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This review discusses the eco-friendly and cost-effective biosynthesis of gold nanoparticles (AuNPs) in viable microorganisms, focusing on microbes-mediated AuNP biosynthesis. This process suits agricultural, environmental, and biomedical applications, offering renewable, eco-friendly, non-toxic, sustainable, and time-efficient methods. Microorganisms are increasingly used in green technology, nanotechnology, and RNAi technology, but several microorganisms have not been fully identified and characterized. Bio-nanotechnology offers eco-friendly and sustainable solutions for nanomedicine, with microbe-mediated nanoparticle biosynthesis producing AuNPs with anti-oxidation activity, stability, and biocompatibility. Ultrasmall AuNPs offer rapid distribution, renal clearance, and enhanced permeability in biomedical applications. The review explores nano-size dependent biosynthesis of AuNPs by bacteria, fungi, and viruses revealing their non-toxic, non-genotoxic, and non-oxidative properties on human cells. AuNPs with varying sizes and shapes, from nitrate reductase enzymes, have shown potential as a promising nano-catalyst. The synthesized AuNPs, with negative charge capping molecules, have demonstrated antibacterial activity against drug-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii strains, and were non-toxic to Vero cell lines, indicating potential antibiotic resistance treatments. A green chemical method for the biosynthesis of AuNPs using reducing chloroauric acid and Rhizopus oryzae protein extract has been described, demonstrating excellent stability and strong catalytic activity. AuNPs are eco-friendly, non-toxic, and time-efficient, making them ideal for biomedical applications due to their antioxidant, antidiabetic, and antibacterial properties. In addition to the biomedical application, the review also highlights the role of microbially synthesized AuNPs in sustainable management of plant diseases, and environmental bioremediation., Competing Interests: Conflict of interestThe authors declare that there are no conflicts of interest among the authors for the publication of this manuscript in this journal., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Chronic kidney disease (CKD) concomitant with diabetes mellitus (DM), anemia and uremia. Thus, monitoring HbA1c levels presents a complex clinical challenge., Methods: This analytical cross-sectional study was conducted from May 2022 to April 2023 at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow. We compared HbA1c values obtained by the turbidimetric inhibition immunoassay (TINIA) and high-pressure liquid chromatography (HPLC) methods among non-dialysis CKD patients (n=127)., Results: HbA1c was not detectable among 27 patients by TINIA but measurable with HPLC, all being's anemic. The remaining 100 patients, it was detectable by both the methods. Among these 100 patients, linear regression analysis showed a very strong positive correlation between TINIA-HbA1c and HPLC-HbA1c (R2=0.861; p<0.0001). The agreement between methods was substantial (Cohen's kappa 0.657; p<0.0001). However, HbA1c levels were detected significantly higher with HPLC (Median 7.9, IQR 2.7) than that of TINIA (Median 7.0, IQR 2.9;p=0.025) in diabetics while the difference was not significant in non-diabetic group with both HPLC (Median 5.4,IQR 0.8) and TINIA (Median 5.1,IQR 1.1). Carbamylated Hb (CHb; as detected by HPLC as a side product) was correlated to both HbA1c by HPLC (r=0.299;p=0.007) and TINIA (r=0.336;p=0.006) as well as to serum urea levels (r=0.439;p<0.0001)., Conclusion: HPLC estimates all HbA1c patients in our study group while TINIA failed to do so in around 21.26% cases. The very low hemoglobin levels and high carbamylated hemoglobin were apparent as two most common causes. Also, the values with TINIA are significantly lower in comparison to HPLC among diabetics with CKD., Competing Interests: Declaration of Conflict of interests The authors of this article declare that there is no conflict of interest with regard to the content of this manuscript., (Copyright © 2024 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Delta and Omicron variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are remarkably contagious, and have been recognized as variants of concern (VOC). The acquisition of spontaneous substitutions or insertion-deletion mutations (indels) in the spike protein-encoding gene substantially increases the binding affinity of the receptor binding domain (RBD)-hACE2 complex and upsurges the transmission of both variants. In this study, we analyzed thousands of genome sequences from 30 distinct SARS-CoV-2 variants, focusing on the unique nucleic acid signatures in the spike gene specific to the Delta and Omicron variants. Using these variant-specific sequences, we synthesized a range of oligonucleotides and optimized a multiplex PCR (mPCR) assay capable of accurately identifying and differentiating between the Delta and Omicron variants. Building on this mPCR assay, we developed a dipstick format by incorporating a tag linker sequence at the 5' end of the forward primer and adding biotin to the 3' end of the oligonucleotides, enhancing the assay's usability and accessibility. Streptavidin-coated latex beads and the dipstick imprinted with a probe for the tag linker sequence in the test strips were used for the detection assay. Our dipstick-based assay, developed as a rapid point-of-care test for identifying and differentiating SARS-CoV-2 variants has the potential to be used in low-resource settings and scaled up to the population level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paul, Verma, Kumar, Talukdar, Jana, Narendrakumar, Kumar, Tanwar, Gosain, Porey Karmakar, Pareek, Mani, Chaudhuri, Kshetrapal, Wadhwa, Bhatnagar, Garg and Das.)

Multilocular cystic nephroma (MLCN) is an unusual, benign slow-growing renal cystic neoplasm which mimics other cystic renal lesions and has such clinical, radiological, and morphological features that causes diagnostic dilemma. MLCN lies in the spectrum of mixed epithelial and stromal tumor (MEST) family of kidney. According to World Health Organization (WHO 2016 classification), MEST encompasses spectrum of tumors ranging from predominantly cystic tumors, adult cystic nephroma (ACN) to tumors that are variably solid (MEST), thus creating diagnostic dilemma. Moreover, it has several benign and malignant differentials due to its several overlapping histomorphological features which when not cautiously dealt with may result in misdiagnosing it as malignant lesion. We hereby present a case of a woman in late twenties who presented with left flank swelling and pain since 6 months which was misdiagnosed as renal cell carcinoma on radiology which turned out to be ACN on histology and further verified on immunohistochemistry., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

In cancer therapy, it is essential to selectively release cytotoxic agents into the tumor to prevent the adverse effects associated with anticancer drugs. Thus, in this study, a stimuli-sensitive polymer-drug conjugate was synthesized for selective drug release. Doxorubicin (DOX) and docetaxel (DTX) were conjugated onto novel poly(jasmine lactone) based copolymer via a thioketal (TK) linker. In addition, a photosensitizer (chlorin e6) was attached to the polymer, which served as a reactive oxygen species generator to cleave the TK linker. The conjugate is readily self-assembled into micelles less than 100 nm in size. Micelles demonstrate a notable increase in their ability to cause cell death when exposed to near-infrared (NIR) light on MDA-MB-231 breast cancer cells. The increase in cytotoxicity is higher than that observed with the combination of free DOX and DTX. The accumulation of DOX in the nucleus after release from the micelles (laser irradiation) was also confirmed by confocal microscopy. In the absence of light, micelles did not show any toxicity while the free drugs were found toxic irrespective of the light exposure. The obtained results suggest the targeted drug delivery potential of micelles regulated by the external stimuli, i.e., NIR light.

