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Epoxide hydrolases (EHs) are a group of ubiquitous enzymes that catalyze hydrolysis of chemically reactive epoxides to yield corresponding dihydrodiols. Despite extensive studies on EHs from different clades, generic rules governing their substrate specificity determinants have remained elusive. Here, we present structural, biochemical and molecular dynamics simulation studies on MiEH2, a plant epoxide hydrolase from Mangifera indica. Comparative structure-function analysis of nine homologs of MiEH2, which include a few AlphaFold structural models, show that the two conserved tyrosines (MiEH2 Y152 and MiEH2 Y232 ) from the lid domain dissect substrate binding tunnel into two halves, forming substrate-binding-pocket one (BP1) and two (BP2). This compartmentalization offers diverse binding modes to their substrates, as exemplified by the binding of smaller aromatic substrates, such as styrene oxide (SO). Docking and molecular dynamics simulations reveal that the linear epoxy fatty acid substrates predominantly occupy BP1, while the aromatic substrates can bind to either BP1 or BP2. Furthermore, SO preferentially binds to BP2, by stacking against catalytically important histidine (MiEH2 H297 ) with the conserved lid tyrosines engaging its epoxide oxygen. Residue (MiEH2 L263 ) next to the catalytic aspartate (MiEH2 D262 ) modulates substrate binding modes. Thus, the divergent binding modes correlate with the differential affinities of the EHs for their substrates. Furthermore, long-range dynamical coupling between the lid and core domains critically influences substrate enantioselectivity in plant EHs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The central region of India boasts a rich tribal heritage and the highest number of tribal populations in the country. Analysing the genetic history of this population can offer valuable insights into various demographic processes that shaped the gene pool of present-day settlers of this region. In this study, we utilize a recently validated Next-generation sequencing (NGS) technique to sequence 24 tribal mitogenomes from the Chhattisgarh population for genetic ancestry and forensic analysis. The identified ancient haplogroups in this population can be traced back to the pre-Last Glacial Maximum (LGM) period. Our Bayesian analysis provides evidence for maternal ancestral expansion following the earliest Out-of-Africa migration, followed by a prolonged steady phase. We identified three basal founding haplogroups, M2, R5, and U2 in the Chhattisgarh region that diversified during the Neolithic period. Indistinct distribution pattern of these haplogroups among tribes and castes suggests that the maternal ancestry of Chhattisgarh population predates any kind of social stratification that exists today in the Indian subcontinent. Furthermore, our analysis suggests that this region remained unaffected by the Last Glacial Maximum. The forensic analysis of the mitogenomes demonstrates a high power of discrimination (0.9256) within the Chhattisgarh population, thus supporting the applicability of mitogenome NGS technology in forensic contexts., 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 © 2024 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Polyhalite-based POLY4, a multi-nutrient source containing potassium, calcium, magnesium, and sulphur, is increasingly recognised for its potential to improve crop yields and soil health in agricultural systems. It is also been considered as a feasible approach for addressing the deficiency in potassium, calcium, and sulphur within a single application source. The present study aimed to investigate the impact of polyhalite-based POLY4 application, either as a complete or partial substitute for traditional potassium fertiliser and gypsum supplement, on the improvement of peanut ( Arachis hypogaea ) growth and soil quality. An extensive field study was conducted from 2021 and 2022, employing ten distinct nutrient management treatments with three replications in a randomised complete block design. The findings of the study indicated that the application of polyhalite (POLY4) in conjunction with only NP fertilisers resulted in a higher yield advantage (approximately 150-200 kg ha -1 ) than in plots treated with NPK + gypsum (at 500 kg ha -1 ) and control plots. The application of polyhalite-based fertiliser (POLY4) at a rate that was 100% equivalent to K along with NP fertilisers resulted in a significant increase in pod yield (5.3-12.8%) over NPK + gypsum and control plots. Thus, the increased crop yield led to an increase in gross returns of 4.88% and in net returns of 4.28% with the application of POLY4 (100%) + NP fertilisers over other treatments. Likewise, variable rates of conventional fertilisers along with POLY4 (100% recommended) + NP + gypsum at 310 kg/ha significantly increased the linoleic acid content (38.5%), oleic acid content, and oil content (48.1%) by reducing palmitic acid (11.96%) content in the groundnut seed. Interestingly, POLY4 use at the 50% recommended rate also resulted in yields that were comparable with those obtained with 100% NPK. Therefore, applying POLY4, a polyhalite fertiliser, in either a 100% or 50% equivalent of essential K can be an effective way of increasing the production of peanut crops and promoting agricultural sustainability., Competing Interests: Authors NA and VM were employed by the company AngloAmerican Crop Nutrients Pvt. Ltd. The remaining 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 Gopinath, Rajanna, Visha Kumari, Singh, Ajay, Awasthi, Mishra, Sukumaran, Venkatesh and Rajkumar.)

The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclax and an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor and cooperates with the loss of KMT2D in lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several proapoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histone H3K4 demethylases restore BIM and BIK expression and synergize with Venetoclax in SETD1B-deficient lymphomas. These results establish SETD1B as an epigenetic regulator of cell death and reveal a pharmacological strategy to augment Venetoclax sensitivity in lymphoma., (© 2024 Portelinha et al.)

Competing Interests: The authors declare no conflicts of interest.

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca 2+ ) in health and disease. In physiological states, Ca 2+ enters via the mitochondrial Ca 2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca 2+ homeostasis is critical: insufficient Ca 2+ impairs stress adaptation, and Ca 2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca 2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca 2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca 2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca 2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na + /Ca 2+ exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca 2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca 2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.

