Sodium Niobate Nanowires Embedded PVA-Hydrogel-Based Triboelectric Nanogenerator for Versatile Energy Harvesting and Self-Powered CO Gas Sensor.

The surging demand for sustainable energy solutions and adaptable electronic devices has led to the exploration of alternative and advanced power sources. Triboelectric Nanogenerators (TENGs) stand out as a promising technology for efficient energy harvesting, but research on fully flexible and environmental friendly TENGs still remain limited. In this study, an innovative approach is introduced utilizing an ionic-solution modified conductive hydrogel embedded with piezoelectric sodium niobate nanowires-based Triboelectric Nanogenerator (NW-TENG), offering intrinsic advantages to healthcare and wearable devices. The synthesized NW-TENG, with a 12.5 cm2 surface area, achieves peak output performance, producing ≈840 V of voltage and 2.3 µC of charge transfer, respectively. The rectified energy powers up 30 LEDs and a stopwatch; while the NW-TENG efficiently charges capacitors from 1µF to 100 µF, reaching 1 V within 4 to 65 s at 6 Hz. Integration with prototype carbon monoxide (CO) gas sensor transform the device into a self-powered gas sensory technology. This study provides a comprehensive understanding of nanowire effects on TENG performance, offering insights for designing highly flexible and environmentally friendly TENGs, and extending applications to portable self-powered gas sensors and wearable devices.

Gold Nanoparticles with N-Heterocyclic Carbene/Triphenylamine Surface Ligands: Stable and Electrochromically Active Hybrid Materials for Optoelectronics.

Organic-hybrid particle-based materials are increasingly important in (opto)electronics, sensing, and catalysis due to their printability and stretchability as well as their potential for unique synergistic functional effects. However, these functional properties are often limited due to poor electronic coupling between the organic shell and the nanoparticle. N-heterocyclic carbenes (NHCs) belong to the most promising anchors to achieve electronic delocalization across the interface, as they form robust and highly conductive bonds with metals and offer a plethora of functionalization possibilities. Despite the outstanding potential of the conductive NHC-metal bond, synthetic challenges have so far limited its application to the improvement of colloidal stabilities, disregarding the potential of the conductive anchor. Here, NHC anchors are used to modify redox-active gold nanoparticles (AuNPs) with conjugated triphenylamines (TPA). The resulting AuNPs exhibit excellent thermal and redox stability benefiting from the robust NHC-gold bond. As electrochromic materials, the hybrid materials show pronounced color changes from red to dark green, a highly stable cycling stability (1000 cycles), and a fast response speed (5.6 s/2.1 s). Furthermore, TPA-NHC@AuNP exhibits an ionization potential of 5.3 eV and a distinct out-of-plane conductivity, making them a promising candidate for application as hole transport layers in optoelectronic devices.

Study of Intrachain Charge Transfer in a Blue Emissive Polyfluorene Random Copolymer.

Photophysics of a blue light-emitting fluorescent random copolymer, consisting of arylated polydioctylfluorene (aryl-F8), polydioctylfluorene (F8), and amine comonomers in a ratio of 80:15:5 is reported. In a solution of 10-6 M, solvatochromism in absorption and photoluminescence (PL) is observed with an increased lifetime of PL as the polarity of the solvent increases. Dual fluorescence is observed in the 10-9 M diluted solution, comprising a structured emission from a localized state in the aryl-F8 comonomer and a broad emission peak from the charge-transfer (CT) state at a lower energy. Emission wavelength-dependent time-resolved photoluminescence studies in different polar media confirm the presence of the emissive intrachain CT state in this copolymer. Analyzing the PL decay kinetics, we calculated the formation rate of the intrachain CT state to be ∼3.0 × 109 s-1. Repopulation of the localized state from the CT state is observed in the lower polarity medium with a rate of 7 × 108 s-1, which is almost absent for the large Stokes-shifted CT emission in the higher polarity medium. Along with the fundamental understanding of the photophysics of the random copolymer, this study suggests that the emission spectrum can be tailored by the concentration of polymer and the polarity of surrounding media.

