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Background: Common Gram-positive bacteria Staphylococcus aureus can cause infections ranging from minor skin conditions to serious illnesses like sepsis.Methicillin-resistant S. aureus (MRSA) emerged in the 1960s and now causes over 50% of hospital infections. In India, MRSA prevalence ranges from 25% in the west to 50% in the south. Contributing factors include prolonged hospital stays and indiscriminate antibiotic use. This study investigates the prevalence and antibiotic resistance patterns of MRSA in clinical isolates from a hospital in Karad. MRSA's resistance to multiple antibiotics, including vancomycin, poses significant treatment challenges, with limited therapeutic options such as vancomycin, linezolid, daptomycin, and teicoplanin remaining effective. The antibiotics mentioned provide a broader context for understanding MRSA resistance. In this study, only those specifically relevant to the hospital's data have been included in detail in the result table antibiogram of MRSA., Material and Methods: A two-year laboratory-based analysis of MRSA strains in a hospital that provides tertiary care was conducted to assess their antibiotic susceptibility profiles., Results: In all, 100 isolates of MRSA were examined for patterns of antibiotic susceptibility in various clinical specimens. Among these 41 (41%) were from pus samples, 18 (18%) from wound swabs/discharge, 15 (15%) from urine, 13 (13%) from blood, 4% from sputum, and 3% from tips were found to have smaller percentages than umbilical swabs (2 (2%)) and tissue (1 (1%)) and vaginal swabs( 1 (1%)) and sinus tract samples (1 (1%)). The frequency of MRSA strains was more in males (59%). Linezolid showed the highest sensitivity at 86%., Conclusion: This study highlights the growing challenge of MRSA and other resistant bacteria in hospital settings, complicating treatment choices. Effective MRSA​​​​​​​ management requires stringent antibiotic policy, infection control procedures, and thorough susceptibility testing. These strategies are critical to preserving viable treatment options and combating antibiotic resistance in healthcare environments., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee of Krishna Institute of Medical Sciences (Deemed To Be University) issued approval 073/2021/2022. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patil et al.)

Caffeine, commonly found in coffee and tea, affects various aspects of eye health as it blocks adenosine receptors, impacting tear production, intraocular pressure, macular perfusion, and choroidal thickness. However, its connection with eye conditions like glaucoma and cataracts remains uncertain due to conflicting research findings. Some studies suggest potential benefits for cataracts, while others warn against frequent caffeine intake in glaucoma and surgical scenarios due to possible increases in intraocular pressure. Conflicting evidence also exists regarding its effects on dry eye, macular degeneration, myopia/hyperopia, diabetic retinopathy, retinopathy of prematurity, and central serous retinopathy. Caffeine does not seem to be a risk factor for dry eye, although studies have shown that caffeine may offer protection against wet age-related macular degeneration, and the metabolite 7-methylxanthine could be a more promising treatment for myopia. Moreover, caffeine can potentially cause tremors and might hinder surgical performance, especially in less experienced surgeons. Recommendations from experts vary, highlighting the need for further research to fully understand how caffeine affects the eye. Individuals genetically predisposed to glaucoma should be cautious due to the possibility of clinically significant elevations in intraocular pressure with caffeine consumption. For delicate procedures like microsurgery, where tremors can be detrimental, caution should be exercised with caffeine. This review underscores the importance of additional studies to provide clearer insights and prudent recommendations regarding caffeine's impact on eye health., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Unilateral virginal hypertrophy of the breast is a rare condition with an unknown etiology, though it is thought to result from hypersensitivity of the end organs to normal levels of gonadal hormones. We present the case of a 17-year-old girl who initially showed gradual growth after thelarche; however, in the last three to four months, there was a rapid increase in size, leading to psychological and physical problems that also impacted her social life. A clinical examination revealed that her left breast was markedly enlarged compared to the right, and she exhibited a drooping posture. Radiological investigations and a true-cut biopsy were performed to detect any underlying pathology, which revealed normocellular stroma consistent with virginal breast hypertrophy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kirdat Patil et al.)

Introduction: Abnormal uterine bleeding (AUB) affects a significant proportion of women, particularly around the ages of menarche and menopause. While ultrasonography is a primary diagnostic tool for AUB, techniques like the International Endometrial Tumor Analysis (IETA) scoring system have enhanced diagnostic accuracy for endometrial abnormalities. IETA provides a standardized approach to evaluating endometrial features, which aids in distinguishing benign from malignant lesions., Methods: This study applied the IETA scoring system to the ultrasound evaluation of 50 women presenting with AUB. The study assessed various endometrial characteristics, including thickness, echogenicity, midline appearance, junction regularity, and vascular patterns. Data were analyzed to correlate IETA scores with histopathological findings and to compare the ultrasound features of benign and malignant lesions., Results: The study found that non-uniform endometrial characteristics and irregular midline appearances were more common in malignant lesions. Specifically, interrupted or irregular endometrial-myometrial junctions, absence of the bright edge, higher color scores, and complex vascular patterns were significantly associated with malignancy. Mean endometrial thickness was notably higher in malignant cases compared to benign ones, with a statistically significant difference. The most frequent IETA scores were 7, 12, and 13., Conclusion: Integrating the IETA scoring system into ultrasound evaluation enhances the detection of endometrial abnormalities, improving the differentiation between benign and malignant lesions. This approach provides a reliable framework for diagnosing and managing AUB, potentially reducing the need for invasive procedures and facilitating better clinical decision-making., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research and Recognition Committee, Faculty of Medicine, Dr. D. Y. Patil Medical College, Hospital & Research Centre issued approval DPU/R&R(M)/1188/167/2022. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patil et al.)

Ewing's sarcoma family of tumors (ESFTs) are a group of small round cell tumors with common morphological and genetic features, including Ewing's sarcoma of bone, primary extra-skeletal Ewing tumors, extraosseous Ewing sarcoma (EES), and Askin tumors. EES presenting as a primary renal mass is an exceedingly uncommon aggressive tumor with limited reported cases in the literature and often mimics other renal malignancies on imaging. We present a case of a 31-year-old man presenting with left flank pain and abdominal fullness of short duration. Radiological imaging studies showed a large heterogenous mass from the left kidney, confirmed to be Ewing's sarcoma on post-operative histopathological examination (HPE) and immunohistochemistry (IHC) studies. Subsequent follow-up showed extensive metastatic disease. EES of the kidney has a nonspecific presentation and imaging appearance necessitating a multi-disciplinary approach comprising radiological imaging with a high index of suspicion, HPE, IHC, and molecular analysis for the correct diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Dr. D.Y. Patil Medical College Institutional Ethics Sub-committee issued approval IESC/W/54/2024. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rangankar et al.)