The elemental composition of the lunar surface provides insights into mechanisms of the formation and evolution of the Moon 1,2 . The chemical composition of lunar regolith have so far been precisely measured using the samples collected by the Apollo, Luna and Chang'e 5 missions, which are from equatorial to mid-latitude regions 3,4 ; lunar meteorites, whose location of origin on the Moon is unknown 5,6 ; and the in situ measurement from the Chang'e 3 and Chang'e 4 missions 7-9 , which are from the mid-latitude regions of the Moon. Here we report the first in situ measurements of the elemental abundances in the lunar southern high-latitude regions by the Alpha Particle X-ray Spectrometer (APXS) experiment 10 aboard the Pragyan rover of India's Chandrayaan-3 mission. The 23 measurements in the vicinity of the Chandrayaan-3 landing site show that the local lunar terrain in this region is fairly uniform and primarily composed of ferroan anorthosite (FAN), a product of the lunar magma ocean (LMO) crystallization. However, observation of relatively higher magnesium abundance with respect to calcium in APXS measurements suggests the mixing of further mafic material. The compositional uniformity over a few tens of metres around the Chandrayaan-3 landing site provides an excellent ground truth for remote-sensing observations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this paper, the work has been done to develop a cost-effective methodology, for the isolation of the potential producer of bacterial nanocellulose. No report is available in the literature, on the use of gram flour and table sugar for the screening of nanocellulose-producing isolates. Since commercially used, Hestrin-Schramm medium is expensive for the isolation of nanocellulose-producing micro-organisms, the possibility of using gram flour-table sugar medium was investigated in this work. Qualitative screening of micro-organisms was done using cost-effective medium, i.e., gram flour-table sugar medium. Qualitative analysis of various nanocellulose-producing bacteria depicted that cellulose layer production occurred on both HS medium and gram flour-table sugar medium. The yield of nanocellulose was also better on air-liquid surface in case of gram flour-table sugar medium as compared to HS medium. 16S rRNA was used for molecular characterization of bacterial strain and the best nanocellulose producer was identified as Novacetimonas hansenii BMK-3_NC240423 (isolated from rotten banana). FTIR and FE-SEM studies of nanocellulose pellicle produced on HS medium and gram flour-table sugar medium demonstrated equivalent structural, morphological, and chemical properties. The cost of newly designed medium (0.01967 $/L) is nearly 90 times lower than the Hestrin-Schramm medium (1.748 $/L), which makes the screening of nanocellulose producers very cost-effective. A strategy of using gram flour extract-table sugar medium for the screening of nanocellulose-producing micro-organisms is a novel approach, which will drastically reduce the screening associated cost of cellulose-producing micro-organisms and also motivate the researchers/industries for comprehensive screening programme for getting high cellulose-producing microbes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Phytase, recognized for its ability to enhance the nutritional value of phytate-rich foods, has has gained significant prominence. The production of this enzyme has been significantly boosted while preserving economic efficiency by utilizing natural substrates and optimizing essential factors. This study focuses on optimizing phytase production through solid-state fermentation and evaluating its effectiveness in enhancing nutrient utilization in chicken diets., Objective: The objective is to optimize phytase production via solid-state fermentation, characterize purified phytase properties, and assess its impact on nutrient utilization in chicken diets. Through these objectives, we aim to deepen understanding of phytase's role in poultry nutrition and contribute to more efficient feed formulations for improved agricultural outcomes., Methodology: We utilized solid-state fermentation with Pichia kudriavzevii FSMP-Y17 yeast on orange peel substrate, optimizing variables like temperature, pH, incubation time, and supplementing with glucose and ammonium sulfate. Following fermentation, we purified the phytase enzyme using standard techniques, characterizing its properties, including molecular weight, optimal temperature and pH, substrate affinity, and kinetic parameters., Results: The optimized conditions yielded a remarkable phytase yield of 7.0 U/gds. Following purification, the enzyme exhibited a molecular weight of 64 kDa and displayed optimal activity at 55 °C and pH 5.5, with kinetic parameters (Km = 3.39 × 10 -3  M and a V max of 7.092 mM/min) indicating efficient substrate affinity., Conclusion: The addition of purified phytase to chicken diets resulted in significant improvements in nutrient utilization and overall performance, including increased feed intake, improved feed conversion ratio, enhanced bird growth, better phosphorus retention, and improved egg production and quality. By addressing challenges associated with phytate-rich diets, such as reduced nutrient availability and environmental pollution, phytase utilization promotes animal welfare and sustainability in poultry production., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Producing sp 3 -hybridized carbon-enriched molecules is of particular interest due to their high success rate in clinical trials. The installation of aliphatic chains onto aromatic scaffolds was accomplished by nickel-catalyzed C(sp 2 )-C(sp 3 ) cross-electrophile coupling with arylsulfonium salts. Thus, simple non-prefunctionalized arenes could be alkylated through the formation of aryldibenzothiophenium salts. The reaction employs an electrochemical approach to avoid potentially hazardous chemical redox agents, and importantly, the one-pot alkylation proved also viable, highlighting the robustness of our approach., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Obesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human-derived commensal bacterium, Clostridium immunis , that protects against metabolic disease by secreting a phosphocholine-modified exopolysaccharide. Genetic interruption of the phosphocholine biosynthesis locus ( licABC ) results in a functionally inactive exopolysaccharide, which demonstrates the critical requirement for this phosphocholine moiety. This C. immunis exopolysaccharide acts via group 3 innate lymphoid cells and modulating IL-22 levels, which results in a reduction in serum triglycerides, body weight, and visceral adiposity. Importantly, phosphocholine biosynthesis genes are less abundant in humans with obesity or hypertriglyceridemia, findings that suggest the role of bacterial phosphocholine is conserved across mice and humans. These results define a bacterial molecule-and its key structural motif-that regulates host metabolism. More broadly, they highlight how small molecules, such as phosphocholine, may help fine-tune microbiome- immune-metabolism interactions.