Genetic toxicity testing assesses the potential of compounds to cause DNA damage. There are many genetic toxicology screening assays designed to assess the DNA damaging potential of chemicals in early drug development aiding the identification of promising drugs that have low-risk potential for causing genetic damage contributing to cancer risk in humans. Despite this, in vitro tests generate a high number of misleading positives, the consequences of which can lead to unnecessary animal testing and/or the abandonment of promising drug candidates. Understanding chemical Mode of Action (MoA) is vital to identifying the true genotoxic potential of substances and, therefore, the risk translation into the clinic. Here we demonstrate a simple, robust protocol for staining fixed, human-lymphoblast p53 proficient TK6 cells with antibodies against ɣH2AX, p53 and pH3S28 along with DRAQ5™ DNA staining that enables analysis of un-lysed cells via microscopy approaches such as imaging flow cytometry. Here, we used the Cytek® Amnis® ImageStream®X Mk II which provides a high-throughput acquisition platform with the sensitivity of flow cytometry and spatial morphological information associated with microscopy. Using the ImageStream manufacturer's software (IDEAS® 6.2), a masking strategy was developed to automatically detect and quantify micronucleus events (MN) and characterise biomarker populations. The gating strategy developed enables the generation of a template capable of automatically batch processing data files quantifying cell-cycle, MN, ɣH2AX, p53 and pH3 populations simultaneously. In this way, we demonstrate how a multiplex system enables DNA damage assessment alongside MN identification using un-lysed cells on the imaging flow cytometry platform. As a proof-of-concept, we use the tool chemicals carbendazim and methyl methanesulphonate (MMS) to demonstrate the assay's ability to correctly identify clastogenic or aneugenic MoAs using the biomarker profiles established., (© 2024. The Author(s).)

Dillenia indica is a medicinal tree of the Dilleniaceae and its flower extract was used for the synthesis of silver nanoparticle (AgNPs). The optimal conditions for AgNPs synthesis were as such: 2 mM AgNO 3 , pH 4.5 and 48-h reaction time. The characteristic band of AgNPs was observed at the wavelength of 435 nm by UV-visible spectroscopic study. Fourier-transform infrared (FTIR) analysis depicted the involvement of several functional groups of plant extracts in the synthesis of AgNPs. Nanoparticles were mostly spherical shaped and uniformly distributed, when observation was made by Transmission electron microscopy (TEM). Energy Dispersive X-Ray (EDX) showed absorption peak approximately at 3 keV thus confirmed the presence of silver metal in AgNP. X-ray diffraction (XRD) investigation and selected area electron diffraction (SAED) patterns showed the crystalline nature of the AgNPs. Dynamic light scattering (DLS) analysis exhibited average size of the nanoparticles as 50.17 nm with a polydispersity index (PDI) value of 0.298. The zeta potential of nanoparticles was observed as -24.9 mV. To assess antibacterial activity, both AgNPs alone or its combination with the antibiotic were tried against six pathogenic bacteria. The combination of AgNPs with antibiotic was maximum effective against Shigella boydii (16.07 ± 0.35) and Klebsiella pneumoniae (15.03 ± 0.20). AgNPs alone showed maximum inhibition for both Gram-positive bacteria: methicillin-resistant Staphylococcus aureus (19.97 ± 0.20 mm) and Enterococcus faecium (19.80 ± 0.15 mm). Maximum inhibition of Enterobactor cloacae and Pseudomonas aeruginosa was observed by antibiotic taken alone. Evaluation through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and DNA nicking assays demonstrated the antioxidant capabilities of the nanoparticles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nishi Kumari reports financial support was provided by Banaras Hindu University. Nishi Kumari reports a relationship with Banaras Hindu University that includes: employment and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Understanding kinase-inhibitor selectivity continues to be a major objective in kinase drug discovery. We probe the molecular basis of selectivity of an allosteric inhibitor (MSC1609119A-1) of the insulin-like growth factor-I receptor kinase (IGF1RK), which has been shown to be ineffective for the homologous insulin receptor kinase (IRK). Specifically, we investigated the structural and energetic basis of the allosteric binding of this inhibitor to each kinase by combining molecular modeling, molecular dynamics (MD) simulations, and thermodynamic calculations. We predict the inhibitor conformation in the binding pocket of IRK and highlight that the charged residues in the histidine-arginine-aspartic acid (HRD) and aspartic acid-phenylalanine-glycine (DFG) motifs and the nonpolar residues in the binding pocket govern inhibitor interactions in the allosteric pocket of each kinase. We suggest that the conformational changes in the IGF1RK residues M1054 and M1079, movement of the ⍺C-helix, and the conformational stabilization of the DFG motif favor the selectivity of the inhibitor toward IGF1RK. Our thermodynamic calculations reveal that the observed selectivity can be rationalized through differences observed in the electrostatic interaction energy of the inhibitor in each inhibitor/kinase complex and the hydrogen bonding interactions of the inhibitor with the residue V1063 in IGF1RK that are not attained with the corresponding residue V1060 in IRK. Overall, our study provides a rationale for the molecular basis of recognition of this allosteric inhibitor by IGF1RK and IRK, which is potentially useful in developing novel inhibitors with improved affinity and selectivity., (© 2024 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

The pharmaceutical industry must maintain stringent quality assurance standards to ensure product safety and regulatory compliance. A key component of the well-known Six Sigma methodology for process improvement and quality control is precise and comprehensive documentation. However, there are a number of significant issues with traditional documentation procedures, including as slowness, human error, and difficulties with regulatory standards. This review research looks at innovative ways to employ machine learning (ML) and artificial intelligence (AI) to enhance Six Sigma documentation processes in the pharmaceutical sector. AI and ML provide cutting-edge technologies that have the potential to drastically alter documentation processes by automating data entry, collection, and analysis. Natural language processing (NLP) and computer vision technologies have the potential to significantly reduce human error rates and increase the efficacy of documentation processes. By applying machine learning algorithms to support real-time data analysis, predictive analytics, and proactive quality management, pharmaceutical organizations may be able to identify potential quality issues early on and take proactive efforts to address them. Combining AI and ML improves documentation accuracy and reliability while also strengthening compliance with stringent regulatory criteria. The primary barriers and limitations to the current state of Six Sigma documentation in the pharmaceutical industry are identified in this study. It examines the fundamentals of AI and ML with an emphasis on their specific applications in quality assurance and potential benefits for Six Sigma processes. The report includes extensive case studies that highlight notable developments and explain how AI/ML enhanced documentation is used in the real world.

537 million people worldwide suffer from diabetes mellitus, a problem of glucose management that is related to a number of major health risks, including cardiovascular diseases. There is a need for new, efficient formulations of diabetic medications to address this condition and its related consequences because existing treatments have a number of drawbacks and limits. This encouraged the development of treatment plans to get around some of these restrictions, like low therapeutic drug bioavailability or patients' disobedience to existing therapies. Approaches based on nanotechnology have a lot of promise to enhance the treatment of diabetic patients. In order to manage blood glucose, this review article highlights recent developments and explores the potential applications of different materials (polymeric, ceramic, dendrimers, etc.) as nanocarriers for the delivery of insulin and other antidiabetic medications. Using an injectable and acid-degradable polymeric network produced by the electrostatic interaction of oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, we reviewed a glucose-mediated release approach for the self-regulated delivery of insulin, in which, after a degradable nano-network was subcutaneously injected into type 1 diabetic mice, in vivo experiments confirmed that these formulations improved glucose management. In addition, a discussion of silica-based nanocarriers, their potential for treating diabetes and controlling blood glucose levels, and an explanation of the role of dendrimers in diabetes treatment have been covered. This is done by utilizing the properties of silica nanoparticles, such as their tuneable particle and pore size, surface chemistry, and biocompatibility. The article summarized the significance of nanomaterials and their uses in the diagnosis and treatment of diabetes overall, illuminating the field's potential and outlining its prospects for the future., (© 2024 IOP Publishing Ltd.)

