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Previous work has shown that binding of target proteins to a sparse, unbiased sample of all possible peptide sequences is sufficient to train a machine learning model that can then predict, with statistically high accuracy, target binding to any possible peptide sequence of similar length. Here, highly sequence-specific molecular recognition is explored by measuring binding of 8 monoclonal antibodies (mAbs) with specific linear cognate epitopes to an array containing 121,715 near-random sequences about 10 residues in length. Network models trained on resulting sequence-binding values are used to predict the binding of each mAb to its cognate sequence and to an in silico generated one million random sequences. The model always ranks the binding of the cognate sequence in the top 100 sequences, and for 6 of the 8 mAbs, the cognate sequence ranks in the top ten. Practically, this approach has potential utility in selecting highly specific mAbs for therapeutics or diagnostics. More fundamentally, this demonstrates that very sparse random sampling of a large amino acid sequence spaces is sufficient to generate comprehensive models predictive of highly specific molecular recognition., (© 2024. The Author(s).)

Skin sensitization is a key endpoint for safety assessment, especially for cosmetics and personal care products. The adverse outcome pathway for skin sensitization and the chemical and biological events driving the induction of human skin sensitization are now well understood. Several non-animal test methods have been developed to predict sensitizer potential by measuring the impact of chemical sensitizers on these key events. In this work, we have focused on Key Event 1 (the molecular initiating step), which is based on formation of a covalent adduct between skin sensitizers and endogenous proteins and/or peptides in the skin. There exists three in-chemico assays approved by the Organization for Economic Co-operation and Development-(1) Direct Peptide Reactivity Assay (DPRA), (2) Amino Acid Derivative Reactivity Assay (ADRA), and (3) Kinetic Direct Peptide Reactivity Assay (kDPRA) to quantify peptide/amino acid derivative depletion after incubation with test chemicals. However, overestimated depletion of the cysteine-based peptide/amino acid derivatives is known in such assays because of the dimerization of the thiol group. In this present work, we report the synthesis and structural confirmation of the dimer of N-(2-[1-naphthyl]acetyl)-L-cysteine (NAC) from the ADRA assay to allow simultaneous determination of (a) peptide depletion by quantifying NAC monomer and (b) peptide dimerization by quantifying NAC dimer thereby eliminating the overestimation. We present a case study with three chemicals to demonstrate the importance of this approach. Thus, this simultaneous assay gives a more informed view of the peptide reactivity of chemicals to better identify skin sensitizers., (© 2024 John Wiley & Sons Ltd.)

Detection and discrimination of similar solvation energies of bioanalytes are vital in medical and practical applications. Currently, various advanced techniques are equipped to recognize these crucial bioanalytes. Each strategy has its own benefits and limitations. One-dimensional response, lack of discrimination power for anions, and reactive oxygen species (ROS) generally limit the utilized fluorescent probe. Therefore, a cutting-edge, refined method is expected to conquer these limitations. The use of 19 F NMR spectroscopy for detecting and discriminating essential analytes in practical applications is an emerging technique. As an alternative strategy, we report two fluorinated boronic acid-appended pyridinium salts 5-F-o-BBBpy ( 1 ) and 5-CF 3 -o-BBBpy ( 2 ). Probe ( 1 ) acts as a chemosensor for identifying and discriminating inorganic anions with similar solvation energies with strong bidirectional 19 F shifts in the lower ppm range. Probe ( 2 ) turns as a chemo dosimeter for the selective detection and precise quantification of hydrogen peroxide (H 2 O 2 ) among other competing ROS. To demonstrate real-life applicability, we successfully quantified H 2 O 2 via probe ( 2 ) in different pharmaceutical, dental, and cosmetic samples. We found that tuning the -F/-CF 3 moiety to the arene boronic acid enables the π-conjugation, a crucial prerequisite for the discrimination of anions and H 2 O 2 . Characteristic 19 F NMR fingerprints in the presence of anions revealed a complementary implication (IMP)/not implication (NIMP) logic function. Finally, the 16 distinct binary Boolean operations on two logic values are defined for " functional completeness " using the special property of the IMP gate. Boolean logic's ability to handle information by utilizing characteristic 19 F NMR fingerprints has not been seen previously in a single chemical platform for detecting and differentiating such anions.

Background: Phantom limb pain (PLP) is a prevalent and distressing occurrence in 60-80% of individuals who have undergone amputations. Recent research underscores the significance of maladaptive cortical plasticity in the genesis of PLP, emphasizing the importance of targeting cortical areas for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive tool for cortical stimulation, demonstrates effectiveness in treating various chronic pain conditions of neuropathic origin. Nevertheless, there exists a limited body of research investigating the application of rTMS as a therapeutic intervention specifically for managing PLP. Notably, the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in central pain processing, suggesting its potential as a key therapeutic target in PLP treatment. There is a lack of adequate data regarding the effectiveness of DLPFC-targeting rTMS in alleviating the pain experienced by PLP patients., Objective: In this study, our aim was to investigate the impact of 10 sessions of DLPFC-targeting rTMS on the pain status of individuals experiencing PLP., Study Design: Randomized controlled trial., Setting: Traumatic amputees reporting to the tertiary care center with PLP., Methods: The study was approved by the Institute Ethics Committee (IECPG-299/27.04.2022) and registered in the Clinical Trials Registry of India (CTRI/2022/07/043938). Nineteen patients suffering from PLP were recruited and randomized into real or sham rTMS groups. In the real rTMS group, patients received 10 sessions of rTMS at the DLPFC contralateral to the amputation site. The rTMS, administered at 90% of the resting motor threshold (RMT), was delivered as 8 trains of 150 pulses per train at the rate of one Hz and an inter-train interval of 60 seconds. The total number of pulses per session was 1,200. The sham group received 10 sessions of sham rTMS through the perpendicular placement of an rTMS coil over the DLPFC. These sessions lasted for the same duration and included the same sounds as the real group but involved no active stimulation. The patients' pain status was evaluated using the Visual Analog Scale (VAS) at baseline, at the end of each session of real or sham rTMS and at the 15th, 30th, and 60th day after the the completion of real or sham therapy., Results: A significant decrease in VAS scores was noted after 10 sessions of real rTMS that targeted the DLPFC, in contrast to the sham rTMS group. The real rTMS group's reduction in VAS scores also persisted during the follow-up., Limitations: A few patients had to drop out due to physical restrictions and financial constraints. Consequently, only a small number of individuals were able to complete the study protocol successfully., Conclusion: A regimen of 10 sessions of real rTMS of the DLPFC was associated with significant pain relief in patients with PLP, and the effects were sustained for 2 months. Therefore, the present study shows that rTMS of the DLPFC has potential as an effective therapeutic intervention for sustained pain relief in PLP patients.

