Heteroannulation of Arynes with α-Bromodifluorohydroxamates: An Efficient and General Approach to Access 2,2-Difluoro Indoxyls.

Herein, we report the first general approach to access N-alkoxy-2,2-difluoro indoxyls, via formal 3 + 2 cycloaddition of aryne and (putative) fluorinated-aza-oxyallyl cation. This transition-metal/oxidant-free transformation occurs under mild reaction conditions with a short reaction time. Mechanistic investigation indicates the possible involvement of the closed form of fluorinated-aza-oxyallyl cation, viz., α-lactam, in the current transformation.

Converging optical and electrochemical detection strategies for multimodal hydrazine sensing: insights into substituent-driven diverse response.

A pair of pyrene-based chalcogen derivatives have been developed, which demonstrate multimodal ratiometric response towards hydrazine. Although these probes share a common pyrene core and differ primarily in the electronic nature of their terminal side arms, they display distinct photophysical properties. Notably, both probes undergo significant spectral changes upon the addition of hydrazine, but probe 1 exhibits a more pronounced interaction (∼5-fold fluorescence enhancement) than probe 2, attributed to the higher level of aggregation in probe 2, rendering the binding site less accessible to the incoming analyte. Additionally, we have explored electrochemical techniques, including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), for hydrazine detection. Our molecular design strategy relies on ratiometric-responsive specific cyclization triggered by hydrazine, leading to the disruption of the π-conjugated system and the subsequent suppression of intramolecular charge transfer (ICT) processes, along with dis-assembly of the aggregated probe molecules. These probes enable the nakеd-eye detection of hydrazine, with a low detection limit of 7.33 ppb and 7.58 ppb for probe 1 and 2, respectively. Furthermore, we have investigated cost-effective probe-coatеd paper strips for the detection of hydrazine in water.

Assessment of Frequency, Patterns, and Causes of Blunt Abdominal Trauma in a North Indian Cohort: An Autopsy-Based Study.

Introduction The abdomen is one of the most frequently damaged areas in trauma patients and is commonly encountered in road traffic accidents (RTAs). The present study evaluates the frequency, etiology, causation, and form of injury in blunt abdominal trauma (BAT) cases who had autopsies. Method An autopsy-based observational prospective study was conducted at the Department of Forensic Medicine and Toxicology, Nalanda Medical College and Hospital Patna, India, during the period from October 2018 to September 2020, which included a total of 940 autopsy cases showing blunt abdominal injuries. A predesigned proforma for the postmortem evaluation of BAT victims was used to collect the required information on the cases. Descriptive statistics were performed, and the data were presented as frequency (%) and mean±SD. Chi-square tests were performed to compare categorical variables between groups. Results BAT accounted for 120 (12.76%) cases of all autopsies performed. The majority of victims were male (92.48%). Victims aged 21-30 years (31, 25.83%) were the ones most usually engaged in BAT cases. Among the mechanisms accountable for BAT, RTAs were the most common (99, 82.50%), followed by assault (16, 13.30%). In most of the cases, the liver was injured (107, 89.16%), followed by the spleen (60, 50.00%) and kidney (24, 20.00%). The majority of blunt abdominal injury-related deaths were accidental (100, 83.33%), followed by homicidal (15, 12.5%) and suicidal cases (5, 4.17%). Hemorrhage and neurogenic shock were the most prevalent causes of mortality, particularly if the individual died within a few hours. Conclusion RTAs are the most frequent cause of BAT in autopsy cases, and the liver is the most affected organ. The majority of deaths occur within the first 24 hours of injury. Since blunt abdominal injuries have the propensity to increase morbidity and mortality, appropriate emphasis on their precise diagnosis and satisfactory therapy is mandated.

Synthetic strategies for the construction of C3-fluorinated oxindoles.

C3-fluorinated oxindoles are important scaffolds known to demonstrate various biological properties. As bio-isosteres of oxindoles, these compounds have shown tremendous potential in drug research discovery programs. Besides, they also serve as starting materials for synthesizing other fluorine-containing new architectures, thus launching research for developing new methods for their synthesis. Consequently, various approaches have been developed over the years to synthesize C3-fluorinated oxindoles. This review highlights the strategies developed to date to access C3-difluoro and monofluorooxindoles via intermolecular and intramolecular approaches. The key findings of the strategies developed are discussed along with the prevailing mechanism.

Feasibility of Including Hands-On Microteaching in the Medical Faculty Development Program in India: A Mixed-Methods Study.