Objective: To determine the effectiveness of the telemedicine-based pulmonary rehabilitation programme in COVID-19 pneumonitis., Design: Prospective intervention study., Setting: Rehabilitation outpatient department, Tertiary-Care institute., Participants: Consecutive sample of patients ( N = 50) in recovered COVID-19 infection., Intervention: Six weeks of telemedicine-based pulmonary rehabilitation in recovered patients of COVID-19 infection., Outcome Measures: All patients were clinically assessed by six minutes walk test (6MWT), Modified Medical Research Council Scale (mMRC), 30s-STS and SF 36 at zero week and six weeks post-intervention., Statistical Analysis: Difference in means of pre- and post-intervention was compared using paired t -test. A P value <0.05 was considered statistically significant., Results: The 6MWT, mMRC Scale, 30 seconds sit-to-stand test, and WHO QoL scale-SF 36 were assessed and post-rehabilitation sessions, all the patients' showed improvement in the prescribed parameters. After six weeks of respiratory rehabilitation, the distance covered in the 6MWT was significantly longer than that of before the intervention. There was a significant difference between zero and six weeks during the PR intervention. mMRC and 30s-STS results showed a significant difference between zero and six weeks (2.36 ± 0.598, 4.54 ± 1.94. Quality of life improved significantly after six weeks of pulmonary rehabilitation in eight domains of the SF-36., Conclusion: Six-week pulmonary rehabilitation programme delivered through telemedicine platform improves respiratory function, QoL and anxiety in patients with post-COVID-19 pneumonia during a recovery phase., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

This mini-review on doping and heterojunctions for catalysis applications provides a comprehensive overview of key aspects. Doping, when carried out adequately with a uniform distribution, creates a new energy level that significantly enhances charge transfer and light absorption. This new level alters the material's morphology and enhances intrinsic defects. For instance, ZnO, despite its exceptional band edge concerning oxygen reduction and water oxidation redox potentials, faces the issue of electron-hole recombination. However, forming a heterojunction can effectively aid charge transfer and prolong electron-hole relaxation without recombination. This is where the role of doping and heterojunctions becomes crucial. Additionally, incorporating noble metals with S- and Z-scheme heterojunctions offers a promising mechanism for charge transfer and visible light harvesting, further amplifying the catalytic properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The current study intended to analyze the impact of ethanol and lactic acid on the bacterial cellulose yield as well as physicochemical and mechanical properties, by using Gluconacetobacter kombuchae . The optimization of ethanol and lactic acid concentration has been done by using one-way ANOVA. Both the supplements significantly enhance the yield of bacterial cellulose (BC) as compared to the standard Hestrin-Schramm medium (control). Optimization leads to significant increase in BC yield as compared to the control, i.e., the addition, of optimized concentration of lactic acid (0.6%) increases the yield from (0.78 ± 0.026) g to (4.89 ± 0.020) g dry weight, and optimized concentration of ethanol (1%) increases the yield from (0.73 ± 0.057) g to (3.7 ± 0.01) g dry weight. Various physicochemical and mechanical properties of BC films produced in different media (i.e., HS, HS + Ethanol, and HS + Lactic acid), such as the crystallinity, structure, tensile strength, strain at break, Young's modulus, and water holding capacity, were also examined, by employing various techniques such as SEM, FTIR, XRD, etc. BC produced in medium supplemented with the optimum concentration of both the additives were found to possesses higher porosity. Though, slight decline in crystallinity was observed. But the tensile strength and strain at break, were upgraded 1.5-2.5 times, 2-2.5 times, respectively. This article attempted to present a method for enhancing BC yields and characteristics that may lead to more widespread and cost-effective use of this biopolymer.

Introduction: Altered DNA methylation pattern in sperms has been associated with infertility in males demonstrating defective spermatogenesis or low semen quality. Vitamin B-12, by affecting 1-carbon metabolism pathways, might alter the DNA methylation pattern. We aimed to study the correlation of serum vitamin B12 levels with aberrant DNA methylation in infertile male patients., Methods: A cross-sectional study was conducted on 17 oligozoospermic infertile males (WHO criteria, 2010) and 10 healthy fertile males. Serum vitamin B12 levels were estimated using the chemiluminescence method. Global methylation was determined using the ELISA system (Imprint Methylated DNA Quantification Kit, Sigma-Aldrich). The levels of global DNA methylation were calculated and compared relative to the methylated (100%) control DNA provided with the kit., Results: Mean serum vitamin B12 concentration in the control group was higher than that of the case group. This difference in serum vitamin B12 concentration in both groups was found statistically significant. Although the results of this study show that oligozoospermic men have relatively lower global DNA methylation as compared to normozoospermic control, the values could not reach a statistically significant level. A small positive correlation was found between serum vitamin B12 levels and percent methylation defect (r = 0.14) but was statistically insignificant., Conclusion: Our study concludes that oligozoospermic infertile males have a significant deficiency of vitamin B12 as compared to normozoospermic fertile males. This study did not find any significant difference in global DNA methylation between the two groups. The present study does not suggest any correlation between serum vitamin B12 level and percent DNA methylation., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Endocrinology and Metabolism.)

Aim and Background: High-quality cardiopulmonary resuscitation (CPR) is associated with improved patient outcomes, but healthcare workers (HCWs) may be frequently undertrained. This study aimed to assess baseline knowledge and skills among HCWs about basic and advanced life support and the effect of simulation-based training on it., Methods: It was a single-center prospective quasi-interventional study among resident doctors and nurses at a Tertiary Center in New Delhi, India. A questionnaire-based assessment was done to assess baseline knowledge. The participants then underwent simulation-based training followed by questionnaire-based knowledge assessment and skill assessment. A repeat questionnaire-based assessment was done 6 months post-training to assess knowledge retention., Results: A total of 82 HCWs (54 doctors and 28 nurses) were enrolled. The participants scored 22.28 ± 6.06 out of 35 (63.65%) in the pre-training knowledge assessment, with low scores in post-cardiac arrest care, advanced life support, and defibrillation. After the training, there was a significant rise in scores to 28.32 ± 4.08 out of 35 (80.9%) ( p < 0.01). The retention of knowledge at 6 months was 68.87% ( p < 0.01). The participants scored 92.61 ± 4.75% marks in skill assessment with lower scores in chest compressions and team leadership roles. There was a positive correlation ( r = 0.35) between knowledge and skills scores ( p < 0.01)., Conclusion: There is a progressive decrease in baseline knowledge of HCWs with the further steps in the adult chain of survival. The simulation training program had a positive impact on the knowledge of HCWs. The training programs should focus on defibrillation, advanced life support, post-cardiac arrest care, and leadership roles., How to Cite This Article: Agarwal A, Baitha U, Ranjan P, Swarnkar NK, Singh GP, Baidya DK, et al . Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India. Indian J Crit Care Med 2024;28(4):336-342., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2024; The Author(s).)