Developing early maturing lentil has the potential to minimize yield losses, mainly during terminal drought. Whole-genome resequencing (WGRS) based QTL-seq identified the loci governing earliness in lentil. The genetic analysis for maturity duration provided a good fit to 3:1 segregation (F 2 ), indicating earliness as a recessive trait. WGRS of Globe Mutant (late parent), late-flowering, and early-flowering bulks (from RILs) has generated 1124.57, 1052.24 million raw and clean reads, respectively. The QTL-Seq identified three QTLs (LcqDTF3.1, LcqDTF3.2, and LcqDTF3.3) on chromosome 3 having 246244 SNPs and 15577 insertions/deletions (InDels) and 13 flowering pathway genes. Of these, 11 exhibited sequence variations between bulks and validation (qPCR) revealed a significant difference in the expression of nine candidate genes (LcGA20oxG, LcFRI, LcLFY, LcSPL13a, Lcu.2RBY.3g060720, Lcu.2RBY.3g062540, Lcu.2RBY.3g062760, LcELF3a, and LcEMF1). Interestingly, the LcELF3a gene showed significantly higher expression in late-flowering genotype and exhibited substantial involvement in promoting lateness. Subsequently, an InDel marker (I-SP-383.9; LcELF3a gene) developed from LcqDTF3.2 QTL region showed 82.35% PVE (phenotypic variation explained) for earliness. The cloning, sequencing, and comparative analysis of the LcELF3a gene from both parents revealed 23 SNPs and InDels. Interestingly, a 52 bp deletion was recorded in the LcELF3a gene of L4775, predicted to cause premature termination of protein synthesis after 4 missense amino acids beyond the 351st amino acid due to the frameshift during translation. The identified InDel marker holds significant potential for breeding early maturing lentil varieties., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Calpain role has been shown in the cumulus cell-oocyte complexes and, corpus luteum. We investigated the association of calpains-1 and -2 in ovarian folliculogenesis using the Sprague-Dawley (SD) rat model and steroidogenesis in the human granulosa cells (hGCs). We induced PCOS in 42-day-old SD rats by letrozole oral gavage for 21 days. Premature ovarian failure (POF) was induced in 21-day-old SD rats by 4-vinylcyclohexene diepoxide (VCD). Ovulation and ovarian hyperstimulatory (OHS) syndrome were induced by pregnant mare gonadotropin (PMSG) + human chorionic gonadotropin (hCG) treatments in 21 days SD rats, respectively. Steroidogenesis is stimulated in human granulosa cells (hGCs) by forskolin and the response of 17-beta-estradiol (E2) on calpains expression was checked in hGCs. The protein expression by immunoblotting and activity by biochemical assay of calpains-1 and -2 showed an oscillating pattern in the ovarian cycle. PMSG-induced follicular recruitment showed upregulation of calpains-1 and -2, but with no change during ovarian function cessation (POF). Upregulated calpain-2 expression and calpain activity was found in the hCG +PMSG-induced ovulation. Letrozole-induced PCOS showed downregulation of calpain-1, but upregulation of calpain-2. PMSG+hCG-induced OHS led to the upregulation of calpain-1. Letrozole and metformin separately increased the expression level of calpains-1 and -2 in the hGCs during luteinization. In conclusion, the expression levels of calpains -1 and -2 are increased with ovarian follicular recruitment by PMSG and calpain-1 is decreased in the PCOS condition, and letrozole and metformin upregulate the expression of calpains-1 and -2 during luteinization in the hGCs possibly via E2 action., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in this manuscript., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

The rich diversity of microbial endophytic communities associated with plants, often referred to as the second genome, serves as a compelling illustration of efficient co-evolution. This noteworthy partnership plays a pivotal role in sustaining plant well-being and enhancing plant adaptability across diverse habitats. Therefore, examining the diversity of endophytic microbes associated with their particular host plant is valuable for gaining insights into the vast spectrum of plant-microbe interactions. The present experiments aimed at investigating the bacterial endophytic diversity in both root and shoot tissues of Pelargonium graveolens, employing culture dependent and culture independent high-throughput metagenomics approach. A total of 614 and 620 operational taxonomic units (OTUs), encompassing 291 and 229 genera, were identified in the shoot and root tissues of P. graveolens, respectively. Furthermore, the subsequent classification of OTUs revealed 15 highly abundant phyla, with Proteobacteria dominating both root and shoot tissues. Notably, an exceptionally high abundance of Firmicutes phyla was observed in the shoot compared to the root. Additionally, 30 bacterial endophytes from the root, stem, petiole, and leaves were isolated and molecularly characterized, unveiling a consistent pattern of diversity distribution between the root and shoot of P. graveolens. Upon screening all isolates for plant growth promoting traits, Pseudomonas oryzihabitans was found to be positive for major biochemical test like nitrogen fixation, phosphate solubilization etc. and on inoculation resulted in about two-fold increase in content of essential oil accompanied by a significant rise in the geraniol and citronellol content. Diving deep into the genetic constitution of P. oryzihabitans unveiled a substantial number of genes directly and indirectly contributing to the endophyte's capability in colonizing host plants effectively. In summary, data obtained from metagenomics and culture dependent approaches including glass house trials suggest potential bacterial endophytes suitable for field applications for yield enhancement and in planta secondary metabolite enhancement investigations., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Post-mastectomy pain Syndrome (PMPS), characterized by chronic neuropathic pain stemming from intercostobrachial nerve lesions, presents a formidable clinical challenge. With the incidence of breast cancer surging, effective interventions for PMPS are urgently needed. To address this, we conducted this double-blind, placebo-controlled, randomized clinical trial to study the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) therapy over the motor cortex on pain, quality of life and thermal sensitivity in PMPS patients., Methods: We delivered 15 rTMS sessions over three weeks in a cohort of 34 PMPS patients. These patients were allocated randomly to either rTMS therapy or sham therapy groups. Pain assessments, utilizing the Visual Analogue Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), alongside quality-of-life evaluations through the Functional Assessment of Cancer Therapy-Breast (FACT-B), were recorded before and after the 15 sessions. Additionally, we assessed thermal sensitivity using Quantitative Sensory Testing (QST)., Results: Our findings demonstrate the superior efficacy of rTMS therapy (over sham therapy) in reducing VAS and SF-MPQ scores (p < 0.0001), improving physical (p = 0.037), emotional (p = 0.033), and functional well-being (p = 0.020) components of quality of life, as quantified by FACT-B. Our investigation also unveiled marked enhancements in thermal sensitivity within the rTMS therapy group, with statistically significant improvements in cold detection threshold (p = 0.0001), warm detection threshold (p = 0.0033), cold pain threshold (p = 0.0078), and hot pain tolerance threshold (p = 0.0078)., Conclusion: The study underscores the profound positive impact of rTMS therapy on pain, quality of life, and thermal sensitivity in patients having PMPS, opening new avenues for pain management strategies., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: Curcumin (Curcuma longa) is a well-known medicinal plant that induces autophagy in various model species, helping maintain cellular homeostasis. Its role as a caloric restriction mimetic (CRM) is being investigated. This study explores the potential of curcumin (CUR), as a CRM, to provide neuroprotection in D galactose induced accelerated senescence model of rats through modulation of autophagy. For six weeks, male rats received simultaneous supplementation of D-gal (300 mg/kg b.w., subcutaneously) and CUR (200 mg/kg b.w., oral)., Method and Results: The oxidative stress indices, antioxidants, and electron transport chain complexes in brain tissues were measured using standard methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) gene expression analysis was used to evaluate the expression of autophagy, neuroprotection, and aging marker genes. Our results show that curcumin significantly (p ≤ 0.05) enhanced the level of antioxidants and considerably lowered the level of oxidative stress markers. Supplementing with CUR also increased the activity of electron transport chain complexes in the mitochondria of aged brain tissue, demonstrating the antioxidant potential of CUR at the mitochondrial level. CUR was found to upregulate the expression of the aging marker gene (SIRT-1) and the genes associated with autophagy (Beclin-1 and ULK-1), as well as neuroprotection (NSE) in the brain. The expression of IL-6 and TNF-α was downregulated., Conclusion: Our findings demonstrate that CUR suppresses oxidative damage brought on by aging by modulating autophagy. These findings imply that curcumin might be beneficial for neuroprotection in aging and age-related disorders., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The systematic identification of insertion/deletion (InDel) length polymorphisms from the entire lentil genome can be used to map the quantitative trait loci (QTL) and also for the marker-assisted selection (MAS) for various linked traits. The InDels were identified by comparing the whole-genome resequencing (WGRS) data of two extreme bulks (early- and late-flowering bulk) and a parental genotype (Globe Mutant) of lentil. The bulks were made by pooling 20 extreme recombinant inbred lines (RILs) each, derived by crossing Globe Mutant (late flowering parent) with L4775 (early flowering parent). Finally, 734,716 novel InDels were identified, which is nearly one InDel per 5,096 bp of lentil genome. Furthermore, 74.94% of InDels were within the intergenic region and 99.45% displayed modifier effects. Of these, 15,732 had insertions or deletions of 20 bp or more, making them amenable to the development of PCR-based markers. An InDel marker I-SP-356.6 (chr. 3; position 356,687,623; positioned 174.5 Kb from the LcFRI gene) was identified as having a phenotypic variance explained (PVE) value of 47.7% for earliness when validated in a RIL population. Thus, I-SP-356.6 marker can be deployed in MAS to facilitate the transfer of the earliness trait to other elite late-maturing cultivars. Two InDel markers viz., I-SP-356.6 and I-SP-383.9 (chr. 3; linked to LcELF3a gene) when tested in 9 lentil genotypes differing for maturity duration, clearly distinguished three early (L4775, ILL7663, Precoz) and four late genotypes (Globe Mutant, MFX, L4602, L830). However, these InDels could not be validated in two genotypes (L4717, L4727), suggesting either absence of polymorphism and/or presence of other loci causing earliness. The identified InDel markers can act as valuable tools for MAS for the development of early maturing lentil varieties., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shivaprasad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: As surgery is an essential aspect of healthcare around the globe, it is necessary to consider complications related to it. Therefore, this study was conducted to evaluate the impact of the World Health Organization Surgical Safety Checklist (WHO SSC) on reducing the incidence of postoperative complications Methods : This single-center, prospective, comparative study was conducted at the Department of Gynecology and Obstetrics in a government hospital in Patna, Bihar. To assess the efficacy of the WHO SSC, the patients were divided into two groups, in which one group undergoing surgery was assessed with the checklist, and the other group was not. The rates of surgery-related complications were then compared in both groups., Results: Our results showed a reduction in surgery-related complications in patients assessed with the WHO SSC. No statistically significant difference in duration of surgery was found between the groups. However, a statistically significant difference was observed in the rates of surgery-related complications between groups, especially in sepsis (p = 0.0009), hemorrhage (p < 0.0001), and infection at the site of surgery (p < 0.0001). Mortality rates were not affected by the use of the SSC., Conclusion: The WHO SSC is a simple yet effective tool for reducing postoperative complications by improving communication between the various team members working in the operation theatre, although it has no effect on reducing mortality. Further research is needed to enhance its successful implementation and ensure its sustained use., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Amrita et al.)

