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Pyrazolic chalcone exhibits diverse therapeutic activities, including anti-inflammatory, antioxidant, antimicrobial, antitumor, and anti-diabetic properties. Structural activity relationship (SAR) studies play a crucial role in understanding the molecular aspects governing their biological effects, guiding the rational design of derivatives with enhanced efficacy and reduced side effects. This review provides an overview of pyrazolic chalcone derivatives, emphasizing their synthesis through both conventional and green methods. In comparison, conventional synthesis methods have been widely employed in the past for the production of pyrazolic chalcones, often relying on traditional chemical processes that may involve the use of hazardous reagents and generate significant waste. On the other hand, green synthesis methods, in harmony with the growing emphasis on sustainable practices in drug discovery, offer a more environmentally friendly alternative. Green synthesis typically involves the use of eco-friendly reagents, solvents, and energy-efficient processes, resulting in reduced environmental impact and improved resource efficiency. Overall, pyrazolic chalcone derivatives represent a promising class of compounds with significant potential for therapeutic applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objectives: Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections., Methods: Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism., Results: Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone ≥2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004)., Conclusion: For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

1H spin-lattice relaxation experiments have been performed for ionic liquid-polymer gel membranes, including 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP) with different proportions. The experiments have been performed in a broad range of resonance frequencies (from about 5 Hz to 40 MHz) vs temperature and complemented with analogous studies for [BMIM][BF4] in bulk as a reference. A model of the relaxation processes in the membranes has been proposed. The model includes two relaxation contributions. One of them corresponds to the concept of restricted, two-dimensional translation diffusion with a residence lifetime, while the second one has the form characteristic of polymers (mathematically similar to the limiting behavior of two-dimensional translation diffusion with a very long residence lifetime). The extensive dataset has been consistently interpreted in terms of the model, revealing two dynamical processes on the time scales of 10-7 s (for the second relaxation contribution) and 10-9 s (for the first one). The relationship of these relaxation contributions to the motion of the polymer or ionic liquid-polymer complexes and to the translation diffusion of BMIM cations in the matrix has been discussed., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: Oral cancer is a widespread global health problem characterised by high mortality rates, wherein early detection is critical for better survival outcomes and quality of life. While visual examination is the primary method for detecting oral cancer, it may not be practical in remote areas. AI algorithms have shown some promise in detecting cancer from medical images, but their effectiveness in oral cancer detection remains Naïve. This systematic review aims to provide an extensive assessment of the existing evidence about the diagnostic accuracy of AI-driven approaches for detecting oral potentially malignant disorders (OPMDs) and oral cancer using medical diagnostic imaging., Methods: Adhering to PRISMA guidelines, the review scrutinised literature from PubMed, Scopus, and IEEE databases, with a specific focus on evaluating the performance of AI architectures across diverse imaging modalities for the detection of these conditions., Results: The performance of AI models, measured by sensitivity and specificity, was assessed using a hierarchical summary receiver operating characteristic (SROC) curve, with heterogeneity quantified through I 2 statistic. To account for inter-study variability, a random effects model was utilized. We screened 296 articles, included 55 studies for qualitative synthesis, and selected 18 studies for meta-analysis. Studies evaluating the diagnostic efficacy of AI-based methods reveal a high sensitivity of 0.87 and specificity of 0.81. The diagnostic odds ratio (DOR) of 131.63 indicates a high likelihood of accurate diagnosis of oral cancer and OPMDs. The SROC curve (AUC) of 0.9758 indicates the exceptional diagnostic performance of such models. The research showed that deep learning (DL) architectures, especially CNNs (convolutional neural networks), were the best at finding OPMDs and oral cancer. Histopathological images exhibited the greatest sensitivity and specificity in these detections., Conclusion: These findings suggest that AI algorithms have the potential to function as reliable tools for the early diagnosis of OPMDs and oral cancer, offering significant advantages, particularly in resource-constrained settings., Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023476706)., 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., (© 2024 Sahoo, Sahoo, Dash, Kumar, Baliarsingh, Panda and Pati.)

Epithelial-Mesenchymal Transition (EMT) is a fundamental biological process involved in embryonic development, wound healing, and cancer progression. In lung cancer, EMT is a key regulator of invasion and metastasis, significantly contributing to the fatal progression of the disease. Age-related factors such as cellular senescence, chronic inflammation, and epigenetic alterations exacerbate EMT, accelerating lung cancer development in the elderly. This review describes the complex mechanism among EMT and age-related pathways, highlighting key regulators such as TGF-β, WNT/β-catenin, NOTCH, and Hedgehog signalling. We also discuss the mechanisms by which oxidative stress, mediated through pathways involving NRF2 and ROS, telomere attrition, regulated by telomerase activity and shelterin complex, and immune system dysregulation, driven by alterations in cytokine profiles and immune cell senescence, upregulate or downregulate EMT induction. Additionally, we highlighted pathways of transcription such as SNAIL, TWIST, ZEB, SIRT1, TP53, NF-κB, and miRNAs regulating these processes. Understanding these mechanisms, we highlight potential therapeutic interventions targeting these critical molecules and pathways., Competing Interests: Declaration of Competing Interest MKK received consultant honoraria from the CBRS, Noida. Rest of the author declares no financial interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Meningococcal disease remains an important public health problem globally. We assessed the non-inferiority and the lot-to-lot consistency of a pentavalent meningococcal ACYWX conjugate vaccine (NmCV-5; Serum Institute of India, Pune, India) versus a quadrivalent meningococcal ACWY conjugate vaccine (MenACWY-D) in healthy adults., Methods: In this observer-blind, randomised, active-controlled, phase 2/3 study, healthy adults aged 18-85 years were recruited from nine hospitals across seven cities in India. Participants were grouped by age (age 18-29, 30-60, and 61-85 years), and within each age group they were randomly assigned (3:1) to receive either NmCV-5 or MenACWY-D (Sanofi Pasteur). In the age 18-29 years group, participants were additionally randomly assigned (1:1:1:1) to either lot A, lot B, or lot C of NmCV-5 or MenACWY-D. Block randomisation was used (block sizes of 4, 8, and 12). Study participants and study personnel were masked to treatment assignment. Participants received either a 0·5 mL dose of NmCV-5, containing 5 μg each of conjugated A, C, W, Y, and X polysaccharides, or 0·5 mL MenACWY-D, containing 4 μg of each of conjugated A, C, W, and Y polysaccharides. Vaccinations were administered intramuscularly in the deltoid muscle. The primary outcomes were seroresponse (non-inferiority margin of -10%) and geometric mean titres (GMTs; non-inferiority margin of 0·5) in all participants, and lot-to-lot consistency of NmCV-5 (in participants aged 18-29 years; consistency was shown if the geometric mean ratio [GMR] 95% CIs were within the limit interval of 0·5 to 2). For non-inferiority, serogroup X immune response in the NmCV-5 group was compared with the lowest immune response among serogroups A, C, W, and Y in the MenACWY-D group. Immunogenicity was assessed with a serum bactericidal activity assay that used baby rabbit serum as the complement (rSBA) on days 1 and 29 in the modified per-protocol population (including all participants who were randomly assigned, received vaccine, had a post-vaccination rSBA measurement up to 121 days after vaccination, and no major protocol violations). Solicited events were collected for 7 days and serious adverse events were collected for 180 days, and assessed in the safety population (all participants who received vaccination). This study is registered with ClinicalTrials.gov, NCT04358731, and CTRI, CTRI/2019/12/022436, and is now complete., Findings: Between Dec 27, 2019, and Sept 19, 2020, 1712 individuals were screened, of whom 1640 were randomly assigned and received NmCV-5 (n=1233) or MenACWY-D (n=407; mean age 26·4 years [SD 12·2], 551 [33·6%] of 1640 were female, and 1089 [66·4%] were male). 1441 participants were aged 18-29 years (362 received lot A, 360 received lot B, and 361 received lot C of NmCV-5 and 357 received MenACWY-D, with one participant mis-randomised by age group and excluded from lot-to-lot consistency analysis). Non-inferiority of NmCV-5 against MenACWY-D was met in terms of seroresponse rates and GMT ratios for all five serogroups. The seroresponse rates were 84·3% (97·5% CI 81·7 to 86·7; serogroup A) or higher in the NmCV-5 group and 54·5% (48·5 to 60·3; serogroup A) or higher in the MenACWY-D group, with the difference in the seroresponse rate between vaccine groups ranging from 0·2 (97·5% CI -2·2 to 2·6) for serogroup W to 29·8 (24·4 to 35·2) for serogroup A. GMTs on day 29 were 7016·9 (97·5% CI 6475·7 to 7603·4; serogroup Y) or higher in the NmCV-5 group and 3646·8 (3188·2 to 4171·5; serogroup Y) or higher in the MenACWY-D group, with GMT ratios between vaccine groups for serogroups A, C, Y, and W ranging from 1·9 (97·5% CI 1·5-2·3) for serogroup W to 2·5 (2·2-2·8) for serogroup A. NmCV-5 induced robust immune responses against serogroup X. Lot-to-lot consistency of NmCV-5 was found for all five serogroups, with 95% CIs for the GMT ratio for each pair of lots being between 0·5 and 2: the lowest lower bound and the highest upper bound of the 95% CI for the GMR between NmCV-5 lot A and lot B were 0·6 and 1·4, between lot A and lot C were 0·7 and 1·6, and between lot B and lot C were 0·8 and 1·6, respectively, for any of the five serogroups. At least one solicited adverse event was reported by 527 (42·7%) of 1233 participants in the NmCV-5 group and 142 (34·9%) of 407 in the MenACWY-D group. No serious adverse events occurred that were determined to be causally related to vaccination., Interpretation: NmCV-5 was non-inferior to MenACWY-D in terms of seroresponse and GMTs, was safe, and demonstrated lot-to-lot consistency. NmCV-5 is prequalified by WHO and was rolled out in the African meningitis belt in April, 2024., Funding: Serum Institute of India., Competing Interests: Declaration of interests CSP is the chairman and managing director of Serum Institute of India. PSK, AD, SG, Ska, SSP, RMD, AM, and DK are employed by Serum Institute of India. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Endometrial cancer is the sixth most common gynecologic cancer, and has been reported as a malignancy arising due to the idiopathic effects of certain anticancer agents. Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients. However, the long-term usage of tamoxifen has been associated with resistance and risk for endometrial malignancy. A direct mechanistic basis for tamoxifen-induced endometrial tumorigenesis is still unclear. Hyperactivation of PAK1 in endometrial cancer correlates with poor overall survival. The present study demonstrates that tamoxifen treatment induces nuclear localization of PAK1 in endometrial carcinoma cells. This nuclear transit is mediated through JAK2 phosphorylation of PAK1 and binding of β-PIX. In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