Metal oxide-based gas sensor array for VOCs determination in complex mixtures using machine learning.

Detection of volatile organic compounds (VOCs) from the breath is becoming a viable route for the early detection of diseases non-invasively. This paper presents a sensor array of 3 component metal oxides that give maximal cross-sensitivity and can successfully use machine learning methods to identify four distinct VOCs in a mixture. The metal oxide sensor array comprises NiO-Au (ohmic), CuO-Au (Schottky), and ZnO-Au (Schottky) sensors made by the DC reactive sputtering method and having a film thickness of 80-100 nm. The NiO and CuO films have ultrafine particle sizes of < 50 nm and rough surface texture, while ZnO films consist of nanoscale platelets. This array was subjected to various VOC concentrations, including ethanol, acetone, toluene, and chloroform, one by one and in a pair/mix of gases. Thus, the response values show severe interference and departure from commonly observed power law behavior. The dataset obtained from individual gases and their mixtures were analyzed using multiple machine learning algorithms, such as Random Forest (RF), K-Nearest Neighbor (KNN), Decision Tree, Linear Regression, Logistic Regression, Naive Bayes, Linear Discriminant Analysis, Artificial Neural Network, and Support Vector Machine. KNN and RF have shown more than 99% accuracy in classifying different varying chemicals in the gas mixtures. In regression analysis, KNN has delivered the best results with an R2 value of more than 0.99 and LOD of 0.012 ppm, 0.015 ppm, 0.014 ppm, and 0.025 ppm for predicting the concentrations of acetone, toluene, ethanol, and chloroform, respectively, in complex mixtures. Therefore, it is demonstrated that the array utilizing the provided algorithms can classify and predict the concentrations of the four gases simultaneously for disease diagnosis and treatment monitoring.

Assessing safety, efficacy and residue depletion in golden mahseer, Tor putitora (Hamilton, 1822): biochemical and physiological responses to graded concentrations of oxytetracycline dietary supplementation.

The safety and effectiveness of oxytetracycline can potentially manage bacterial infections in fish. This, in turn, might reduce the concerns related to its use in aquaculture and human consumption, such as toxicity, antimicrobial resistance, and other associated risks. The primary objective of this study was to assess how adding oxytetracycline dihydrate to the diet affects its effectiveness, safety, and the presence of residues in T. putitora. T. putitora fingerlings, subjected to experimental infection with Aeromonas hydrophila at a concentration of 108 CFU mL- 1, received an oral administration of oxytetracycline dihydrate. The oxytetracycline dihydrate was added to the feed (corresponding to 2% of the fish body weight) at concentrations of 44.1, 88.2, 132.3 and 176.4 mg Kg- 1 fish body weight per day. This treatment was carried out for 10 consecutive days. The biochemical and physiological responses of T. putitora and efficacy of oxytetracycline dihydrate were determined through estimation of microbial load (CFU mL- 1), haematogram, serum biomarkers, behavioral characteristics, non-specific immunity and residue depletion. Experimentally infected fish showed disease progression and induced histopathological conditions with highest microbial load (CFU mL- 1) in the muscle of both control and treated fish. The fish haematogram showed increased leucocyte and haemoglobin content, influenced by dietary oxytetracycline dihydrate. The fish demonstrated adaptive physiological response to oxytetracycline dihydrate at 44.1 to 88.2 mg and resulted in increased albumin and globulin content. The serum-enzyme assay showed significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and plasma alkaline phosphatase (ALP) activities in the test fish (< 0.05). Oxytetracycline dihydrate at 88.2 to 132.3 mg Kg- 1 fish body weight per day recorded higher feed intake (75%), significant survivability (66-68%) and histopathological recovery. The suppressed immune response was manifested with decreased respiratory burst and lysozyme activity. The palatability, treatment of bacterial infection, histopathological changes and survivability by fingerlings of golden mahseer determined the safety and optimized the therapeutic potential of the oxytetracycline dihydrate at 88.2 mg Kg- 1 fish body weight per day for 10 days to contain the infection by A. hydrophila. A withdrawal period of 8-d was recommended as oxytetracycline dihydrate concentration depleted below the legal maximum residue limit (MRL 2.0 mg g- 1) in the edible muscle of the golden mahseer reared at an average water temperature of 20 °C. This is considered safe for human consumption.