Key Message: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Rich data on diverse patients and their treatments and outcomes within Electronic Health Record (EHR) systems can be used to generate real world evidence. A health recommender system (HRS) framework can be applied to a decision support system application to generate data summaries for similar patients during the clinical encounter to assist physicians and patients in making evidence-based shared treatment decisions., Objective: A human-centered design (HCD) process was used to develop a HRS for treatment decision support in orthopaedic medicine, the Informatics Consult for Individualized Treatment (I-C-IT) . We also evaluate the usability and utility of the system from the physician's perspective, focusing on elements of utility and shared decision-making in orthopaedic medicine., Methods: The HCD process for I-C-IT included 6 steps across three phases of analysis, design, and evaluation. A team of informaticians and comparative effectiveness researchers directly engaged with orthopaedic surgeon subject matter experts in a collaborative I-C-IT prototype design process. Ten orthopaedic surgeons participated in a mixed methods evaluation of the I-C-IT prototype that was produced., Results: The HCD process resulted in a prototype system, I-C-IT, with 14 data visualization elements and a set of design principles crucial for HRS for decision support. The overall standard system usability scale (SUS) score for the I-C-IT Webapp prototype was 88.75 indicating high usability. In addition, utility questions addressing shared decision-making found that 90% of orthopaedic surgeon respondents either strongly agreed or agreed that I-C-IT would help them make data informed decisions with their patients., Conclusion: The HCD process produced an HRS prototype that is capable of supporting orthopaedic surgeons and patients in their information needs during clinical encounters. Future research should focus on refining I-C-IT by incorporating patient feedback in future iterative cycles of system design and evaluation., Competing Interests: Competing interests: The authors declare that they have no competing interests. Additional Declarations: No competing interests reported.

Exitrons are exonic introns. This subclass of intron retention alternative splicing does not contain a Pre-Terminating stop Codon. Therefore, when retained, they are always a part of a protein. Intron retention is a frequent phenomenon predominantly found in plants, which results in either the degradation of the transcripts or can serve as a stable intermediate to be processed upon induction by specific signals or the cell status. Interestingly, exitrons have coding ability and may confer additional attributes to the proteins that retain them. Therefore, exitron-containing and exitron-spliced isoforms will be a driving force for creating protein diversity in the proteome of an organism. This review establishes a basic understanding of exitron, discussing its genesis, key features, identification methods and functions. We also try to depict its other potential roles. The present review also aims to provide a fundamental background to those who found such exitronic sequences in their gene(s) and to speculate the future course of studies., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company.)

MicroRNAs (miRNAs) play a crucial role in cancer progression by selectively inducing translational degradation of messenger RNA (mRNA) via sequence-specific interactions with the 3'-untranslated region (3'-UTR). The potential targeting of miRNA has been recognized as a significant avenue for investigating the biological progression of diverse cancer types. Consequently, targeting of pri-miRNA and pre-miRNA by phytochemicals emerges as a viable strategy in the realm of anticancer therapies. Among phytochemicals, triterpenoids have garnered significant recognition for their chemotherapeutic and chemopreventive capabilities in combating multiple cancers. To date, there is a dearth of literature about the molecular interactions between triterpenoids and miRNAs. The primary objective of this investigation is to discern the potential triterpenoids that can function as modulators for specific miRNAs, namely pri-miRNA-19b-2, pre-miR21, microRNA 20b, pri-miRNA-208a, pri-miRNA-378a, pri-miRNA-320b-2, and pri-miRNA-300, achieved through the use of in silico investigations. The study primarily focused on performing drug-likeness, computer-aided toxicity, and pharmacokinetic prediction studies for triterpenoids. Furthermore, molecular docking and simulation techniques were employed to investigate these compounds. The triterpenoids studied were shown to have drug-likeness characteristics, although asiatic acid, lupeol, and pristimerin were able to pass all toxicity tests. Among the triterpenoids that underwent docking, pristimerin had a significant binding energy of -10.9 kcal/mol during its interaction with pri-miR-378a. The stable interaction between the pristimerin and miRNA complex was demonstrated by molecular dynamics simulation. As a result, pristimerin has the potential to act as a modulator of carcinogenic miRNAs, making it a promising candidate for cancer prevention and treatment due to its tailored modulation of miRNA activity., 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 B.V. All rights reserved.)

Aims: This retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management., Methods: This study was done on liver archival tissue of our department from the period of January 2016 to December 2022. Of these, cases of copper overload on paediatric biopsies were retrieved. The histopathological features were scrutinised independently by three pathologists, correlating with their clinico-radiological investigations., Results: Five children in infancy to middle childhood presented with features of chronic liver disease in the form of jaundice and abdominal distention, were included in the study. Characteristic firm hepatomegaly with sharp margins and transaminitis was noted in all cases. Autoimmune, viral and metabolic workup were negative in all these patients except one which showed positive autoimmunity and another whose Coomb's test was positive. Normal ceruloplasmin levels and unremarkable slit lamp examination excluded the possibility of Wilson's disease. The histological features of marked ballooning degeneration with diffuse Mallory Denk, pericellular fibrosis, absence of steatosis and panlobular copper deposits clinched the diagnosis of ICC., Conclusions: ICC once believed to be extinct has still not vanished and remains underdiagnosed in routine practice. It is a rapidly fatal disease with a debatable pattern of inheritance and controversial role of copper as etiological agent. The clinical presentation is often deceptive and lack of awareness leads to misdiagnosis. Histopathological attributes are pathognomonic and possibility of ICC should be kept in all cases of cryptogenic cirrhosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The causal attributions we make to the events in our lives reflect our Cognitive Style. The use of substances can be precipitated by stressful life events, and substance use can be a result of maladaptive coping to alleviate negative effects in stressful situations. So, individuals with substance dependence may infer situations differently. The inferences made about the cause of these stressful events can give an understanding of their cognition and can further help in therapeutic interventions. Purpose The present study aims to assess the cognitive style of young patients with substance use disorder. Methods A cross-sectional research design was used and a total of 50 participants were chosen through purposive sampling from the in-patient departments of Psychiatric Hospitals and De-addiction centers. The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to assess the specific substances used by the patients and the Cognitive Style Questionnaire-Short form (CSQ-SF) was used to assess the negative cognitive style of the patients. Results Results revealed a more negative cognitive style among young patients with Dual Substance Use than patients with Multiple Substance Use, indicating that patients with Substance Use Disorder tend to attribute stressful events to causes like internal (because of self), global (applicable to all domains of life) and stable (consistent), as well as the negative consequences (leading to other bad things) and self-worth implications (something wrong in self)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Chawla et al.)