With the swift advancement of technology and growing popularity of internet in business and communication, cybersecurity posed a global threat. This research focuses new Deep Learning (DL) model referred as FinSafeNet to secure loose cash transactions over the digital banking channels. FinSafeNet is based on a Bi-Directional Long Short-Term Memory (Bi-LSTM), a Convolutional Neural Network (CNN) and an additional dual attention mechanism to study the transaction data and influence the observation of various security threats. One such aspect is, relying these databases in most of the cases imposes a great technical challenge towards effective real time transaction security. FinSafeNet draws attention to the attack and reproductive phases of Hierarchical Particle Swarm Optimization (HPSO) feature selection technique simulating it in a battle for extreme time performance called the Improved Snow-Lion optimization Algorithm (I-SLOA). Upon that, the model then applies the Multi-Kernel Principal Component Analysis (MKPCA) accompanied by Nyström Approximation for handling the MKPCA features. MKPCA seeks to analyze and understand a non-linear structure of data whereas, Nyström Approximation reduces the burden on computational power hence allows the model to work in situations where large sizes of datasets are available but with no loss of efficiency of the model. This causes FinSafeNet to work easily and still be able to make accurate forecasts. Besides tackling feature selection and dimensionality reduction, the model presents advanced correlation measures as well as Joint Mutual Information Maximization to enhance variable correlation analysis. These improvements further help the model to detect the relevant features in transaction data that may present a threat to the security of the system. When tested on commonly used database for testing banks performance, for instance the Paysim database, FinSafeNet significantly improves upon the previous and fundamental approaches, achieving accuracy of 97.8%., (© 2024. The Author(s).)

In this study, the chaotic behavior of a second-order circuit comprising a nonlinear resistor and Chua's diode is investigated. This circuit, which includes a nonlinear capacitor and resistor among its components, is considered one of the simplest nonautonomous circuits. The research explores various oscillator characteristics, emphasizing their chaotic properties through bifurcations, Lyapunov exponents, periodicity, local Lyapunov region, and resonance. The system exhibits both stable equilibrium points and a chaotic attractor. Additionally, the second objective of this study is to develop a novel cryptographic technique by incorporating the designed circuit into the S-box method. The evaluation results suggest that this approach is suitable for secure cryptographic applications, providing insights into constructing a cryptosystem for images and text based on its complex behavior. Real-life data were analyzed using various statistical and performance criteria after applying the proposed methodology. These findings enhance the reliability of the cryptosystems. Moreover, The proposed methods are assessed using a range of statistical and performance metrics after testing the text and images. The cryptographic results are compared with existing techniques, reinforcing both the developed cryptosystem and the performance analysis of the chaotic circuit., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rasappan 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.)

Aflatoxins are major food contaminants, which cause hepatotoxicity, eventually leading to Hepatocellular carcinoma. Activated AFB1 forms adducts with DNA, which in turn activates checkpoint control. We show that AFB1 activates PI3K-Akt signaling, which is critical for cell survival. Simultaneous activation of both DNA checkpoint and proliferative signaling leads to Oncogene-Induced Senescence, a major tumorigenesis barrier. AFB1 downregulates ARID3A and ARID3B proteins to overcome this senescence program to induce hepatic tumors., 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 Ltd. All rights reserved.)

Helicobacter pylori, a pathogenic bacterium responsible for multiple gastrointestinal disorders, has emerged as a major global concern due to rise in antibiotic resistance. Unwanted side effects of antibiotics therapy are further complicating the treatment strategies. Consequently, an alternative approach, using probiotics has emerged as a promising solution for treating H. pylori infections. Probiotics have shown considerable potential in increasing the cure rate and reducing the side effects through diverse mechanisms. Among the widely employed probiotics, Lactobacillus spp. has garnered particular attention in this review. After reviewing the studies on effects of Lactobacillus spp. on H. pylori, it is evident that several Lactobacillus spp. have demonstrated their potential efficacy against H. pylori infection, when administered alone or in conjunction with antibiotics, in a strain-specific manner. Furthermore, the inclusion of Lactobacillus spp. in the treatment regimen has also been associated with a reduction in the side effects related to antibiotic-based therapies. Future research may focus on identifying optimal strains and treatment regimens, understanding the long-term impacts of use, and determining their role in preventing H. pylori infection in various populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Micromotors are the backbone of material research as they are small-sized, self-propelled, intelligent systems capable of performing multiple tasks ranging from biomedicine to environmental monitoring. One of the primary obstacles the field faces is the live detection and differentiation of individual units through a complex environment. In this study, we demonstrate a facile approach for designing light-activated dye-tagged micromotors on a large scale. The micromotors are titanium dioxide (TiO 2 )/copper oxide (Cu 2 O)-silica Janus spheres that are self-propelled under the illumination of low-intensity light in aqueous peroxide medium. The micromotors were modified with different dyes, such as Alq3, Alizarin, zinc phthalocyanine, etc . The fabrication of micromotors and coating with dyes were performed using a simple and versatile physical vapor deposition-based glancing angle deposition (GLAD) technique. The fluorescent dyes help to detect the motion and position of micromotors independently. Moreover, they also help to identify the swimming direction as well as differentiate the micromotors in a complex medium consisting of similar configurations of other particles (bacteria and passive fluorescent particles). Light provides full control over the dynamics as well as the fluorescence nature of micromotors. To present the versatility of our design scheme, micromotors of different shapes, materials, and dye coatings are designed and explored for fluorescence-based observations. The simplistic design approach with easy-to-load multiple fluorescent dyes is an interesting feature that makes the micromotors suitable candidates for various microfluidic and lab-on-a-chip studies, including biological or fluorescent samples.