Characterizing the spatio-temporal distribution, detection, and prediction of aerosol atmospheric rivers on a global scale.

Aerosol Atmospheric Rivers (AARs) are elongated and narrow regions that carry high concentrations of aerosols (tiny particles suspended in the atmosphere) across large distances, exerting effects on both air quality and human health (Chakraborty et al., 2021, 2022). Monitoring and modeling these aerosols present distinct challenges due to their dynamic nature and complex interactions within the atmosphere. In this context, the present study detects and predicts the AARs using MERRA-2 reanalysis datasets with their seasonal climatology of key aerosol species, including Black Carbon (BC), Dust (DU), Organic Carbon (OC), Sea Salt (SS), and Sulphates (SU). The study employs an innovative Integrated Aerosol Transport (IAT) based AAR algorithm from 2015 to 2022. A total count of 44,020 BC AARs, 13,280 DU AARs, 21,599 OC AARs, 17,925 SS AARs, and 31,437 SU AARs were detected globally. The seasonal climatology of BC and OC AARs intensifies in areas such as the Amazon rainforest and Congo during AMJJAS (April-September) due to forest fires. Similarly, DU AARs are more frequent in regions near the Saharan desert, primarily around the equator during AMJJAS. SS AARs tend to predominate over the oceans, while SU AARs are predominantly found in the northern hemisphere, primarily due to higher anthropogenic emissions. Furthermore, convolutional autoencoder-based models were developed for key aerosol species, strengthening predictive accuracy by effectively capturing complex data relationships and delivering precise predictions for the last 5-time frames. During validation, the model evaluation parameters for image prediction such as the Structural Similarity Index ranged from 0.86 to 0.94, Peak Signal-to-Noise Ratio fluctuated between 1.14 and 42.25 dB, Root Mean Square Error varied from 2.39 to 296.4 mg/(m-sec), and Mean Square Error fell within the range of 1.55-17.22 mg/(m-sec). These collectively reflect image closeness, quality, dissimilarity, and accuracy in AAR prediction. This study demonstrates the effectiveness of advanced machine and deep learning models in predicting AARs, offering the potential for advanced forecasting and enhancing resilience in high-aerosol concentration regions.

New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.

Heat waves characteristics intensification across Indian smart cities.

Indian cities have frequently observed intense and severe heat waves for the last few years. It will be primarily due to a significant increase in the variation in heat wave characteristics like duration, frequency, and intensity across the urban regions of India. This study will determine the impact of future climate scenarios like SSP 245 and 585 over the heat wave characteristics. It will present the comparison between heat waves characteristics in the historical time (1981 to 2020) with future projections, i.e., D1 (2021-2046), D2 (2047-2072), and D3 (2073-2098) for different climate scenarios across Indian smart cities. It is observed that the Coastal, Interior Peninsular, and North-Central regions will observe intense and frequent heat waves in the future under SSP 245 and 585 scenarios. A nearly two-fold increase in heat wave' mean duration will be observed in the smart cities of the Interior Peninsular, Coastal, and North Central zones. Thiruvananthapuram city on the west coast has the maximum hazard associated with heat waves among all the smart cities of India under both SSPs. This study assists smart city policymakers in improving the planning and implementation of heat wave adaptation and mitigation plans based on the proposed framework for heat action plans and heat wave characteristics for improving urban health well-being under hot weather extremes in different homogeneous temperature zones.

Understanding non-stationarity of hydroclimatic extremes and resilience in Peninsular catchments, India.

