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Abstract Oxidative stress (OS) refers to the disruption in the balance between free radical generation and antioxidant defenses, leading to potential tissue damage. Reactive oxygen species (ROS) can interact with biological components, triggering processes like protein oxidation, lipid peroxidation, or DNA damage, resulting in the generation of several volatile organic compounds (VOCs). Recently, VOCs provided new insight into cellular metabolism and can serve as potential biomarkers. The objective is to investigate the impact of OS on cell metabolism by analyzing the release or alterations of VOCs in the headspace of differentiated 3T3-L1 adipocytes. An OS model in differentiated 3T3-L1 cell lines was constructed using hydrogen peroxide (H2O2) treatment. The effect of OS on cell metabolism was analyzed by detecting VOCs in the headspace of the cells using solid phase micro extraction (SPME) and gas chromatography-mass spectrometry (GCMS). Our findings indicate that H2O2 concentrations exceeding 300 µM induce significant OS, leading to adipocyte apoptosis, as evidenced by various assays. Of the twenty VOCs identified, ten were upregulated in the cells. VOCs such as diphenyl ether, 1,3,5-trioxane, 5-methyl tridecane, 2-ethyl-1-hexanol, and 2,4-di-tert-butyl phenol emerged as potential biomarkers for OS. This study demonstrates that elevated OS alters VOC profiles in differentiated 3T3-L1 adipocytes, providing insights into the effects of OS on adipose tissue and identifying potential OS biomarkers.

Abstract About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53R175H (p53R172H in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53R175H could prove immensely value. We aimed to evaluate the in vitro and in vivo binding properties of two novel anti-p53R175H monoclonal antibodies and to assess their performance as agents for molecular imaging. In vitro, 125I-4H5 and 125I-7B9 demonstrated long shelf life and antigen-specific binding. Our in vivo study design allowed head-to-head comparison of the antibodies in a double tumor model using repeated SPECT/CT imaging, followed by biodistribution and autoradiography. Both tracers performed similarly, with marginally faster blood clearance for 125I-7B9. Repeated molecular imaging demonstrated suitable imaging characteristics for both antibodies, with the best contrast images occurring at 48 h post-injection. Significantly higher uptake was detected in the mut-p53-expressing tumors, confirmed by ex vivo autoradiography. We conclude that molecular imaging with an anti-p53R175H tracer could be a promising approach for cancer diagnostics and could be further applied for patient stratification and treatment response monitoring of mutant p53-targeted therapeutics.

Abstract One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) which are often essential for viral replication, transcription, or translation. In this report, we discovered a series of coumarin derivatives that bind to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a sequencing-based method namely cgSHAPE-seq, in which an acylating probe was directed to crosslink with the 2’-OH group of ribose at the binding site to create read-through mutations during reverse transcription. cgSHAPE-seq unambiguously determined a bulged G in SL5 as the primary binding site, which was validated through mutagenesis and in vitro binding experiments. The coumarin derivatives were further used as a warhead in designing RNA-degrading chimeras to reduce viral RNA expression levels. The optimized RNA-degrading chimera C64 inhibited live virus replication in lung epithelial carcinoma cells.

Enhanced photo-induced electron utilization leads to efficient photocatalytic hydrogen production. The inefficient separation of photo-induced electron–hole pairs has hindered this process. This study introduces a synergistic approach using defect-rich SnS2 and Ti3C2 MXene as cocatalysts in a two-step hydrothermal process to address this challenge. By integrating these materials with TiO2 nanosheets, we create a novel composite, SnS2/Ti3C2/TiO2 (STT), that significantly boosts photocatalytic hydrogen evolution. The defect-rich SnS2 provides abundant active sites for hydrogen generation, while Ti3C2 MXene facilitates photo-induced charge separation. The synergistic combination of charge carrier diffusion enhances chromophore absorption, thereby increasing the overall photocatalytic hydrogen-production rate, achieving several grams of hydrogen per hour per gram of double cocatalysts with molybdenum vacancies. Characterization techniques confirm the phase composition of the composite (STT). Compared to pristine TiO2 and other composites, the STT composite, optimized with a 150 °C hydrothermal treatment, shows a photocatalytic H2-production rate nearly 192 times higher than that of pure TiO2 and 6 times higher than that of other composites. The presence of molybdenum vacancies in SnS2 further enhances its specific activity for hydrogen evolution by suppressing carrier recombination and providing additional active sites. Moreover, Ti3C2 MXene and SnS2 act as dual cocatalysts, improving electronic conductivity and electron-transfer efficiency. Our findings demonstrate the potential of combining defect-rich SnS2 and Ti3C2 MXene to develop highly efficient and sustainable photocatalysts for hydrogen production. TiO2 has been in situ grown on highly conductive Ti3C2 MXene, and SnS2, rich in molybdenum vacancies, is uniformly distributed on the TiO2/Ti3C2 composite through the two-step hydrothermal method. The presence of molybdenum vacancies in SnS2 further enhances its specific activity for hydrogen evolution by suppressing carrier recombination and providing additional active sites. Moreover, Ti3C2 MXene and SnS2 act as dual cocatalysts, improving electronic conductivity and electron-transfer efficiency. Our findings demonstrate the potential of combining defect-rich SnS2 and Ti3C2 MXene to develop highly efficient and sustainable photocatalysts for hydrogen production.