Albumin is a nature-derived, versatile protein carrier, that has been explored extensively by researchers for anticancer drug delivery due to its role in enhancing drug stability, solubility, circulation time, targeting capabilities, and overall therapeutic efficacy. Albumin nanoparticles possess inherent biocompatibility, biodegradability, and passive tumor-targeting ability due to the enhanced permeability and retention effect. However, non-specific accumulation of cytotoxic agents in healthy tissues remains a challenge. In this paper, the functionalization of albumin nanoparticles using various biomolecules including antibodies, nucleic acids, proteins and peptides, vitamins, chondroitin sulfate, hyaluronic acid, and lactobionic acid have been discussed which enables specific recognition and binding to cancer cells. Furthermore, we highlight the supremacy of such a targeted approach in tumor-specific drug delivery, minimization of off-target effects, potential improvement in therapeutic efficacy, cellular internalization, reduced side effects, and better clinical outcomes. This review centers on how they have revolutionized the field of biomedical research and tuned into an excellent targeted approach. In conclusion, this review highlights in detail the role of albumin as a nanocarrier for tumor-targeted delivery using biomolecules as ligands., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

This study aims to investigate Polylactic Acid (PLA) and Polycaprolactone (PCL) polymers for microencapsulation of hydrophilic and hydrophobic anti-glaucoma drugs using an emulsion-based solvent evaporation technique. Microparticle size was analysed using optical microscopy, while drug-polymer interactions through Dynamic-Light-Scattering (DLS) and Fourier-Transform-Infra-red/Attenuated-Total-Reflection spectroscopy (FTIR/ATR). In vitro , drug release studies were performed to investigate drug encapsulation and release profiles. Spherical microparticles, with particle size 94 ± 6.9 μm for PCL-based and 100 ± 3.74 μm for PLA-based formulation, were obtained. Drug release studies showed 100% release over about 32 days, with encapsulation efficiency (%EE) and drug loading (%w/w) reaching up to 95 and 2.84% for PLA-based and 97 and 2.91% for PCL-based microparticles, respectively. DLS studies reveal an increase in hydrodynamic radius ( R H ), which correlates to enhanced drug encapsulation. So, the nature of the drug and polymer significantly impacts drug encapsulation and release, with drug-polymer interactions playing a crucial role alongside experimental parameters.

Despite notable advancements in cancer therapy, it remains a formidable global health challenge. The emergence of combinational treatments, particularly the integration of chemotherapy with photodynamic therapy (chemo-PDT), offers a glimmer of hope. This study introduces the development of zinc-coordinated quercetin-based self-assembled nanoparticles (ZnQ NPs) for advanced dual-mode cancer therapy. These cutting-edge ZnQ nanoparticles were synthesized in a rapid 15-minute single-step process, in stark contrast to the conventional hours or days required. Using Density Functional Theory (DFT) calculations, the optimal binding configurations of ZnQ NPs were precisely determined and further supported by band gap calculations between frontier molecular orbitals. Quercetin, a potent anticancer flavonoid, was used for the first time both as an active drug and as an organic ligand, resulting in pH-responsive nanoparticles with exceptional water dispersibility, stability, and biocompatibility. Additionally, these novel nanoparticles (NPs) were able to load chlorin e6 (Ce6), a photosensitizer known for its high singlet oxygen production, due to hydrophobic interactions within the pores. The ZnQ@Ce6 nanocomposite demonstrated remarkable Ce6 loading (19.03%) and significantly enhanced therapeutic effects, achieving a 77% cell inhibition rate under specific light conditions. This dual-functional platform, enhancing the solubility and bioavailability of Ce6 while harnessing the anticancer properties of quercetin, underscores the potential of ZnQ NPs in clinical nanomedicine, promising improved cancer treatment outcomes.

Ammonia (NH 3 ) acts as a key precursor of the particulate matter, could reduce visibility, deplete stratospheric ozone, and trigger perturbation in ecosystems. Being an agrarian country with a large livestock population and uncontrolled fertilizer application, India could be accountable as a major stakeholder of global NH 3 emissions. This study developed a comprehensive gridded (0.1° x 0.1°) ammonia inventory for India considering 24 types of sources. The total NH 3 emission is estimated to be 10.54 Tg/yr in 2022, where synthetic fertilizer application accounts for ∼47 % followed by livestock (∼34 %). Minor unattended sectors such as biomass burning, agricultural soil, human excrement, waste disposal, etc. contribute 0.68 Tg/yr, 0.32 Tg/yr, 0.3 Tg/yr, and 0.14 Tg/yr, respectively. The overall uncertainty of the inventory ranges around ± 55 %. These emission datasets are essential for atmospheric chemistry models and could be a crucial tool for policymakers to combat ammonia pollution., 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. All rights reserved.)

Aims: Lactobacilli have drawn a great deal of attention due to the heterogeneity of their cells, as well as their remarkable ability to adapt to a range of harsh conditions. One such adaptation response by Lactiplantibacillus plantarum was forming a V-shaped cell structure in low acidic pH conditions. This study aims to identify low pH induced-biofilm formation in L. plantarum and Limosilactobacillus reuteri and their antagonistic interactions with an opportunistic pathogen, Pseudomonas aeruginosa PAO1., Methods and Results: Dual species bacterial interactions revealed a Lactobacilli biofilm-mediated suppression of PAO1 biofilms and pyocyanin pigment. Furthermore, filtrates from Lactobacilli grown at low acidic pH (pH 3.5) effectively arrest the pathogenesis of P. aeruginosa PAO1, including biofilm, swarming motility, and pyocyanin formation. Liquid chromatography-mass spectroscopy analysis revealed the presence of several Lactobacilli-secreted metabolites and dipeptides that exhibited strong LasR receptor antagonistic interactions in molecular docking analysis. Prolyl-tyrosine showed the best lasR antagonistic and PAO1 biofilm inhibitory activities of the identified dipeptides., Conclusion: Overall, the results will contribute to the development of anti-infective drugs against P. aeruginosa using Lactobacilli secreted dipeptides. Furthermore, the investigation identifies several dipeptides that can be extracted from V-shaped Lactobacilli for antimicrobial protein therapy against P. aeruginosa and other pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background : Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enriched in high-impact rare alleles, which might play a crucial role in the etiology and susceptibility of CRC. Methods : In this study, an exome-wide association analysis was performed in 146 patients with high-risk CRC in the Middle East and 1395 healthy controls. The aim was to identify rare germline variants in coding regions and their splicing sites associated with high-risk CRC in the Middle Eastern population. Results : Rare inactivating variants (RIVs) in APC had the strongest association with high-risk CRC (6/146 in cases vs. 1/1395 in controls, OR = 59.7, p = 5.13 × 10 -12 ), whereas RIVs in RIMS1 , an RAS superfamily member, were significantly associated with high-risk CRC (5/146 case vs. 2/1395 controls, OR = 24.7, p = 2.03 × 10 -8 ). Rare damaging variants in 17 genes were associated with high-risk CRC at the exome-wide threshold ( p < 2.5 × 10 -6 ). Based on the sequence kernel association test, nonsynonymous variants in six genes ( TNXB , TAP2 , GPSM3 , ADGRG4 , TMEM229A , and ANKRD33B ) had a significant association with high-risk CRC. RIVs in APC -the most common high-penetrance genetic factor-were associated with patients with high-risk CRC in the Middle East. Individuals who inherited APC RIVs had an approximate 60-fold increased risk of developing CRC and were likely to develop the disease earlier. Conclusions : We identified new potential CRC predisposition variants in other genes that could play a role in CRC inheritance. However, large collaborative studies are needed to confirm the association of these variants with high-risk CRC. These results provide information for counseling patients with high-risk CRC and their families in our population.