Climate change significantly impacts the global hydrological cycle, leading to pronounced shifts in hydroclimatic extremes such as increased duration, occurrence, and intensity. Despite these significant changes, our understanding of hydroclimatic risks and hydrological resilience remains limited, particularly at the catchment scale in peninsular India. This study aims to address this gap by examining hydroclimatic extremes and resilience in 54 peninsular catchments from 1988 to 2011. We initially assess extreme precipitation and discharge indices and estimate design return levels using non-stationary Generalized Extreme Value (GEV) models that use global climate modes (ENSO, IOD, and AMO) as covariates. Further, hydrological resilience is evaluated using a convex model that inputs simulated discharge from the best hydrological model among SVM, RVM, random forest, and a conceptual model (abcd). Our analysis shows that the spatial patterns of mean extreme precipitation indices (R1 and R5) mostly resemble with extreme discharge indices (Q1 and Q5). Additionally, all extreme indices, including R1, Q1, R5, and Q5, demonstrate non-stationary behavior, indicating the substantial influence of global climate modes on extreme precipitation and flooding across the catchments. Our results indicate that the random forest model outperforms the others. Furthermore, we find that 68.52% of the catchments exhibit low to moderate hydrological resilience. Our findings emphasize the importance of understanding hydroclimatic risks and catchment resilience for accurate climate change impact predictions and effective adaptation strategies.

Breast cancer: miRNAs monitoring chemoresistance and systemic therapy.

With a high mortality rate that accounts for millions of cancer-related deaths each year, breast cancer is the second most common malignancy in women. Chemotherapy has significant potential in the prevention and spreading of breast cancer; however, drug resistance often hinders therapy in breast cancer patients. The identification and the use of novel molecular biomarkers, which can predict response to chemotherapy, might lead to tailoring breast cancer treatment. In this context, accumulating research has reported microRNAs (miRNAs) as potential biomarkers for early cancer detection, and are conducive to designing a more specific treatment plan by helping analyze drug resistance and sensitivity in breast cancer treatment. In this review, miRNAs are discussed in two alternative ways-as tumor suppressors to be used in miRNA replacement therapy to reduce oncogenesis and as oncomirs to lessen the translation of the target miRNA. Different miRNAs like miR-638, miR-17, miR-20b, miR-342, miR-484, miR-21, miR-24, miR-27, miR-23 and miR-200 are involved in the regulation of chemoresistance through diverse genetic targets. For instance, tumor-suppressing miRNAs like miR-342, miR-16, miR-214, and miR-128 and tumor-promoting miRNAs like miR101 and miR-106-25 cluster regulate the cell cycle, apoptosis, epithelial to mesenchymal transition and other pathways to impart breast cancer drug resistance. Hence, in this review, we have discussed the significance of miRNA biomarkers that could assist in providing novel therapeutic targets to overcome potential chemotherapy resistance to systemic therapy and further facilitate the design of tailored therapy for enhanced efficacy against breast cancer.

Late presentation of Swyer syndrome: A case report.