Introduction: Approximately 33 million people suffer catastrophic health expenditure (CHE) from surgery and/or anesthesia costs. The aim of this systematic review is to evaluate catastrophic and impoverishing expenditure associated with surgery and anesthesia in low- and middle-income countries (LMICs)., Methods: We performed a systematic review of all studies from 1990 to 2021 that reported CHE in LMICs for treatment of a condition requiring surgical intervention, including cesarean section, trauma care, and other surgery., Results: 77 studies met inclusion criteria. Tertiary facilities (23.4%) were the most frequently studied facility type. Only 11.7% of studies were conducted in exclusively rural health-care settings. Almost 60% of studies were retrospective in nature. The cost of procedures ranged widely, from $26 USD for a cesarean section in Mauritania in 2020 to $74,420 for a pancreaticoduodenectomy in India in 2018. GDP per capita had a narrower range from $315 USD in Malawi in 2019 to $9955 USD in Malaysia in 2015 (Median = $1605.50, interquartile range = $1208.74). 35 studies discussed interventions to reduce cost and catastrophic expenditure. Four of those studies stated that their intervention was not successful, 18 had an unknown or equivocal effect on cost and CHE, and 13 concluded that their intervention did help reduce cost and CHE., Conclusions: CHE from surgery is a worldwide problem that most acutely affects vulnerable patients in LMICs. Existing efforts are insufficient to meet the true need for affordable surgical care unless assistance for ancillary costs is given to patients and families most at risk from CHE., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Biodiesel production through the synthesis of Datura stramonium L. oil is studied to explore the most efficient approaches to suggest an alternate feedstock for biodiesel production. The main objective of this work is to optimize the process variables of biodiesel synthesis by using some statistical approach (Taguchi method, grey relational analysis (GRA), and response surface methodology (RSM) analyzing three parameters, i.e., alcohol-to-oil molar ratio, catalyst (NaOH) concentration, and process temperature for achieving maximum biodiesel derived from Datura stramonium L. oil. The transesterification process is applied by using an ultrasonic-assisted technique. Grey relational analysis (GRA) was successfully applied with the Taguchi method resulting in the optimum combination of A 2 B 1 C 1 . Based on the findings, the best operating conditions for transesterifying are attained with the RSM approach consisting of a 5.697:1 molar ratio (level 2), 0.3 (wt.%) NaOH concentration (level 1), and 70 °C process temperature (level 1). With a value of 87.02%, these ideal operating conditions produce the maximum yield as compared to grey relational analysis (GRA) yields 83.99%. The obtained results have been verified through the characterization of oil and biodiesel as well. Also, the fuel qualities of DSL biodiesel were identified and assessed. DSL oil was found 137.6 degrees of unsaturation during fatty acid profile analysis. DSL biodiesel was found the best kinematic viscosity (4.2 mm 2 /s) and acid value (0.49) when compared to Karanja and palm biodiesel. D. stramonium L. was recognized as a suitable species for biodiesel feedstock according to the findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The use of insufficiently treated wastewater or Faecal sludge in agriculture raises concerns because of the pathogen content. Helminth eggs (HE) are one of the most crucial pathogens for ensuring public health and safety. Widely used disinfection treatment methods do not guarantee the complete inactivation of helminth eggs. The current study evaluated the effectiveness of anaerobic digestion and electrochemical process on helminth ( Ascaris suum ) egg inactivation., Methods: Lab-scale biochemical methane potential (BMP) assay was conducted by spiking A. suum eggs in a serum bottle. Total solid (TS), volatile solid (VS), pH, biogas production and its composition, and volatile fatty acids (VFA) were analyzed along with A. suum inactivation every third day for the initial 15 days and fifth day for 45 days. In the second set of experiments, a hypochlorite (4700 ppm) solution was generated by electrolysis of aqueous NaCl solution in a membrane-less electrochemical cell. The hypochlorite was diluted (940, 470, 235, and 156ppm) in wastewater, spiked with A. suum eggs and then examined for inactivation at regular intervals., Results: The results of the anaerobic digestion treatment documented 98% inactivation of A. suum eggs (0.15 eggs/mL) in 35 days and remained at 0.14 eggs/mL until day 45. Correlation analysis revealed a positive relationship between non-viable eggs and pH and a negative relationship with all the other parameters. Electrochemical treatment achieved 10% inactivation at 940 ppm concentration in 24h., Conclusions: This study revealed that the inactivation of A. suum eggs by anaerobic digestion or electrochemical treatment is a combined effect of more than one parameter., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Patil PP and Mutnuri S.)

An insulated building-integrated photovoltaic (PV) roof prototype is designed, developed, and experimentally monitored for the composite climatic conditions in the current work. The prototype is monitored based on hourly indoor room temperature, relative humidity, discomfort index, decrement factor time lag, and power generation. To validate the results, a heat conduction equation was developed and simulated considering actual lower income group (LIG) building size and materials. Second-order polynomial equations were derived from simulation results to optimize insulation thickness. Additionally, the economic analysis of the insulated building-integrated Photovoltaic (BIPV) roof was analyzed and compared to the reinforced concrete cement (RCC) roof. The results reveal that insulated BIPV roofs outperform the RCC roof, reducing indoor temperatures by 3.34 ℃ to 1.37 ℃ within an optimum thickness range of 0.0838-0.1056 m. A time lag of 1 h and a significant reduction in decrement factor up to 0.29 are achieved. The average discomfort index of the proposed roof during sunshine hours was found to be between 23 and 26.5. The insulated BIPV roofs with levelized cost of electricity (LCOE) of the 3.38 Rs/kWh gave a payback period of 6.32 years and a higher internal rate of return of 29.4 compared to RCC roof. The current study increases the feasibility of PV modules to be used as building material., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study was conducted to investigate the immunological and clinical response to COVID-19 vaccination in rheumatoid arthritis (RA) patients receiving disease modifying antirheumatic drugs (DMARDs)., Methods: A cross-sectional study was conducted among RA patients who received two doses of COVID-19 vaccine within 6 months to one year. Demographic information, comorbidities, vaccination details, and past COVID-19 infection details were collected. Hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were estimated. Disease Activity Score-28 (DAS-28) was calculated for RA patients. Anti-spike antibody (ASA) concentrations were measured, and compared with a healthy control population. Correlations of ASA with age, sex, disease parameters, medication use, and comorbidities were assessed., Results: A total of 103 RA patients and 185 controls were included in the study. RA patients had higher mean age, lower mean Hb, higher ESR, and elevated IL-6 levels. Both groups showed positive results for anti-spike antibodies, with a higher percentage in controls. Among RA patients majority had low DAS-28 score. The number of DMARDs used showed a negative correlation with antibody levels. There was a slight positive correlation between ASA concentration and DAS-28 score. Comorbidities did not significantly influence antibody concentration. No significant differences were found in antibody levels based on the type of COVID-19 vaccine or previous COVID-19 infection or booster dose vaccination among RA patients., Conclusion: The study revealed that RA patients showed a reduced antibody response following COVID-19 vaccination compared to the control group and potentially influenced by immunosuppressive treatments and disease-related factors., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

