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BACKGROUND AND OBJECTIVES: Exposure to endocrine-disrupting chemicals and organic dye pollution is associated with an increased risk of toxicity, hazard, and cancer due to their widespread use. Exogenous endocrine disruptors are responsible for interfering with reproduction and development because they can either stimulate or decrease endogenous hormone responses. This work explores the feasibility of human hair biochar as a potential adsorbent for possible solid waste management processes to minimize environmental pollution. Malachite green and bisphenol-A were selected as model pollutants, and the response surface methodology was used to identify the maximal removal of these hazardous substances.METHODS: Samples of human hair waste are collected and processed. After air drying for 24 hours, it was carbonized in a hot air oven at 200 degrees Celsius for 3 hours to obtain the human hair biochar. The biochar was subjected to various instrumental analyses to ascertain the characteristics of the biochar. Both malachite green and bisphenol-A adsorption experiments are performed in a batch method. Initial pollutant concentration (100 milligrams per liter), the volume of pollutant solution (50 milliliters), temperature (37 degrees Celsius), and agitation speed of orbital shaker (150 rotation per minute) are established as constants in this investigation. Data obtained from an Ultra Violet-Visible spectrophotometer was used to design expert software to calculate adsorption efficiency. Data variables A, B, and C included the potential of hydrogen (3, 6, 9), duration (60, 150, 240 minutes), and adsorbent dose (0.1, 0.3, 0.5 gram per liter) in the Response Surface Methodology experiment.FINDINGS: The human hair biochar is characterized by analytical methods, and Brunauer, Emmett, and Teller analysis revealed that it has a porous nature and extensive surface area, an amorphous structure, and various functional groups. The efficiency of adsorbent investigated over Malachite green and bisphenol-A in a batch experiment and performance variation of three parameters: A: potential of hydrogen (3, 6, 9), B: duration (60, 150, 240 minutes), and C: Human hair biochar dose (0.1, 0.3, 0.5 gram per liter) were evaluated via box-behnken design. Through analysis of variance and numerical expectation, the optimal potential of hydrogen, duration, and Human hair biochar dose was predicted as 3, 150 minutes, and 0.5 grams per liter, which resulted in a maximum removal of 96 percent for malachite green and 83 percent for bisphenol-A.CONCLUSION: This study demonstrated the facile heat-assisted development of biochar from human hair waste as a potential candidate for environmental remediation. The topography, structure, surface area, and functional group analysis of human hair biochar were carried out using analytical techniques that reveal the biochar has the potential for adsorbent characteristics. The adsorption efficiency of human hair biochar was demonstrated for malachite green (96 percent) and bisphenol-A (83 percent) response surface methodology under optimal conditions. The results suggested the model's relevance for the sorption of dyes and contaminants. The current study concludes that biochar can be prepared using a less expensive method and can be an alternate option to remove the dyes and other emerging contaminants in the aqueous matrix.

Heterostructure photocatalyst of CuWO4 modified SnO2 (CuWO4/SnO2) was fabricated by in simple wet-impregnation process and evaluated via degradation of rose Bengal (RB) under visible light irradiation. The samples had been completely characterized by Ultraviolet-visible diffuse reflectance spectroscopy (UV-vis-DRS), X-ray diffraction (XRD), Scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), High-resolution TEM (HR-TEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett and Teller surface analysis (BET). The result divulged that amongst the catalysts, CuWO4/SnO2 displayed higher photocatalytic activity than CuWO4 or SnO2. The enhanced photocatalytic efficiencies are attributed to the charge transfer from SnO2 to CuWO4 nanoparticles, which efficiently decrease electron-hole recombination energy level. The time required for maximum degradation of rosebengal (RB) under visible light over CuWO4/SnO2 was 180 min. The other parameters such as pH (pH=8), photocatalyst dosage (0.2 g/L) and dye concentration (20 µM) were optimized to achieve high degradation efficiency (98.5%). The excellent photocatalytic activity of CuWO4/SnO2 is due to efficient separation of photogenerated electron-hole pairs. The holes (h+) and superoxide radicals (O2•-) are the reactive species involved in photocatalytic mechanism for gdegradation of RB.

Orally fast-disintegrating tablets (OFDTs) have seen a significant increase in popularity over the past decade, becoming a rapidly expanding sector in the pharmaceutical market. The aim of the current study is to use machine learning (ML) methods to predict the disintegration time (DT) of OFDTs. In this study, we have developed seven ML models using the TPOT AutoML platform to predict the DT of OFDTs. These models include the decision tree regressor (DTR), gradient boost regressor (GBR), random forest regressor (RFR), extra tree regressor (ETR), least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and deep learning (DL). The results indicate that ML methods are effective in predicting the DT, especially with ETR. However, after fine-tuning the deep neural network with a 10-point cross-validation scheme, the DL model showed superior performance with an NRMSE of 6.2% and an R2 of 0.79. The key factors influencing the DT of OFDTs were identified using the SHAP method.