Contamination of ground water with pollutants released from various anthropogenic activities is a major concern due to its adverse effects on the environment and human health. Rapid and efficient detection of such pollutants is the first step toward remediation of the problem. Herein we report a two-point fluorescence turn OFF-ON detection method for Hg 2+ ions using nitrogen doped carbon dots (NCDs). The NCDs obtained through solvothermal treatment of ammonium citrate tribasic in DMF at 190 °C for four hours exhibited a quantum yield of 9.67%. Hg 2+ detection is demonstrated in two steps, first the quenching of the fluorescence of NCDs by Hg 2+ and second the fluorescence recovery upon addition of ascorbic acid from different sources. A rapid filter paper-based detection device is demonstrated based on the principles developed.

Backround: The present investigation aimed to enhance the postharvest shelf-life of broccoli using vacuum impregnation (VI). Broccoli florets were impregnated with physiologically active chemicals, i.e. calcium chloride and ascorbic acid. Post-impregnation broccoli florets were packed in three different packaging materials (poly(ethylene terephthalate) punnets, low-density polyethylene pouches and shrink-wrap film) and stored at two temperatures (5 and 25 °C). The effects of impregnation solutions, packaging materials and storage temperature on physicochemical attributes (weight loss, total soluble solids, ascorbic acid, total chlorophylls and carotenoid content), antioxidant and phenolic contents, and shelf life were studied. The changes in the chemical structure post-impregnation and during storage were investigated using Fourier transform infrared (FTIR) spectroscopy., Results: Results showed that impregnated broccoli florets exhibited significantly (P < 0.05) higher levels of biochemical attributes immediately after impregnation. During storage, the physicochemical and antioxidant properties of broccoli florets declined for all the samples. However, the reduction in these properties was significantly (P < 0.05) lower in impregnated florets as compared to untreated control samples. Principal component analysis and FTIR results also indicated a clear difference in the impregnated and control samples. The shelf-life of broccoli florets stored at 25 °C was assessed as 4 and 3 days for impregnated and control samples, respectively; whereas the samples stored at 5 °C had a shelf-life of 12 days for impregnated samples and 5 days for the control samples. The findings of the study elucidate the potential of VI in enhancing the initial quality and shelf-life of broccoli., Conclusion: The deterioration during storage is primarily due to physiological weight loss, a natural loss of water and volatile compounds that occur following harvest due to transpiration and respiration. Excessive transpiration can lead to dehydration, which reduces the quality and shelf-life of the product. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The hypothesis that conserved core catalytic sites could represent ancestral aminoacyl-tRNA synthetases (AARS) drove the design of functional TrpRS, LeuRS, and HisRS 'urzymes'. We describe here new urzymes detected in the genomic record of the arctic fox, Vulpes lagopus. They are homologous to the α-subunit of bacterial heterotetrameric Class II glycyl-tRNA synthetase (GlyRS-B) enzymes. AlphaFold2 predicted that the N-terminal 81 amino acids would adopt a 3D structure nearly identical to our designed HisRS urzyme (HisCA1). We expressed and purified that N-terminal segment and the spliced open reading frame GlyCA1-2. Both exhibit robust single-turnover burst sizes and ATP consumption rates higher than those previously published for HisCA urzymes and comparable to those for LeuAC and TrpAC. GlyCA is more than twice as active in glycine activation by adenosine triphosphate as the full-length GlyRS-B α2 dimer. Michaelis-Menten rate constants for all three substrates reveal significant coupling between Exon2 and both substrates. GlyCA activation favors Class II amino acids that complement those favored by HisCA and LeuAC. Structural features help explain these results. These minimalist GlyRS catalysts are thus homologous to previously described urzymes. Their properties reinforce the notion that urzymes may have the requisite catalytic activities to implement a reduced, ancestral genetic coding alphabet., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study presents a biosensor utilizing electrospun SnO 2 nanofiber films for real-time monitoring of C2C12 cells. The biosensor demonstrates sensitivity towards cellular behaviours, including adhesion, proliferation, and detachment. Alterations in semi-circle and dielectric properties are validated through Nyquist plot and an EEC model, highlighting the biosensor's potential for analyzing cellular dynamics.

Fungal infection poses a major global threat to public health because of its wide prevalence, severe mortality rate, challenges involved in diagnosis and treatment, and the emergence of drug-resistant fungal strains. Millions of people are getting affected by fungal infection, and around 3.8 million people face death per year due to fungal infection, as per the latest report. The polyene antibiotic AmB has an extensive record of use as a therapeutic moiety against systemic fungal infection and leishmaniasis since 1960. AmB has broad-spectrum fungistatic and fungicidal activity. AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.

Noninvasive control over the reversible generation of singlet oxygen ( 1 O 2 ) has found the enormous practical implications in the field of biomedical science. However, metal-free pure organic emitters, connected with a photoswitch, capable of generating "on-demand" 1 O 2 via triplet harvesting remain exceedingly rare; therefore, the utilization of these organic materials for the reversible control of singlet oxygen production remains at its infancy. Herein, an ambient triplet mediated emission in quinoline-dithienylethene (DTE)-core-substituted naphthalene diimide (cNDI) derivative is unveiled via delayed fluorescence. The quinoline-DTE-cNDI triad displayed enhanced photoswitching efficiency via double FRET mechanism. It was found to have direct utilization in controlled photosensitized organic transformations via efficient generation of singlet oxygen (yield Φ Δ ~0.55 in DCM and 0.73 in methanol). The designed molecule exhibits a long-lived emission (τ∼1.1 μs) and very small singlet-triplet splitting (ΔE ST ) of 0.13 eV empowering it to display delayed fluorescence. Comprehensive steady state and time-resolved emission spectroscopy (TRES) analyses along with DFT calculations offer detailed understandings into the excited-state manifolds of organic compound and energy transfer (ET) pathways involved in 1 O 2 generation., (© 2024 Wiley-VCH GmbH.)

In recent times, diaryliodonium reagents (DAIRs) have witnessed a resurgence as arylating reagents, especially under photoinduced conditions. However, reactions proceeding through electron donor-acceptor (EDA) complex formation with DAIRs are restricted to electron-rich reacting partners serving as donors due to the well-known cage effect. We discovered a practical and high-yielding visible-light-induced EDA platform to generate aryl radicals from the corresponding DAIRs and use them to synthesize key chalcogenides. In this process, an array of DAIRs and dichalcogenides react in the presence of 1,4 diazabicyclo[2.2.2]octane (DABCO) as a cheap and readily available donor, furnishing a variety of di(hetero)aryl and aryl/alkyl chalcogenides in good yields. The method is scalable, features a broad scope with good yields, and operates under open-to-air conditions. The photoinduced chalcogenation technology is suitable for late-stage functionalizations and disulfide bioconjugations and facilitates access to biologically relevant thioesters, dithiocarbamates, sulfoximines, and sulfones. Moreover, the method applies to synthesizing diverse pharmaceuticals, such as vortioxetine, promazine, mequitazine, and dapsone, under amenable conditions., (© 2024 Wiley-VCH GmbH.)