Swyer syndrome-a rare syndrome associated with complete gonadal dysgenesis-is seen in phenotypically female patients with 46-XY karyotype. They usually present with primary amenorrhea or delayed puberty. The dysgenetic gonad, which is nonfunctional, is prone to undergo malignant transformation such as dysgerminoma, gonadoblastoma, etc. Timely diagnosis helps in deciding appropriate management strategies for the patient such as hormone replacement therapy and gonadectomy. Thirty-year-old patient with a female external phenotype presented to us with complaints of primary amenorrhea. There was no similar family history of infertility, amenorrhea, abnormal external genitalia development, or cryptorchidism. On physical examination, the breast development of the patient was within normal limits for her age (Tanner stage 5), however; the axillary and pubic hair were underdeveloped (Tanner stage 2). Pelvic and inguinal ultrasound of the patient showed a hypoplastic uterus along with a cystic structure in left pelvis with no evidence of any testes like structure in inguinal region, pelvis, or abdomen. The patient was further evaluated with MRI of pelvis which confirmed the ultrasound findings of a hypoplastic uterus along with a dysplastic cystic left gonad with no evidence of any ovary or ovary-like structure/testes/testes-like structure in abdomen. Possibility of complete gonadal dysgenesis was given which was further confirmed by the hormonal assay that showed hypergonadotropic-hypogonadism with raised serum follicular stimulating hormone (FSH) and serum luteinizing hormone (LH) levels and a low estradiol, low testosterone, and low anti-Mullerian hormone (AMH) levels. Serum prolactin (PRL), serum thyroid stimulating hormone (TSH), and serum beta human chorionic gonadotropin (beta hCG) levels were within normal range. The cytogenetic report of the patient showed a 46-XY karyotype confirming our diagnosis. The patient was advised to undergo prophylactic gonadectomy for the left gonad. Swyer syndrome is a rare disorder of sexual development which needs vigorous clinical, laboratory, and radiological evaluation. Ultrasound is the primary investigation of choice whereas MRI is used as a problem-solving tool in localizing the streak gonads. Early diagnosis is crucial in these patients since prophylactic gonadectomy reduces the risk of developing germ cell tumor.

Digital Transformation in Toxicology: Improving Communication and Efficiency in Risk Assessment.

Toxicology is undergoing a digital revolution, with mobile apps, sensors, artificial intelligence (AI), and machine learning enabling better record-keeping, data analysis, and risk assessment. Additionally, computational toxicology and digital risk assessment have led to more accurate predictions of chemical hazards, reducing the burden of laboratory studies. Blockchain technology is emerging as a promising approach to increase transparency, particularly in the management and processing of genomic data related with food safety. Robotics, smart agriculture, and smart food and feedstock offer new opportunities for collecting, analyzing, and evaluating data, while wearable devices can predict toxicity and monitor health-related issues. The review article focuses on the potential of digital technologies to improve risk assessment and public health in the field of toxicology. By examining key topics such as blockchain technology, smoking toxicology, wearable sensors, and food security, this article provides an overview of how digitalization is influencing toxicology. As well as highlighting future directions for research, this article demonstrates how emerging technologies can enhance risk assessment communication and efficiency. The integration of digital technologies has revolutionized toxicology and has great potential for improving risk assessment and promoting public health.

Novel Bottom-Side Polished PCF-Based Plasmonic Biosensor for Early Detection of Hazardous Cancerous Cells.

This work presents a single-core bowl-shaped bottom-side polished (BSP) photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) concept for the early detection of hazardous cancer cells in human blood, skin, cervical, breast, and adrenal glands. We have studied liquid samples of cancer-affected and healthy samples with their concentrations/refractive indices in the sensing medium. To induce a plasmonic effect in the PCF sensor, the bottom flat section of a silica PCF fiber is coated with a 40nm plasmonic material, such as gold. To strengthen this effect, a thin TiO2 layer of 5 nm is sandwiched between fiber and gold as it strongly holds gold nanoparticles with smooth fiber surface. When the cancer-affected sample is introduced to the sensor's sensing medium, it produces a different absorption peak in the form of a resonance wavelength than the healthy sample. This reallocation of the absorption peak is used to determine sensitivity. Hence, the obtained sensitivities for blood cancer, cervical cancer, adrenal gland cancer, skin cancer, and breast cancer (type-1and type-2) cells are 22,857nm/RIU, 20000nm/RIU, 20714nm/RIU, 20000nm/RIU, 21428nm/RIU, and 25000nm/RIU, respectively, with highest detection limit 0.024. These strong findings indicate that our proposed cancer sensor PCF is a viable choice for early cancer cell detection.

Biosafety, histological alterations and residue depletion of feed administered anti-parasitic drug emamectin benzoate in golden mahseer, Tor putitora (Hamilton, 1822) as a model candidate fish for sport fishery and conservation in temperate waters.