For decades, the expression of immediate early genes (IEGs) such as FOS has been the most widely used molecular marker representing neuronal activation. However, to date, there is no equivalent surrogate available for the decrease of neuronal activity. Here, we developed an optogenetic-based biochemical screen in which population neural activities can be controlled by light with single action potential precision, followed by unbiased phosphoproteomic profiling. We identified that the phosphorylation of pyruvate dehydrogenase (pPDH) inversely correlated with the intensity of action potential firing in primary neurons. In in vivo mouse models, monoclonal antibody-based pPDH immunostaining detected activity decreases across the brain, which were induced by a wide range of factors including general anesthesia, chemogenetic inhibition, sensory experiences, and natural behaviors. Thus, as an inverse activity marker (IAM) in vivo, pPDH can be used together with IEGs or other cell-type markers to profile and identify bi-directional neural dynamics induced by experiences or behaviors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective In light of several advancements and considerations in endodontic dentistry, there still remains a need to comprehensively evaluate the outcome disparities between repairing and replacing broken dental restorations. This study aims to compare the effectiveness of repairing dental restorations versus replacing them, focusing on how each method affects the structural strength and longevity of the restorations. Methods The study included 60 freshly removed human maxillary premolars. Initial processing involved rigorous washing, descaling, and polishing of the teeth. To ensure preservation, the specimens were stored in sterile, distilled water. To occlude the root canals, a self-hardening composite resin was used, and the roots were coated with two coats of clear nail polish to prevent moisture penetration. A 245 carbide bur attached to a high-speed dental handpiece with air and water spray cooling produced standardized Class II cavities on the occluso-proximal surfaces. Each cavity had a buccolingual breadth of 2 mm, an occluso-cervical length of 4 mm, and a gingival boundary that was 1 mm coronal to the cement-enamel junction. Following this preparation, the teeth were randomly separated into three groups (Group A, Group B, and Group C), each containing 20 teeth. Results Our analysis showed that teeth with entirely replaced restorations had a higher average fracture resistance than those with repaired restorations. However, the difference in fracture resistance between the repair and replacement groups for each type of material was not statistically significant. Conclusion Based on the findings, repairing a dental restoration can be a conservative and less invasive alternative to a full replacement without a significant compromise in the restoration's ability to withstand fracture. Therefore, dental professionals might consider full restoration as a viable option, taking into account the need to preserve dental tissue as well as the restoration's durability and structural integrity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sachan et al.)

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events., Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA., Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations., Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA., Competing Interests: Current affiliation: Neeraj K. Garg: FR & D Non Orals, Sun Pharmaceuticals Industries Ltd. Tandalja, Vadodara, Gujarat, India; Sheetal Saini: Infectious Diseases Labs, A*STAR, Singapore; Praveen Sharma: Department of Molecular Medicine, Long School of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA. The authors declare that they have no conflicts of interest for this work., (© 2024 Negi et al.)

This study was conducted to test the efficacy of 5-fluorouracil (5-FU) as an anticancer drug against the human pyruvate kinase isozyme M2 (PKM2) using spectroscopic, molecular docking and molecular dynamic simulation studies. PKM2 fluorescence quenching studies in the presence of 5-FU performed at three different temperatures indicates dynamic quenching processes with single-set of binding ( n  ≈ 1) profile. The biomolecular quenching constants ( k q ) obtained are shown to increase with temperature. The calculated enthalpy (ΔH) and entropy changes (ΔS) are estimated to be -118.06 kJ/mol and 146.14 kJ/mol/K respectively, which suggest the possible mode of interaction as electrostatic and hydrogen bonding. Further, these values were used to estimate the free energy changes (ΔG) and that increases with temperature. The negative ΔG values clearly indicates spontaneous binding process that stabilizes the complex formed between 5-FU and PKM2. Far-UV CD spectra of PKM2 in the presence of 5-FU shows decrease in α-helix contents which point towards the destabilization of secondary structure that weakens the biological activity of PKM2. The intrinsic fluorescence study and circular dichroism (CD) spectra showed minor conformational changes of PKM2 in the presence of 5-FU. Additionally, the results obtained from molecular docking and all-atom molecular dynamic simulation study supports the insight of the spectroscopic binding studies, and strengthens the dynamic stability of the complex between 5-FU and PKM2 through H-bonding. This study establishes a paradigm of 5-FU-PKM2 complexation and the efficacy of 5-FU that compromises the biological activity of the targeted PKM2.Communicated by Ramaswamy H. Sarma.K b ) obtained are shown to increase with temperature. The calculated enthalpy (ΔH) and entropy changes (ΔS) are estimated to be -118.06 kJ/mol and 146.14 kJ/mol/K respectively, which suggest the possible mode of interaction as electrostatic and hydrogen bonding. Further, these values were used to estimate the free energy changes (ΔG) and that increases with temperature. The negative ΔG values clearly indicates spontaneous binding process that stabilizes the complex formed between 5-FU and PKM2. Far-UV CD spectra of PKM2 in the presence of 5-FU shows decrease in α-helix contents which point towards the destabilization of secondary structure that weakens the biological activity of PKM2. The intrinsic fluorescence study and circular dichroism (CD) spectra showed minor conformational changes of PKM2 in the presence of 5-FU. Additionally, the results obtained from molecular docking and all-atom molecular dynamic simulation study supports the insight of the spectroscopic binding studies, and strengthens the dynamic stability of the complex between 5-FU and PKM2 through H-bonding. This study establishes a paradigm of 5-FU-PKM2 complexation and the efficacy of 5-FU that compromises the biological activity of the targeted PKM2.Communicated by Ramaswamy H. Sarma.

The world of medicine demands from the research community solutions to the emerging problem of SARS-CoV-2 variants and other such potential global pandemics. With advantages of specificity over small molecule drugs and designability over antibodies, miniprotein therapeutics offers a unique solution to the threats of rapidly emerging SARS-CoV-2 variants. Unfortunately, most of the promising miniprotein binders are de novo designed and it is not viable to generate molecules for each new variant. Therefore in this study, we demonstrate a method for design of miniprotein mimics from the interaction interphase of human angiotensin converting enzyme 2 (ACE2). ACE2 is the natural interacting partner for the SARS-CoV-2 spike receptor binding domain (RBD) and acts as a recognition molecule for viral entry into the host cells. Starting with ACE2 N-terminal triple helix interaction interphase, we generated more than 70 miniprotein sequences. Employing Rosetta folding and docking scores we selected 10 promising miniprotein candidates amongst which 3 were found to be soluble in lab studies. Further, using molecular mechanics (MM) calculations on molecular dynamics (MD) trajectories we test interaction of miniproteins with RBD from various variants of concern (VOC). Presently, we report two key findings; miniproteins in this study are generated using less than 10 lab testing experiments, yet when tested through in-vitro experiments, they show submicro to nanomolar affinities towards SARS-CoV-2 RBD. Also in simulation studies, when compared with previously developed therapeutics, our miniproteins display remarkable ability to mimic ACE2 interphase; making them an ideal solution to the ever evolving problem of VOCs.Communicated by Ramaswamy H. Sarma.