Since ancient times, plants have been used as a remedy for numerous diseases. The pharmacological properties of plants are due to the presence of secondary metabolites like terpenoids, flavonoids, alkaloids, etc. Anthraquinones represent a group of naturally occurring quinones found generously across various plant species. Anthraquinones attract a significant amount of attention due to their reported efficacy in treating a wide range of diseases. Their complex chemical structures, combined with inherent medicinal properties, underscore their potential as agents for therapy. They demonstrate several therapeutic properties such as laxative, antitumor, antimalarial, antibacterial, antifungal, antioxidant, etc. Anthraquinones are found in different forms (derivatives) in plants, and they exhibit various medicinal properties due to their structure and chemical nature. The precursors for the biosynthesis of anthraquinones in higher plants are provided by different pathways such as plastidic hemiterpenoid 2-C-methyl-D-erthriol4-phosphate (MEP), mevalonate (MVA), isochorismate synthase and polyketide. By conducting a thorough analysis of scientific literature, this review provides insights into the intricate interplay between anthraquinone biosynthesis and its broad-ranging contributions to human health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Supramolecular biomaterials can recapitulate the structural and functional facets of the native extracellular matrix and react to biochemical cues, leveraging the unique attributes of noncovalent interactions, including reversibility and tunability. However, the low mechanical properties of supramolecular biomaterials can restrict their utilization in specific applications. Combining the advantages of supramolecular polymers with covalent polymers can lead to the fabrication of tailor-made biomaterials with enhanced mechanical properties/degradability. Herein, we demonstrate a synergistic coassembled self-healing gel as a multifunctional supramolecular material. As the supramolecular polymer component, we chose folic acid (vitamin B 9 ), an important biomolecule that forms a gel comprising one-dimensional (1D) supramolecular polymers. Integrating polyvinyl alcohol (PVA) into this supramolecular gel alters its ultrastructure and augments its mechanical properties. A drastic improvement of complex modulus (G*) (∼3674 times) was observed in the folic acid-PVA gel with 15% w / v PVA (33215 Pa) compared with the folic acid gel (9.04 Pa). The coassembled hydrogels possessed self-healing and injectable/thixotropic attributes and could be printed into specific three-dimensional (3D) shapes. Synergistically, the supramolecular polymers of folic acid also improve the toughness, durability, and ductility of the PVA films. A nanocomposite of the gels with silver nanoparticles exhibited excellent catalytic efficiency and antibacterial activity. The folic acid-PVA coassembled gels and films also possessed high cytocompatibility, substantiated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live-dead assays. Taken together, the antibacterial and cell-adhesive attributes suggest potential applications of these coassembled biomaterials for tissue engineering and wound healing.

Hypercalcemia of Malignancy is a complicated condition often linked to parathyroid hormone, parathyroid hormone-related peptide, or bone metastasis. This report presents a unique case of calcitriol-mediated hypercalcemia in an 89-year-old female with primary pancreatic lymphoma, highlighting the rarity and complexity of this presentation. Initially, the patient's condition was thought to be related to sarcoidosis, but the recurrence of hypercalcemia led to the discovery of pancreatic B-cell lymphoma as the underlying cause. It also emphasizes the need to explore new treatment options. Interestingly, it demonstrates the successful use of cinacalcet in treating calcitriol-induced hypercalcemia in malignancies, which could be a potential therapeutic option for such cases. It also serves as a reminder of the critical need for ongoing research and innovative therapeutic strategies to improve outcomes in managing hypercalcemia caused by malignancies. The case underscores the potential complexities of calcitriol-mediated hypercalcemia, especially in uncommon presentations like primary pancreatic lymphoma., Competing Interests: Conflict of interest: The authors have no conflict of interest to declare., (© 2024 Greater Baltimore Medical Center.)

Background: Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on cardiovascular outcomes in coronavirus disease 2019 (COVID-19) hospitalizations with varied obesity levels is scarce. Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels., Aim: To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity., Methods: COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease -10 CM codes in the 2020 National Inpatient Sample database. Overweight and Obesity Classes I, II, and III (body mass index 30-40) were compared. Major adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) were compared between groups. Multivariable regression analyses adjusted for sociodemographic, hospitalization features, and comorbidities., Results: Our analysis comprised 13260 hospitalizations, 7.3% of which were overweight, 24.3% Class I, 24.1% Class II, and 44.3% Class III. Class III obesity includes younger patients, blacks, females, diabetics, and hypertensive patients. On multivariable logistic analysis, Class III obese patients had higher risks of MACCE, inpatient mortality, and respiratory failure than Class I obese patients. Class II obesity showed increased risks of MACCE, inpatient mortality, and respiratory failure than Class I, but not significantly. All obesity classes had non-significant risks of MACCE, inpatient mortality, and respiratory failure compared to the overweight group., Conclusion: Class III obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class I. Using the overweight group as the reference, unfavorable outcomes were not significantly different. Morbid obesity had a greater risk of MACCE regardless of the referent group (overweight or Class I obese) compared to overweight NAFLD patients admitted with COVID-19., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Antimicrobial resistance (AMR) is a serious worldwide public health concern that needs immediate action. Probiotics could be a promising alternative for fighting antibiotic resistance, displaying beneficial effects to the host by combating diseases, improving growth, and stimulating the host immune responses against infection. This study was conducted to evaluate the probiotic, antibacterial, and antibiofilm potential of Streptomyces levis strain HFM-2 isolated from the healthy human gut., Results: In vitro antibacterial activity in the cell-free supernatant of S. levis strain HFM-2 was evaluated against different pathogens viz. K. pneumoniae sub sp. pneumoniae, S. aureus, B. subtilis, VRE, S. typhi, S. epidermidis, MRSA, V. cholerae, M. smegmatis, E. coli, P. aeruginosa and E. aerogenes. Further, the ethyl acetate extract from S. levis strain HFM-2 showed strong biofilm inhibition against S. typhi, K. pneumoniae sub sp. pneumoniae, P. aeruginosa and E. coli. Fluorescence microscopy was used to detect biofilm inhibition properties. MIC and MBC values of EtOAc extract were determined at 500 and 1000 µg/mL, respectively. Further, strain HFM-2 showed high tolerance in gastric juice, pancreatin, bile, and at low pH. It exhibited efficient adhesion properties, displaying auto-aggregation (97.0%), hydrophobicity (95.71%, 88.96%, and 81.15% for ethyl acetate, chloroform and xylene, respectively), and showed 89.75%, 86.53%, 83.06% and 76.13% co-aggregation with S. typhi, MRSA, S. pyogenes and E. coli, respectively after 60 min of incubation. The S. levis strain HFM-2 was susceptible to different antibiotics such as tetracycline, streptomycin, kanamycin, ciprofloxacin, erythromycin, linezolid, meropenem, amikacin, gentamycin, clindamycin, moxifloxacin and vancomycin, but resistant to ampicillin and penicillin G., Conclusion: The study shows that S. levis strain HFM-2 has significant probiotic properties such as good viability in bile, gastric juice, pancreatin environment, and at low pH; proficient adhesion properties, and antibiotic susceptibility. Further, the EtOAc extract of Streptomyces levis strain HFM-2 has a potent antibiofilm and antibacterial activity against antibacterial-resistant clinical pathogens., (© 2024. The Author(s).)