Background: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks., Methods: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement., Results: A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research., Conclusions: We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care., Competing Interests: Competing interests: EA: grants from Swiss Academy for Anesthesia Research, Bbraun, Swiss National Science Foundation. Honoraria from Bbraun and Sintetica. JG: consulting fees from Pacira Biosciences and Pajunk Medical. AP: honoraria from FuijiFilm Sonosite. MW: advisory Board for Sintetica, Honoraria from Wisonic and Medovate. SA: Advisory Panel for DATAR innovations. JA: moderator of the Working Group Regional Anaesthesia Switzerland, Honoraria from Medtronic and Sintetica. AMRA: honoraria form AllerganSébastien Bloc—Consulting fees from BBraun—GE Medical Systems—Pajunk—Pfizer SAS. JB: Consulting fees from Intelligent Ultrasound. BC: jonoraria from Bbraun and Rivanna, Consulting from Stryker and Flat Medical, Research funding from Pacira, Share Options from Flat Medical. AC: speaking honoraria from GE Healthcare, royalties from textbook Oxford University Press. SC: consulting fees from MSD, Bbraun Medical, Wisonic, research grants from BARA (Belgian association of Regional anesthesia), ESRA and BeSARP (Belgian anesthesia society) HE-Consulting/Advisory Board Neuronoff, SPR, GateScience, NeuronoffBenjamin Fox—Speaking fees from Medovate and Sintetica. SG: consulting and speaking fees from MSD Switzerland. PH: royalties from Bestek Products. NH: Honoraria from Butterfly Network. RMGH- Honoraria from GE Healthcare. MH: consulting fees from Pacira Biosciences, Honoraria from Parcira Biosciences and Pajunk Medical. BMI: research funding to institution from SPR Therapeutics, Infutronix, Epimed International. AM: Consultant fees from Intelligent Ultrasound. CM: consultant fees from Masimo Corporation. SGM: Owner SGM Consulting, Partner Parvizi Surgical Innovations, Patent for Multicatheter infusion system. AN: Research support from SPR Therapeutics. SLO: Royalties from book Wolters-Kluwer. APawa: Honoraria from GE Healthcare, Consulting fees from Pacira Biosciences. PP: equipment support from Sonosiite Fujifilm Canada. MPS: Medovate speaking but no honoraria paid. SKS- Cofounder of Gate Science (developing a catheter for performing nerve blocks) JS: consulting fees from Sintetica. RT: Consulting fees from Clarius Mobile Health. VU: Associate Editor of the Canadian Journal of Anesthesia and Regional Anesthesia & Pain Medicine journals. TV: honoraria from CSL Behring, Pajunk., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Protein arginine methyltransferases (PRMTs) are important post-translational modifying enzymes in eukaryotic proteins and regulate diverse pathways from gene transcription, RNA splicing, and signal transduction to metabolism. Increasing evidence supports that PRMTs exhibit the capacity to form higher-order oligomeric structures, but the structural basis of PRMT oligomerization and its functional consequence are elusive. Herein, we revealed for the first time different oligomeric structural forms of the predominant arginine methyltransferase PRMT1 using cryogenic electron microscopy, which included tetramer (dimer of dimers), hexamer (trimer of dimers), octamer (tetramer of dimers), decamer (pentamer of dimers), and also helical filaments. Through a host of biochemical assays, we showed that PRMT1 methyltransferase activity was substantially enhanced as a result of the high-ordered oligomerization. High-ordered oligomerization increased the catalytic turnover and the multi-methylation processivity of PRMT1. Presence of a catalytically-dead PRMT1 mutant also abled enhanced activity of wild-type PRMT1, pointing out a non-catalytic role of oligomerization. Structural modeling demonstrates that oligomerization enhances substrate retention at the PRMT1 surface through electrostatic force. Our studies offered key insights into PRMT1 oligomerization and established that oligomerization constitutes a novel molecular mechanism that positively regulates the enzymatic activity of PRMTs in biology., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Main Conclusion: The pearl millet gene PgPM19 inhibits seed dormancy by negatively regulating the ABA biosynthesis and ABA signaling pathways in response to salinity stress in Arabidopsis. Abscisic acid (ABA) plays a pivotal role in orchestrating plant stress responses and development. However, how the ABA signal is transmitted in response to stresses remains primarily uncertain, particularly in monocotyledonous plants. In this study, PgPM19, a gene whose expression is induced by drought, salinity, heat, and ABA in both leaf and root tissues, was isolated from pearl millet. The expression of PgPM19 in yeast cells did not influence their growth when subjected to mannitol, sorbitol, or NaCl stress. However, Arabidopsis plants overexpressing PgPM19 (PgPM19&#95;OE plants) exhibited increased germination rates, greater fresh weights and longer roots under salinity stress during germination, compared to wild-type (WT) plants. Conversely, the pm19L1 (SALK&#95;075435) mutant, featuring a transfer DNA insertion in a closely related PgPM19 homolog (AT1G04560) in Arabidopsis, demonstrated reduced germination rates and smaller fresh weights under salinity-stressed condition than did WT and PgPM19&#95;OE plants. A pivotal ABA biosynthesis gene, NCED3, ABA signaling pathway genes, such as PYL6 and SnRK2.7, alongside downstream ABI genes and stress-responsive genes RAB28 and RD29, were downregulated in PgPM19&#95;OE plants, as evidenced by both transcriptome analysis and quantitative reverse transcription-PCR. These findings raise the possibility that PgPM19 is involved in regulating seed germination by mediating ABA biosynthesis and signaling pathway in response to salinity stress in Arabidopsis. This study contributes to a better understanding of PgPM19 in response to salinity stress and establishes a foundation for unraveling the crosstalk of stress responses and ABA in Arabidopsis and other plant species., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Antioxidants help safeguard sperm cells from damage during the freeze-thaw process. Melatonin and its metabolites have an antioxidative effect. The current study aimed to evaluate the impact of melatonin supplementation in tris-based extenders at various concentrations (0.5, 1.0 and 2 mM) on the freezability of Jamnapari goat spermatozoa. A total of 48 ejaculates were collected twice a week from four Jamnapari bucks (n = 12 × 4) using an artificial vagina during the period of October to November 2023. Selected ejaculates diluted with tris-citric acid egg yolk extender were divided into four equal aliquots, and melatonin (dissolved in 0.1% dimethyl sulfoxide) was added later at 0.5, 1.0 and 2.0 mM to the control group (C) (extender and 0.1% DMSO) and treatment groups T1, T2 and T3, respectively. Various seminal attributes such as progressive motility, livability, acrosomal integrity, sperm abnormalities, sperm plasma membrane integrity, sperm penetration distance by vanguard spermatozoa in polyacrylamide gel and seminal plasma enzyme leakage (AST, ALT, ACP and AKP) were evaluated at post-dilution and post-thawed stages. Our findings revealed that all semen quality parameters were superior in melatonin-treated groups than the C, and the differences were noticeably higher in the T2 group (1.0 mM) than the other groups. Adding 1.0 mM melatonin proved to be the most effective to safeguard sperm cells from cryopreservation induced cryodamage of Jamnapari buck., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Urban noise pollution poses significant challenges to public health and environmental sustainability, particularly in rapidly developing tourist destinations. Noise pollution and associated annoyance level in five major intersections of Cox's Bazar City, Bangladesh, was assessed in this study during the peak tourist season. Noise measurements were conducted using various indices (L 10 , L eq , and TNI) across morning, midday, and afternoon time slots. TNI scores were compared with Mean Dissatisfaction Score (MDS) standards to assess traffic-induced noise annoyance levels. Additionally, a survey of 675 respondents was conducted to assess their perceptions of noise pollution. Statistical analyses included linear regression for noise indices, multinomial logistic regression for TNI-related dissatisfaction, and ordinal logistic regression for respondents' perceived annoyances. Results revealed significant noise pollution issues, with L eq scores consistently exceeding national guidelines across all intersections and time periods, particularly on weekends during afternoon timeslots. TNI values frequently surpassed standard dissatisfaction regulations, with 19 out of 105 time slots exhibiting extreme dissatisfaction levels. Link Road and Kolatoli Circle intersections consistently showed higher noise levels and dissatisfaction. Over 95% of survey respondents perceived increased noise pollution during peak tourist seasons, with 87.11% describing it as "extremely" or "very" noisy. Longer exposure duration and awareness of health risks were significantly associated with reported perceived annoyance levels. Respondents reported various health impacts, including annoyance (84.44%), headaches (62.37%), and cognitive impairment (44.44%). This comprehensive study provides valuable insights for policymakers, city planners, and environmentalists to develop sustainable urban strategies that balance the acoustic environment with the well-being of residents and tourists alike., 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., (© 2024 The Authors.)