Macrophages play a key role in maintaining systemic iron homeostasis and immunity. During pro-inflammatory stage macrophages retain iron due to the decrease of the unique iron exporter ferroportin. Increased cellular iron is sequestered in to storage protein ferritin by iron chaperone poly(rC)-binding protein 1 (PCBP1). However, the fate of PCBP1 and its interaction with ferritin in pro-inflammatory macrophages has not been studied so far. Here we report that PCBP1 protein level is down-regulated in lipopolysaccharide (LPS) treated macrophages. LPS did not alter PCBP1 mRNA and protein stability suggesting inhibition of translation as a mechanism of PCBP1 down-regulation that was confirmed by 35 S-methionine incorporation assay. PCBP1 interacts with ferritin-H (Ft-H) subunit to load iron into ferritin. We detected a decreased interaction between PCBP1 and Ft-H after LPS-stimulation. As a result iron loading in to ferritin was affected with simultaneous increase in labile iron pool (LIP). Pre-treatment of cells with iron chelator dampened LPS-induced expression of TNF-α, IL-1β and IL-6 mRNA. Silencing of PCBP1 increased the magnitude of expression of these cytokines compared to control siRNA transfected LPS-treated macrophages. In contrast, overexpression of PCBP1 resulted a decrease in expression of these cytokines compared to vector transfected macrophages. Our results reveal a novel regulation of PCBP1 and its role in expression of cytokines in LPS-induced pro-inflammatory macrophages., 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. Published by Elsevier Ltd.)

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Contrary to our initial hypothesis, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that human and mouse gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivo culture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion. This finding has important implications for our understanding of energy extraction and subsequent uptake in gastrointestinal tract. FPS may therefore be viewed as an informative functional readout, providing new insights into the metabolic state of the gut microbiome., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Background & Aims: The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, additional strategies to mitigate the spread/severity of COVID-19 continue to be needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; thus, probiotics may be a low-risk, low-cost, and easily implementable modality to reduce risk of COVID-19., Methods: In this initial study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lacticaseibacillus rhamnosus GG (LGG) as postexposure prophylaxis for COVID-19 in 182 participants who had household exposure to someone with confirmed COVID-19 diagnosed within ≤7 days. Participants were randomized to receive oral LGG or placebo for 28 days. The primary outcome was development of illness symptoms within 28 days of COVID-19 exposure. Stool was collected to evaluate microbiome changes., Results: Intention-to-treat analysis showed LGG treatment led to a lower likelihood of developing illness symptoms versus placebo (26.4 % vs. 42.9 %, p = 0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank, p = 0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8 % vs. 15.4 %, p = 0.17)., Conclusions: This data suggests LGG is associated with prolonged time to COVID-19 infection, reduced incidence of illness symptoms, and gut microbiome changes when used as prophylaxis ≤7 days post-COVID-19 exposure, but not overall incidence. This initial work may inform future COVID-19 prevention studies worldwide, particularly in developing nations where Lacticaseibacillus probiotics have previously been utilized to reduce other non-COVID infectious-morbidity., Trial Registration: ClinicalTrials.gov, NCT04399252, Date: 22/05/2020. https://clinicaltrials.gov/ct2/show/NCT04399252., Competing Interests: Conflict of interest P.E.W. has received unrestricted gift funding from DSM/iHealth and has an investigator-initiated research grant from Abbott Inc. related to work focused on microbiome and probiotic research. P.E.W. has presented CME lectures for DSM on probiotic research. All other authors declare no competing interests. A.D.S has grants from Merck Sharpe & Dohme, consulting for Targazyme, and receipt of supplies from Clasado., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques., Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal short-chain fatty acids and bile acids., Results: Composition of the early-life gut microbial communities in nursery-reared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterella -related metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG., Discussion: Our findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota-vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Jiang, Goswami, Dennis, Heimsath, Kozlowski, Ardeshir, Van Rompay, De Paris, Permar and Surana.)

Parthenium hysterophorous , a widespread weed in India, contributes a substantial amount of lignocellulosic biomass. The key objective of this study is to evaluate the feasibility of producing xylanase enzyme from P. hysterophorus weed biomass using the fungus Aspergillus niger . The impact of various physiological factors was confirmed through a two-step approach: first, a one-factor-at-a-time (OFAT) investigation, and subsequently, employing the RSM-based CCD method in statistical design. This research revealed that the RSM-based model led to the optimization of enzyme activity, resulting in a value of 2098.08 IU/gds for xylanase. This was achieved with an incubation time of 4.5 days, a medium pH of 6, and a cultivation temperature of 32.5 °C. Additionally, a pretreatment involving 1% NaOH and a 30-min autoclave treatment was found to alter the chemical composition of lignocellulose substrates (cellulose 43.87% and xylan 28.7%), thereby enhancing the efficiency of enzymatic hydrolysis. Moreover, fermentable sugars were produced by autoclave-assisted alkali pretreatment (NaOH-1.0% w / v ) at rates of 219.6 ± 2.05 mg/gds -1 by utilizing the crude xylanase from A. niger and 291.3 ± 1.2 mg/gds -1 from commercial xylanase enzyme. Our study revealed that P. hysterophorus served as a viable and affordable substrate for fermentable sugar liberation, and xylanase is a rate-limiting enzyme in enzymatic saccharification., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© King Abdulaziz City for Science and Technology 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.)