In the present experiment, the attempt has been made to study the biosafety, toxicity, residue depletion and drug tolerance of graded doses of emamectin benzoate (EB) in juveniles of golden mahseer, Tor putitora as a model candidate fish for sport fishery and conservation in temperate waters through an extended medicated feeding. The graded doses of EB viz., 1× (50 µg/kg fish/day), 2 × (100 µg/kg fish/day), 5 × (250 µg/kg fish/day) and 10 × (500 µg/kg fish/day) were administered to golden mahseer juveniles through medicated diet for 21 days at water temperature of 18.6°C. The higher doses of EB did not cause any mortality during and 30 days after the end of medication period, but considerable variations in feeding and behavior were observed. Severe histological alterations observed after EB-diets (5 × and 10×) were vacuolation, pyknotic nuclei, melanomacrophage centre and necrosis in liver; Bowman's capsule dilation, degenerated renal tubules in kidney; myofibril disintegration, muscle oedema, splitting of muscle fibres, migration of inflammatory cells in muscle; and abundant goblet cells, dilated lamina propria and disarrangement of mucosa in intestine tissues. The residual concentrations of EB metabolites Emamectin B1a and B1b were analyzed using muscle extracts and were found to be peaked during medication period followed by gradual depletion in post-medication period. The outcome of this study showed that the Emamectin B1a residual concentration in fish muscle in 1×, 2×, 5×, and 10× EB treatment groups were 1.41 ± 0.49, 1.2 ± 0.7, 9.7 ± 3.3, and 37.4 ± 8.2 µg/kg at 30 days of post-medication period, respectively, which falls under the maximum residue limits (MRLs) of 100 µg/kg. The results support the biosafety of EB at recommended dose of 50 µg/kg fish/day for 7 days. As residue of EB is recorded falling within the MRL, no withdrawal period is recommended for golden mahseer.

Association of MARCH7 with tumor progression and T-cell infiltration in esophageal cancer.

MARCH7 is an E3 ubiquitin ligase known to regulate neuronal development,T-cell proliferation, and cell and tissue differentiation. But, the altered expression of MARCH7 has been observed in various malignancies. Herein, the cellular localization and role of MARCH7 have been elucidated in esophageal squamous cell carcinoma (ESCC), the information regarding which is currently limited. To check the expression of MARCH7 and its correlation with immune cells infiltration in ESCC, immunohistochemical analysis was performed. RNAi approach was used to investigate the role of MARCH7 in esophageal cancer cells. Interestingly, we found a significantly higher expression of MARCH7 protein in 84% of ESCC tissues than in distant matched non-malignant tissues (p ≤ 0.001). In addition to this, immunohistochemistry results have shown a negative correlation between MARCH7 protein expression and tumor-infiltrating immune cells such as CD8 + T cells (r = - 0.633, p = 0.001) and PD1 + T cells (r = - 0.560, p = 0.005). Furthermore, MARCH7 silencing inhibited the ESCC cell growth and reduced the clonogenic and invasion/migration potential of ESCC cells. MARCH7 silencing also significantly increased E-cadherin protein levels in ESCC cells relative to those in negative control cells (p < 0.05). Thus, MARCH7 is oncogenic and might have a possible role in esophageal carcinogenesis. Moreover, E-cadherin may be a downstream target of MARCH7 in ESCC.

A broadly neutralizing monoclonal antibody overcomes the mutational landscape of emerging SARS-CoV-2 variants of concern.

The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.

Human Behavior-Inspired Linchpin-Directed Catalysis for Traceless Precision Labeling of Lysine in Native Proteins.