Integrating spatial inequality perspectives in strategic decision-making can ensure positive impacts on resource distribution for public welfare and sustainable development. This study aims to apply evidence-based approaches in deploying permanent deacons. The empirical case study has been conducted at the St Helens denary of the Liverpool archdiocese, UK. Assisting with charitable works is one of three served areas by the Roman Catholic Church facilitated by deacons. The deployment of permanent deacons could benefit from being evidence-based so that a deacon can serve to ease the socio-economic (e.g., population density, long-term health conditions, housing system, employment status, education level, social status) inequality in the most deprived area. We used geographic information system (GIS) based algorithms, Getis-Ord Gi* for hot spot analysis to find the clustered area by considering the socio-economic factors. The open/freely available government census dataset was found to help extract socio-economic parameters. Furthermore, a GIS-based multi-criteria assessment technique was conducted by applying map algebra (raster calculator) to identify the deprived area with ranks considering multiple socio-economic conditions, where served areas by the existing deacons were considered to constrain. The served areas were estimated by applying network analysis where OpenStreetMap and location existing deacons were used as input. Our empirical case study identified the central and northern parts of the deanery as the most and least deprived areas, respectively. Finally, Liverpool archdiocese could consider deploying new permanent deacons in St Helens denary based on suggested deprivation ranks. Therefore, the appropriate number of deacons in the deprived areas can quickly and effectively respond to the needy and enhance communities' resilience and sustainable development by ensuring proportionate resource distribution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Islam, Rooney, McGrail, Sikder and Charlesworth.)

Introduction: Klippel-Trenaunay Syndrome (KTS) is a medical condition that involves the abnormal enlargement of bones and soft tissues, along with the presence of arterio-venous malformations and cutaneous vascular nevus. This is an uncommon condition that is present from birth and affects the blood vessels. There are relatively few documented cases of how to treat fractures in the lower limbs of individuals with this condition., Case Report: A 37-year-old Indian male patient presented to our emergency room with a history of trivial trauma resulting from slipping and falling on the floor. From a clinical perspective, there was a bone deformity observed on the right thigh, accompanied by large dilated veins on the affected limb. The radiographs revealed osteoporotic bone with a fracture in the middle third of the right femur, as well as several small calcified masses dispersed throughout the affected lower leg. A Computed Tomography angiography was performed, revealing the presence of developmental venous malformations along with dilated deep and superficial venous channels. The diagnosis of KTS was ultimately confirmed by integrating clinical and radiological observations. The patient had surgical management with closed intramedullary nailing. Subsequent examinations showed strong indications of bone union without any significant complications., Conclusion: the surgical treatment of orthopaedic injuries in patients with KTS has been demonstrated to be linked to higher amounts of blood loss during the operation. In such circumstances, it is essential to do a comprehensive clinic-radiological assessment and careful preoperative planning to effectively treat or prevent surgical problems in these patients., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Introduction: Mucoid degeneration of the cruciate ligament is a well-known entity, but symptomatic lesions are rare. It is even rarer to find symptomatic posterior cruciate ligament mucoid degeneration than the anterior cruciate ligament., Case Report: A 63-year-old male presented to our hospital complaining of posterior knee pain was induced when the knee approached full flexion without episodes of trauma, despite conservative treatment over the preceding 8 months, his symptoms persisted. Physical examination of the right knee revealed on terminal flexion and cross-leg sitting pain get exaggerated. Right knee ROM 0-110° and a further terminal flexion was limited and painful. On ligament examination, posterior sagging and Lachman test were negative, and no clinical finding indicative of ligament insufficiency was noted. Magnetic resonance imaging showed a diffusely thickened posterior cruciate ligament with increased signal intensity on the T2-weighted sequence. A intact PCL fibers were observed with continuous margins from origin to insertion. Based on the patient's history and the magnetic resonance imaging findings, we suspected mucoid degeneration of the posterior cruciate ligament as the cause of the patient's symptoms. Since conservative treatment had failed to relieve the symptoms, arthroscopic treatment was indicated. Arthroscopic examination revealed yellowish crumbly tissues along the thickened posterior cruciate ligament. Tension and bulk of the posterior cruciate ligament were well preserved. Curettage of degenerative tissue and decompression of the posterior cruciate ligament resulted in symptom relief without instability of the knee joint. We did a notchplasty of the medial wall and roof to accommodate the posterior cruciate ligament and avoid impingement., Conclusions: Arthroscopic decompression of the posterior cruciate ligament may relieve knee pain and facilitate early return with good functional results., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Background: Patients with substance use disorders are common in general medical practice and are a major risk factor for several non-communicable diseases. Appropriate screening is a vital step for providing brief interventions which can provide a good opportunity to tackle this crisis and in achieving target 3.5 of the sustainable development goal which includes strengthening the prevention and treatment of substance abuse., Objectives: To study the magnitude of substance use and factors associated with it among people seeking health care services at primary care settings., Methods: The cross-sectional study recruited people seeking services at primary care settings to screen for substance users (SU) and determine the associated factors. The data was collected using a pretested semi-structured questionnaire including socio-demographic characteristics, health status and the Alcohol, Smoking and Substance Involvement Screening Test tool., Results: The study showed that 43.4% of the participants were SU. The current use of smokeless tobacco was higher compared to tobacco smoking (21.3% and 4.7%). The multivariate logistic regression showed that advancing age (AOR: 2.61 and 95% CI of 1.01-6.79), male gender (AOR: 705 and 95% CI of 4.25-11.70), primary and middle school (AOR: 3.24 and 95% CI of 1.52-6.92) literacy status, unemployed (AOR: 0.49 and 95% CI of 0.25-0.95), religion and other backward caste (AOR: 2.42 and 95% CI of 1.37-4.30) were significant correlates of SU., Conclusion: Substance use was reported by two-fifths of the participants seeking services at primary care centres in our study and stresses the need for incorporating brief interventions to prevent higher degrees of dependence and its complications., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© 2024 The Author(s).)

Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Glucuronoxylan is present mainly in the dicot of the secondary cell walls, often O-acetylated, which stabilizes cell structure by maintaining interaction with cellulose and other cell wall components. Some members of the Golgi localized Trichome Birefringence-Like (TBL) family function as xylan O-acetyl transferase (XOAT). The primary XOAT in the stem of Arabidopsis is ESKIMO1/TBL29, and its disruption results in decreased xylan acetylation, stunted plant growth, and collapsed xylem vessels. To elucidate the effect on metabolic reprogramming and identify the underlying cause of the stunted growth in eskimo1, we performed transcriptomic, targeted, and untargeted metabolome analysis, mainly in the inflorescence stem tissue. RNA sequencing analysis revealed that the genes involved in the biosynthesis, regulation, and transport of aliphatic glucosinolates (GSLs) were upregulated, whereas those responsible for indolic GSL metabolism were unaffected in the eskimo1 inflorescence stem. Consistently, aliphatic GSLs, such as 4-methylsulfinylbutyl (4MSOB), were increased in stem tissues and seeds. This shift in the profile of aliphatic GSLs in eskimo1 was further supported by the quantification of the soluble acetate, decrease in accumulation of GSL precursor, i.e., methionine, and increase in the level of jasmonic acid., (© 2024 Scandinavian Plant Physiology Society.)

Older patients with multiple myeloma (MM) exhibit wide heterogeneity in their baseline physiologic and functional status, which demands an individualized treatment approach based on biological rather than chronological age. Various frailty scores have been developed for older patients with MM, but they are underutilized in clinical trials and in practice. Older patients with MM are underrepresented in therapeutic clinical trials, and treatment recommendations are currently derived from clinical trials of transplant-ineligible patients. This article provides a summary of phase II and III clinical trials in transplant-ineligible patients with newly diagnosed MM, highlighting outcomes in patients aged ≥75 years and frailty-based outcomes. The data available thus far show that triplet regimens are more efficacious than doublets in older patients but may be associated with higher toxicity. DRd (daratumumab/lenalidomide/dexamethasone) and VRd (bortezomib/lenalidomide/dexamethasone) are good options in patients who are nonfrail, whereas dose-adjusted DRd and VRd-lite should be offered to frail patients. Frailty should be assessed regularly to guide treatment intensification and/or deescalation. It is important that frailty measures are incorporated in clinical trials evaluating novel treatments to inform how older and frail patients will benefit from these treatments.