Emergence of carbapenem-resistant A. baumannii (CRAB) is a global, ongoing healthcare concern. CRAB is among the topmost priority pathogens, with various studies focusing on its global population structure and resistant allelic profiles. However, carbapenem-susceptible A. baumannii (CSAB) isolates are often overlooked due to their sensitivity to beta-lactams, which can provide important insights into origin of CRAB lineages and isolates. In the present study, we report genomic investigation of CRAB and CSAB coexisting in Indian hospital setting. MLST based population structure and phylogenomics suggest they mainly follow distinct evolutionary routes forming two phylogroups. PG-I exclusively for a successful clone (ST2) of CRAB and PG-II comprises diversified CSAB isolates except PG3373, which is CRAB. Additionally, there are few CRAB isolates not belonging to PG-I and sharing clonal relationship with CSAB isolates indicating role of genome plasticity towards extensive drug resistance in the nosocomial environment. Further, genealogical analysis depicts prominent role of recombination in emergence and evolution of a major CRAB lineage. Further, CRAB isolates are enriched in resistomes as compared to CSAB isolates, which were encoded on the genomic island. Such comparative genomic insights will aid in our understanding and localized management of rapidly evolving pandrug resistant nosocomial pathogens., Competing Interests: Declaration of Competing Interest 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Haematococcus lacustris is an important species of green algae because it produces the high-value carotenoid astaxanthin. Astaxanthin production is enhanced by various stress conditions causing the transformation of green vegetative cells to red cells with high amounts of astaxanthin, which plays various photoprotective and antioxidant roles. Although intensive research has been conducted to reveal the regulation of astaxanthin production, the photosynthetic capacity of the various cell forms is unresolved at the single-cell level. In this work, we characterized the photosynthetic and morphological changes of Haematococcus cells, using a combination of microfluidic tools and microscopic chlorophyll fluorescence imaging. We found marked but reversible changes in the variable chlorophyll fluorescence signatures upon the transformation of green cells to red cells, and we propose that the photosynthetic activity as revealed by single-cell chlorophyll fluorescence kinetics serves as a useful phenotypic marker of the different cell forms of Haematococcus ., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2023 Patil et al.)

ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and β-cell function. Recently, biallelic variants in ONECUT1 were reported as a cause of neonatal diabetes mellitus (NDM) in two subjects, and missense monoallelic variants were associated with type 2 diabetes and possibly maturity-onset diabetes of the young (MODY). Here we examine the role of ONECUT1 variants in NDM, MODY, and type 2 diabetes in large international cohorts of subjects with monogenic diabetes and >400,000 subjects from UK Biobank. We identified a biallelic frameshift ONECUT1 variant as the cause of NDM in one individual. However, we found no enrichment of missense or null ONECUT1 variants among 484 individuals clinically suspected of MODY, in whom all known genes had been excluded. Finally, using a rare variant burden test in the UK Biobank European cohort, we identified a significant association between heterozygous ONECUT1 null variants and type 2 diabetes (P = 0.006) but did not find an association between missense variants and type 2 diabetes. Our results confirm biallelic ONECUT1 variants as a cause of NDM and highlight monoallelic null variants as a risk factor for type 2 diabetes. These findings confirm the critical role of ONECUT1 in human β-cell function., (© 2023 by the American Diabetes Association.)

In recent years, many metal oxides have been rigorously studied to be employed as solid electrolytes for resistive switching (RS) devices. Among these solid electrolytes, lanthanum oxide (La 2 O 3 ) is comparatively less explored for RS applications. Given this, the present work focuses on the electrodeposition of La 2 O 3 switching layers and the investigation of their RS properties for memory and neuromorphic computing applications. Initially, the electrodeposited La 2 O 3 switching layers are thoroughly characterized by various analytical techniques. The electrochemical impedance spectroscopy (EIS) and Mott-Schottky techniques are probed to understand the in situ electrodeposition, RS mechanism, and n-type semiconducting nature of the fabricated La 2 O 3 switching layers. All the fabricated devices exhibit bipolar RS characteristics with excellent endurance and stable retention. Moreover, the device mimics the various bio-synaptic properties such as potentiation-depression, excitatory post-synaptic currents, and paired-pulse facilitation. It is demonstrated that the fabricated devices are non-ideal memristors based on double-valued charge-flux characteristics. The switching variation of the device is studied using the Weibull distribution technique and modeled and predicted by the time series analysis technique. Based on electrical and EIS results, a possible filamentary-based RS mechanism is suggested. The present results assert that La 2 O 3 is a promising solid electrolyte for memory and brain-inspired applications., (© 2023 Wiley-VCH GmbH.)

Purpose: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children., Methods: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing., Results: A total of 55 patients aged 3-18 with 79 examinations were included. No patient was excluded from the retrospective case review because of lack of recorded data. The main indications for oral FA included uveitis, retinal vasculopathy, disk pathology, and retinal lesions. Three children had transient side effects, and 1 had delayed urticaria 4 hours after examination. No child had anaphylaxis. One patient had suboptimal imaging due to nonadherence to the guidelines-recommended fasting protocol. All other examinations (78/79), where guidelines were followed, provided images adequate for clinical decision making., Conclusions: Based on our experience, we recommend that oral FA be considered, especially in children where intravenous access is less well tolerated while awake. Informed consent that includes the possibility of delayed side effects is advisable., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Resistive-switching-based memory devices meet most of the requirements for use in next-generation information and communication technology applications, including standalone memory devices, neuromorphic hardware, and embedded sensing devices with on-chip storage, due to their low cost, excellent memory retention, compatibility with 3D integration, in-memory computing capabilities, and ease of fabrication. Electrochemical synthesis is the most widespread technique for the fabrication of state-of-the-art memory devices. The present review article summarizes the electrochemical approaches that have been proposed for the fabrication of switching, memristor, and memristive devices for memory storage, neuromorphic computing, and sensing applications, highlighting their various advantages and performance metrics. We also present the challenges and future research directions for this field in the concluding section.