The allosteric inhibition of insulin-like growth factor receptor 1 kinase (IGF1RK) is a potential strategy to overcome selectivity barriers for targeting receptor tyrosine kinases. We constructed structural models of a series of 12 indole-butyl-amine derivatives that have been reported as allosteric inhibitors of IGF1RK. We further studied the dynamics and interactions of each inhibitor in the allosteric pocket via all-atom explicit-solvent molecular dynamics (MD) simulations. We discovered that a bulky carbonyl substitution at the R1 indole ring is structurally unfavorable for inhibitor binding in the IGF1RK allosteric pocket. Moreover, we found that the most potent derivative (termed C11) acquires a distinct conformation: forming an allosteric pocket channel with better shape complementarity and interactions with the receptor. In addition to a hydrogen-bonding interaction with V1063, the cyano derivative C11 forms a stable hydrogen bond with M1156, which is responsible for its unique binding conformation in the allosteric pocket. Our findings show that the positioning of chemical substituents with different pharmacophore features at the R1 indole ring influences molecular interactions and binding conformations of indole-butyl-amine derivatives and, hence, dramatically affects their potencies. Our results provide a structural framework for the design of allosteric inhibitors with improved affinities and specificities against IGF1RK.

Mucormycosis is an aggressive, fatal fungal infection. The fungal organisms are ubiquitous and easily affect immunocompromised patients. The main aim of this article is to emphasize over the knowledge of different diagnostic methods (diagnostic nasal endoscopy, ct/ contrast mri pns + orbit + brain, Wet KOH mount), the importance of practising an aggressive surgical resection, medical treatments (liposomal amphotericin B, amphotericin gel, tablet posaconazole, nasal douching, retrorbital amphotericin injection), suction cleaning and regular follow up of the patient after surgical management. This can greatly help in minimizing the recurrence of mucormycosis even in immunocompromised patients in a population. The study performed was a prospective study conducted from April 2021 to July 2021 in which we included 500 patients who presented to the OPD & Department of ENT or Emergency Department of Maharaja Yashwantrao Hospital with complaints suggestive of mucormycosis. The patients who were surgically fit were operated. Out of the 500 patients who were diagnosed with Mucormycosis, from April 2021 to July 2021 complete cure was achieved in 456 patients( 91.2%) and only 44 patients (8.8%) have shown recurrence due to various causes (specially those who did not came for regular follow up). Rhinorbital was the most common site to be involved. In the study it was found that most of the patients which showed recurrence were male, post covid and immunocompromised. Diabetes mellitus was found to be most common among immunocompromised patients. The recurrence in patients with mucormycosis can be minimise by educating the masses regarding importance of public and personal hygiene, and multidisciplinary management with regular follow up offers a better approach to treat this life-threatening condition. The study shows the importance of clinical diagnosis, concurrent surgical treatment, medical treatment, post op care, suction cleaning and regular follow up advice. It is necessary us to take the step forward in this regard, so that in the future we will be better prepared for such type of epidemic., Competing Interests: Conflict of interestThe author(s) declare none., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Rhinocerebralmucormycosis, is a progressive fungal invasion of a hard palate, paranasal sinuses, orbit, and brain. Post covid the huge number of mucor cases reported in our institute. To combat them a uniform assessment scale was needed as multiple healthcare workers were involved. Thus, a novel linear grading system on nasal endoscopy was developed for the early management of patients to prevent morbidity and mortality. A Prospective study of 650 patients in Epidemic duration from April to June 2021 in a tertiary health center, Central India. Patients subjected to Nasal Endoscopy with 0degree 4 mm Telescope and classified into 5 categories according to the severity of the disease. In a novel grading system, minimum patients were of grade 0, maximum was in Grade I. Maxillary sinus was most commonly involved. This novel grading system on nasal endoscopy makes the management of patients much easier in an epidemic, reducing human errors, morbidity, and mortality of the fulminant disease., Competing Interests: Conflict of interestsThe author(s) declare none., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction The horizontal lip position and esthetic plane are two important parameters to define facial beauty, and these factors are always given importance in children undergoing fixed orthodontic therapy. The purpose of this study was to evaluate horizontal lip position in primary and mixed dentition children with class I occlusion and to analyze its association with gender among preschool and schoolchildren of villages in the Bankura district in West Bengal. Materials and methods Researchers screened 437 children for the study and selected those who met the inclusion criteria. A total of 407 children were segregated: 201 children aged three to five years with the flush terminal plane and mesial step in primary teeth and 206 children aged seven to eleven years with class I occlusion in mixed dentition were selected from schools in villages in Bankura district, West Bengal, India. The subjects were instructed to hold the head in the natural head position by looking straight, and points were marked on the nose and chin tip, respectively. A metallic ruler was placed from nose to chin, representing Rickett's esthetic line. The horizontal lip distance to the esthetic plane of both upper and lower lips was measured as a linear distance from the most anterior part of the lip to the metallic ruler. The data were recorded, compared with gender, and statistically analyzed using the Chi-square test using the Statistical Package of Social Sciences software (SPSS version 19.0, 2015, IBM Corp., Armonk, NY). Results The most prevalent horizontal lip distance for both upper and lower lips to the esthetic line for primary and mixed dentition in the Bankura region of West Bengal was category I, where the lip is seen beyond the E plane, followed by category II, where lips are at a horizontal distance in the range of 0-1.5 mm from the esthetic line. A significant correlation of lip position with Rickets aesthetic plane was also illustrious with gender in primary dentition, but a non-significant association with gender was noted in mixed dentition. Conclusion Children with class I occlusion from the Bankura district of West Bengal showed a higher percentage of lip position beyond the esthetic plane in both primary and mixed dentition, which is not in line with the inference of Ricketts's studies on the Caucasian population. There is a definite association between gender and horizontal lip distance in Ricketts esthetic plane. Protrusive upper lips were seen more in males, and retrusive lips were seen more in females. Clinical significance  The horizontal lip position with reference to Ricketts esthetic plane has been documented in the literature for adults and teens undergoing fixed orthodontic treatment. However, there is no study done to define these measurements in preschool and school-going children, which can assist in determining future esthetic profiles and in preparing a protocol for early age interceptive orthodontics along with aesthetic rehabilitation of the anterior area of the mouth., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ahuja et al.)