Neurological ailments, including stroke, Alzheimer's disease (AD), epilepsy, Parkinson's disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain's substantia nigra regions. It affects cognitive and motor activities, resulting in tremors during rest, slow movement, and muscle stiffness. There are various traditional approaches for the management of PD, but they provide only symptomatic relief. Thus, a survey for finding new biomolecules or substances exhibiting the therapeutic potential to patients with PD is the main focus of present-day research. Medicinal plants, herbal formulations, and natural bioactive molecules have been gaining much more attention in recent years as synthetic molecules orchestrate a number of undesired effects. Several in vitro, in vivo, and in silico studies in the recent past have demonstrated the therapeutic potential of medicinal plants, herbal formulations, and plant-based bioactives. Among the plant-based bioactives, polyphenols, terpenes, and alkaloids are of particular interest due to their potent anti-inflammatory, antioxidant, and brain-health-promoting properties. Further, there are no concise, elaborated articles comprising updated mechanism-of-action-based reviews of the published literature on potent, recently investigated (2019-2023) medicinal plants, herbal formulations, and plant based-bioactive molecules, including polyphenols, terpenes, and alkaloids, as a method for the management of PD. Therefore, we designed the current review to provide an illustration of the efficacious role of various medicinal plants, herbal formulations, and bioactives (polyphenols, terpenes, and alkaloids) that can become potential therapeutics against PD with greater specificity, target approachability, bioavailability, and safety to the host. This information can be further utilized in the future to develop several value-added formulations and nutraceutical products to achieve the desired safety and efficacy for the management of PD.

Bacteria are considered mini chemical factories that help us in providing a wide range of products for various purposes. These days, bacterial cellulose (BC) is getting attention by researchers due to its quality, eco-friendly nature, and excellent physical-mechanical qualities. It is being used in the fabrication of nanocomposites. Its nanocomposites can be used in various industries, including medicine, food, leather, textiles, environment, electronics, and cosmetics. This area of research is emerging and still in its infancy stage, as new applications are still coming up. Most of the work on BC has been done during the last two decades and serious inputs are required in this direction in order to make the production process commercially viable and ultimately the application part. Biowastes, such as fruits and vegetables wastes, can be used as a cost-effective medium to minimize the cost for large-scale production of BC-based nanocomposites thus will valorize the biowaste material into a valuable product. Using biowaste as media will also aid in better waste management along with reduction in detrimental environmental effects. This review will help the readers to understand the potential applications of BC and its nanocomposites as well as their vital role in our daily lives., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

Maintaining body temperature is calorically expensive for endothermic animals 1 . Mammals eat more in the cold to compensate for energy expenditure 2 , but the neural mechanism underlying this coupling is not well understood. Through behavioural and metabolic analyses, we found that mice dynamically switch between energy-conservation and food-seeking states in the cold, the latter of which are primarily driven by energy expenditure rather than the sensation of cold. To identify the neural mechanisms underlying cold-induced food seeking, we used whole-brain c-Fos mapping and found that the xiphoid (Xi), a small nucleus in the midline thalamus, was selectively activated by prolonged cold associated with elevated energy expenditure but not with acute cold exposure. In vivo calcium imaging showed that Xi activity correlates with food-seeking episodes under cold conditions. Using activity-dependent viral strategies, we found that optogenetic and chemogenetic stimulation of cold-activated Xi neurons selectively recapitulated food seeking under cold conditions whereas their inhibition suppressed it. Mechanistically, Xi encodes a context-dependent valence switch that promotes food-seeking behaviours under cold but not warm conditions. Furthermore, these behaviours are mediated by a Xi-to-nucleus accumbens projection. Our results establish Xi as a key region in the control of cold-induced feeding, which is an important mechanism in the maintenance of energy homeostasis in endothermic animals., (© 2023. The Author(s).)

Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is binary, where microbiota instruct in situ interleukin-17 (IL-17) production and concomitant expression of the inhibitory receptor programmed cell death protein 1 (PD-1). Microbiota-driven expression of PD-1 and IL-17 and preferential adoption of a PD-1 high phenotype are conserved for γδ17 cells across multiple mucosal barriers. Importantly, microbiota-driven PD-1 inhibits in situ IL-17 production by mucosa-resident γδ17 effectors, linking microbiota to their simultaneous activation and suppression. We further show the dynamic nature of this microbiota-driven module and define an inflammation-associated activation state for γδ17 cells marked by augmented PD-1, IL-17, and lipid uptake, thus linking the microbiota to dynamic subset-specific activation and metabolic remodeling to support γδ17 effector functions in a microbiota-dense tissue environment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this study, we investigated a new, simple, sensitive, selective and precise high-performance thin-layer chromatography (HPTLC) fingerprint and quantitative estimation method for the routine analysis of curcumin in Curcuma species viz. Curcuma amada, Curcuma caesia, Curcuma longa and Curcuma zedoaria. Linear ascending development was carried out in a twin-trough glass chamber saturated with toluene:acetic acid (4:1; v/v with 20 minutes of saturation). The plate was dried and analyzed by CAMAG TLC scanner III at white light and 366 nm. The system was found to give compact spots for curcumin (Rf 0.42). The relationship between the concentration of standard solutions and the peak response is linear within the concentration range of 10-70 ng/spot for curcumin. In result, curcumin was not detected in any of C. caesia extracts. The percentage of curcumin was found between 0.042 and 4.908 (%w/w) in different Curcuma species obtained by two different extraction methods viz. Soxhlet and sonication, respectively. Further, extraction via Soxhlet method is most suitable method to get higher curcumin content from rhizomes. The proposed HPTLC method may be use for routine quality testing and quantification of curcumin in Curcuma samples., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The major objective of present work was to fabricate poly(hydroxybutyrate) based luminescent films for genuine food packaging applications. These films were synthesized by incorporating varying Chromone (CH) concentrations (5, 10, 15, 20, and 25 wt%) into poly(hydroxybutyrate) (PHB) matrix through solvent-casting. Different characteristics of prepared films were examined using Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), Mechanical testing, and Time-resolved photoluminescence (TRPL). UV-blocking properties and water vapor permeation were also examined. FTIR spectra indicated the occurrence of hydrogen bonding between PHB and CH. Among all prepared film samples, PHB/CH15 showed maximum tensile strength (22.5 MPa) with enhanced barrier ability against water vapor and UV rays, thermal stability, and luminescent performance. After overall analysis, PHB/CH15 film was selected to investigate its X-ray diffraction, release behavior, DPPH scavenging, and antimicrobial potential. Release kinetics revealed that the cumulative release percentage of CH was higher in fatty acid stimulant. Moreover, results suggested that this film demonstrated antioxidant activity (>55 %) and superior antimicrobial potential against Aspergillus niger, Staphylococcus aureus, and Escherichia coli. Furthermore, packaging of bread samples using PHB/CH15 film demonstrated the complete inhibition of microbial growth in bread up to 10 days of storage and ensure the safety of genuine food products., 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. Published by Elsevier B.V.)