In recent years, viral infections such as COVID-19, Zika virus, Nipah virus, Ebola, Influenza, Monkeypox, and Dengue have substantially impacted global health. These outbreaks have led to heightened global health initiatives and collaborative efforts to address and mitigate these significant threats effectively. Thus, developing antiviral treatments and research in this field has become highly important. Heterocycles, particularly indole motifs, have been a valuable resource in drug discovery, as they can be used as treatments or inspire the synthesis of new potent candidates. Indole-containing drugs, such as enfuvirtide (T-20), arbidol, and delavirdine, have demonstrated significant efficacy in treating viral diseases. This review aims to comprehensively assess the latest research and developments in novel indoles as potential scaffolds for antiviral activity. We have compiled detailed information about indoles as potential antivirals by conducting a thorough literature survey from the past ten years. The review includes discussions on synthetic protocols, inhibitory concentrations, SAR study, and computational study. This review shall identify new antiviral indoles that may help to combat new viral threats in the future., Competing Interests: Declaration of competing interest I, Prof Leena Khanna declare that the submitted review paper is my original work and no part of it has been published anywhere else in the past. I take full responsibility, that if in the future, the paper is found invalid according to basic rules, the last decision will be of the Authorities concerned., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: Wound patches are essential for wound healing, yet developing patches with enhanced mechanical and biological properties remains challenging. This study aimed to enhance the mechanical and biological properties of polyurethane (PU) by incorporating magnesium chloride (MgCl 2 ) into the patch., Methodology: The composite patch was fabricated using the electrospinning technique, producing nanofibers from a mixture of PU and MgCl 2 solutions. The electrospun PU/MgCl 2 was then evaluated for various physico-chemical characteristics and biological properties to determine its suitability for wound healing applications., Results: Tensile strength testing showed that the mechanical properties of the composite patch (10.98 ± 0.18) were significantly improved compared to pristine PU (6.66 ± 0.44). Field scanning electron microscopy (FESEM) revealed that the electrospun nanofiber patch had a smooth, randomly oriented non-woven structure (PU - 830 ± 145 nm and PU/MgCl 2 - 508 ± 151 nm). Fourier infrared spectroscopy (FTIR) confirmed magnesium chloride's presence in the polyurethane matrix via strong hydrogen bond formation. Blood compatibility studies using coagulation assays, including activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolysis assays, demonstrated improved blood compatibility of the composite patch (APTT - 174 ± 0.5 s, PT - 91 ± 0.8s, and Hemolytic percentage - 1.78%) compared to pristine PU (APTT - 152 ± 1.2s, PT - 73 ± 1.7s, and Hemolytic percentage - 2.55%). Antimicrobial testing showed an enhanced zone of inhibition (Staphylococcus aureus - 21.5 ± 0.5 mm and Escherichia coli - 27.5 ± 2.5 mm) compared to the control, while cell viability assays confirmed the non-cytotoxic nature of the developed patches on fibroblast cells., Conclusion: The study concludes that adding MgCl 2 to PU significantly improves the mechanical, biological, and biocompatibility properties of the patch. This composite patch shows potential for future wound healing applications, with further studies needed to validate its efficacy in-vivo., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Mani et al.)

Herein, we establish the release of aliphatic acids in water upon excitation of 7-diethylaminothio-4-coumarinyl derivatives encapsulated within the organic host octa acid (OA). The 7-diethylaminothio-4-coumarinyl skeleton, employed here as the trigger, photoreleases caged molecules from the excited triplet state, in contrast to its carbonyl analogue, where the same reaction is known to occur from the excited singlet state. Encapsulation in OA solubilizes molecules in water that are otherwise water-insoluble, and retains the used trigger within itself following the release of the aliphatic acid. Such supramolecular characteristics usher in new features to the photorelease methodology. The thiocarbonyl chromophore extends the absorption of coumarinyl trigger to visible range while enhancing the intersystem crossing (ISC) to the triplet state, making it the reactive state. Despite the non-polar environment within the OA capsules the photocleavage occurs in a heterolytic fashion to release the conjugate base and the used trigger as triplet carbocation in an adiabatic process. Interestingly, the triplet carbocation crosses to the ground singlet surface (closed shell singlet carbocation) with the help of water molecules, possibly aided by C = S chromophore. Utilizing the known excited state dynamics of related thiocoumarinyl and coumarinyl systems, we have identified a few of the important mechanistic features of the photorelease process of 7-diethylaminothio-4-coumarinyl derivatives. Ultrafast excited state dynamic studies and quantum chemical calculations planned should help us better understand the photorelease process so as to effectively exploit the proposed system for potential applications., Competing Interests: Declarations Conflict of interest Authors have financial or non-financial interests that are directly or indirectly related to the work reported in this publication., (© 2024. The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology.)

This observational study analyzed data from 502 participants undergoing cesarean section (CS) procedures at an obstetrics and gynecology department, aiming to explore anesthesia practices, neonatal outcomes, and demographic characteristics within the cohort. Participants, aged 17 to 59 years with a mean age of 32.23 years, were enrolled based on the clinical necessity for cesarean delivery during the study period. Informed consent was obtained from each participant or their guardians before data collection, which included detailed demographic information, medical histories, specifics of the cesarean section procedure, and APGAR scores of neonates immediately postbirth (at 0 and 5 minutes). Primary outcomes focused on APGAR scores, critical indicators of neonatal health, while secondary outcomes included the distribution of patient ages, reasons for cesarean sections, and the administration of Bupivacaine during anesthesia. Data were rigorously analyzed using descriptive and inferential statistics to summarize participant demographics, anesthesia practices, and neonatal outcomes. Statistical methods included measures of central tendency and dispersion, correlation analyzes to explore associations between variables, and regression models to identify predictors of neonatal APGAR scores. The study identified a range of indications for cesarean sections, with common reasons including fetal distress and maternal health complications. Findings indicated an average APGAR score of 7.02 at 0 minutes and 7.84 at 5 minutes, reflecting generally favorable immediate neonatal outcomes. Anesthesia protocols predominantly involved Bupivacaine, with doses ranging from 1.8 to 2.2 mL, administered based on clinical requirements. In conclusion, this study underscores the importance of comprehensive data collection and rigorous statistical analysis in evaluating cesarean section procedures. Future research could further explore long-term neonatal outcomes and refine anesthesia protocols to optimize maternal and neonatal health during cesarean deliveries., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Indirect greenhouse gases (GHGs) play a key role in modulating both regional and global atmospheric chemistry and act as air pollutants that degrade air quality. The rising number of premature deaths and notable health hazards could be linked to increasing concentration of these air pollutants in the atmosphere. As a developing nation, India is often regarded as one of the most polluting countries due to increasing anthropogenic activities. Therefore, identifying the sources of these indirect GHGs gases such as CO, NO x , VOC and SO 2 and quantifying their emissions has become a critical requirement for understanding regional atmospheric chemistry. In this study, we developed a comprehensive, technology-driven gridded emission inventory for India at a high resolution (0.1°×0.1°) for the base year 2020. Using the IPCC bottom-up approach, the study estimated the total emissions of CO (45 Tg/yr), NO x (22.8 Tg/yr), VOC (10.8 Tg/yr) and SO 2 (15.1 Tg/yr) from all the dominating sources. Vehicle exhaust contributes the most NO x and VOC whereas the residential and power sectors are the highest emitters of CO and SO 2 , respectively. This newly reported surface emission data would be an essential tool for policymakers in formulating mitigation strategies and will also serve as a vital input for atmospheric chemistry and climate studies., 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 Ltd. All rights reserved.)