Over the last few decades, an alarming rise in the percentage of individuals with cancer and those with multi-resistant illnesses has forced researchers to explore possibilities for novel therapeutic approaches. Numerous medications currently exist to treat various disorders, and the development of small molecules as anticancer agents has considerable potential. However, the widespread prevalence of resistance to multiple drugs in cancer indicates that it is necessary to discover novel and promising compounds with ideal characteristics that could overcome the multidrug resistance issue. The utilisation of metallo-drugs has served as a productive anticancer chemotherapeutic method, and this approach may be implemented for combating multi-resistant tumours more successfully. Schiff bases have been receiving a lot of attention as a group of compounds due to their adaptable metal chelating abilities, innate biologic properties, and versatility to tweak the structure to optimise it for a specific biological purpose. The biological relevance of Schiff base and related complexes, notably their anticancer effects, has increased in their popularity as bio-inorganic chemistry has progressed. As a result of learning about Schiff bases antitumor efficacy against multiple cancer cell lines and their complexes, researchers are motivated to develop novel, side-effect-free anticancer treatments. According to study reports from the past ten years, we are still seeking a powerful anticancer contender. This study highlights the potential of Schiff bases, a broad class of chemical molecules, as potent anticancer agents. In combination with other anticancer strategies, they enhance the efficacy of treatment by elevating the cytotoxicity of chemotherapy, surmounting drug resistance, and promoting targeted therapy. Schiff bases also cause cancer cell DNA repair, improve immunotherapy, prevent angiogenesis, cause apoptosis, and lessen the side effects of chemotherapy. The present review explores the development of potential Schiff base and their d and f block metal complexes as anticancer agents against various cancer cell lines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Objectives: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants., Methods: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants., Results: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination., Interpretation Conclusions: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant., (Copyright © 2024 Copyright: © 2024 Indian Journal of Medical Research.)

Background: The COVID-19 pandemic influenced many to consider methods to reduce human contact and ease the burden placed on health care workers. Conversational agents or chatbots are a set of technologies that may aid with these challenges. They may provide useful interactions for users, potentially reducing the health care worker burden while increasing user satisfaction. Research aims to understand these potential impacts of chatbots and conversational recommender systems and their associated design features., Objective: The objective of this study was to evaluate user perceptions of the helpfulness of an artificial intelligence chatbot that was offered free to the public in response to COVID-19. The chatbot engaged patients and provided educational information and the opportunity to report symptoms, understand personal risks, and receive referrals for care., Methods: A cross-sectional study design was used to analyze 82,222 chats collected from patients in South Carolina seeking services from the Prisma Health system. Chi-square tests and multinomial logistic regression analyses were conducted to assess the relationship between reported risk factors and perceived chat helpfulness using chats started between April 24, 2020, and April 21, 2022., Results: A total of 82,222 chat series were started with at least one question or response on record; 53,805 symptom checker questions with at least one COVID-19-related activity series were completed, with 5191 individuals clicking further to receive a virtual video visit and 2215 clicking further to make an appointment with a local physician. Patients who were aged >65 years (P<.001), reported comorbidities (P<.001), had been in contact with a person with COVID-19 in the last 14 days (P<.001), and responded to symptom checker questions that placed them at a higher risk of COVID-19 (P<.001) were 1.8 times more likely to report the chat as helpful than those who reported lower risk factors. Users who engaged with the chatbot to conduct a series of activities were more likely to find the chat helpful (P<.001), including seeking COVID-19 information (3.97-4.07 times), in-person appointments (2.46-1.99 times), telehealth appointments with a nearby provider (2.48-1.9 times), or vaccination (2.9-3.85 times) compared with those who did not perform any of these activities., Conclusions: Chatbots that are designed to target high-risk user groups and provide relevant actionable items may be perceived as a helpful approach to early contact with the health system for assessing communicable disease symptoms and follow-up care options at home before virtual or in-person contact with health care providers. The results identified and validated significant design factors for conversational recommender systems, including triangulating a high-risk target user population and providing relevant actionable items for users to choose from as part of user engagement., (©Akanksha Singh, Benjamin Schooley, Nitin Patel. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 14.12.2023.)

Curcumin, a biphenolic substance derived from turmeric ( Curcuma longa ), offers a number of health-beneficial effects, including anti-inflammatory, cardiovascular protection, anti-cancerous, and anti-angiogenic. By interacting with the PPARγ (Peroxisome Proliferator-Activated Receptor-γ), curcumin inhibits NF-κB. These biological outcomes seem to be the outcome of NF-κB inhibition mediated by curcumin. The current study explores the in vivo impact of curcumin on several inflammatory parameters during aging in Wistar rats. An in-silico docking simulation study using Maestro and Desmond, Schrödinger, was carried out to further validate the experimental findings. According to our observation, rats given curcumin supplementation had a considerably ( p  ≤ 0.05) reduced level of inflammation. By generating numerous polar and hydrophobic interactions and exhibiting little conformational deviation throughout the simulation, in silico investigations showed that the proposed ligand curcumin had a high affinity for the enzyme COX-2. During simulation, protein-ligand complexes of curcumin with the other targets viz. 5-LOX, TNF-α and IL-6 also demonstrated improved binding and minimal fluctuation. The COX-2 and 5-LOX enzymes and the cytokines (TNF-α and IL-6) implicated in inflammation may have been inhibited by curcumin, highlighting its function as a multi-target inhibitor. Our study provides convincing support for the idea that eating a diet high in curcumin may help to reduce inflammation and help to explain some of its health-beneficial effects.Communicated by Ramaswamy H. Sarma.

The field of injectable hydrogels has demonstrated a paramount headway in the myriad of biomedical applications and paved a path toward clinical advancements. The innate superiority of hydrogels emerging from organic constitution has exhibited dominance in overcoming the bottlenecks associated with inorganic-based hydrogels in the biological milieu. Inorganic hydrogels demonstrate various disadvantages, including limited biocompatibility, degradability, a cumbersome synthesis process, high cost, and ecotoxicity. The excellent biocompatibility, eco-friendliness, and manufacturing convenience of organo-hydrogels have demonstrated to be promising in therapizing biomedical complexities with low toxicity and augmented bioavailability. This report manifests the realization of biomimetic organo-hydrogels with the development of bioresponsive and self-healing injectable organo-hydrogels in the emerging pharmaceutical revolution. Furthermore, the influence of click chemistry in this regime as a backbone in the pharmaceutical conveyor belt has been suggested to scale up production. Moreover, we propose an avant-garde design stratagem of developing a hyaluronic acid (HA)-based injectable organo-hydrogel via click chemistry to be realized for its pharmaceutical edge. Ultimately, injectable organo-hydrogels that materialize from academia or industry are required to follow the standard set of rules established by global governing bodies, which has been delineated to comprehend their marketability. Thence, this perspective narrates the development of injectable organo-hydrogels via click chemistry as a prospective elixir to have in the arsenal of pharmaceuticals.

Flavour molecules are generated now-a-days through microbial fermentation on a commercial scale. γ-Decalactone (GDL) is an important molecule due to its long-lasting flavouring impact as buttery, coconut and peach-type. In the current study, 33 microorganisms were isolated from different fruit sources, and their screening for target GDL production was performed. Using DNA sequencing, two potential strains yielding good amounts of GDL were identified from pineapple and strawberry fruits. The identified strains were Metschnikowia vanudenii (OP954735) and Candida parapsilosis (OP954733), and further optimized by Taguchi method. The effectiveness of lactone production is influenced by the rate of microbial growth under various operating conditions. The factors such as substrate concentration, pH, temperature, cell density and rotation (rpm) with 3 levels were applied for the GDL production using M. vanudenii (OP954735) and C. parapsilosis (OP954733) strains. The results revealed that the highest molar conversion of GDL was 24.69% (115.7 mg/g quantitative yield) and 52.69% (272.0 mg/g quantitative yield) at the optimal conditions using SB-62 and PA-19 strains, respectively. The two novel strains are reported for the first time for production of γ-decalactone and overall, this study opens up the possibility of using Taguchi design for large scale up process development for producing food flavours utilising environmentally friendly natural strains., 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 B.V. All rights reserved.)