Background and objective : Doxorubicin is extensively utilized chemotherapeutic drug, and it causes damage to the heart, liver, and kidneys through oxidative stress. Theobroma cacao L (cocoa) is reported to possess protective effects against several chemical-induced organ damages and also acts as an anticancer agent. The study aimed to determine whether the administration of cocoa bean extract reduces doxorubicin-induced organ damage in mice with Ehrlich ascites carcinoma (EAC) without compromising doxorubicin efficacy. Methodology : Multiple in vitro methods such as cell proliferation, colony formation, chemo-sensitivity, and scratch assay were carried out on cancer as well as normal cell lines to document the effect of cocoa extract (COE) on cellular physiology, followed by in vivo mouse survival analysis, and the organ-protective effect of COE on DOX-treated animals with EAC-induced solid tumors was then investigated. In silico studies were conducted on cocoa compounds with lipoxygenase and xanthine oxidase to provide possible molecular explanations for the experimental observations. Results: In vitro studies revealed potent selective cytotoxicity of COE on cancer cells compared to normal. Interestingly, COE enhanced DOX potency when used in combination. The in vivo results revealed reduction in EAC and DOX-induced toxicities in mice treated with COE, which also improved the mouse survival time; percentage of lifespan; antioxidant defense system; renal, hepatic, and cardiac function biomarkers; and also oxidative stress markers. COE reduced DOX-induced histopathological alterations. Through molecular docking and MD simulations, we observed chlorogenic acid and 8'8 methylenebiscatechin, present in cocoa, to have the highest binding affinity with lipoxygenase and xanthine oxidase, which lends support to their potential in ameliorating oxidative stress. Conclusion: The COE reduced DOX-induced organ damage in the EAC-induced tumor model and exhibited powerful anticancer and antioxidant effects. Therefore, COE might be useful as an adjuvant nutritional supplement in cancer therapy., 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 © 2023 Patil, Kumar, Khanal, Patil, Darasaguppe, Bhandare, Bhatkande, Shukla, Joshi, Patil and Roy.)

Introduction Cardiac autonomic neuropathy (CAN) is a frequent and life-threatening complication of type 2 diabetes. Failure to diagnose can lead to high mortality and morbidity. In patients who have diabetes mellitus, microalbuminuria is an independent marker for cardiovascular disease. This study aimed to assess the corrected QT interval with microalbuminuria in type 2 diabetes mellitus. The objective of this study was to estimate the corrected QT interval in subjects with type 2 diabetes mellitus and to determine the association of the corrected QT interval with microalbuminuria type 2 diabetes mellitus. Methodology Ninety-five adult patients (>18 years to 65 years) diagnosed with type 2 diabetes mellitus with microalbuminuria were included in this study. Data were collected on the proforma through history taking and a general physical and systemic examination. An electrocardiograph was taken on the day of admission; the most prolonged QT interval was measured, and the RR interval was calculated. The data were statistically analyzed using IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York, United States). Results There was a significant difference in the corrected QT interval prolongation prevalence between diabetic patients with microalbuminuria and without microalbuminuria (P-value <0.001). The mean corrected QT interval distribution did not differ significantly across various age groups of cases studied with microalbuminuria (P-value 0.98). The distribution of mean corrected QT interval did not differ significantly between the group of male cases and group of female cases studied with microalbuminuria (P-value 0.66). The mean corrected QT interval distribution did not differ significantly across various duration of diabetes groups among the cases studied with microalbuminuria (P-value 0.60). The mean corrected QT interval distribution did not differ significantly across different types of anti-diabetic treatment groups among the cases studied with microalbuminuria (P-value 0.64). Conclusion Type 2 diabetes has been prevalent in Indian and Asian populations. The early management of type 2 diabetes is necessary since the early stages of the disease can reduce the risk of CAN. Therefore, these patients should be diagnosed as early as possible and treated to reduce associated mortality and risk and to improve quality of care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sawarthia et al.)

Metallic nanoparticles (NPs) manufactured by ecofriendly strategies have also received much interest because of their elastic scattering properties and performance in nanomaterials. Aluminium oxide nanomaterials stand out among nanomaterials due to their tremendous uses in ceramic products, fabrics, therapeutic agents, catalyst supports, sewage sludge, and biosensors. The current paper investigates the effect of the nanoparticle composition and layer sequential on the mechanical characteristics of jute (J)-hemp (H) incorporated with an aluminium oxide polymer composite. NaOH is used to change the physical aspects of both plant fibres. A total of 20 specimens were tested with varying stacking sequences and padding weight ratios. Mechanical properties like a nanocomposite's tension, bending, and ILSS was measured. Stacked series and flowability substantially impact the nanocomposite. The Group 3 nanocomposite with 2% Al 2 O 3 has the highest tensile strength, 54.28% of the Group 1 and 2 combinations. The stack series significantly influences the material properties of nanomaterials. Because of the alternating layers of natural fabrics, Group 4 specimens have the maximum flexural strength. Group 3 composite materials have the highest ILSS because they have hemp on the outermost surface. It has been discovered that Group 4 material with a 2% Al 2 O 3 concentration is possibly the most substantial material. The existence of Al 2 O 3 nanoparticles in the green synthesis was confirmed by XRD analysis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 L. Natrayan et al.)