Cerebral hypoperfusion is associated with enhanced cognitive decline and increased risk of neuropsychiatric disorders. Erythropoietin (EPO) is a neurotrophic factor known to improve cognitive function in preclinical and clinical studies of neurodegenerative and psychiatric disorders. However, the clinical application of EPO is limited due to its erythropoietic activity that can adversely elevate hematocrit in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered non-erythropoietic derivative of EPO, does not alter hematocrit and maintains neurotrophic and behavioral effects comparable to EPO. Our study aimed to investigate the role of CEPO in cerebral hemodynamics. Magnetic resonance imaging (MRI) analysis indicated increased blood perfusion in the hippocampal and striatal region without altering tight junction integrity. In vitro and in vivo analyses indicated that hippocampal neurotransmission was unaltered and increased cerebral perfusion was likely due to EDRF, CGRP, and NOS-mediated vasodilation. In vitro analysis using human umbilical vein endothelial cells (HUVEC) and hippocampal vascular gene expression analysis showed CEPO to be a non-angiogenic agent which regulates the MEOX2 gene expression. The results from our study demonstrate a novel role of CEPO in modulating cerebral vasodilation and blood perfusion.

Background and Aims: We aim to determine the prevalence of anemia in hospitalized patients with diabetic foot ulcers (DFUs) and estimate the relationship between the severity of anemia and diabetic foot ulcer., Materials and Methods: We retrospectively collected and evaluated the data of 323 patients hospitalized with diabetic foot ulcer (DFU). We included 299 type 2 diabetic patients with foot ulcers of neuropathic or neuroischemic nature with infection. Anemia was defined based on World Health Organization (WHO) criteria, and the severity of DFU was classified in University of Texas (UT) grades., Results: Anemia was detected in 94.3% of DFU, and the prevalence of mild, moderate, and severe anemia was 16.7%, 55.7%, and 27.6%, respectively. There was a significant difference in the mean hemoglobin (Hb) levels among the patients with varying grades of severity of DFU (1B: Hb=10.17±2.08 gm/dL, 2B: Hb=9.27±2.04 gm/dL, 3B: Hb=8.03±1.829 gm/dL; p value=<0.0001). The iron study was available in 141 (47.15%) patients and was suggestive of anemia of chronic disorder (mean serum iron=40.22±23.81 mcg/dL, mean total iron-binding capacity (TIBC)=239.34±67.24 mcg/dL, mean ferritin=378.05±141.337 ng/mL). TIBC significantly decreased (1B=262.13±61.05, 2B=233.65±71.26, 3B=222.43±74.18; p=0.04), and ferritin significantly increased (1B=309.9±70.76, 2B=351.73±94.22, 3B=488.58±170.4; p<0.0001) with increasing DFU severity. Hemoglobin was significantly decreased at the time of discharge in comparison to that at admission (9.3±2.1 gm/dL versus 8.8±1.5 gm/dL; p value=0.01). Red blood cell (RBC) counts, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), lymphocyte counts, albumin, calcium, and high-density lipoprotein (HDL) significantly decreased with the increase of DFU severity. The duration of hospitalization, total leucocyte counts, neutrophil counts, and neutrophil-to-lymphocyte ratio (NLR) increased with the severity of DFU., Conclusions: The prevalence of anemia was very high in DFU and more than three-fourths of the patients had moderate to severe anemia. The severity of anemia was associated with the severity of DFU. The most common cause of anemia was anemia of chronic disorder secondary to diabetic foot infection. During the period of hospitalization, hemoglobin decreased despite improvement in DFU infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kumar et al.)

Due to rapid urbanization and exponential growth in transportation; traffic noise has become a major area of concern. Noise not only disturbs our day-to-day life but also have severe adverse health effects over humans which further may lead to mortality. This paper focuses on the behavior of noise levels of Lucknow city over a decade and establishes its correlation with impact on human health in terms of annoyance and sleep disturbance. Apart from L eq , different noise parameters like L 10 , L 50 , L 90 , Traffic Noise Index (TNI), Noise Pollution Index (NPI), and Noise Climate (NC) have also been analyzed to understand the variation of noise. At all the locations, the noise level has been found exceeding their prescribed standards during day time and night time except at Amausi. Out of nine locations, TNI was found to be exceeding at three locations during day time and NPI exceeding at one location. However, during night time both values of TNI and NPL were observed within the limit at all the locations. From the noise map of the city during day time and night time, among all sampling locations, Charbagh has been found to be worst affected by noise pollution. A strong positive correlation has been observed among the total population, vehicular count, and day and night time noise data, which directly contribute to a higher percentage of sleep disturbance and annoyance among residents. Due to the increase in noise levels over a period of time, almost four times the population get affected by high annoyance and almost double the population get affected by sleep disturbance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

High thoracic epidural anesthesia in cardiac surgery as the sole anesthetic technique is used in a select groups of patients having severe pulmonary co morbidities. We describe a case series of three patients at high risk for post operative pulmonary complications where this technique was used along with dexmedetomidine infusion for conscious sedation in off pump coronary artery bypass grafting. Proper selection of patients, proper placement of the epidural catheter at the appropriate level and timing of catheter insertion and removal are of paramount importance.