Many plants possess immense pharmacological properties because of the presence of various therapeutic bioactive secondary metabolites that are of great importance in many pharmaceutical industries. Therefore, to strike a balance between meeting industry demands and conserving natural habitats, medicinal plants are being cultivated on a large scale. However, to enhance the yield and simultaneously manage the various pest infestations, agrochemicals are being routinely used that have a detrimental impact on the whole ecosystem, ranging from biodiversity loss to water pollution, soil degradation, nutrient imbalance and enormous health hazards to both consumers and agricultural workers. To address the challenges, biological eco-friendly alternatives are being looked upon with high hopes where endophytes pitch in as key players due to their tight association with the host plants. The intricate interplay between plants and endophytic microorganisms has emerged as a captivating subject of scientific investigation, with profound implications for the sustainable biosynthesis of pharmaceutically important secondary metabolites. This review delves into the hidden world of the "secret wedlock" between plants and endophytes, elucidating their multifaceted interactions that underpin the synthesis of bioactive compounds with medicinal significance in their plant hosts. Here, we briefly review endophytic diversity association with medicinal plants and highlight the potential role of core endomicrobiome. We also propose that successful implementation of in situ microbiome manipulation through high-end techniques can pave the way towards a more sustainable and pharmaceutically enriched future., (© 2023. The Author(s).)

Central Arctic, interglacial intervals have traditionally been associated with diverse and intense bioturbation, and abundant foraminifera, interpreted as indicating relatively low sea-ice concentrations and productive surface waters, while glacial intervals, typically barren, support the inverse. In this respect, the Yermak Plateau is anomalous. Biomarker studies suggest that glacial intervals were characterized by comparatively open water, while interglacials are marked by severe sea-ice conditions. Here we study downcore Ethological Ichno Quotient (EIQ) variations in trace fossils and bioturbation to test the hypothesis that different ethological classes vary in accordance with late Pleistocene changes in sea-ice extent, with deposit feeders increasing during reduced sea-ice cover and chemosymbiotic traces increasing during periods of thick perennial sea-ice conditions. Our results generally demonstrate that the abundance of traces like Planolites, Scolicia, and burrows produced by deposit feeders increase during episodes of seasonal sea-ice cover. In contrast, intervals with more severe sea-ice conditions are characterized by chemosymbiotic traces such as Chondrites and Trichichnus/Mycellia, suggesting lower food delivery and poorly ventilated bottom water conditions. The study thus confirms previous reconstructions of sea-ice conditions on the Yermak Plateau during interglacials, demonstrating that bioturbation variation provides insights into bentho-pelagic coupling under variable sea ice regimes in the Arctic Ocean., (© 2023. Springer Nature Limited.)

Grasspea ( Lathyrus sativus L.) is recognized as a highly drought-tolerant legume. However, excessive consumption of its seeds and green tissues causes neurolathyrism, a condition characterized by an irreversible paralysis of the legs induced by a neurotoxin amino acid called β-N-oxalyl-L-α, β- diaminopropionic acid (β-ODAP). The present study investigated the effects of heat, and combined heat + drought during the reproductive phase on physiological and phenological parameters, yield-related factors, ODAP content, and seed protein of 24 genotypes representing 11 Lathyrus species under controlled conditions. Analysis of variance revealed a highly significant effect ( p < 0.001) of stress treatments and genotypes for all the traits. In general, heat stress individually or in combination with drought expedited phenology, reduced relative leaf water content, stimulated proline synthesis, and influenced chlorophyll concentration; the effects were more severe under the combined heat + drought stress. ODAP content in seeds ranged from 0.06 to 0.30% under no-stress conditions. However, under heat stress, there was a significant increase of 33% in ODAP content, and under combined stress (heat + drought), the increase reached 83%. Crude protein content ranged from 15.64 to 28.67% among no stress plants and decreased significantly by 23% under heat stress and by 36% under combined stress. The findings of this study also indicated substantial reductions in growth and grain yield traits under both heat stress and combined heat + drought stress. Six accessions namely IG 66026 , IG 65018 , IG 65687 , IG 118511 , IG 64931 , and IG65273 were identified as having the most favorable combination of yield, protein content, and seed ODAP levels across all conditions. ODAP content in these six accessions varied from 0.07 to 0.11% under no stress and remained at moderate levels during both heat stress (0.09-0.14%) and combined stress (0.11-0.17%). IG 66026 was identified as the most stable genotype under drought and heat stress conditions with high protein content, and low ODAP content. By identifying those promising accessions, our results have established a basis for forthcoming grasspea breeding initiatives while paving the way for future research exploration into the fundamental mechanisms driving ODAP variation in the presence of both heat and drought stress conditions.

Mungbean ( Vigna radiata L. Wilczek) is one of the important warm-season food legumes, contributing substantially to nutritional security and environmental sustainability. The genetic complexity of yield-associated agronomic traits in mungbean is not well understood. To dissect the genetic basis of phenological and agronomic traits, we evaluated 153 diverse mungbean genotypes for two phenological (days to heading and days to maturity) and eight agronomic traits (leaf nitrogen status using SPAD, plant height, number of primary branches, pod length, number of pods per plant, seeds per pod, 100-seed weight, and yield per plant) under two environmental conditions. A wide array of phenotypic variability was apparent among the studied genotypes for all the studied traits. The broad sense of heritability of traits ranged from 0.31 to 0.95 and 0.21 to 0.94 at the Delhi and Ludhiana locations, respectively. A total of 55,634 genome-wide single nucleotide polymorphisms (SNPs) were obtained by the genotyping-by-sequencing method, of which 15,926 SNPs were retained for genome-wide association studies (GWAS). GWAS with Bayesian information and linkage-disequilibrium iteratively nested keyway (BLINK) model identified 50 SNPs significantly associated with phenological and agronomic traits. In total, 12 SNPs were found to be significantly associated with phenological traits across environments, explaining 7%-18.5% of phenotypic variability, and 38 SNPs were significantly associated with agronomic traits, explaining 4.7%-27.6% of the phenotypic variability. The maximum number of SNPs (15) were located on chromosome 1, followed by seven SNPs each on chromosomes 2 and 8. The BLAST search identified 19 putative candidate genes that were involved in light signaling, nitrogen responses, phosphorus (P) transport and remobilization, photosynthesis, respiration, metabolic pathways, and regulating growth and development. Digital expression analysis of 19 genes revealed significantly higher expression of 12 genes, viz . VRADI01G08170 , VRADI11G09170 , VRADI02G00450 , VRADI01G00700 , VRADI07G14240 , VRADI03G06030 , VRADI02G14230 , VRADI08G01540 , VRADI09G02590 , VRADI08G00110 , VRADI02G14240 , and VRADI02G00430 in the roots, cotyledons, seeds, leaves, shoot apical meristems, and flowers. The identified SNPs and putative candidate genes provide valuable genetic information for fostering genomic studies and marker-assisted breeding programs that improve yield and agronomic traits in mungbean., 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 Manjunatha, Aski, Mishra, Gupta, Devate, Singh, Bansal, Kumar, Nair and Dikshit.)

Over the past ten years, microfluidic paper-based analytical devices (micro-PADs) have attracted a lot of attention as a viable analytical platform. It is expanding as a result of advances in manufacturing processes and device integration. Conventional microfluidics approaches have some drawbacks, including high costs, lengthy evaluation times, complicated fabrication, and the necessity of experienced employees. Hence, it is extremely important to construct a detection system that is quick, affordable, portable, and efficient. Nowadays, micro-PADs are frequently employed, particularly in electrochemical analyses, to replicate the classic standard laboratory experiments on a miniature paper chip. It has benefits like rapid assessment, small sample consumption, quick reaction, accuracy, and multiplex function. The goal of this review is to examine modern paper microfluidics-based electrochemical sensing devices for the detection of macromolecules, small molecules, and cells in a variety of real samples. The design and fabrication of micro-PADs using conventional and the latest techniques have also been discussed in detail. Lastly, the limitations and potential of these analytical platforms are examined in order to shed light on future research.