One of the more enticing, ecologically responsible, as well as safe and sustainable methodologies is eco-friendly nanomaterial synthesis. Vegetation materials will be used as reductants instead of toxic substances for synthesising nanoparticles. The current study used Ruellia tuberosa (RT) leaf extract digest to synthesise FeO nanomaterials, which were then characterised using XRD. Following that, microbially produced FeO molecules were mixed with a Kevlar-based polymeric matrix to study the blended consequences. To examine the interbreeding, the current experimental analyses were performed, including both static and dynamic mechanical characteristics. The addition of FeO nanofillers improved the elastic modulus, tensile strength, and storage modulus of the nanocomposite. Impact force uptake has been raised to a certain extent by the addition of nanoparticles. The findings of this research show that incorporating FeO nanofillers into Kevlar fabrics is a promising technique for increasing the mechanical characteristics of hybrid laminated composites. As per DMA evaluation, the sample without nanomaterials had a more volcanic lava response, which is a useful thing for body systems for missile use. Another critical aspect of a nanoparticles-filled nanocomposite that must be addressed is the relatively uniform scattering of padding as well as the development of interfacial adhesion in such a combination. The presence of FeO fillers in polymeric composites is confirmed by XRD analysis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 L. Natrayan et al.)

Introduction: Burkholderia cepacia complex (Bcc) clonal complex (CC) 31, the predominant lineage causing devastating outbreaks globally, has been a growing concern of infections in non-cystic fibrosis (NCF) patients in India. B. cenocepacia is very challenging to treat owing to its virulence determinants and antibiotic resistance. Improving the management of these infections requires a better knowledge of their resistance patterns and mechanisms., Methods: Whole-genome sequences of 35 CC31 isolates obtained from patient samples, were analyzed against available 210 CC31 genomes in the NCBI database to glean details of resistance, virulence, mobile elements, and phylogenetic markers to study genomic diversity and evolution of CC31 lineage in India., Results: Genomic analysis revealed that 35 isolates belonging to CC31 were categorized into 11 sequence types (ST), of which five STs were reported exclusively from India. Phylogenetic analysis classified 245 CC31 isolates into eight distinct clades (I-VIII) and unveiled that NCF isolates are evolving independently from the global cystic fibrosis (CF) isolates forming a distinct clade. The detection rate of seven classes of antibiotic-related genes in 35 isolates was 35 (100%) for tetracyclines, aminoglycosides, and fluoroquinolones; 26 (74.2%) for sulphonamides and phenicols; 7 (20%) for beta-lactamases; and 1 (2.8%) for trimethoprim resistance genes. Additionally, 3 (8.5%) NCF isolates were resistant to disinfecting agents and antiseptics. Antimicrobial susceptibility testing revealed that majority of NCF isolates were resistant to chloramphenicol (77%) and levofloxacin (34%). NCF isolates have a comparable number of virulence genes to CF isolates. A well-studied pathogenicity island of B . cenocepacia , GI11 is present in ST628 and ST709 isolates from the Indian Bcc population. In contrast, genomic island GI15 (highly similar to the island found in B . pseudomallei strain EY1) is exclusively reported in ST839 and ST824 isolates from two different locations in India. Horizontal acquisition of lytic phage ST79 of pathogenic B . pseudomallei is demonstrated in ST628 isolates Bcc1463, Bcc29163, and BccR4654 amongst CC31 lineage., Discussion: The study reveals a high diversity of CC31 lineages among B. cenocepacia isolates from India. The extensive information from this study will facilitate the development of rapid diagnostic and novel therapeutic approaches to manage B . cenocepacia infections., 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 © 2023 Saroha, Patil, Rana, Kumar, Kumar, Singhal, Gautam and Patil.)

Introduction: Careya arborea , Punica granatum , and Psidium guajava are traditionally used to treat diarrheal diseases in India and were reported to show anti-Cholera toxin activity from our earlier studies. As polyphenols are reported to neutralize Cholera toxin (CT), the present study investigated the inhibitory activity of selected polyphenols from these plants against CTB binding to GM1 receptor using in silico , in vitro , and in vivo approaches., Methods: Molecular modelling approach was used to investigate the intermolecular interactions of selected 20 polyphenolic compounds from three plants with CT using DOCK6. Based on intermolecular interactions, two phenolic acids, Ellagic acid (EA) and Chlorogenic acid (CHL); two flavonoids, Rutin (RTN) and Phloridzin (PHD) were selected along with their respective standards, Gallic acid (GA) and Quercetrin (QRTN). The stability of docked complexes was corroborated using molecular dynamics simulation. Furthermore, in vitro inhibitory activity of six compounds against CT was assessed using GM1 ELISA and cAMP assay. EA and CHL that showed prominent activity against CT in in vitro assays were investigated for their neutralizing activity against CT-induced fluid accumulation and histopathological changes in adult mouse., Results and Discussion: The molecular modelling study revealed significant structural stability of the CT-EA, CT-CHL, and CT-PHD complexes compared to their respective controls. All the selected six compounds significantly reduced CT-induced cAMP levels, whereas EA, CHL, and PHD exhibited > 50% binding inhibition of CT to GM1. The EA and CHL that showed prominent neutralization activity against CT from in vitro studies, also significantly decreased CT-induced fluid accumulation and histopathological changes in adult mouse. Our study identified bioactive compounds from these three plants against CT-induced diarrhea., 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 © 2023 Charla, Patil, Patil, Bhandare, Karoshi, Balaganur, Joshi, Harish and Roy.)