The complex social ecosystem regulates the spectrum of human behavior. However, it becomes relatively easier to understand if we disintegrate the contributing factors, such as locality and interacting partners. Interestingly, it draws remarkable similarity with the behavior of a residue placed in a social setup of functional groups in a protein. Can it inspire principles for creating a unique environment for the precision engineering of proteins? We demonstrate that localization-regulated interacting partner(s) could render precise and traceless single-site modification of structurally diverse native proteins. The method targets a combination of high-frequency Lys residues through an array of reversible and irreversible reactions. However, excellent simultaneous control over chemoselectivity, site selectivity, and modularity ensures that the user-friendly protocol renders acyl group installation, including post-translational modifications (PTMs), on a single Lys. Besides, it offers a chemically orthogonal handle for the installation of probes. Also, a purification protocol integration delivers analytically pure single-site tagged protein bioconjugates. The precise labeling of a surface Lys residue ensures that the structure and enzymatic activities remain conserved post-bioconjugation. For example, the precise modification of insulin does not affect its uptake and downstream signaling pathway. Further, the method enables the synthesis of homogeneous antibody-fluorophore and antibody-drug conjugates (AFC and ADC; K183 and K249 labeling). The trastuzumab-rhodamine B conjugate displays excellent serum stability along with antigen-specific cellular imaging. Further, the trastuzumab-emtansine conjugate offers highly specific antiproliferative activity toward HER-2 positive SKBR-3 breast cancer cells. This work validates that disintegrate theory can create a comprehensive platform to enrich the chemical toolbox to meet the technological demands at the chemistry, biology, and medicine interface.

Linchpin-directed precise labeling of lysine in native proteins, purification, and analysis.

The proteins are critical building blocks of living systems and serve as a tool for their investigation and intervention. Their precision engineering enables its tuning and expands the functional landscape. Among various proteinogenic amino acids, high-frequency lysine offers a promising bioconjugation target. However, it is also among the most challenging candidates for homogeneous single-site modification. The linchpin-directed modification (LDM) addresses this concern by offering chemoselective, site-selective, and modular protein bioconjugation. The protocol outlines a general method for single-site modification of a native protein. At first, the selected LDM reagent constructs a stable bioconjugate through acylation of the Lys side chain. Subsequently, its chemically orthogonal handle creates an opportunity to install desired probes directly. Alternatively, the same group enables bioconjugate enrichment through ordered immobilization. The subsequent release, coupled with probe installation, renders analytically pure single-site tagged protein bioconjugate. The analysis of these constructs involves intact MS of protein bioconjugate, peptide mapping, and MS-MS for the site of modification and homogeneity.

COVID-19-Associated Mucormycosis in a Tertiary Care Hospital in India: A Case Series.

Mucormycosis is a disease that usually occurs in immunocompromised patients or those with uncontrolled diabetes mellitus. The second wave of the coronavirus disease 2019 (COVID-19) pandemic in India was accompanied by an unexpected rise in mucormycosis cases, ranging from the most commonly occurring Rhino-orbital-cerebral mucormycosis (ROCM) to rare cases of pulmonary and gastrointestinal mucormycosis. The majority of cases that presented to our hospital were individuals with underlying diabetes mellitus who received steroids for COVID-19 before being diagnosed with mucormycosis. In this case series, we present five rhino-orbital-cerebral mucormycosis cases that were histopathologically positive and treated at a tertiary-care hospital in India. Magnetic resonance imaging (MRI) of all of the patients demonstrated orbital apex syndrome and diffuse or focal infiltration of the cavernous sinus. Cases were treated with anti-fungal drugs, transcutaneous retrobulbar injection of amphotericin B (TRAM B), along with appropriate surgical excision and debridement of the involved tissue. The essential elements for successfully managing this fatal infection are control of the predisposing factors, early detection, anti-fungal drugs, and surgical debridement of the involved tissues.

Could Behavioral Economics Mitigate Shortcomings in Shared Decision-Making?

While shared decision-making (SDM) is generally considered to be the standard in current clinical practice, strict application of SDM can result in adverse outcomes in certain contexts. This article examines two illustrative cases-antibiotic over-prescription and decision-making at or near the end of life-to highlight how strictly applied SDM can result in suboptimal outcomes. The article continues to describe how strategies from libertarian paternalism, particularly default setting, framing, and nudging, can be valuable tools in supplementing strict applications of SDM, resulting in improved outcomes and patient care on both individual and societal levels.