Background: Oral cancer is one of the ten most common cancers worldwide and the sixth most common type of all cancer in India. Among the oral malignancies, oral squamous cell carcinoma (OSCC) is the most common, accounting for more than 90% of oral cancer and hence a significant public health concern. Aim: The aim of this study was to evaluate clinicopathological and demographic profiling of OSCC in a district and adjacent area of lower Assam. Settings and Design: This was a retrospective observational study. Materials and Methods: A total of 140 histologically confirmed OSCC patients diagnosed at the Regional Cancer Centre in the district between the period 2022 April and 2023 October constitute our study sample size in this study. The duration of the study was 1½ years. Statistical Analysis: The clinical and histopathological features were analyzed using descriptive statistics. Statistical Package for the Social Science (SPSS) version 23.0 was used. Results: OSCC constitutes 23.97% of head-and-neck cancer. The incidence of OSCC was higher in males. The highest number of patients was in the age group of 50–59. The most common site of OSCC was the buccal mucosa followed by the tongue. Most of the cases were well differentiated, the number being 82 (58.57%). Most of the patients were in Stage III and Stage IV. Conclusions: The present study highlights that in the lower Assam region, the majority of the OSCC patients are middle-aged male patients with advanced stages of OSCC. The findings from the present study can be used to compare the scenario of OSCC in other parts of Assam and North East India and also can be used for a follow-up study.

Background: Gallstones are the most important risk factor for gall bladder carcinoma. Understanding the burden of asymptomatic gallstone and its associated factors is essential to identify risk group likely to develop complication. Objectives: To estimate the burden of asymptomatic gallstone (AGS) and assess the factors contributing towards the same. Material and methods: A cross-sectional study was done during February to August 2023 in a tertiary care teaching hospital among adults aged above 18 years undergoing ultrasound of the abdomen as a part of routine master health check-up. A questionnaire was used collect the socio-demographic details, medical history and laboratory investigation. A total 1300 individuals were screened for AGS and included for analysis. Results: The mean age of study participants was 55.99 ± 15.83 years. The study found 36 individuals with AGS i.e 2.8% (95% CI:1.9-3.8%). The mean size of gallstone was 8.19 ± 4.6 mm with a range of 2 to 25 mm. Medical condition such as diabetes, hypertension and body mass index was found to be associated with AGS (p

Rapeseed (Brassica napus L.) is known for its high-quality seed oil and protein content. However, its use in animal feed is restricted due to antinutritional factors present in the seedcake, with sinapine being one of the main compounds that reduces palatability. Attempts to develop rapeseed germplasm with lower sinapine levels through traditional breeding methods have shown limited progress. Genetic transformation methods could create new genotypes with reduced sinapine levels by silencing key genes involved in sinapine biosynthesis, though these methods often result in transgenic or genetically modified plants. The recent development of CRISPR-Cas technology provides a precise and efficient approach to crop improvement, with the potential to generate transgene-free mutants. In this study, we targeted the BnaX.SGT.a genes for knockout using CRISPR-Cas editing. By utilizing our newly established protoplast regeneration and transfection protocol for rapeseed, we demonstrated that DNA-free CRISPR editing via protoplast-based ribonucleoprotein (RNP) delivery was highly effective. We achieved successful knockout of the BnaX.SGT.a paralogues, with an average mutation efficiency of over 30%. Sequencing results revealed a variety of mutation types, from 1 bp insertions to 10 bp deletions, with most mutants exhibiting frameshift mutations that led to premature stop codons. The mutants displayed no visible phenotypic differences in growth patterns or flowering compared to the wild type. Importantly, sinapine content was significantly reduced in all T2 generation mutants analysed, while seed weight remained comparable between mutants and the wild type.