Background Medical faculty development programs (FDPs) often lack hands-on training in teaching skills. Microteaching, a short, focused teaching practice, could be a feasible way to bridge this gap. This study aimed to explore the feasibility of including hands-on microteaching in a medical FDP in India. Methodology This mixed-methods study involved fresh medical faculty members who never attended FDP on the basics of medical education technologies, stakeholders, and students from a recently established autonomous medical institute of national importance in India. Participants completed a pre-test survey on their teaching skills and received a hands-on microteaching session during an FDP. After the session, participants completed a post-test survey and provided feedback on the feasibility and acceptability of hands-on microteaching in the program. Program evaluation was done by application of Kirkpatrick's Model levels one, two, and three. Results According to the Kirkpatrick Model of Evaluation level one (Reaction), the participants reported improved teaching skills and greater confidence in their ability to teach after the microteaching session. They also reported that hands-on microteaching was an effective way to learn teaching skills and receive feedback. Stakeholders opined that microteaching is a very effective tool for improving teaching skills and should be a part of FDP. Evaluation at level two (Learning) shows that there was a significant improvement in the mean score of post-tests. As per level three (Behaviour Change) evaluation, the majority of the students informed that there is observable improvement in the effectiveness of teaching of faculties in the past two months, i.e., since the participation of faculty in hands-on microteaching in FDP. Conclusions Hands-on microteaching could be a feasible and effective way to enhance the teaching skills of medical faculty members in India. The study findings suggest that including hands-on microteaching in FDPs could help bridge the gap between theoretical knowledge and practical teaching skills.

Perception regarding COVID-19 vaccine and COVID appropriate behavior among adolescents at a tertiary hospital, West Bengal: A longitudinal survey.

Background: Vaccination against COVID 19 and observing COVID appropriate behavior are effective measures to control, manage and prevent COVID-19 infection. With India starting its adolescent vaccination program, this study aimed to explore the adolescents' perception of vaccination, their COVID-appropriate behavior, compliance with two doses of COVID-19 vaccines and the experienced side effects following vaccination. Methods: A longitudinal survey was conducted among 440 adolescents visiting the COVID Vaccination Center (CVC) of a tertiary hospital in West Bengal. In the survey, adolescents were asked about family socio-demographic characteristics, their opinions on COVID-19 vaccines, and COVID-19 Appropriate Behavior (CAB) practices. Voluntary participants were given a questionnaire to fill and a telephonic interview was taken regarding side effects experienced following the vaccination and their compliance to both doses of vaccine. Results: The majority of adolescents (99.3%) had taken vaccines by their own wish. The reason for willingness to take the vaccine was the fear of being infected with COVID-19 infection (50.5%). Maximum adolescents got information regarding the COVID vaccination program through the internet (41.8%) followed by family members (30.5%). The majority of adolescents (70.9%) had a good perception of COVID-19 vaccination. A significant number of adolescents (44.8%) strongly disagreed with the statement that they don't need to follow COVID appropriate behavior after vaccination. Conclusion: The majority of adolescents had a good perception regarding COVID-19.

Review and Perspective: Gas Separation and Discrimination Technologies for Current Gas Sensors in Environmental Applications.

Presently, numerous state-of-the-art approaches are being adapted for gas sensing and monitoring. These include hazardous gas leak detection as well as ambient air monitoring. Photoionization detectors, electrochemical sensors, and optical infrared sensors are a few of the commonly widely used technologies. Extensive reviews on the current state of gas sensors have been summarized. These sensors, which are either nonselective or semiselective, are affected by unwanted analytes. On the other hand, volatile organic compounds (VOCs) can be heavily mixed in many vapor intrusion situations. To determine the individual VOCs in a highly mixed gas sample using nonselective or semiselective gas sensors, gas separation and discrimination technologies are highly warranted. These technologies include gas permeable membranes, metal-organic frameworks, microfluidics and IR bandpass filters for different sensors, respectively. The majority of these gas separation and discrimination technologies are currently being developed and evaluated in laboratory-controlled environments and have not yet been extensively utilized in the field for vapor intrusion monitoring. These technologies show promise for continued development and application in the field for more complex gas mixtures. Hence, the present review focuses on the perspectives and a summary of the existing gas separation and discrimination technologies for the currently popular reported gas sensors in environmental applications.

Access to Sterically Hindered Thioethers (α-Thioamides) Under Mild Conditions Using α-Halohydroxamates: Application toward 1,4-Benzothiazinones and 4,1-Benzothiazepinones.