The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in severe respiratory issues and persistent complications, particularly affecting glucose metabolism. Patients with or without pre-existing diabetes often experience worsened symptoms, highlighting the need for innovative therapeutic approaches. AMPK, a crucial regulator of cellular energy balance, plays a pivotal role in glucose metabolism, insulin sensitivity, and inflammatory responses. AMPK activation, through allosteric or kinase-dependent mechanisms, impacts cellular processes like glucose uptake, fatty acid oxidation, and autophagy. The tissue-specific distribution of AMPK emphasizes its role in maintaining metabolic homeostasis throughout the body. Intriguingly, SARS-CoV-2 infection inhibits AMPK, contributing to metabolic dysregulation and post-COVID-19 complications. AMPK activators like capsaicinoids, curcumin, phytoestrogens, cilostazol, and momordicosides have demonstrated the potential to regulate AMPK activity. Compounds from various sources improve fatty acid oxidation and insulin sensitivity, with metformin showing opposing effects on AMPK activation compared to the virus, suggesting potential therapeutic options. The diverse effects of AMPK activation extend to its role in countering viral infections, further highlighting its significance in COVID-19. This review explores AMPK activation mechanisms, its role in metabolic disorders, and the potential use of natural compounds to target AMPK for post-COVID-19 complications. Also, it aims to review the possible methods of activating AMPK to prevent post-COVID-19 diabetes and cardiovascular complications. It also explores the use of natural compounds for their therapeutic effects in targeting the AMPK pathways. Targeting AMPK activation emerges as a promising avenue to mitigate the long-term effects of COVID-19, offering hope for improved patient outcomes and a better quality of life., 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 Inc. All rights reserved.)

Detecting brain tumors early on is critical for effective treatment and life-saving efforts. The analysis of the brain with MRI scans is fundamental to the diagnosis because it contains detailed structural views of the brain, which is vital in identifying any of its abnormalities. The other option of performing an invasive biopsy is very painful and uncomfortable, which is not the case with MRI as it is free from surgically invasive margins and pieces of equipment. This helps patients to feel more at ease and hasten the diagnostic procedure, allowing physicians to formulate and practice action plans quicker. It is very difficult to locate a human brain tumor by manual because MRI scans produce large numbers of three-dimensional images. Complete applicability of pre-written computerized diagnostics, affords high possibilities in providing areas of interest earlier through the application of machine learning techniques and algorithms. The proposed work in the present study was to develop a deep learning model which will classify brain tumor grade images (BTGC), and hence enhance accuracy in diagnosing patients with different grades of brain tumors using MRI. A MobileNetV2 model, was used to extract the features from the images. This model increases the efficiency and generalizability of the model further. In this study, six standard Kaggle brain tumor MRI datasets were used to train and validate the developed and tested model of a brain tumor detection and classification algorithm into several types. This work consists of two key components: (i) brain tumor detection and (ii) classification of the tumor. The tumor classifications are conducted in both three classes (Meningioma, Pituitary, and glioma) and two classes (malignant, benign). The model has been reported to detect brain tumors with 99.85% accuracy, to distinguish benign and malignant tumors with 99.87% accuracy, and to type meningioma, pituitary, and glioma tumors with 99.38% accuracy. The results of this study indicate that the described technique is useful in the detection and classification of brain tumors., (© 2024. The Author(s).)

Studies comparing the intentional increase in oxygen delivery and normal oxygen delivery during general anaesthesia in elderly patients undergoing major abdominal surgery are limited and have reported contradictory findings. Therefore, the study aimed to evaluate the effect of intraoperative increase in systemic oxygen delivery on postoperative outcomes and quality of life in elderly patients undergoing major abdominal surgery. This randomised, blinded, parallel-arm, pragmatic clinical trial included elderly patients of >60 years of age undergoing major abdominal surgery. The patients in the intervention arm received noradrenaline or increased fractional inspiration of oxygen to augment central venous oxygen saturation ⩾75%. The primary outcome measure was composite of in-hospital mortality and major organ complications. The secondary outcome measure included comparison of quality of life. A total of 160 patients were assessed for eligibility, and 146 were randomised in the study groups. The mean arterial and central venous oxygen saturation increased and were significantly higher in the intervention arm. The composite primary outcome occurred in 49.31% in the intervention arm and 57.53% in the usual care arm (relative risk; 95% confidence interval: 0.85; 0.63-1.16; absolute risk reduction; 8.22%; p = 0.32). Furthermore, quality of life at the end of three months was similar (0.658 ± 0.19 versus 0.647 ± 0.19; p = 0.771). In conclusion, central venous oxygen saturation-guided increase in systemic oxygen delivery during the intraoperative period of major abdominal surgery in elderly patients did not reduce predefined composite outcome of in-hospital mortality or organ-specific complications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Thrombosis, the formation of blood clots in arteries or veins, poses a significant health risk by disrupting the blood flow. It can potentially lead to major cardiovascular complications such as acute myocardial infarction or ischemic stroke (arterial thrombosis) and deep vein thrombosis or pulmonary embolism (venous thrombosis). Nevertheless, over the course of several decades, researchers have observed an association between different cardiovascular events and neurodegenerative diseases, which progressively harm and impair parts of the nervous system, particularly the brain. Furthermore, thrombotic complications have been identified in numerous clinical instances of neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Substantial research indicates that endothelial dysfunction, vascular inflammation, coagulation abnormalities, and platelet hyperactivation are commonly observed in these conditions, collectively contributing to an increased risk of thrombosis. Thrombosis can, in turn, contribute to the onset, pathogenesis, and severity of these neurological disorders. Hence, this concise review comprehensively explores the correlation between cardiovascular diseases and neurodegenerative diseases, elucidating the cellular and molecular mechanisms of thrombosis in these neurodegenerative diseases. Additionally, a detailed discussion is provided on the commonly employed antithrombotic medications in the context of these neuronal diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Regulated precursor messenger RNA (pre-mRNA) splicing modulates gene expression and promotes alternative splicing. The process is regulated by modifications of spliceosomal proteins and small nuclear RNAs (snRNAs). Here, we show that the protein phosphatase Psr1, known for its plasma membrane localisation and function in general stress response in Saccharomyces cerevisiae, also plays a regulatory role in pre-mRNA splicing. Independently of its presence at the plasma membrane, Psr1 binds and dephosphorylates the core splicing factor Snu66. The enzyme is not an integral component of the spliceosome. Psr1 deletion in yeast, or tethering of its catalytic mutant to Snu66, results in splicing defects of introns with non-canonical 5' splice sites (ss). While the Psr1 binding site on Snu66 is distinct from the Hub1 interaction domains (HIND), Hub1 displaces Psr1 from Snu66. Thus, Psr1 phosphatase plays a regulatory role in pre-mRNA splicing by modulating Snu66 functions., (© 2024 Federation of European Biochemical Societies.)

Objectives: Previous studies generally used cross-sectional data and focused on under-five children to assess the risk factors for malnutrition among Indian children. Some recent studies have reported that recovery from or faltering in malnutrition is possible after five years of age, but socio-demographic subgroup disparities have not been explored. This study aims to find the longitudinal disparity in height-for-age Z-scores (HAZ) and body-mass-index-for-age Z-scores (BMIAZ scores) across various sub-groups of a cohort from childhood to adolescence., Methods: This study used a cohort from the Young Lives Survey, which followed children aged of 1-15 years between 2002 and 2016-17 in the states of Andhra Pradesh and Telangana, India. Mixed-effect models were applied to find the main, time, and interaction effects of HAZ scores and BMIAZ scores. In addition, an extended Kitagawa-Oaxaca-Blinder decomposition approach to assess group-based differences over time was used., Results: The cross-sectional prevalence of stunting reduced across all subgroups, while thinness rose during the same period. The interactions of child sex, mother's education, place of residence, wealth index, and antenatal care with time were statistically significant at p <0.05. The gender disparity in adjusted HAZ score  decreased from 0.214 units at 1 year to 0.011 units at 15 years, whereas BMIAZ score differential increased from 0.106 to 0.538 units over same timeframe. Disparities in scores were also observed across rural-urban, maternal education, social group, religion, socioeconomic status, maternal age at birth, antenatal care, and premature birth status., Conclusion: The study sheds light on the nuanced dynamics of paediatric growth, emphasising the importance of longitudinal approaches in understanding and addressing the health disparities across different stages of childhood and adolescence., (© 2024 John Wiley & Sons Ltd.)