Background  Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis  We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods  In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results  Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions  Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

To assess how oral health education (OHE) techniques using braille affect visually impaired children's awareness of oral health, oral hygiene status and practices, plaque, gingival health, and dental caries status. From 2010 to 2020, a thorough literature search will be conducted for studies in the English language using PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, and Open Grey. Data extraction will be done after two reviewers extensively evaluate the papers for qualifying requirements. In accordance with the research designs, a quality evaluation of the chosen studies will be conducted. With the use of the program Review Manager 5.3, a meta-analysis will be completed., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Aim: The study's objective was to assess the dimensional accuracy of hybrid polyether and polyvinyl siloxane materials for implant impressions., Materials and Methods: Nine groups were created from 45 samples of various building materials and construction techniques from the study. Five samples were tested, and 45 impressions were recorded., Results: The hybrid non-splinted technique has improved implant site replication, accuracy, and low interimplant distance alterations., Conclusion: The finest possible reproduction of implant sites on the master cast was made feasible by the use of an open, non-splinted method and a hybrid polyvinyl siloxane-polyether impression material., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Introduction: Synovial hemangioma is a benign soft-tissue tumor of vascular origin. Hemangioma only accounts for 1% of all bone lesions and is mostly an incidental finding among the primary skeleton tumors. A delay in diagnosis results in joint degeneration and osteoarthritic damage because of infiltrating tumor growth., Case Presentation: We presented a rare case of an intra-articular synovial hemangioma in a 13- year-old pediatric patient who was asymptomatic for 5 years. She attended orthopedics OPD at AIIMS, Mangalagiri. Surgical excision of the mass and partial synovectomy was done. Synovial hemangioma came out to be the diagnosis following a histologic study., Conclusion: As radiography has limited diagnostic ability, synovial hemangiomas are difficult and challenging to identify on an outpatient basis. Histological examination and magnetic resonance imaging are extremely helpful. To minimize the hemarthrosis risks, early complete excision can be used as the best treatment modality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The emergence of the new SARS-CoV-2 variants has led to major concern regarding the efficacy of approved vaccines. Nucleocapsid is a conserved structural protein essential for replication of the virus. This study focuses on identifying conserved epitopes on the nucleocapsid (N) protein of SARS-CoV-2. Using 510 unique amino acid sequences of SARS-CoV-2 N protein, two peptides (193 and 215 aa) with 90% conservancy were selected for T cell epitope prediction. Three immunogenic peptides containing multiple T cell epitopes were identified which were devoid of autoimmune and allergic immune response. These peptides were also conserved (100%) in recent Omicron variants reported in Jan-August 2023. HLA analysis reveals that these peptides are predicted as binding to large number of HLA alleles and 71-90% population coverage in six continents. Identified peptides displayed good binding score with both HLA class I and HLA class II molecules in the docking study. Also, a vaccine construct docked with TLR-4 receptor displays strong interaction with 20 hydrogen bonds and molecular simulation analysis reveals that docked complex are stable. Additionally, the immunogenicity of these N protein peptides was confirmed using SARS-CoV-2 convalescent serum samples. We conclude that the identified N protein peptides contain highly conserved and antigenic epitopes which could be used as a target for the future vaccine development against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

The emergence and spread of antibiotic-resistant bacterial pathogens are a critical public health concern across the globe. Mobile genetic elements (MGEs) play an important role in the horizontal acquisition of antimicrobial resistance genes (ARGs) in bacteria. In this study, we have decoded the whole genome sequences of multidrug-resistant Vibrio cholerae clinical isolates carrying the ARG-linked SXT, an integrative and conjugative element, in their large chromosomes. As in others, the SXT element has been found integrated into the 5'-end of the prfC gene (which encodes peptide chain release factor 3 involved in translational regulation) on the large chromosome of V. cholerae non-O1/non-O139 strains. Further, we demonstrate the functionality of SXT-linked floR and strAB genes, which confer resistance to chloramphenicol and streptomycin, respectively. The floR gene-encoded protein FloR belongs to the major facilitator superfamily efflux transporter containing 12 transmembrane domains (TMDs). Deletion analysis confirmed that even a single TMD of FloR is critical for the export function of chloramphenicol. The floR gene has two putative promoters, P1 and P2. Sequential deletions reveal that P2 is responsible for the expression of the floR . Deletion analysis of the N- and/or C-terminal coding regions of strA established their importance for conferring resistance against streptomycin. Interestingly, qPCR analysis of the floR and strA genes indicated that both of the genes are constitutively expressed in V. cholerae cells. Further, whole genome-based global phylogeography confirmed the presence of the integrative and conjugative element SXT in non-O1/non-O139 strains despite being non-multidrug resistant by lacking antimicrobial resistance (AMR) gene cassettes, which needs monitoring.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that presents challenges in communication, social interaction, repetitive behaviour, and limited interests. Detecting ASD at an early stage is crucial for timely interventions and an improved quality of life. In recent times, Artificial Intelligence (AI) has been increasingly used in ASD research. The rise in ASD diagnoses is due to the growing number of ASD cases and the recognition of the importance of early detection, which leads to better symptom management. This study explores the potential of AI in identifying early indicators of autism, aligning with the United Nations Sustainable Development Goals (SDGs) of Good Health and Well-being (Goal 3) and Peace, Justice, and Strong Institutions (Goal 16). The paper aims to provide a comprehensive overview of the current state-of-the-art AI-based autism classification by reviewing recent publications from the last decade. It covers various modalities such as Eye gaze, Facial Expression, Motor skill, MRI/fMRI, and EEG, and multi-modal approaches primarily grouped into behavioural and biological markers. The paper presents a timeline spanning from the history of ASD to recent developments in the field of AI. Additionally, the paper provides a category-wise detailed analysis of the AI-based application in ASD with a diagrammatic summarization to convey a holistic summary of different modalities. It also reports on the successes and challenges of applying AI for ASD detection while providing publicly available datasets. The paper paves the way for future scope and directions, providing a complete and systematic overview for researchers in the field of ASD., Competing Interests: Declaration of competing interest All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is it under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hand sanitizer usage has proven to be a common and practical method for reducing the spread of infectious diseases which can be caused by many harmful pathogens. There is a need for alcohol-free hand sanitizers because most hand sanitizers on the market are alcohol-based, and regular use of them can damage the skin and can be hazardous. India is the world's largest producer of fruits and one of the major problems after fruit consumption is their peels, causing waste management problems and contributing to the formation of greenhouse gases leading to air pollution and adding to the problem of climate change. Valorization of such wastes into other value-added products and their incorporation into formulations of eco-friendly alcohol-free hand sanitizers would solve these issues, save the environment, benefit the society, and help in achieving the sustainable development goals. Thus, this research focuses on formulating an effective natural alcohol-free hand sanitizer that harnesses the antimicrobial properties of the various types of bioactive components found in fruit peels of pomegranate, sweet lime, and lemon. The peel extracts and the formulated sanitizer proved considerable antimicrobial activity against the pathogenic Escherichia coli and hand microflora. Molecular docking was also applied to examine ligand-protein interaction patterns and predict binding conformers and affinity of the sanitizer phytocompounds towards target proteins in COVID-19, influenza, and pneumonia viruses. The binding affinities and the protein-ligand interactions virtual studies revealed that the sanitizer phytocompounds bind with the amino acids in the target proteins' active sites via hydrogen bonding interactions. As a result, it is possible to formulate a natural, alcohol-free hand sanitizer from fruit peels that is effective against pathogenic germs and viruses using the basic structure of these potential findings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 J. Verma et al.)

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD., Competing Interests: No potential conflict of interest was reported by any of the author(s) listed in this manuscript., (© 2023 The Author(s).)