Kinase enzymes play an important role in cellular proliferation, and inhibition of their activity is a major goal of cancer therapy. Protein kinase inhibitors as benzimidazole derivatives can be applied for prevention or treatment of cancers through inhibition of cell proliferation. To evaluate their protein kinase inhibitory effects, as well as the in silico study for active benzimidazole derivatives. Benzimidazole derivatives has presented significant therapeutic potential against several disorders and known to have numerous biological activities (such as antibacterial, antiviral and anti-inflammatory). Benzimidazole derivatives have shown significant potential in the reduction of viral load as well as in enhancing immunity. To forecast absorption, distribution, metabolism, excretion and toxicity, simply known as ADMET and the Lipinski rule of five parameters of the examined substances, the admetSAR and Swiss ADME were used. The ADMET predictions revealed that the compounds had good and safe pharmacokinetic features, making them acceptable for further development as therapeutic candidates in clinical trials. This study primarily focused on blocking 2 key targets of kinase proteins (CDK4/CycD1 and Aurora B). 2-Phenylbenzimidazole has shown the greatest inhibitory potential (with a binding energy of −8.2 kcal/mol) against protein kinase inhibitors. This study results would pave the potential lead medication for anticancer therapeutic strategies.

Context: Polycystic ovary syndrome (PCOS) and thyroid are the most common endocrine disorders affecting women of childbearing age, causing anovulation and infertility. There is an increased prevalence of thyroid dysfunction reported among PCOS women. Aims: To evaluate the benefits of acarbose plus myo-inositol therapy on the thyroid profile of PCOS. Methods: An open-labelled, parallel randomised clinical trial on 80 PCOS women based on inclusion and exclusion criteria was performed at the Department of Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur. Institutional ethics committee approval and prior informed consent were obtained. The trial was registered in CTRI (No: CTRI/2022/04/041877). Group A (n = 38) received metformin 500 mg TID, and group B (n = 39) received acarbose 50 mg TID along with myoinositol 1000 mg BID. Assessment of metabolic and hormonal profile was done at baseline and at the end of six months. Results: Both groups showed significant reductions in luteinising hormone (p

The escalating global food waste crisis presents both a challenge and an opportunity for sustainable development. Every year, millions of tons of food are wasted, contributing to environmental degradation and resource inefficiency. This wasted food not only represents a loss of valuable resources but also contributes to significant greenhouse gas emissions when disposed of in landfills. In response to this pressing issue, food waste valorization biorefineries have emerged as a promising solution, transforming waste into valuable bioproducts through innovative biotechnological processes. This review critically examines recent trends in food waste biorefining, focusing on the latest advancements in microbial and enzymatic conversion technologies. Various valorization pathways that convert food waste into biofuels, biochemicals, and bio-based materials are explored, thereby integrating principles of the circular economy to minimize waste and maximize resource utilization. Key developments in the field include the optimization of microbial consortia for enhanced degradation and conversion efficiency, as well as the engineering of enzymes to improve specificity and activity. These advancements have led to significant improvements in the efficiency and feasibility of converting food waste into high-value products. The environmental benefits of these biorefineries are also discussed in depth, encompassing the reduction of greenhouse gas emissions, decreased reliance on fossil fuels, and the mitigation of environmental pollution. By diverting food waste from landfills and transforming it into renewable resources, these biorefineries play a crucial role in promoting environmental sustainability. Despite these advancements, several challenges remain. Feedstock variability affects process consistency, leading to fluctuations in product yield and quality. There is a need for process optimization to improve yield and cost-effectiveness, ensuring that biorefinery operations are economically viable at an industrial scale. Issues related to scalability and industrial implementation, such as the development of infrastructure and supply chains, also pose significant hurdles. By synthesizing current research, this review underscores the considerable potential of food waste biorefineries to contribute to sustainable agriculture and biocatalysis. Critical gaps in knowledge are identified, and areas for future research are proposed, such as developing robust and flexible biorefining systems capable of handling diverse feedstocks and integrating advanced biotechnological tools for process monitoring and control. The review also highlights the importance of interdisciplinary collaboration and public-private partnerships in driving innovation and commercialization in this field. Ultimately, this review aims to provide a comprehensive understanding of the current state of food waste biorefining and to offer a roadmap for future research and industrial implementation. By highlighting the role of these biorefineries in achieving sustainable development goals, the review emphasizes the need for continued research, technological innovation, and supportive policy frameworks. Through these efforts, food waste valorization biorefineries can play a pivotal role in creating a sustainable and resilient future, addressing both environmental and economic challenges posed by food waste.