The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The peculiar properties of 2-D nano-materials have always inspired the research community for the further discovery of novel materials. Although III-V nitrides have been extensively explored for various remarkable phenomena, phosphides of the same group are yet to be explored. Taking a step in this direction, here we report the structural and electronic properties of zigzag BP nanoribbons (ZBPNR) with coved edge defects. The effect of sp 2 and sp 3 edge passivation has also been compared to reveal interesting findings. The position of coved defect is considered in a number of different possibilities. It is observed that all the structures are energetically stable and maintain planar geometries. The H-passivated ribbons exhibit a semiconductor behavior with their band gap reciprocal to the ribbon width. However, for coved edge nanoribbons, a semiconductor as well as pure metallic nature has been predicted depending upon the site of the coved defect. Furthermore, the nature of the band gap is direct in H-passivated nanoribbons whereas for coved edges a direct to indirect alternation has been observed. The obtained wide range of electronic band gap (0.15 eV to 1.34 eV) indicates that ZBPNR could be useful for designing beyond silicon semiconductor devices., 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 Inc. All rights reserved.)

Nanoribbons with different edge functionalization display interesting electronic properties for various device applications. It requires the necessity of exploring the novel passivating elements commensurate to various technological applications. In this direction, here we have compared the effect of H and F-passivation on the edges of zigzag SiC nanoribbons (ZSiCNR) using density functional theory based calculations. Remarkably, present study reveals that F could be used as an effective passivating element for ZSiCNR similar to widely explored H-passivations. Various possible combinations of F/H are found to have stable structural integrity for practical applications. The effect of F-adatom adsorption is also discussed which present peculiar electronic properties. The half-metallic behavior is observed to be realized via F-adsoprtion which is further confirmed with the transport calculations. The obtained negative differential resistance along the spin dependent electron transport pledges towards wide spread applications of considered ZSiCNR interacting with F., 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 Inc. All rights reserved.)

The use of face masks aids to stop the transmission of various deadly communicable ailments, and therefore widespread mask wearing habit is advocated by nearly all health organisations including the WHO to curb the COVID-19 pandemic. Recent studies predicted a shocking requirement of masks globally, approximately billions of masks per week in a single country, and maximum of them are disposable masks, which are made up of nonbiodegradable material such as polypropylene. With expanding review on improper masks disposal, it is imperative to perceive this inherent environmental hazard and avert it from resulting in the subsequent problematic situation due to plastic. The shift towards biodegradable biopolymers alternatives such as bacterial cellulose and newly evolving sustainable scientific knowledge would be significant to dealt with upcoming environmental problem. Bacterial cellulose possesses various desirable properties to replace the conventional mask material. This review gives an overview of data about accumulation of waste masks and its potential harm on environment. It also focuses on diverse characteristics of bacterial cellulose which make it suitable material for making mask and the challenges in the way of bacterial cellulose production and their possible solution. The current review also discussed the report on global bacterial cellulose market growth., Competing Interests: 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., (© 2022 Elsevier B.V. All rights reserved.)

Chemotherapy is still the first line of treatment for most cancer patients. Patients receiving chemotherapy are generally prone to infections, which result in complications, such as sepsis, mucositis, colitis, and diarrhoea. Several nutritional approaches have been trialled to counter the chemotherapy-associated side effects in cancer patients, but none have yet been approved for routine clinical use. One of the approaches to reduce or avoid chemotherapy-associated complications is to restore the gut microbiota. Gut microbiota is essential for the healthy functioning of the immune system, metabolism, and the regulation of other molecular responses in the body. Chemotherapy erodes the mucosal layer of the gastrointestinal tract and results in the loss of gut microbiota. One of the ways to restore the gut microbiota is through the use of probiotics. Probiotics are the 'good' bacteria that may provide health benefits if consumed in appropriate amounts. Some studies have highlighted that the consumption of probiotics in combination with prebiotics, known as synbiotics, may provide better health benefits when compared to probiotics alone. This review discusses the different nutritional approaches that have been studied in an attempt to combat chemotherapy-associated side effects in cancer patients with a particular focus on the use of pre-, pro- and synbiotics.

The objective of current study was to develop Poly(hydroxybutyrate) (PHB) based active packaging film with long lasting antimicrobial potential in food-packaging applications. For developing such films, PHB was incorporated with poly(ethylene glycol) (PEG) as a plasticizer, nano-silica (n-Si) as strengthening material and clove essential oil (CEO) as an antimicrobial agent. These solvent-casted films with varying concentration of n-Si (0.5, 1, 1.5, 2 %) and 30 % CEO of total polymer matrix weight i.e., PHB/PEG (90/10) were prepared and studied on the basis of morphological, mechanical, thermal, degradation and antimicrobial behaviours. The presence of CEO and n-Si was confirmed by Fourier transform infrared spectroscopy (FTIR). Scanning Electron Microscopy (SEM) and X-ray diffraction (XRD) were used to investigate homogeneous dispersal of n-Si in polymer matrix. PHB/PEG/CEO/Si 1.0 film was selected as optimized one after mechanical testing and therefore further carried for antimicrobial testing. This selected film extended the shelf-life of brown bread up to 10 days comparable to bread wrapped in polyethylene. This revealed that PHB/PEG/CEO/Si 1.0 exhibited superior antibacterial activity against the food borne microbes i.e., Escherichia coli, Staphylococcus aureus and Aspergillus niger. Our findings indicate that this film improved the shelf-life of packaged bread and has promising features for active food packaging., 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. Published by Elsevier B.V.)

Rice straw is a suitable alternative to a cheaper carbohydrate source for the production of ethanol. For pretreatment efficiency, different sodium hydroxide concentrations (0.5-2.5% w/v) were tested. When compared to other concentrations, rice straw processed with 2% NaOH (w/v) yielded more sugar (8.17 ± 0.01 mg/ml). An alkali treatment induces effective delignification and swelling of biomass. The pretreatment of rice straw with 2% sodium hydroxide (w/v) is able to achieve 55.34% delignification with 53.30% cellulose enrichment. The current study shows the effectiveness of crude cellulolytic preparation from Aspergillus niger resulting in 80.51 ± 0.4% cellulose hydrolysis. Rice straw hydrolysate was fermented using ethanologenic Saccharomyces cerevisiae (yeast) and Zymomonas mobilis (bacteria). Overall, superior efficiency of sugar conversion to ethanol 70.34 ± 0.3% was obtained with the yeast compared to bacterial strain 39.18 ± 0.5%. The current study showed that pretreatment with sodium hydroxide is an effective method for producing ethanol from rice straw and yeast strain S. cerevisiae having greater fermentative potential for bioethanol production than bacterial strain Z. mobilis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)