Importance: Macrophages curtail the proliferation of the pathogen Candida albicans within human body niches. Within macrophages, C. albicans adapts its metabolism and switches to invasive hyphal morphology. These adaptations enable fungal growth and immune escape by triggering macrophage lysis. Transcriptional programs regulate these metabolic and morphogenetic adaptations. Here we studied the roles of chromatin in these processes and implicate lysine crotonylation, a histone mark regulated by metabolism, in hyphal morphogenesis and macrophage interactions by C. albicans . We show that the short-chain fatty acid crotonate increases histone crotonylation, reduces hyphal formation within macrophages, and slows macrophage lysis and immune escape of C. albicans . Crotonate represses hyphal gene expression, and we propose that C. albicans uses diverse acylation marks to regulate its cell morphology in host environments. Hyphal formation is a virulence property of C. albicans . Therefore, a further importance of our study stems from identifying crotonate as a hyphal inhibitor., Competing Interests: The authors declare no conflict of interest.

Prognostic survival prediction in colorectal cancer (CRC) plays a crucial role in guiding treatment decisions and improving patient outcomes. In this research, we explore the application of deep learning techniques to predict survival outcomes based on histopathological images of human colorectal cancer. We present a retrospective multicenter study utilizing a dataset of 100,000 nonoverlapping image patches from hematoxylin & eosin-stained histological images of CRC and normal tissue. The dataset includes diverse tissue classes such as adipose, background, debris, lymphocytes, mucus, smooth muscle, normal colon mucosa, cancer-associated stroma, and colorectal adenocarcinoma epithelium. To perform survival prediction, we employ various deep learning architectures, including convolutional neural network, DenseNet201, InceptionResNetV2, VGG16, VGG19, and Xception. These architectures are trained on the dataset using a multicenter retrospective analysis approach. Extensive preprocessing steps are undertaken, including image normalization using Macenko's method and data augmentation techniques, to optimize model performance. The experimental findings reveal promising results, demonstrating the effectiveness of deep learning models in prognostic survival prediction. Our models achieve high accuracy, precision, recall, and validation metrics, showcasing their ability to capture relevant histological patterns associated with prognosis. Visualization techniques are employed to interpret the models' decision-making process, highlighting important features and regions contributing to survival predictions. The implications of this research are manifold. The accurate prediction of survival outcomes in CRC can aid in personalized medicine and clinical decision-making, facilitating tailored treatment plans for individual patients. The identification of important histological features and biomarkers provides valuable insights into disease mechanisms and may lead to the discovery of novel prognostic indicators. The transparency and explainability of the models enhance trust and acceptance, fostering their integration into clinical practice. Research demonstrates the potential of deep learning models for prognostic survival prediction in human colorectal cancer histology. The findings contribute to the understanding of disease progression and offer practical applications in personalized medicine. By harnessing the power of deep learning and histopathological analysis, we pave the way for improved patient care, clinical decision support, and advancements in prognostic prediction in CRC., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

The SARS-CoV-2, responsible for the COVID-19 pandemic has wrecked devastation throughout the globe. The SARS-CoV-2 spike (S) glycoprotein plays crucial role in virus attachment, fusion, and entry. This study aims to identify inhibitors targeting the receptor binding domain (RBD) of the S protein using computational and experimental techniques. We carried out virtual screening of four datasets against the S-RBD. Six potential candidate inhibitors were selected for experimental evaluation. Here, we provide experimental evidence that the molecules 9‴-MethyllithosperMate, Epimedin A, Pentagalloylglucose, and Theaflavin-3-gallate have a high binding affinity towards SARS-CoV-2 S-RBD. 9‴-MethyllithosperMate with a K D value of 1.3 nM serves as the best inhibitor, followed by others with K D values in micromolar range. We performed molecular dynamics simulation to assess the binding stability of these inhibitors. Hence, our study reports novel inhibitors against the SARS-CoV-2 S-RBD and their predicted binding mode also suggest the possibility to interfere with the ACE2 binding.Communicated by Ramaswamy H. Sarma.

In this study, we attempt to look at the various presentations, comorbidities and association of the recent epidemic of rhino-orbital cerebral mucormycosis with Covid-19 in central India. A prospective study of 612 patients diagnosed with mucormycosis from April to July 2021. Detailed history was taken and thorough clinical examination was done. The relation of mucormycosis with Covid-19 and other morbidities was studied. Nasal endoscopy, imaging and management findings were tabulated and analyzed. Male predominance of the disease was noted. The most common age group affected was found to be 41-50 years group having 33.1% of all patients. 83.2% patients had history of Covid-19 infection. Majority of the patients (41.6%) had mucormycosis symptoms within 1 month of Covid-19 symptom onset. Nasal symptoms predominated with 61.1% patients having one or more of the several nasal symptoms. Most common comorbidity was diabetes mellitus (75.8% cases). Nasal and sinus debridement was performed in 584 patients (95.4%). Mucormycosis turned into a widespread epidemic during the second wave of Covid-19 in India. Diabetes mellitus was the most common associated comorbidity that increased the risk of mucormycosis in patients with history of Covid-19 infection. A high index of suspicion in patients presenting with early symptoms in the context of Covid-19, along with prompt diagnosis using radiological, endoscopic and microbiological tools will help reduce mortality to a great extent. Mainstay of treatment is aggressive surgical and medical management, controlling comorbidities and adequate post-operative care., Competing Interests: Competing interestsThe author(s) declare none., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Celecoxib (CLX), a poorly soluble anti-inflammatory drug, requires administration in higher concentrations to produce therapeutic effects, oftentimes resulting in cardiac toxicity. Therefore, in this study, we employed a nanoemulsion technology to improve the solubility of CLX using poly(δ-decalactone) (PDL) polymer as an oil and mPEG-b-PDL as a surfactant. The nanoemulsion (NE) was successfully prepared via the nanoprecipitation method. In vitro characterization was performed for size, drug release, and stability. In vivo studies were performed to establish anti-inflammatory activity, CLX induced cardiac toxicity, and pharmacokinetic profile of NE, post-oral administration. The globular size of less than 100 nm was obtained in NE with high CLX loading. The in vitro drug release studies suggested ∼90% of CLX release from NE within 96 h. A significant anti-inflammatory activity with lowered cardiac marker values was observed for CLX NE compared to a marketed drug formulation. The pharmacokinetic study revealed that the mean retention time of CLX was significantly increased with NE in contrast to the marketed formulation, suggesting the advantage of administering CLX in the form of NE owing to the higher solubility and sustained release pattern. The long-term storage stability study reveals that NE does not show significant changes in terms of size with only a slight decrement in CLX content was observed after 24 months. The obtained results indicate that CLX bioavailability has been considerably improved without being toxic to the heart with the aid of NE and advocate the use of PDL NE for developing oral formulations for poorly soluble drugs., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The association of traditional cardiovascular disease (CVD) risk factors with outcomes of Takotsubo syndrome (TTS) is not well-defined. This study examined how modifiable CVD risk factors affect composite cardiovascular outcomes in TTS hospitalizations. TTS admissions were identified using ICD-10 codes and compared for demographics and comorbidities using the 2019 National Inpatient Sample. A multivariable regression examined the association of traditional CVD risk variables with adverse composite cardiovascular outcomes in TTS, controlling for confounders including sociodemographic or hospital-level characteristics and other relevant comorbidities. A total of 16,055 (38.1%) of the 41,855 adult TTS admissions had composite cardiovascular outcomes (TACCO). The TACCO cohort was 81.5% white, 77.3% female, and 72 years old. This group had higher rates of diabetes and peripheral vascular disease (PVD). The results showed that a higher prevalence of diabetes with chronic complications (OR = 1.18) and complicated hypertension (HTN) (OR = 1.1) predicted TACCO, whereas tobacco use disorder (OR = 0.84), hyperlipidemia (OR = 0.76), and uncomplicated HTN (OR = 0.65) ( p < 0.001) showed a paradoxical effect with TACCO. TACCO had fewer routine discharges (35.3% vs. 63.4%), longer stays (6 vs. 3 days), and higher median hospital costs (78,309 USD vs. 44,966 USD). This population-based study found that complicated HTN and DM with chronic complications are strongly associated with adverse cardiovascular outcomes in TTS hospitalizations. But still, some risk factors, such as hyperlipidemia and uncomplicated HTN, have counterintuitive effects that require further evaluation. To prevent cardiac events in TTS patients, traditional CVD risk factors must be addressed.