Effective building energy management systems need a reliable approach to estimating future energy needs using renewable energy sources. However, nonlinear and nonstationary trends in building energy use data make prediction more challenging for integrating the photovoltaic system. To estimate future energy forecast, this work presents a hybrid approach based on random forest (RF) and long short-term memory (LSTM) using complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN). Initial steps in our suggested procedure include utilizing CEEMDAN to translate the raw energy usage data into multiple components. Then, the component with the most significant frequency is predicted using RF, and the other components are forecasted using hybrid LSTM. Finally, all of the individual parts' predictions are combined to form a whole. Real-world output energy usage data has been predicted to test the suggested strategy. Results from the experiments show that the suggested strategy outperforms the reference methods., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Small towns are becoming hotspots of pollution due to industrial, urbanisation, and domestic activities. Air pollution affects human health and it is also responsible for physiological changes in plants. Green belt development programmes are cost-effective for the minimisation of air pollution. In the present study, to calculate air pollution tolerance index (APTI) and anticipated performance index (API), samples of 25 plant species were collected from each area i.e. the industrial (I), urban (U), and rural (R) areas and analysed for different parameters. Amongst all three areas, APTI of Artocarpus heterophyllus (46.74), Calotropis gigantea (43.63), and Bauhinia racemose (42.11) have shown the highest values and these plants can act as an inhibitor of air pollution. Also, the APTI of Ocimum tenuiflorum has found to be the lowest (12.05, 11.32, 12.86) as compared to other plant species amongst the three areas. Statistical analysis reveals that values of R 2 are consistent in case of total chlorophyll (TC) and ascorbic acid (AA). API index showed the efficiency of Calotropis gigantea (excellent), Artocarpus heterophyllus (very good), and Mangifera indica (very good) for the green belt development around the selected areas. It is recommended to plant above-mentioned plant species along the roadside by considering their air pollution tolerance ability and medicinal as well as economic importance. Furthermore, it is suggested to plant species of Artocarpus heterophyllus (jackfruit) and Mangifera indica (Alphonso mango) which will generate income source for the local government bodies (Ratnagiri Municipal Council), as the fruits and wood of these plants can be exported and sold., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aim: The purpose of this study was to establish a mode of action for diosgenin against breast cancer employing a range of system biology tools and to corroborate its results with experimental facts. Methodology: The diosgenin-regulated domains implicated in breast cancer were enriched in the Kyoto Encyclopedia of Genes and Genomes database to establish diosgenin-protein(s)-pathway(s) associations. Later, molecular docking and the lead complexes were considered for molecular dynamics simulations, MMPBSA, principal component, and dynamics cross-correlation matrix analysis using GROMACS v2021. Furthermore, survival analysis was carried out for the diosgenin-regulated proteins that were anticipated to be involved in breast cancer. For gene expression analyses, the top three targets with the highest binding affinity for diosgenin and tumor expression were examined. Furthermore, the effect of diosgenin on cell proliferation, cytotoxicity, and the partial Warburg effect was tested to validate the computational findings using functional outputs of the lead targets. Results: The protein-protein interaction had 57 edges, an average node degree of 5.43, and a p -value of 3.83e-14. Furthermore, enrichment analysis showed 36 KEGG pathways, 12 cellular components, 27 molecular functions, and 307 biological processes. In network analysis, three hub proteins were notably modulated: IGF1R , MDM2 , and SRC , diosgenin with the highest binding affinity with IGF1R (binding energy -8.6 kcal/mol). Furthermore, during the 150 ns molecular dynamics (MD) projection run, diosgenin exhibited robust intermolecular interactions and had the least free binding energy with IGF1R (-35.143 kcal/mol) compared to MDM2 (-34.619 kcal/mol), and SRC (-17.944 kcal/mol). Diosgenin exhibited the highest cytotoxicity against MCF7 cell lines (IC 50 12.05 ± 1.33) µg/ml. Furthermore, in H 2 O 2 -induced oxidative stress, the inhibitory constant (IC 50 7.68 ± 0.51) µg/ml of diosgenin was lowest in MCF7 cell lines. However, the reversal of the Warburg effect by diosgenin seemed to be maximum in non-cancer Vero cell lines (EC 50 15.27 ± 0.95) µg/ml compared to the rest. Furthermore, diosgenin inhibited cell proliferation in SKBR3 cell lines more though. Conclusion: The current study demonstrated that diosgenin impacts a series of signaling pathways, involved in the advancement of breast cancer, including FoxO, PI3K-Akt, p53, Ras, and MAPK signaling. Additionally, diosgenin established a persistent diosgenin-protein complex and had a significant binding affinity towards IGF1R , MDM2 , and SRC . It is possible that this slowed down cell growth, countered the Warburg phenomenon, and showed the cytotoxicity towards breast cancer cells., 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 © 2023 Khanal, Patil, Bhandare, Patil, Patil, Dwivedi, Bhattacharya, Harish and Roy.)

Phosphogypsum (CaSO 4 ) is produced as a waste by-product during phosphoric acid production in the fertilizer industry. Only 15% of worldwide phosphogypsum production is recycled, while 85% is stored in the vicinity of factories as huge piles resulting in environmental and health hazards. An extensively studied biotransformation of phosphogypsum to calcium carbonate or calcite (CaCO 3 ) using sulfate reducing bacteria (SRBs) is a prolonged process and results in the formation of extremely hazardous H 2 S gas. Here we report for the first time a novel approach for biotransformation of phosphogypsum to CaCO 3 using urease producing Lysinibacillus sphaericus strain GUMP2. The strain could effectively transform phosphogypsum to crystalline, bead-shaped CaCO 3 precipitates. In a batch reactor with the PG loading rate of 60 g/L, 100% biotransformation was observed within seven days. After calcite recovery, the ammonium sulfate formed in the supernatant was recovered by precipitation. Urease-producing L. sphaericus strain GUMP2 could be used to remove the hazardous phosphogypsum from the environment by converting it to the industrially useful CaCO 3 and ammonium sulfate, a valuable agricultural fertilizer. This novel and sustainable approach could be a promising solution for the hazardous phosphogypsum in the phosphoric acid industries.

Hypermutation due to DNA mismatch repair (MMR) deficiencies can accelerate the development of antibiotic resistance in Pseudomonas aeruginosa. Whether hypermutators generate resistance through predominantly similar molecular mechanisms to wild-type (WT) strains is not fully understood. Here, we show that MMR-deficient P. aeruginosa can evolve resistance to important broad-spectrum cephalosporin/beta-lactamase inhibitor combination antibiotics through novel mechanisms not commonly observed in WT lineages. Using whole-genome sequencing (WGS) and transcriptional profiling of isolates that underwent in vitro adaptation to ceftazidime/avibactam (CZA), we characterized the detailed sequence of mutational and transcriptional changes underlying the development of resistance. Surprisingly, MMR-deficient lineages rapidly developed high-level resistance (>256 μg/mL) largely without corresponding fixed mutations or transcriptional changes in well-established resistance genes. Further investigation revealed that these isolates had paradoxically generated an early inactivating mutation in the mexB gene of the MexAB-OprM efflux pump, a primary mediator of CZA resistance in P. aeruginosa, potentially driving an evolutionary search for alternative resistance mechanisms. In addition to alterations in a number of genes not known to be associated with resistance, 2 mutations were observed in the operon encoding the RND efflux pump MexVW. These mutations resulted in a 4- to 6-fold increase in resistance to ceftazidime, CZA, cefepime, and ceftolozane-tazobactam when engineered into a WT strain, demonstrating a potentially important and previously unappreciated mechanism of resistance to these antibiotics in P. aeruginosa. Our results suggest that MMR-deficient isolates may rapidly evolve novel resistance mechanisms, sometimes with complex dynamics that reflect gene inactivation that occurs with hypermutation. The apparent ease with which hypermutators may switch to alternative resistance mechanisms for which antibiotics have not been developed may carry important clinical implications., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RAB reports grants from Entasis, Merck, Wockhardt, Shionogi, and Venatorx. None of these entities were involved in any part of this study in any way. The other authors declare no conflicts of interest., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The current work focuses on peanut shells and agricultural wastes richly in many nations subjected to pyrolysis treatment at various temperatures in the range of 500-800°C to determine the feasible physiochemical characteristics of the biochar. The biochars with the high surface area were employed to adsorb Pb 2+ (lead) ions, the heaviest pollutants in the water bodies. The raw material, biochar, and pyrolyzed biochar were characterized by SEM, FTIR, partial and elemental analysis, and BET tests. The adsorption characteristics of the biochar, pre- and postpyrolysis treatment, were studied with the assistance of batch adsorption tests under varying test conditions. Adsorbing conditions were determined by evaluating the effects of adsorbing parameters like initial concentration of the lead in water, pH of the adsorbent, contact time, and mixing speed on the effective adsorption of Pb 2+ ions from water. Langmuir, Freundlich, and Themkin isotherm expressions were employed to study the experimental results. The adsorption kinetics study showed that the synthesized biochars were chemically stable enough to adsorb the Pb ions onto the surface., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 L. Natrayan et al.)