Polycystic ovary syndrome (PCOS) is most common in women of reproductive age, giving rise to androgen excess and anovulation, leading to infertility and non-reproductive complications. We explored the ameliorating effect of naringenin in PCOS using the Sprague Dawley (SD) rat model and human granulosa cells. Letrozole-induced PCOS rats were given either naringenin (50 mg/kg/day) alone or in combination with metformin (300 mg/kg/day), followed by the estrous cycle, hormonal analysis, and glucose sensitivity test. To evaluate the effect of naringenin on granulosa cell (hGC) steroidogenesis, we treated cells with naringenin (2.5 μM) alone or in combination with metformin (1 mM) in the presence of forskolin (10 μM). To determine the steroidogenesis of CYP-17A1, -19A1, and 3βHSD2, the protein expression levels were examined. Treatment with naringenin in the PCOS animal groups increased ovulation potential and decreased cystic follicles and levels of androgens. The expression levels of CYP-17A1, -19A1, and 3βHSD2, were seen restored in the ovary of PCOS SD rats' model and in the human ovarian cells in response to the naringenin. We found an increased expression level of phosphorylated-AKT in the ovary and hGCs by naringenin. Naringenin improves ovulation and suppress androgens and cystic follicles, involving AKT activation., (© 2023 John Wiley & Sons Ltd.)

Crop domestication and the subsequent expansion of crops have long been thought of as a linear process from a wild ancestor to a domesticate. However, evidence of gene flow from locally adapted wild relatives that provided adaptive alleles into crops has been identified in multiple species. Yet, little is known about the evolutionary consequences of gene flow during domestication and the interaction of gene flow and genetic load in crop populations. We study the pseudo-cereal grain amaranth that has been domesticated three times in different geographic regions of the Americas. We quantify the amount and distribution of gene flow and genetic load along the genome of the three grain amaranth species and their two wild relatives. Our results show ample gene flow between crop species and between crops and their wild relatives. Gene flow from wild relatives decreased genetic load in the three crop species. This suggests that wild relatives could provide evolutionary rescue by replacing deleterious alleles in crops. We assess experimental hybrids between the three crop species and found genetic incompatibilities between one Central American grain amaranth and the other two crop species. These incompatibilities might have created recent reproductive barriers and maintained species integrity today. Together, our results show that gene flow played an important role in the domestication and expansion of grain amaranth, despite genetic species barriers. The domestication of plants was likely not linear and created a genomic mosaic by multiple contributors with varying fitness effects for today's crops., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Acarbose (ACA), a well-studied and effective inhibitor of α-amylase and α-glucosidase, is a postprandial-acting antidiabetic medicine. The membrane of the erythrocyte is an excellent tool for analyzing different physiological and biochemical activities since it experiences a range of metabolic alterations throughout aging. It is uncertain if ACA modulates erythrocyte membrane activities in an age-dependent manner. As a result, the current study was conducted to explore the influence of ACA on age-dependent deteriorated functions of transporters/exchangers, disrupted levels of various biomarkers such as lipid hydroperoxides (LHs), protein carbonyl (PCO), sialic acid (SA), total thiol (-SH), and erythrocyte membrane osmotic fragility. In addition to a concurrent increase in Na + /H + exchanger activity and concentration of LH, PCO, and osmotic fragility, we also detected a considerable decrease in membrane-linked activities of Ca 2+ -ATPase (PMCA) and Na + /K + -ATPase (NKA), as well as concentrations of SA and -SH in old-aged rats. The aging-induced impairment of the activities of membrane-bound ATPases and the changed levels of redox biomarkers were shown to be effectively restored by ACA treatment.

Lung cancer is still the most frequent cause of cancer-related death, accounting for nearly two million cases yearly. As cancer is a multifactorial disease, developing novel molecular therapeutics that can simultaneously target multiple associated cellular processes has become necessary. Ion channels are diverse regulators of cancer-related processes such as abnormal proliferation, invasion, migration, tumor progression, inhibition of apoptosis, and chemoresistance. Among the various families of ion channels, the transient receptor potential canonical channel family steps out in the context of lung cancer, as several members have been postulated as prognostic markers for lung cancer. Phytochemicals have been found to have health benefits in the treatment of a variety of diseases and disorders. Among phytochemicals, monoterpenes are effective in treating both the early and late stages of cancer. The molecular docking interaction analysis was conducted to evaluate the binding potential of selected monoterpenes with TRPC3, TRPC4, TRPC5, and TRPC6 involved in different phases of carcinogenesis. Amongst the selected monoterpenes, thymoquinone exhibited the highest binding energy of -6.7 kcal/mol against the TRPC4 channel, and all amino acid binding residues were similar to those of the known inhibitor for TRPC4. In addition, molecular-dynamic simulation results parameters, such as RMSD, RMSF, and Rg, indicated that thymoquinone did not impact the protein compactness and exhibited stability during the interaction. The average interaction energy between thymoquinone and TRPC4 protein was -26.85 kJ/mol. In-silico Drug-likeness and ADMET profiling indicated that thymoquinone is a druggable candidate with minimal toxicity. We propose further investigation and evaluation of thymoquinone for lead optimization and drug development.Communicated by Ramaswamy H. Sarma.

Iron and zinc malnutrition is a global humanitarian concern that mostly affects newborns, children, and women in low- and middle-income countries where plant-based diets are regularly consumed. This kind of malnutrition has the potential to result in a number of immediate and long-term implications, including stunted growth, an elevated risk of infectious diseases, and poor development, all of which may ultimately cause children to not develop to the fullest extent possible. A determination of the contributions from genotype, environment, and genotype by environment interactions is necessary for the production of nutrient-dense lentil varieties that offer greater availability of iron and zinc with a high level of trait stability. Understanding the genotype and environmental parameters that affect G x E (Genotype x Environment) interactions is essential for plant breeding. We used GGE(Genotype, Genotype x Environment interactions) and AMMI (Additive Main effects and Multiplicative Interaction) models to study genetic stability and GE(Genotype x Environment interactions) for grain Fe, Zn, Al, and anti-nutritional factors like phytic acid content in sixteen commercially produced lentil cultivars over several different six geographical locations across India. Significant genetic variability was evident in the Fe and Zn levels of different genotypes of lentils. The amounts of grain iron, zinc, and phytic acid varied from 114.10 to 49.90 mg/kg, 74.62 to 21.90 mg/kg, and 0.76 to 2.84 g/100g (dw) respectively. The environment and GE (Genotype x Environment interactions) had an impact on the concentration of grain Fe, Zn, and phytic acid (PA). Heritability estimations ranged from low to high (53.18% to 99.48%). The study indicated strong correlation between the contents of Fe and Zn, a strategy for simultaneously increasing Fe and Zn in lentils may be recommended. In addition, our research revealed that the stable and ideal lentil varieties L4076 (Pusa Shivalik) for Fe concentration and L4717 (Pusa Ageti) for Zn content, which have lower phytic acid contents, will not only play an essential role as stable donors in the lentil bio-fortification but will also enable the expansion of the growing area of bio-fortified crops for the security of health and nutrition., 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 Aski, Mishra, Tokkas, Yadav, Rai, Bansal, Singh, Gupta, Kumar, Parihar, Kumar, Kumar, Saxsena, Das, Kumar and Dikshit.)