Environmental chemical exposure can cause dysregulation in adipogenesis that can result in metabolic syndrome, which includes insulin resistance, type 2 diabetes, cardiovascular disease, as well as excessive body weight. The role of autophagy in adipocyte differentiation is debatable since both positive and negative effects have been reported. Type-I and type-II synthetic pyrethroids α-cypermethrin (CPM) and permethrin (PER), respectively, are reported to increase adipogenesis in vitro and in vivo. However, it is not known how these pyrethroids affect mesenchymal stem cells (MSCs). Thus, this study focused on evaluating the effect of pyrethroids (CPM and PER) pre-treatment (24 h) on MSC commitment and the regulatory role of autophagy in adipogenic lineage commitment. The formation of adipocytes was observed through nile red staining, perilipin expression by immunoflourescence, and adipogenic markers PPARγ, C/EBPα, and FABP4 by western blotting. It was found that the adipogenic differentiation ability of MSCs was significantly increased upon CPM or PER pre-treatment at 100 μM concentration as evident by lipid accumulation and enhanced expression of adipogenic markers. To assess the involvement of autophagy, the expression of p62 and LC3II were evaluated following pre-treatment. Immunoblotting results revealed an increased expression of p62 and LC3II in CPM or PER pretreated MSCs suggesting CPM and PER mediated inhibition of autophagy at 24 h. Further, an increase was observed in adipogenesis upon CPM or PER pre-treatment in combination with chloroquine, while use of rapamycin during pre-treatment abrogated the effect of CPM and PER. Thus, this study concludes that CPM or PER pre-treatment increases the adipogenic differentiation of MSCs. Since chloroquine also demonstrated similar adipogenic response, it further highlights that 24 h pre-treatment with autophagy modulators to inhibit basal autophagy primes MSCs towards adipogenic lineage., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Every sixth person in the world dies due to cancer, making it the second leading severe cause of death after cardiovascular diseases. According to WHO, cancer claimed nearly 10 million deaths in 2020. The most common types of cancers reported have been breast (lung, colon and rectum, prostate cases), skin (non-melanoma) and stomach. In addition to surgery, the most widely used traditional types of anti-cancer treatment are radio- and chemotherapy. However, these do not distinguish between normal and malignant cells. Additional treatment methods have evolved over time for early detection and targeted therapy of cancer. However, each method has its limitations and the associated treatment costs are quite high with adverse effects on the quality of life of patients. Use of individual atoms or a cluster of atoms (nanoparticles) can cause a paradigm shift by virtue of providing point of sight sensing and diagnosis of cancer. Nanoparticles (1-100 nm in size) are 1000 times smaller in size than the human cell and endowed with safer relocation capability to attack mechanically and chemically at a precise location which is one avenue that can be used to destroy cancer cells precisely. This review summarises the extant understanding and the work done in this area to pave the way for physicians to accelerate the use of hybrid mode of treatments by leveraging the use of various nanoparticles., (© 2023. The Author(s).)

Fruit flies of Tephritidae family pose a serious threat to cultivation of fruits and vegetables across the world. Among them, melon fruit fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae) is a devastating pest of plants from Cucurbitaceae family. In a rising concern about the harmful effects associated with the use of chemical insecticides and development of resistance in pest insects, safer pest management strategies such as, use of biopesticides of microbial origin are being contemplated. Therefore, the present study aimed to evaluate the insecticidal potential of Streptomyces sp. SP5 protein extract against Z. cucurbitae. MTT assay, Ames mutagenicity, DNA nicking, and comet assay were conducted to determine the biosafety of protein extract. Second instar larvae of Z. cucurbitae were treated with various concentrations (1, 100, 200, 300, 400, and 500 μg/ml) of Streptomyces sp. SP5 protein extract. The protein extract showed significant larvicidal effects with LC 50 value of 308.92 μg/ml. The percentage of adults emerged declined with increase in concentration. There was significant prolongation in developmental durations of the larvae. Various morphological aberrations in the form of deformed adults and pupae and decline in pupal weight were also observed. The nutritional physiology of the treated larvae was also adversely affected. The results from biosafety evaluation revealed antimutagenic and non-toxic nature of Streptomyces sp. proteins. This study indicates that Streptomyces sp. SP5 has the potential to be used as an ecologically safe biocontrol agent against Z. cucurbitae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid-polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core-shell nanoparticles, hollow core-shell nanoparticles, biomimetic lipid-polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications. However, core-shell nanoparticles having a polymeric core surrounded by a highly biocompatible lipid shell are the most commonly explored LPHNPs for the treatment of various diseases. In this review, we will shed light on the composition, methods of preparation, classification, surface functionalization, release mechanism, advantages and disadvantages, patents, and clinical trials of LPHNPs, with an emphasis on core-shell-structured LPHNPs.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that bla CTX-M-15 , bla CMY-42 , bla NDM-5 , and aadA (2) were prevalent in Escherichia coli , and bla TEM-1B , bla OXA-232 , bla NDM-1 , rmtB , and rmtC were dominant in Klebsiella pneumoniae . In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored bla VEB , bla VIM-2 , aph( 3'), strA/B , bla OXA-23 , aph (3') variants, and amrA , respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae , A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