Coconut haustorium is a tropical delicacy that mobilizes nutrients from the endosperm to nourish the germinating embryo. This study profiles coconut haustorium for sugars, organic acids, phenolics, and flavonoids using advanced chromatographic techniques. Fructose (62.70%) and glucose (18.21%) were the major sugars with negligible lactose, suggesting potential use in baby food and for lactose-intolerant individuals. Malic acid (71.79%), citric acid (12.80%), and shikimic acid (7.59%) were the prominent organic acids, contributing to the haustorium’s unique taste and refreshing flavor. Ferulic acid (60.96%) and p-coumaric acid (22.05%) were the prominent phenolic acids, while naringenin (35.36%) and catechin (29.68%) were the primary flavonoids. Total phenols, flavonoids, and antioxidant activity (61.18%) were also recorded, confirming the presence of bioactive compounds. The study reveals coconut haustorium as a rich source of readily available natural sugars, organic acids, phenols, and flavonoids offering potential for developing innovative nutraceuticals and functional foods.

The demand for sustainable, high-performance materials has driven interest in natural fiber-based composites. This research investigates the development of a hybrid composite using fibers from Prosopis Juliflora and Phoenix Sylvestris combined with glass fibers and epoxy resin. The natural fibers underwent a 10% NaOH treatment to enhance their mechanical properties. Hand layup techniques were employed to fabricate the samples, followed by comprehensive mechanical testing, including tensile, flexural, impact, hardness, and delamination tests. The composite, composed of 60% natural fibers, and 30% resin, and treated with NaOH, exhibited superior mechanical performance, surpassing similar composites in literature. Scanning electron microscopy (SEM) analysis revealed improved fiber-matrix adhesion, while wear testing indicated potential applications in brake linings. The results suggest this hybrid composite offers a viable, sustainable alternative for high-performance engineering applications, particularly in the automotive industry.

Background and Aims: Regional techniques are a part of multimodal analgesia following cesarean delivery. Cesarean delivery warrants a regional technique, which can provide somatic and visceral analgesia-like quadratus lumborum block (QLB) and erector spinae plane block (ESPB). In this study, we investigated the non-inferiority of ESPB at T12 and transmuscular-QLB (TQLB) at L2-L3 for postoperative analgesia in cesarean delivery. Material and Methods: In this prospective, randomized, non-inferiority trial, 124 patients undergoing cesarean delivery were enrolled to receive bilateral TQLB or ESPB with 20 mL of 0.25% ropivacaine on each side. All patients received prophylactic acetaminophen and ketorolac for 2 days. Our primary objective was to compare the total tramadol consumption in the first 48 h between the two groups. Secondary objectives were to compare cumulative tramadol consumption, postoperative Numeric Rating Scale (NRS) score at rest, and with movement at various time points, the time for first rescue analgesic requirement, development of complications related to the block, and patient satisfaction with analgesia between the two groups. Results: The total tramadol consumption in 48 h (47.3 ± 34.9 mg in ESPB and 50.9 ± 38.7 mg in TQLB), duration of first rescue analgesic (22.8 ± 15.8 h in ESPB and 22.7 ± 15.6 h in TQLB), and patient satisfaction were similar between the two groups. Both groups had similar pain scores except at rest at 6 h and on movement at 4 h, 6 h, and 36 h, whereas the ESPB group had lower NRS scores (P < 0.05). Conclusion: The analgesic effect of bilateral ESPB at T12 was non-inferior to that of bilateral TQLB post-caesarean delivery.