Background: A core set of requirements for designing AI-based Health Recommender Systems (HRS) is a thorough understanding of human factors in a decision-making process. Patient preferences regarding treatment outcomes can be one important human factor. For orthopaedic medicine, limited communication may occur between a patient and a provider during the short duration of a clinical visit, limiting the opportunity for the patient to express treatment outcome preferences (TOP). This may occur despite patient preferences having a significant impact on achieving patient satisfaction, shared decision making and treatment success. Inclusion of patient preferences during patient intake and/or during the early phases of patient contact and information gathering can lead to better treatment recommendations., Aim: We aim to explore patient treatment outcome preferences as significant human factors in treatment decision making in orthopedics. The goal of this research is to design, build, and test an app that collects baseline TOPs across orthopaedic outcomes and reports this information to providers during a clinical visit. This data may also be used to inform the design of HRSs for orthopaedic treatment decision making., Methods: We created a mobile app to collect TOPs using a direct weighting (DW) technique. We used a mixed methods approach to pilot test the app with 23 first-time orthopaedic visit patients presenting with joint pain and/or function deficiency by presenting the app for utilization and conducting qualitative interviews and quantitative surveys post utilization., Results: The study validated five core TOP domains, with most users dividing their 100-point DW allocation across 1-3 domains. The tool received moderate to high usability scores. Thematic analysis of patient interviews provides insights into TOPs that are important to patients, how they can be communicated effectively, and incorporated into a clinical visit with meaningful patient-provider communication that leads to shared decision making., Conclusion: Patient TOPs may be important human factors to consider in determining treatment options that may be helpful for automating patient treatment recommendations. We conclude that inclusion of patient TOPs to inform the design of HRSs results in creating more robust patient treatment profiles in the EHR thus enhancing opportunities for treatment recommendations and future AI applications., 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., (© 2023 Singh, Schooley, Floyd, Pill and Brooks.)

Salinity is a significant concern in crop production, causing severe losses in agricultural yields. Ocimum sanctum , also known as Holy Basil, is an important ancient medicinal plant used in the Indian traditional system of medicine. The present study explores the use of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-producing strains of plant-growth-promoting bacteria (PGPB) namely Str-8 ( Halomonas desiderata) , Sd-6 ( Brevibacterium halotolerans) , Fd-2 ( Achromobacter xylosoxidans ), Art-7 ( Burkholderia cepacia) , and Ldr-2 ( Bacillus subtilis) , and T. harzianum (Th), possessing multi-functional properties like growth promotion, stress alleviation, and for enhancing  O. sanctum  yield under salt stress. The results showed that co-inoculation of Th and PGPBs enhanced plant height and fresh herb weight by 3.78-17.65% and 7.86-58.76%, respectively; highest being in Th + Fd-2 and Th + Art-7 compared to positive control plants. The doubly inoculated plants showed increased pigments, phenol, flavonoids, protein, sugar, relative water content, and nutrient uptake (Nitrogen and Phosphorous) as compared to monocultures and untreated positive control plants. In addition, co-inoculation in plants resulted in lower Na + , MDA, H 2 O 2 , CAT, APX activities, and also lower ACC accumulation (49.75 to 72.38% compared to non-treated salt- stressed plant) in O. sanctum , which probably played a significant role in minimizing the deleterious effects of salinity. Finally, multifactorial analysis showed that co-inoculation of Th and PGPBs improved O. sanctum growth, its physiological activities, and alleviated salt stress compared to single inoculated and positive control plants. These microbial consortia were evaluated for the first time on  O. sanctum under salt stress. Therefore, the microbial consortia application could be employed to boost crop productivity in poor, marginalized and stressed agricultural fields., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01328-2., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest regarding the publication of this paper., (© Prof. H.S. Srivastava Foundation for Science and Society 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.)

Purpose: The utility of the Bethesda system for reporting thyroid cytopathology is debatable in determining the risk of malignancy in pediatric patients. Moreover, the upper age limit for defining the pediatric group has varied across different studies. The aim of this study is to compare the risk of malignancy (ROM) and risk of neoplasia (RON) across different Bethesda categories between the pediatric, young adult, and adult patients., Methods: This is a retrospective multi-institutional study performed in three Indian hospitals. ROM was calculated and compared across Bethesda categories in adult (>18 years) and pediatric age groups (≤18 years), with a subgroup analysis in young adults (19-21 years)., Results: Thyroid nodules from a total of 5958 patients were subjected to fine needle aspiration. Of these 199 were pediatric (3.3%) and follow-up histology was available in 2276. The ROM and RON rates, including overall ROM/RON, were significantly higher in pediatric age group as compared to adults. Overall ROM of suspicious for malignancy and malignant categories was higher in children as compared to adults. The overall surgical resection rates were also higher in pediatric patients (45.2% vs. 35.7%; p < 0.01). The similar trend of increased ROM, RON and resection rates was seen among young adults as compared to adult age group., Conclusion: Thyroid nodules presenting in children are more likely to be malignant than those in adults. Importantly, the young adult group behaved in a similar manner with regard to surgical resection rates, ROM and RON to pediatric., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Curcumin, a strong natural compound with numerous health benefits, is extracted from the Curcuma longa. According to recent research findings, it also acts as a calorie restriction mimetic. We examined established aging biomarkers in erythrocytes and plasma and tested a persistent oral dietary dose of curcumin in young and D-galactose-induced accelerated rat aging models. For four weeks, D-gal (300 mg/kg b.w. subcutaneously) and curcumin (200 mg/kg b.w. oral) were administered simultaneously to test the protective effects of curcumin against D-galactose-induced accelerated aging and oxidative stress. In the accelerated senescent rat model, we discovered a significant rise in protein carbonyl, malonaldehyde (MDA), and advanced oxidation protein products. Increased levels of catalase, superoxide dismutase, ferric-reducing antioxidant potential, and reduced glutathione (GSH) were observed. Our findings reveal that curcumin has characteristics resembling a calorie restriction mimic and can successfully maintain redox equilibrium throughout the aging process in rat erythrocytes and plasma., (© 2023. Akadémiai Kiadó Zrt.)

Background: Legumes can fix atmospheric nitrogen (N) and facilitate N availability to their companion plants in crop mixtures. However, biological nitrogen fixation (BNF) of legumes in intercrops varies largely with the identity of the legume species. The aim of our study was to understand whether BNF and concentration of plant nutrients by common bean is influenced by the identity of the companion plant species in crop mixtures. In this greenhouse pot study, common beans were cultivated with another legume (chickpea) and a cereal (Sorghum). We compared BNF, crop biomass and nutrient assimilation of all plant species grown in monocultures with plants grown in crop mixtures., Results: We found beans to exhibit low levels of BNF, and to potentially compete with other species for available soil N in crop mixtures. The BNF of chickpeas however, was enhanced when grown in mixtures. Furthermore, biomass, phosphorous and potassium values of chickpea and Sorghum plants were higher in monocultures, compared to in mixtures with beans; suggesting competitive effects of beans on these plants. Concentration of calcium, magnesium and zinc in beans was higher when grown with chickpeas than with Sorghum., Conclusions: It is generally assumed that legumes benefit their companion plant species. Our study highlights the contrary and shows that the specific benefits of cereal-legume mixtures are dependent on the growth rate of the species concerned. We further highlight that the potential of legume-legume mixtures is currently undervalued and may play a strong role in increasing N use efficiency of intercrop-based systems., (© 2023. The Author(s).)