Careya arborea, Punica granatum, Psidium guajava, Holarrhena antidysenterica, Aegle marmelos, and Piper longum are commonly used traditional medicines against diarrhoeal diseases in India. This study investigated the inhibitory activity of these plants against cytotoxicity and enterotoxicity induced by toxins secreted by Vibrio cholerae. Cholera toxin (CT) and non-membrane damaging cytotoxin (NMDCY) in cell free culture filtrate (CFCF) of V. cholerae were quantified using GM1 ELISA and cell-based assays, respectively. Hydro-alcoholic extracts of these plants and lyophilized juice of P. granatum were tested against CT-induced elevation of cAMP levels in CHO cell line, binding of CT to ganglioside GM1 receptor and NMDCY-induced cytotoxicity. Significant reduction of cAMP levels in CFCF treated CHO cell line was observed for all extracts except P. longum. C. arborea, P. granatum, H. antidysenterica and A. marmelos showed >50% binding inhibition of CT to GM1 receptor. C. arborea, P. granatum, and P. guajava effectively decreased cytotoxicity and morphological alterations caused by NMDCY in CHO cell line. Further, the efficacy of these three plants against CFCF-induced enterotoxicity was seen in adult mice ligated-ileal loop model as evidenced by decrease in volume of fluid accumulation, cAMP levels in ligated-ileal tissues, and histopathological changes in intestinal mucosa. Therefore, these plants can be further validated for their clinical use against cholera.

Industrial wastes contain more toxins that get dissolved in the rivers and lakes, which are means of freshwater reservoirs. The contamination of freshwater leads to various issues for microorganisms and humans. This paper proposes a novel method to remove excess copper from the water. The nanotubes are used as a powder in membrane form to remove the copper from the water. The multiwalled carbon nanotube is widely used as a membrane for filtration. It contains many graphene layers of nm size that easily adsorbs the copper when the water permeates through it. Activated carbon is the earliest and most economical method that also adsorbs copper to a certain extent. This paper proposes the methods of involving the activated carbon in the multiwalled carbon nanotube to improve the adsorption capability of the copper. Here, activated carbon is impregnated on the multiwalled carbon nanotube's defect and imperfect surface areas. It makes more adsorption sites on the surface, increasing the adsorption amount. The same method is applied to Hydroxyl functionalized multiwalled carbon nanotubes. Both the methods showed better results and increased the copper removal. The functionalized method removed 93.82% copper, whereas the nonfunctionalized method removed 80.62% copper from the water., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 L. Natrayan et al.)

The main focus of this research is to enhance the use of eco-friendly materials these days. The current materials used in building construction are chemical-based and are harmful to humans and the environment. This research work has developed a new type of hybrid brick by using natural fibres and waste materials. This research focuses on fabricating novel bricks reinforced with different percentages of coconut waste fibre, wheat straw fibre, waste wood animal dung ash, gypsum, sand, and cement. The fabricated novel brick's physical, mechanical, chemical, acoustic, and heat-absorbing properties were evaluated., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Naresh Kumar et al.)

Natural fibre reinforcement is used in important sectors such as medical, aerospace, automobile, and many other fields. Many articles have reported that natural fibre has the potential to replace synthetic fibres. Natural fibre reinforcement has given good results as a brake friction material. It has already been proven that asbestos causes lung cancer and mesothelioma in brakes. Many people died from the effects of asbestos. According to the World Health Organization's trending brake report, this material leads to serious health issues. This work is going on for the replacement of these materials. Mulberry fibre is a unique material, and PAN fibre is combined with mulberry fibre and used as a brake reinforcement material to replace Kevlar fibre. The brake pads were fabricated with the various wt% of mulberry fibres and PAN fibre [3-12%] with an equal ratio and aramid fibre [3-6%] in the hydraulic hind brake moulding machine. The mechanical, chemical, physical, tribological, and thermal properties were evaluated. MF-2 [6 wt%] mulberry-PAN-fibre-based brake pad composites have shown better results for ultimate shear strength and proof stress, tensile strength, compressive strength, and impact energy., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Naresh Kumar et al.)

Background and Objective: Doxorubicin is a widely used chemotherapeutic agent that causes oxidative stress leading to cardiotoxicity, hepatotoxicity, and nephrotoxicity. In contrast, Theobroma cacao L. has been recorded as an anticancer agent and found to be protective against multiple chemical-induced organ injuries, including heart, liver, and kidney injuries. The present study investigated the possible role of extracts from T. cacao beans for organ-protective effects in doxorubicin-induced toxicity in mice bearing Ehrlich ascites carcinoma (EAC)., Methodology: After survival analysis in rodents, cocoa bean extract (COE) was investigated for its efficacy against EAC-induced carcinoma and its organ-protective effect against doxorubicin-treated mice with EAC-induced carcinoma., Results: Significant reductions in EAC and doxorubicin-induced alterations were observed in mice administered the COE, either alone or in combination with doxorubicin. Furthermore, COE treatment significantly increased the mouse survival time, life span percentage, and antioxidant defense system. It also significantly improved cardiac, hepatic, and renal function biomarkers and markers for oxidative stress, and it also reduced doxorubicin-induced histopathological changes., Conclusion: COE acted against doxorubicin-induced organ toxicity; potent antioxidant and anticancer activities were also reflected by the COE itself. The COE may therefore serve as an adjuvant nutraceutical in cancer chemotherapy.