The rise of New Delhi metallo beta-lactamase (NDM) producing bacteria imposes a significant threat to the treatment of bacterial infections due to their broad spectrum against beta-lactams. The activity of metallo beta-lactamases is affected by active site residues as well as residues near the active site. Therefore, we aimed to identify the amino acid residues around the active site of NDM-4 which influence its function. To achieve that, seven substitution mutations (S191A, D192A, S213A, K216A, S217A, D223A and D225A) of NDM-4 were generated through site-directed mutagenesis. Out of these, expression of NDM-4&#95;D192A and NDM-4&#95;S217A in Escherichia coli cells increased the beta-lactam susceptibility as compared to NDM-4. Further, proteins were purified to assess the effect of substitution mutations on zinc content, in vitro catalytic efficiency, and stability of NDM-4. The catalytic efficiency was reduced for these mutants (D192A and S217A) towards beta-lactam substrates, while the thermal stability remained insubstantial as compared to NDM-4. However, the purified NDM-4&#95;D192A exhibited altered zinc content. In silico studies reveal that these changes might be the outcomes of alterations in hydrogen bonding networks and substrate interactions. Taken together, we infer that the D192 and the S217 residues play a substantial role in the activity of NDM-4., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dissemination of class D OXA-type carbapenemases is one of the significant causes of beta-lactam resistance in Gram-negative bacteria. The amino acid residues present near the active site are involved in hydrolytic mechanism of class D carbapenemases, though it is not identified in OXA-23. Here, with the help of site-directed mutagenesis, we aimed to explicate the importance of the residues W165, L166 and V167 of the possible omega loop and residue D222 in the short β5-β6 loop on the activity of OXA-23. All the residues were substituted with alanine. The resultant proteins were assayed for the changes in activity in E. coli cells and purified for in vitro activity, and stability assessment. E. coli cells harboring OXA-23&#95;W165A and OXA-23&#95;L166A, individually, exhibited a significant decrease in resistance towards beta-lactam antibiotics as compared to OXA-23. Further, purified OXA-23&#95;W165A and OXA-23&#95;L166A imparted about >4-fold decrease in catalytic efficiency and displayed reduced thermal stability as compared to OXA-23. Bocillin-FL binding assay revealed that W165A substitution results in improper N-carboxylation of K82, leading to deacylation deficient OXA-23. Therefore, we infer that the residue W165 maintains the integrity of N-carboxylated lysine (K82) of OXA-23 and the residue L166 might be responsible for properly orientating the antibiotic molecules., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

We report the development of a coating system relying on the incorporation of SiO 2 @ZnO core-shell nanospheres in polyurethane media as a novel approach to achieve longevity and sustainability in marine transport. This polymeric coating showed significant improvement in surface abrasion resistance, the transition from a hydrophilic state to a hydrophobic state (~ 125.2° ± 2°), improved antifungal, antibacterial and antialgae effects which make the proposed coating ideal to protect steel surfaces against biofouling. To substantiate our claims, we performed X-ray diffraction, Transmission electron microscopy, Fourier transform infrared spectroscopy, scanning acoustic microscopy, Thermogravimetric analysis (TGA), contact angle measurements, antimicrobial (antialgal, antibacterial, antifungal) tests and Taber abrasion tests (ASTM D1044 and D4060) to highlight the mechanical and biological functionality as well as the bonding configuration of this coating. The wear analysis of the Taber abraded coating using SEM and optical microscopy showed significant improvement in the adhesion and shear resistance achieved by the SiO 2 @ZnO core-shell nanospheres incorporated PU coating which was a contrasting feature compared to using PU alone. The overall investigations we performed led us to find out that the addition of 4% (wt.) SiO 2 @ZnO core-shell nanoparticles to the PU media deposited on the low carbon steel surface demonstrated remarkable antimicrobial performance with almost no bacterial growth, significant reductions in growth for algae to about 90% and fungus to about 95%., (© 2023. The Author(s).)

Background: Diabetic nephropathy is a progressive kidney disease that frequently results in end-stage renal disorders and is characterized by proteinuria, albuminuria, decreased filtration, and renal fibrosis. Despite the fact that there are a number of therapeutic alternatives available, DN continues to be the main contributor to end-stage renal disease. Therefore, significant innovation is required to enhance outcomes in DN patients., Methods: Information was collected from online search engines like, Google Scholar, Web of Science, PubMed, Scopus, and Sci-Hub databases using keywords like diabetes, nephropathy, kidney disease, autophagy, etc., Results: Natural compounds have anti-inflammatory and antioxidant properties and impact various signaling pathways. They ameliorate kidney damage by decreasing oxidative stress, inflammatory process, and fibrosis and enhance the antioxidant system, most likely by activating and deactivating several signaling pathways. This review focuses on the role of metabolic memory and various signaling pathways involved in the pathogenesis of DN and therapeutic approaches available for the management of DN. Special attention is given to the various pathways modulated by the phytoconstituents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the current study, Streptomyces levis strain HFM-2 has been isolated from healthy human gut. Streptomyces sp. HFM-2 was identified based on the polyphasic approach that included cultural, morphological, chemotaxonomical, phylogenetic, physiological, and biochemical characteristics. 16S rRNA gene sequence of strain HFM-2 exhibited 100% similarity with Streptomyces levis strain 15423 (T). The EtOAc extract of Streptomyces levis strain HFM-2 showed potential antioxidant activity, along with 69.53 ± 0.19%, 64.76 ± 0.13%, and 84.82 ± 0.21% of scavenging activity for ABTS, DPPH, and superoxide radicals, respectively at 600 µg/mL. The IC 50 values i.e. 50% scavenging activity for DPPH, ABTS, and superoxide radicals were achieved at 497.19, 388.13, and 268.79 (µg/mL), respectively. The extract's reducing power and total antioxidant capacity were determined to be 856.83 ± 0.76 and 860.06 ± 0.01 µg AAE/mg of dry extract, respectively. In addition, the EtOAc extract showed protection against DNA damage from oxidative stress caused by Fenton's reagent, and cytotoxic activity against HeLa cervical cancer, Skin (431) cancer, Ehrlich-Lettre Ascites-E (EAC) carcinoma, and L929 normal cell lines. The IC 50 values against HeLa, 431 skin, and EAC carcinoma cell lines were found to be 50.69, 84.07, and 164.91 µg/mL, respectively. The EtOAc extract showed no toxicity  towards L929 normal cells. In addition, flow cytometric analysis exhibited reduced mitochondrial membrane potential (MMP), and enhanced levels of reactive oxygen species (ROS). The EtOAc extract was chemically analyzed using GCMS to determine the components executing its bioactivities., (© 2023. The Author(s).)

Problem: The determinants of COVID-19 vaccine acceptance, hesitancy, and refusal remain poorly understood. We assessed the general population of Pune after visiting tertiary care hospital for their willingness to accept the vaccine and the reason for their hesitancy and refusal., Methodology: A six-month descriptive cross-sectional study with 386 community members over the age of 18 who visited the Tertiary Hospital OPD was conducted. The vaccine acceptance and hesitancy was assessed using a self designed detailed questionnaire with a one-time face-to-face interview., Results: Acceptance for vaccine was observed in 235 (60.8%) participants, while 151 (39.2%) hesitated and refused. Participants with lower education (P < 0.00001), no employment did not readily accept the vaccine (P < 0.00001). Pregnant, breast-feeding women (21.8%) hesitated vaccine because of lack of evidence regarding vaccine safety. Participants (73.6%) were readily accepting (third dose) booster dose of vaccine when available. The reason for vaccine hesitance was the concern about side effects (58.2%) and reason for acceptance was to get immunity against COVID-19 (76.1%). Vaccine information source appears to be an influential aspect, as participants who obtained vaccination information from healthcare providers had no concerns regarding vaccination., Conclusion: The study has found a link between average education level, unemployment and vaccine acceptance and hesitancy. Factors influencing vaccine hesitancy include lack of vaccine information, vaccine side effects, and misinformation spread via social media. Clinical pharmacists can play an important role in boosting up vaccine acceptance by providing appropriate information in community., Competing Interests: There is no Conflict Of Interest in this study., (© 2023 The Authors.)