Mitochondria influence cellular function through both cell-autonomous and non-cell autonomous mechanisms, such as production of paracrine and endocrine factors. Here, we demonstrate that mitochondrial regulation of the secretome is more extensive than previously appreciated, as both genetic and pharmacological disruption of the electron transport chain caused upregulation of the Alzheimers disease risk factor apolipoprotein E (APOE) and other secretome components. Indirect disruption of the electron transport chain by gene editing of SLC25A mitochondrial membrane transporters as well as direct genetic and pharmacological disruption of either complexes I, III, or the copper-containing complex IV of the electron transport chain elicited upregulation of APOE transcript, protein, and secretion, up to 49-fold. These APOE phenotypes were robustly expressed in diverse cell types and iPSC-derived human astrocytes as part of an inflammatory gene expression program. Moreover, age- and genotype-dependent decline in brain levels of respiratory complex I preceded an increase in APOE in the 5xFAD mouse model. We propose that mitochondria act as novel upstream regulators of APOE-dependent cellular processes in health and disease.

Global protein consumption is increasing exponentially, which requires efficient identification of potential, healthy, and simple protein sources to fulfil the demands. The existing sources of animal proteins are high in fat and low in fiber composition, which might cause serious health risks when consumed regularly. Moreover, protein production from animal sources can negatively affect the environment, as it often requires more energy and natural resources and contributes to greenhouse gas emissions. Thus, finding alternative plant-based protein sources becomes indispensable. Rapeseed is an important oilseed crop and the world’s third leading oil source. Rapeseed byproducts, such as seed cakes or meals, are considered the best alternative protein source after soybean owing to their promising protein profile (30%–60% crude protein) to supplement dietary requirements. After oil extraction, these rapeseed byproducts can be utilized as food for human consumption and animal feed. However, anti-nutritional factors (ANFs) like glucosinolates, phytic acid, tannins, and sinapines make them unsuitable for direct consumption. Techniques like microbial fermentation, advanced breeding, and genome editing can improve protein quality, reduce ANFs in rapeseed byproducts, and facilitate their usage in the food and feed industry. This review summarizes these approaches and offers the best bio-nutrition breakthroughs to develop nutrient-rich rapeseed byproducts as plant-based protein sources.

The aim of the present study was to evaluate the haemodynamics of uterine blood flow in uterine torsion and record the period of resumption of ovarian cyclicity in cattle with uterine torsion. Crossbred cows with term gestation and straining for parturition due to post-cervical uterine torsion were selected for the study. Transrectal ultrasonographic assessment for measuring the doppler indices of middle uterine artery for both ipsilateral and contralateral side before and after detorsion was studied. Haemodynamic parameters such as blood flow volume (BFV), time-averaged peak velocity (TAP), resistance index (RI) and pulsatility index (PI) were assessed by using minimum three cardiac cycles. Blood samples were collected for haematological and biochemical assessment. Before detorsion, the PI value was high in ipsilateral side of uterine torsion and significant decrease could be observed after detorsion. However, BFV significantly increased after detorsion in both ipsilateral and contralateral side of uterine torsion when compared to the pre-detorsion values. Haematological and serum biochemical values were within the reference values and no significant observation could be made out of this in torsion affected cows. Two out of six animals (33.33%) exhibited the heat signs within three months of calving. In conclusion the blood flow volume was evidently increased after detorsion; however, the viability of the fetus was decided by the occurrence, duration and degree of uterine torsion.

CXCR4 is a ubiquitously expressed chemokine receptor that regulates leukocyte trafficking and arrest in both homeostatic and pathological states. It also participates in organogenesis, HIV-1 infection, and tumor development. Despite the potential therapeutic benefit of CXCR4 antagonists, only one, plerixafor (AMD3100), which blocks the ligand-binding site, has reached the clinic. Recent advances in imaging and biophysical techniques have provided a richer understanding of the membrane organization and dynamics of this receptor. Activation of CXCR4 by CXCL12 reduces the number of CXCR4 monomers/dimers at the cell membrane and increases the formation of large nanoclusters, which are largely immobile and are required for correct cell orientation to chemoattractant gradients. Mechanistically, CXCR4 activation involves a structural motif defined by residues in TMV and TMVI. Using this structural motif as a template, we performed in silico molecular modeling followed by in vitro screening of a small compound library to identify negative allosteric modulators of CXCR4 that do not affect CXCL12 binding. We identified AGR1.137, a small molecule that abolishes CXCL12-mediated receptor nanoclustering and dynamics and blocks the ability of cells to sense CXCL12 gradients both in vitro and in vivo while preserving ligand binding and receptor internalization.