Small RNAs (sRNAs) such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) are short 20-24-nucleotide non-coding RNAs. They are key regulators of gene expression in plants and other organisms. Several 22-nucleotide miRNAs trigger biogenesis cascades of trans-acting secondary siRNAs, which are involved in various developmental and stress responses. Here we show that Himalayan Arabidopsis thaliana accessions having natural mutations in the miR158 locus exhibit robust cascade silencing of the pentatricopeptide repeat (PPR)-like locus. Furthermore, we show that these cascade sRNAs trigger tertiary silencing of a gene involved in transpiration and stomatal opening. The natural deletions or insertions in MIR158 led to improper processing of miR158 precursors, thereby blocking synthesis of mature miR158. Reduced miR158 levels led to increased levels of its target, a pseudo-PPR gene that is targeted by tasiRNAs generated by the miR173 cascade in other accessions. Using sRNA datasets derived from Indian Himalayan accessions, as well as overexpression and knockout lines of miR158, we show that absence of miR158 led to buildup of pseudo-PPR-derived tertiary sRNAs. These tertiary sRNAs mediated robust silencing of a gene involved in stomatal closure in Himalayan accessions lacking miR158 expression. We functionally validated the tertiary phasiRNA that targets NHX2, which encodes a Na + -K + /H + antiporter protein, thereby regulating transpiration and stomatal conductance. Overall, we report the role of the miRNA-TAS-siRNA-pseudogene-tertiary phasiRNA-NHX2 pathway in plant adaptation., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Aims and objectives This study was carried out to evaluate the efficacy of 8.4% sodium bicarbonate-buffered local anesthetic solution and conventional local anesthetic in patients requiring bilateral maxillary orthodontic extractions in terms of pain on injection, onset of action, and duration of action. Methods 102 patients requiring bilateral maxillary orthodontic extractions were included in the study. Buffered local anesthetic was administered on one side while conventional local anesthesia (LA) was administered on the other side. Pain on injection was measured using a visual analogue scale, while onset of action was measured by probing the buccal mucosa after 30 seconds of administration and duration of action was measured by the time after which the patient experienced pain or took a rescue analgesic. The data was statistically analyzed to determine the significance. Results The pain during injection was found to be lesser at sites where buffered local anesthetic was administered (mean visual analogue scale (VAS) score = 2.4) as compared to conventional local anesthetic (mean VAS score = 3.9). The onset of action was faster with buffered local anesthetic (mean value = 62.3 seconds) as compared to conventional local anesthetic (mean value = 157.16 seconds). Lastly, the duration of action was found to be longer for buffered local anesthetic group (mean value = 225.65 minutes) as compared to conventional local anesthetic (mean value = 187 minutes). Conclusion 8.4% sodium bicarbonate-buffered local anesthetic was found to be more efficient than conventional local anesthetic in terms of reduction in pain on injection as well as faster onset and longer duration of action., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Valiulla et al.)

Aging is a natural phenomenon, which is characterised by progressive physiological changes at cellular and organ level. During aging, the defence mechanism of an organism declines over the period of time. The aim of this study was to investigate the biological efficacy of berberine in D-galactose induced aging rat models. For the study, rats were divided into four groups: Control received only vehicle, BBR received berberine orally, D-Gal received D-galactose subcutaneously and BBR + D-Gal received D-galactose and berberine simultaneously. D-galactose treatment increased the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl, plasma membrane redox system (PMRS) and advanced oxidation protein products (AOPP) in the erythrocytes or plasma. It reduced the anti-oxidant level such as reduced glutathione (GSH), ferric reducing ability of plasma (FRAP), plasma thiols, sialic acid and membrane transporters like Na + /K + ATPase and Ca 2+ ATPase activity in the erythrocyte membrane. Co-treatment of berberine in D-galactose induced aging rat models restored pro-oxidants and anti-oxidants in erythrocytes. Berberine also restored the activity of Na + /K + ATPase and Ca 2+ ATPase in the erythrocyte membrane. On the basis of these findings, we suggest that berberine treatment could attenuate erythrocyte aging in rats through stabilisation of the redox equilibrium., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

In this communication, the time series data of three major countries USA, France, and Japan from 1965 to 2020 for CO 2 emission, GDP, and nuclear energy (NE) are evaluated. It also analyzed and validated the EKC hypothesis while using nuclear energy for electricity generation. Fourier ARDL is used to investigate the hypothesis criteria, and the Fourier bootstrap Toda-Yamamoto (FBTY) causality test is used for causal linkage between the variables as well as the wavelet coherence; it is also presented the time and frequency dependency of the variables. The CO 2 mitigation by using the NE is also assessed for all three countries and assessed that the France, Japan, and USA mitigated the CO 2 per year is 0.0463 million metric ton (MMT), 0.0239 and 0.0728 MMT per year respectively. Similar to that the SO 2 is reduced by using the NE is 24.322, 43.527, and 132.592 MMT/year, and NOx is reduced by approximately 0.2847, 0.147, and 0.4478 MMT/year by France, Japan, and USA respectively by applying the NE for power generation. The evidence of the EKC, Fourier bootstrap and Toda-Yamamoto clarifies the important role of nuclear energy in terms of carbon mitigation to achieve UN net zero carbon emission by 2050. Hence, in order to meet the UN target of net zero carbon emission by 2050, the USA and Japan should increase the production of nuclear energy as France meets its 74.1% energy demand through NE by validating the EKC hypothesis; on the other hand, all the three countries should increase the production of tidal energy due to their geographical location as tides are much more predictable than wind and sun keeping in consideration to the expenses incurred and a full proof plan for disposing NE residuals in a safe place as NE residuals are highly radioactive and contains traces of thorium and uranium., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: In obese humans, Coleus forskohlii root extract (CF) protects against weight gain owing to the presence of forskolin, an adenylate cyclase (AC) activator. As AC increases intracellular cyclic adenosine monophosphate (cAMP) levels in osteoblasts that has an osteogenic effect, we thus tested the skeletal effects of a standardized CF (CFE) in rats., Methods: Concentrations of forskolin and isoforskolin were measured in CFE by HPLC. CFE and forskolin (the most abundant compound present in CFE) were studied for their osteogenic efficacy in vitro by alkaline phosphatase (ALP), cAMP and cyclic guanosine monophosphate (cGMP) assays. Femur osteotomy model was used to determine the osteogenic dose of CFE. In growing rats, CFE was tested for its osteogenic effect in intact bone. In adult ovariectomized (OVX) rats, we assessed the effect of CFE on bone mass, strength and material. The effect of forskolin was assessed in vivo by measuring the expression of osteogenic genes in the calvarium of rat pups., Results: Forskolin content in CFE was 20.969%. CFE increased osteoblast differentiation and intracellular cAMP and cGMP levels in rat calvarial osteoblasts. At 25 mg/kg (half of human equivalent dose), CFE significantly enhanced calcein deposition at the osteotomy site. In growing rats, CFE promoted modeling-directed bone formation. In OVX rats, CFE maintained bone mass and microarchitecture to the level of sham-operated rats. Moreover, surface-referent bone formation in CFE treated rats was significantly increased over the OVX group and was comparable with the sham group. CFE also increased the pro-collagen type-I N-terminal propeptide: cross-linked C-telopeptide of type-I collagen (PINP : CTX-1) ratio over the OVX rats, and maintained it to the sham level. CFE treatment decreased the OVX-induced increases in the carbonate-to-phosphate, and carbonate-to-amide-I ratios. CFE also prevented the OVX-mediated decrease in mineral crystallinity. Nanoindentation parameters, including modulus and hardness, were decreased by OVX but CFE maintained these to the sham levels. Forskolin stimulated ALP, cAMP and cGMP in vitro and upregulated osteogenic genes in vivo ., Conclusion: CFE, likely due to the presence of forskolin displayed a bone-conserving effect via osteogenic and anti-resorptive mechanisms resulting in the maintenance of bone mass, microarchitecture, material, and strength., Competing Interests: Authors AG and LH were employed by Pharmanza Herbal 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 © 2023 Kulkarni, Sharma, Porwal, Rajput, Sadhukhan, Singh, Singh, Baranwal, Kumar, Girme, Pandey, Singh, Sashidhara, Kumar, Hingorani and Chattopadhyay.)

Elucidation of structure and dynamics of alternative higher-order structures of DNA such as in branched form could be targeted for therapeutics designing. Herein, we are reporting the intrinsically dynamic and folds transitions of an unusual DNA junction with sequence d(CGGCGGCCGC)4 which self-assembles into a four-way DNA junction form with sticky ends using long interval molecular simulations under various artificial physiological conditions. The original crystal structure coordinates (PDB ID: 3Q5C) for the selected DNA junction was considered for a total of 1.1 μs molecular dynamics simulation interval, including different temperature and pH, under OPLS-2005 force field using DESMOND suite. Following, post-dynamics structure parameters for the DNA junction were calculated and analyzed by comparison to the crystal structure. We show here that the self-assembly dynamics of DNA junction is mitigated by the temperature and pH sensitivities, and discloses peculiar structural properties as function of time. From this study it can be concluded on account of temperature sensitive and pH dependent behaviours, DNA junction periodic arrangements can willingly be synthesized and redeveloped for multiple uses like genetic biomarkers, DNA biosensor, DNA nanotechnology, DNA Zipper, etc. Furthermore, the pH dis-regulation behaviour may be used to trigger the functionality of DNA made drug-releasing nanomachines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)