2 months old died and a necropsy revealed the presence of a pathognomic gross lesion of the myocardial form of FMD known as "tigroid heart". Histopathology confirmed myocarditis. This study also reports the relevance of clinical and histopathological findings and biochemical markers in diagnosing FMD-related myocarditis in suckling calves.

Responses of plankton community to threshold metal concentrations of cadmium and lead in a mesocosm experiment at Bay of Bengal.

Metals are essential at trace levels to aquatic organisms for the function of many physiological and biological processes. But their elevated levels are toxic to the ecosystem and even brings about shifts in the plankton population. Threshold limits such as Predicted No Effect Concentration (PNEC - 0.6 µg/l of Cd; 2.7 µg/l of Pb), Criterion Continuous Concentration (CCC - 3.0 µg/l of Cd; 4.5 µg/l of Pb) and Criterion Maximum Concentration (CMC - 23 µg/l of Cd; 130 µg/l of Pb) prescribed for Indian coastal waters were used for the study. Short-term mesocosm experiments (96 h) were conducted in coastal waters of Visakhapatnam to evaluate responses of the planktonic community on exposure to threshold concentrations of cadmium and lead for the first time. Four individual experimental bags of 2500 L capacity (Control, PNEC, CCC & CMC) were used for the deployment and ambient water samples were analysed simultaneously to evaluate the impacts of the threshold levels in the natural waters. Chaetoceros sp. were dominant group in the control system whereas, Prorocentrum sp. Ceratium sp. Tintinopsis sp. Chaetoceros sp. and Skeletonema sp. were major groups in the test bags. Throughout the experiment the phytoplankton community did not show any significant differences with increased nutrients and plankton biomass (Chl-a <8.64 mg/m3). Positive response of plankton community was observed in the experimental bags. High abundance of diatoms were observed in PNEC, CCC & CMC bags at 48 h and the abundance decreased with shift in the species at 72-96 h. The catalase activity in phytoplankton (5.99 nmol/min/ml) and the zooplankton (4.77 nmol/min/ml) showed induction after exposure to PNEC. The present mesocosm study is confirmed that short-term exposure to threshold metal concentration did not affects the phytoplankton community structure in PNEC, but CCC and CMC affects the community structure beyond 24 h. The insights from this study will serve as a baseline information and help develop environmental management tools. We believe that long-term mesocosm experiments would unravel metal detoxification mechanisms at the cellular level and metal transfer rate at higher trophic levels in real-world environment.

General Installation of (4H)-Imidazolone cis-Amide Bioisosteres Along the Peptide Backbone.

Imidazolones represent an important class of heterocycles present in a wide range of pharmaceuticals, metabolites, and bioactive natural products and serve as the active chromophore in green fluorescent protein. Recently, imidazolones have received attention for their ability to act as a nonaromatic amide bond bioisotere which improves pharmacological properties. Herein, we present a tandem amidine installation and cyclization with an adjacent ester to yield (4H)-imidazolone products. Using amino acid building blocks, we can access the first examples of α-chiral imidazolones that have been previously inaccessible. Additionally, our method is amenable to on-resin installation which can be seamlessly integrated into existing solid-phase peptide synthesis protocols. Finally, we show that peptide imidazolones are potent cis-amide bond surrogates that preorganize linear peptides for head-to-tail macrocyclization. This work represents the first general approach to the backbone and side-chain insertion of imidazolone bioisosteres at various positions in linear and cyclic peptides.

Activation of fluoride anion as nucleophile in water with data-guided surfactant selection.

A principal component surfactant_map was developed for 91 commonly accessible surfactants for use in surfactant-enabled organic reactions in water, an important approach for sustainable chemical processes. This map was built using 22 experimental and theoretical descriptors relevant to the physicochemical nature of these surfactant-enabled reactions, and advanced principal component analysis algorithms. It is comprised of all classes of surfactants, i.e. cationic, anionic, zwitterionic and neutral surfactants, including designer surfactants. The value of this surfactant_map was demonstrated in activating simple inorganic fluoride salts as effective nucleophiles in water, with the right surfactant. This led to the rapid development (screening 13-15 surfactants) of two fluorination reactions for ß-bromosulfides and sulfonyl chlorides in water. The latter was demonstrated in generating a sulfonyl fluoride with sufficient purity for direct use in labelling of chymotrypsin, under physiological conditions.

One-step hydrothermal synthesis of CuS/MoS2 composite for use as an electrochemical non-enzymatic glucose sensor.

Early diagnosis may be crucial for the prevention of chronic diabetes mellitus. For that herein, we prepared a CuS/MoS2 composite for a non-enzymatic glucose sensor through a one-step hydrothermal method owing to the synergetic effect of CuS/MoS2. The surface morphology of CuS/MoS2 was studied by Field Emission Scanning Electron Microscopy (FESEM) and Cs-corrected Scanning Transmission Electron Microscopy (Cs-STEM). The crystallinity and surface composition of CuS/MoS2 were analyzed by X-ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS) respectively. The working electrode was prepared from CuS/MoS2 electrocatalyst, and for that dispersed solution of electrocatalyst was used to fabricate the material-loaded glassy carbon electrode (GC). CuS/MoS2 composite shows the viability of electrocatalyst to oxidize glucose in an alkaline solution with sensitivity and detection limit of 252.71 µA mM-1 cm-2 and 1.52 µM respectively. The proposed glucose sensor showed reasonable stability and potential selectivity during electrochemical analysis. Accordingly, the CuS/MoS2 composite has potential as a viable material for glucose sensing in diluted human serum.

Temperature-induced disruptive growth rate behavior due to streaming instability in semiconductor quantum plasma with nanoparticles.

The nature of the growth rate due to streaming instability in a semiconductor quantum plasma implanted with nanoparticles has been analyzed using the quantum hydrodynamic model. In this study, the intriguing effect of temperature, beam electron speed, and electron-hole density on growth rate and frequency is investigated. The results show that the growth rate demonstrates a nonlinear behavior, strongly linked to the boron implantation, beam electron streaming speed and quantum correction factor. A noteworthy finding in this work is the discontinuous nature of the growth rate of streaming instability in boron implanted semiconducting plasma system. The implantation leads to a gap in the growth rate which further gets enhanced upon increase in concentration of implantation. This behavior is apparent only for a specific range of the ratio of thermal speed of the electrons to that of the holes.

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity.

Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium from five exposome-relevant databases using a data-centric approach, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs). By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.