Herein, we report a new and highly efficient approach for synthesizing congested α-thioamides under mild reaction conditions (mild base, room temperature, and short duration) using α-halo hydroxamates as direct alkylating agents. The reaction works well with both (hetero)aryl and alkyl thiols, tolerating a broad functional group and diverse substrate scope, including benzeneselenol for selenoether construction. The strategy enables efficient synthesis of biologically relevant 1,4 benzothiazinone and 4,1-benzothiazepinone cores, along with various other functionalized sulfur-based scaffolds of biological importance.

Disposable Miniaturized Electrochemical Sensing Platform With Laser-Induced Reduced Graphene Oxide Electrodes for Multiplexed Biochemical Analysis.

Metabolic biomarkers, such as Dopamine (DA), Uric acid (UA), and Ascorbic acid (AA), have significant roles in determining the physiological functioning of the human body. These are often analyzed through clinical lab-based procedures which are bulky and require skilled technicians. In view of this, the design, development, and fabrication of a portable, cost-effective, user-friendly, and disposable device for electro-analytical detection, leading to point-of-care (POC) detection of these metabolic biomarkers is a pressing need. This work reports a laser-induced reduced graphene oxide (LIrGO) based miniaturized paper device fabricated by laser ablation of a lab-grade paper using a blue diode laser (450 nm). A three-electrode electrochemical platform was designed with the LIrGO electrodes, whereby bare rGO electrodes were employed as working and counter electrodes, and Ag/AgCl ink-coated rGO was used as the reference electrode. The device was characterized morphologically by Scanning Electron Microscopy (SEM) and electrochemically by a potentiostat. The prepared device was subjected to electrochemical sensing of Dopamine (DA), Uric Acid (UA), and Ascorbic Acid (AA). Furthermore, the effects of several sensory parameters, such as concentration, pH, and interference, were analyzed. A linear range of 10- [Formula: see text] was obtained for all three analytes with the limit of detection (LoD) being [Formula: see text], [Formula: see text], [Formula: see text], and the limit of quantification (LoQ) being [Formula: see text], [Formula: see text], [Formula: see text] for DA, UA and AA, respectively. Finally, the device was tested for non-interference with co-analytes and validated by testing a real sample of human blood serum. This work demonstrates a proof-of-principle of utilizing bare LIrGO for selective sensing which will open door to multiplexed and POC sensing.

Heteroarylation of Congested α-Bromoamides with Imidazo-Heteroarenes and Indolizines via Aza-Oxyallyl Cations: Enroute to Dibenzoazepinone and Zolpidem Analogues.

Herein, we report a highly efficient and unprecedented approach for heteroarylation of congested α-bromoamides via electrophilic aromatic substitution of imidazo-heteroarenes and indolizines under mild reaction conditions (room temperature, metal, and oxidant free). The participation of an in situ generated aza-oxyallyl cation as an alkylating agent is the hallmark of this transformation. The method was readily adapted to synthesize novel imidazo-heteroarene-fused dibenzoazepinone architectures of potential medicinal value.

Trends in willingness to receive COVID-19 vaccines among healthcare workers in India: Findings from repeated cross-sectional national surveys.

Background: COVID-19 vaccination of the healthcare workers (HCWs) is a key priority in the fight against the SARS-CoV-2 pandemic. India launched its COVID-19 vaccination program in January 2021. We aimed to understand the trends in willingness to receive COVID-19 vaccines and its associated factors among HCWs in India. Methods: Using a repeated cross-sectional survey design, we collected information from HCWs in three critical time points: before (n = 937, October 2020), during (n = 1346, January 2021); and after (n = 812, May 2021) the introduction of COVID-19 vaccines in India. The third survey coincided with the peak of the second wave of COVID-19 pandemic in India. Findings: Of the study participants, 43.7, 60.2, and 73.2% were willing to receive COVID-19 vaccines during the first, second and third rounds of surveys, respectively. In multivariable logistic regression analysis, participants who trusted the health care system were more likely to report willingness to receive a COVID-19 vaccine; medical trust emerged as a significant factor in all the three rounds of surveys (First survey-aOR: 2.24, 95% CI: 1.67-2.99; Second survey-aOR: 3.38, 95% CI: 2.64-4.33; Third survey-aOR: 2.54, 95% CI: 1.65-3.91). Having confidence in domestic vaccines (Second survey-aOR: 2.21, 95% CI: 1.61-3.02; Third survey-aOR: 2.05, 95% CI: 1.24-3.37); and high perceived risk of contracting COVID-19 (Second survey-aOR: 1.48, 95% CI: 1.13-1.93; Third survey-aOR: 2.02, 95% CI: 1.31-3.13) were found to be associated with willingness to receive vaccines. Among socio-demographic characteristics, being married (aOR: 1.71, 95% CI: 1.08-2.71) and having high socio-economic status (aOR: 3.01, 95% CI: 1.65-5.51) emerged as significant factors associated with willingness to receive COVID-19 vaccines in the third round of the surveys. Interpretation: Willingness to receive COVID-19 vaccine increased with time, as the severity of the pandemic increased. To increase COVID-19 acceptance and coverage among HCWs, it is important to instill confidence in domestic vaccines and assist in accurate assessment of risk toward contracting COVID-19 infection.

Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates.

Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates 1, 9, and 32, conjugate 32 with a 4-oxybenzyl linker showed sufficient stability in buffer solutions, potent LSD1 inhibition, efficient LSD1-dependent vorinostat release, and potent and selective antiproliferative activity toward LSD1-expressing human breast cancer and small-cell lung cancer cell lines. These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs.

Community health workers willingness to participate in COVID-19 vaccine trials and intention to vaccinate: A cross-sectional survey in India.

Background: Vaccine hesitancy is of considerable concern as it threatens the great potential of a vaccine against COVID-19. This study aims to determine factors associated with community health workers' willingness to participate in clinical trials of COVID-19 vaccine, and their vaccination intention, in India. Methods: A cross-sectional study was conducted among 377 community health workers using self-administered anonymous questionnaire during the lockdown periods in India. Participant's socio-demographics, willingness-to-participate in COVID-19 vaccine trials, intention to accept COVID-19 vaccine were recorded in a Likert scale. Data were analysed descriptively, and a multivariate logistic regression model was used to investigate factors associated with willingness to participate and accept the vaccine. Results: Among 377 CHWs, 70 (19%) intended to participate in COVID-19 vaccine trial, 151 (40%) responded positively regarding their intention to get vaccinated. Those with knowledge on development of COVID-19 vaccine [aOR 3.05 (95% CI: 1.18-7.88), p = 0.021], and men [aOR 3.69 (95% CI: 1.51-8.97), p = 0.004] were more willing to participate in clinical-trial, while an undergraduate degree, and trust in domestic vaccines were identified as deterrents for the same. Perceiving COVID-19 as risk [aOR 2.31 (95% CI: 1.24-4.31), p = 0.009], and male gender [aOR 2.39 (95% CI: 1.17-4.88), p = 0.017] were factors associated with intention to get vaccinated. Respondents who had knowledge about COVID-19 virus were less likely to uptake the hypothetical vaccine [aOR 0.32 (95% CI: 0.12-0.88), p = 0.027]. Conclusions: Increasing knowledge regarding COVID-19 is not enough to improve vaccine acceptance rates. Targeted interventions addressing socio-demographic determinants related to COVID-19 vaccination should help improve acceptance.

Parents' Perceptions and Intention to Vaccinate Their Children Against COVID-19: Results From a Cross-Sectional National Survey in India.

Background: Despite the success of adult vaccination against COVID-19, providing vaccines to children remains a challenge for policymakers globally. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination in India. Methods: A cross-sectional web-based study was designed, parents or caregivers (N = 770) were recruited through snowball sampling using Google form. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with sociodemographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior. Multivariable logistic regression analysis was performed to compute the predictors of child vaccination intention among Indian parents. Results: Seven hundred and seventy parents across the country have completed the survey. Of the 770 participants, 258 (33.5%) have shown intent to vaccinate their children. The stated likelihood of child vaccination was greater among parents who had a bachelor's degree or higher education (aOR: 1.98, 95% CI: 1.15-3.51); as well as among parents who intended to vaccinate themselves (aOR: 2.35, 95% CI: 1.30-4.67). Parental concerns centered around vaccine safety and side effects. Conclusion: Indian parents reported high knowledge of the COVID-19 virus and were aware of the development of a vaccine. However, about one-third of parents intended to vaccinate their children, and about half of them were not sure whether to vaccinate their children or not against the COVID-19 virus. The study highlighted the need for health promotion strategies that promote vaccine uptake among parents.

Sociodemographic Determinants of Willingness and Extent to Pay for COVID-19 Vaccine in India.