Activation of inhibitor of nuclear factor NF-κB kinase subunit-β (IKKβ), characterized by phosphorylation of activation loop serine residues 177 and 181, has been implicated in the early onset of cancer. On the other hand, tissue-specific IKKβ knockout in Kras mutation-driven mouse models stalled the disease in the precancerous stage. In this study, we used cell line models, tumor growth studies, and patient samples to assess the role of IKKβ and its activation in cancer. We also conducted a hit-to-lead optimization study that led to the identification of 39-100 as a selective mitogen-activated protein kinase kinase kinase (MAP3K) 1 inhibitor. We show that IKKβ is not required for growth of Kras mutant pancreatic cancer (PC) cells but is critical for PC tumor growth in mice. We also observed elevated basal levels of activated IKKβ in PC cell lines, PC patient-derived tumors, and liver metastases, implicating it in disease onset and progression. Optimization of an ATP noncompetitive IKKβ inhibitor resulted in the identification of 39-100, an orally bioavailable inhibitor with improved potency and pharmacokinetic properties. The compound 39-100 did not inhibit IKKβ but inhibited the IKKβ kinase MAP3K1 with low-micromolar potency. MAP3K1-mediated IKKβ phosphorylation was inhibited by 39-100, thus we termed it IKKβ activation modulator (IKAM) 1. In PC models, IKAM-1 reduced activated IKKβ levels, inhibited tumor growth, and reduced metastasis. Our findings suggests that MAP3K1-mediated IKKβ activation contributes to KRAS mutation-associated PC growth and IKAM-1 is a viable pretherapeutic lead that targets this pathway.

A medical postgraduate course in the field of Laboratory Medicine for the Bachelor of Medicine and Bachelor of Surgery (MBBS) degree holders has existed for more than two decades in India, initiated and offered by the All India Institute of Medical Sciences, New Delhi, which was created under the special Act of Parliament of India 1956. This course has recently been included in the draft of National Medical Commission's Post Graduate Regulation 2021 list of medical courses, and the foundation guidelines have been laid for other medical colleges and teaching hospitals across the country to start this course. This article, written purely in academic interest, describes the past, present and future of this postgraduate training program in India with an aim to answer several doubts regarding this unique and holistic course with a view to providing a direction to those who are willing to become a laboratory physician through this post-graduation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Flash-induced chlorophyll fluorescence relaxation is a powerful tool to monitor the reoxidation reactions of the reduced primary quinone acceptor, Q A - by Q B and the plastoquinone (PQ) pool, as well as the charge recombination reactions between the donor and acceptor side components of Photosystem II (PSII). Under certain conditions, when the PQ pool is highly reduced (e.g. in microaerobic conditions), a wave phenomenon appears in the fluorescence relaxation kinetics, which reflects the transient reoxidation and re-reduction of Q A - by various electron transfer processes, which in cyanobacteria is mediated by NAD(P)H dehydrogenase (NDH-1). The wave phenomenon was also observed and assigned to the operation of type 2 NAD(P)H dehydrogenase (NDH-2) in the green alga Chlamydomonas reinhardtii under hydrogen-producing conditions, which required a long incubation of algae under sulphur deprivation (Krishna et al. J Exp Bot 70 (21):6321-6336, 2019). However, the conditions that induce the wave remained largely uncharacterized so far in microalgae. In this work, we investigated the wave phenomenon in Chlamydomonas reinhardtii under conditions that lead to a decrease of PSII activity by applying hydroxylamine treatment, which impacts the donor side of PSII in combination with a strongly reducing environment of the PQ pool (microaerobic conditions). A similar wave phenomenon could be induced by photoinhibitory conditions (illumination with strong light in the presence of the protein synthesis inhibitor lincomycin). These results indicate that the fluorescence wave phenomenon is activated in green algae when the PSII activity decreases relative to Photosystem I (PS I) activity and the PQ pool is strongly reduced. Therefore, the fluorescence wave could be used as a sensitive indicator of altered intersystem electron transfer processes, e.g. under stress conditions., (© 2022. The Author(s).)

Photosynthesis is a series of redox reactions, in which several electron transport processes operate to provide the energetic balance of light harvesting. In addition to linear electron flow, which ensures the basic functions of photosynthetic productivity and carbon fixation, alternative electron transport pathways operate, such as the cyclic electron flow (CEF), which play a role in the fine tuning of photosynthesis and balancing the ATP/NADPH ratio under stress conditions. In this work, we characterized the electron transport processes in microalgae species that have high relevance in applied research and industry (e.g., Chlorella sorokiniana , Haematococcus pluvialis , Dunaliella salina , Nannochloropsis sp.) by using flash-induced fluorescence relaxation kinetics. We found that a wave phenomenon appeared in the fluorescence relaxation profiles of microalgae to different extents; it was remarkable in the red cells of H. pluvialis , D. salina and C. sorokiniana , but it was absent in green cells of H. pluvialis and N. limnetica . Furthermore, in microalgae, unlike in cyanobacteria, the appearance of the wave required the partial decrease in the activity of Photosystem II, because the relatively high Photosystem II/Photosystem I ratio in microalgae prevented the enhanced oxidation of the plastoquinone pool. The wave phenomenon was shown to be related to the antimycin A-sensitive pathway of CEF in C. sorokiniana but not in other species. Therefore, the fluorescence wave phenomenon appears to be a species-specific indicator of the redox reactions of the plastoquinone pool and certain pathways of cyclic electron flow.

Genus Pseudoxanthomonas represents a relatively newly characterized group of gamma-proteobacterium of environmental origin. Species of the genus have very similar morphology to strains belonging to Xanthomonas, Xylella and Stenotrophomonas . However, the genome resource of this genus was largely unexplored. The species belonging to the genus are from a wide range of environmental sites including hydrocarbon polluted fields. Here, we have provided the whole genome sequence of all available type strains of the genus of Pseudoxanthomonas . In order to deduce the differences with closely related genera, we have employed the whole genome-based investigation of the type species of genus Pseudoxanthomonas ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2022 The Authors. Published by Elsevier Inc.)