Background: Responding to the fast transmission rates and increasing fatality rates, countries across the world expedited the development and deployment of the vaccine for coronavirus disease 2019 (COVID-19). Evaluation of individuals' willingness to pay (WTP) would provide pertinent information regarding future demand and financing preferences, which shall help to devise the effective payment strategy for COVID-19 vaccination. Methods: A nationwide, cross-sectional, and self-administered online survey using a structured questionnaire was conducted to identify the sociodemographic determinants of willingness and extent to pay for COVID-19 vaccine in India. A non-probability convenience sampling followed by snowball sampling was employed to recruit participants (n = 3,341). The likelihood of sociodemographic determinants to predict willingness and extent to pay was modeled using the multivariate binary logistic regression analysis. Results: Out of 3,341 participants, 68% (n = 2,271) were willingness to pay for COVID-19 vaccine. Results showed significantly higher odds for willingness to pay among participants who were single [adjusted odds ratio (aOR) = 1.394, p < 0.01] and having a family size of 4 members (aOR = 1.346, p < 0.01). The adjusted odds ratio sizably increased from 1.396 for participants whose monthly income was between INR 10,000 and 20,000/month to 2.240 for participants whose monthly income was above INR 50,000/month. Further, out of 2,271 of those participants who were willingness to pay for COVID-19 vaccine, majority (n = 1,246, 54.9%) of participants were willingness to pay below 50% of COVID-19 vaccine cost. This study found that those who are single (aOR = 0.688, p < 0.01), having an income between INR 20,000 and 50,000/month (aOR = 0.686, p < 0.05), and those who belonged to socially disadvantaged category (aOR = 0.450, p < 0.01) were estimated to have significantly lower odds of willingness to pay more than 50% of COVID-19 vaccine cost. Conclusion: This study observed that majority of those participants who willingness to pay for COVID-19 vaccine were willingness to pay only up to 50% of COVID-19 vaccine and income was observed as a precursor predictor of the willingness and extent to pay for COVID-19 vaccine. The understanding on the willingness and extent to pay for COVID-19 vaccine and its sociodemographic determinants will be helpful for making the strategic decisions related to the financing of COVID vaccine in India.

Status of drug resistant tuberculosis among patients attending a tuberculosis unit of West Bengal: A record based cross-sectional study.

Context: Tuberculosis (TB) is one of the main causes of death due to infectious diseases worldwide. Multidrug resistance/rifampicin resistance (MDR/RR) TB remains a public health crisis. India has the highest burden of tuberculosis and multidrug resistant TB (MDR TB) in the world. There is wide geographical variation in the epidemic and its trends that can be updated by regular reporting and sound surveillance systems. The current study tries to fill this gap by analyzing the data of TB patients from a Tuberculosis Unit, studying socio-demographic and clinical profile from December 2017 to November 2019 in Nadia district of West Bengal. Aims: The aims of this work were to study socio-demographic and clinical profile of TB patients attending Tuberculosis Unit of West Bengal, and to find out factors associated with drug-resistant TB. Settings and Design: Record-based study from Tuberculosis Unit. Methods: Records of all patients who undergo CBNAAT in TU are stored as monthly unit. We randomly selected 10 months from a period of December 2017 to November 2019 by using lot method. Data of all patients undergoing CBNAAT at Kalyani - Gayeshpur Tuberculosis Unit during randomly selected 10 months were accessed. Statistical Analysis Used: Monthly data was entered in Microsoft Excel and descriptive tests of significance, proportions and Chi-square were applied. Results: There was male preponderance for testing of tuberculosis. Seven percent of the TB suspects were HIV positive. The positivity rate of MTB by CBNAAT was 23%. Four percent of the samples were Rifampicin resistance. Tobacco consumption, contact with TB case and Diabetes were common risk factors of TB. Most of the information was missing in the records. Conclusions: Most of Rifampicin Resistant cases showed very low Ct value in CBNAAT. Previous history of TB treatment and positive HIV status was significantly associated with RR TB. There is a need to capture complete information on the records of presumptive TB cases.

Joint Communication and Sensing: A Proof of Concept and Datasets for Greenhouse Monitoring Using LoRaWAN.

In recent years, greenhouse-based precision agriculture (PA) has been strengthened by utilization of Internet of Things applications and low-power wide area network communication. The advancements in multidisciplinary technologies such as artificial intelligence (AI) have created opportunities to assist farmers further in detecting disease and poor nutrition of plants. Neural networks and other AI techniques need an initial set of measurement campaigns along with extensive datasets as a training set to baseline and evolve different applications. This paper presents LoRaWAN-based greenhouse monitoring datasets over a period of nine months. The dataset has both the network and sensing information from multiple sensor nodes for tomato crops in two different greenhouse environments. The goal is to provide the research community with a dataset to evaluate performance of LoRaWAN inside a greenhouse and develop more efficient PA monitoring techniques. In this paper, we carried out an exploratory data analysis to infer crop growth by analyzing just the LoRaWAN signals and without inclusion of any extra hardware. This work uses a multilayer perceptron artificial neural network to predict the weekly plant growth, trained using RSSI value from sensor data and manual measurement of plant height from the greenhouse. We developed this proof of concept of joint communication and sensing by using generated dataset from the "Proefcentrum Hoogstraten" greenhouse in Belgium. Results for the proposed method yield a root mean square error of 10% in detecting the average plant height inside a greenhouse. In future, we can use this concept of landscape sensing for different supplementary use-cases and to develop optimized methods.

In-Silico Tool for Predicting, Scanning, and Designing Defensins.

Defensins are host defense peptides present in nearly all living species, which play a crucial role in innate immunity. These peptides provide protection to the host, either by killing microbes directly or indirectly by activating the immune system. In the era of antibiotic resistance, there is a need to develop a fast and accurate method for predicting defensins. In this study, a systematic attempt has been made to develop models for predicting defensins from available information on defensins. We created a dataset of defensins and non-defensins called the main dataset that contains 1,036 defensins and 1,035 AMPs (antimicrobial peptides, or non-defensins) to understand the difference between defensins and AMPs. Our analysis indicates that certain residues like Cys, Arg, and Tyr are more abundant in defensins in comparison to AMPs. We developed machine learning technique-based models on the main dataset using a wide range of peptide features. Our SVM (support vector machine)-based model discriminates defensins and AMPs with MCC of 0.88 and AUC of 0.98 on the validation set of the main dataset. In addition, we created an alternate dataset that consists of 1,036 defensins and 1,054 non-defensins obtained from Swiss-Prot. Models were also developed on the alternate dataset to predict defensins. Our SVM-based model achieved maximum MCC of 0.96 with AUC of 0.99 on the validation set of the alternate dataset. All models were trained, tested, and validated using standard protocols. Finally, we developed a web-based service "DefPred" to predict defensins, scan defensins in proteins, and design the best defensins from their analogs. The stand-alone software and web server of DefPred are available at https://webs.iiitd.edu.in/raghava/defpred.

Identification of Potent and Selective Inhibitors of Fat Mass Obesity-Associated Protein Using a Fragment-Merging Approach.

Fat mass obesity-associated protein (FTO) is a DNA/RNA demethylase involved in the epigenetic regulation of various genes and is considered a therapeutic target for obesity, cancer, and neurological disorders. Here, we aimed to design novel FTO-selective inhibitors by merging fragments of previously reported FTO inhibitors. Among the synthesized analogues, compound 11b, which merges key fragments of Hz (3) and MA (4), inhibited FTO selectively over alkylation repair homologue 5 (ALKBH5), another DNA/RNA demethylase. Treatment of acute monocytic leukemia NOMO-1 cells with a prodrug of 11b decreased the viability of acute monocytic leukemia cells, increased the level of the FTO substrate N6-methyladenosine in mRNA, and induced upregulation of MYC and downregulation of RARA, which are FTO target genes. Thus, Hz (3)/MA (4) hybrid analogues represent an entry into a new class of FTO-selective inhibitors.

Residual immune activation in HIV-Infected individuals expands monocytic-myeloid derived suppressor cells.

HIV-infected individuals on combined antiretroviral therapy (ART) with virologic suppression exhibit sustained immune dysfunction. Our recent work has highlighted that monocytic myeloid derived suppressor cells (M-MDSC) are elevated in these individuals and suppress immune responses. Factors responsible for M-MDSC expansion in vivo are unknown. Here we compared circulating frequency of M-MDSC in HIV-infected persons from the US and India where HIV subtype-B or -C predominate, respectively. We further investigated soluble mediators of residual immune activation in two cohorts and determined their correlation with M-MDSC expansion. Our findings show that M-MDSC are elevated and correlate with plasma levels of IL-6 in both cohorts. Chemokines CXCL10, CCL4 and CXCL8 were also elevated in HIV-infected individuals, but did not correlate with M-MDSC. These findings support that IL-6 is important in M-MDSC expansion which is independent of HIV subtype.