Abstract Background Megalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of 68Ga- and 99mTc-labeled 15-mer peptide developed to target the vascular endothelial growth factor (VEGF) receptor in oncology radiodiagnostics. Results The gene editing in the LRP2 KO model was verified by testing two well-known megalin ligands when higher viability of KO cells was observed after gentamicin treatment at cytotoxic concentrations and lower FITC-albumin internalization by the KO cells was detected in accumulation studies. Fluorescent-activated cell sorting was used to separate genetically modified LRP2 KO cell subpopulations. Moreover, flow cytometry with a specific antibody against megalin confirmed LRP2 knockout. The verified KO model identified both 68Ga- and 99mTc-radiolabeled 15-mer peptides as megalin ligands in accumulation studies. We found that both radiolabeled 15-mers enter LRP2 KO HK2 cells to a lesser extent compared to parent cells. Differences in megalin-mediated cellular uptake depending on the radiolabeling were not observed. Using biomolecular docking, the interaction site of the 15-mer with megalin was also described. Conclusion The CRISPR/Cas9 knockout of LRP2 in human kidney HK2 cells is an effective approach for the determination of radiopeptide internalization mediated by megalin. This in vitro method provided direct molecular evidence for the cellular uptake of radiolabeled anti-VEGFR 15-mer peptides via megalin. Graphical abstract

Background: NTRK1, NTRK2, and NTRK3 are members of the neurotrophic receptor tyrosine kinases (NTRK) family, which encode TrkA, TrkB, and TrkC receptors, respectively. Hematologic cancers are also linked to point mutations in the NTRK gene's kinase domain. Trk fusions are the most common genetic change associated with oncogenic activity in Trk-driven liquid tumors. Thus, point mutations in NTRK genes may also play a role in tumorigenesis. The structural and functional effect of mutations in Trk-B & Trk-C proteins remains unclear. Methods: In this research, Homology (threading-based approach) modeling and the all-atom molecular dynamics simulations approaches are applied to examine the structural and functional behavior of native and mutant Trk-B and Trk-C proteins at the molecular level. Results: The result of this study reveals how the mutations in Trk-B (A203T & R458G) and Trk-C (E176D & L449F) proteins lost their stability and native conformations. The Trk-B mutant A203T became more flexible than the native protein, whereas the R458G mutation became more rigid than the native conformation of the Trk-B protein. Also, the Trk-C mutations (E176D & L449F) become more rigid compared to the native structure. Conclusions: This structural transition may interrupt the function of Trk-B and Trk-C proteins. Observing the impact of NTRK-2/3 gene alterations at the atomic level could aid in discovering a viable treatment for Trk-related leukemias.

Background: Abrus precatorius L. is a noxious vein native to south east asia and popularly called as Gunja in Ayurveda. The seeds of this plant are considered as a potent raw drug used in various herbal formulations such as Gunjadi tailam, Gunjagarbha rasa etc. and used to treat various ailments such as dermal disorders, cysts, snake poisoning and may other conditions. Before utilizing for the herbal formulations, the seeds are classically processed due to the presence of well reported toxic protalbumin named Abrin with the human fatal dose of 0.1–1 µg/kg. Methods: In this work three varieties of Abrus precatorius L. seeds (Red, White and Black) were collected from the southern part of India and subjected for the detoxification process in order to analyze the efficiency of technique on different varieties of seeds. For processing the seeds, the classically fermented supernatant of rice gruel named kanjika was prepared and the pH was analyzed. Before and after processing, the seeds were analyzed for phytoconstituents with histochemistry technique and the hydroalcoholic extracts were prepared and qualitatively estimated for phytochemicals. The detoxification efficiency was analysed using HPTLC method by qualitative and quantitative estimation of Abrin levels by comparing with standard marker. Following that, cytotoxicity study was conducted against Vero (Healthy kidney) cell lines to ensure reduced toxicity in in-vitro conditions. Results: The process of Shodhana has changed the phytochemical levels in the processed seeds in comparison with unprocessed seeds in all three varieties. In connection to that, the extracts prepared with processed seeds have expressed lesser cytotoxicity and can be used as a drug with lesser side effects in whatever indications applicable. Conclusion: It is concluded that Shodhana with kanjika is efficient in processing all three varieties of Abrus precatorius seeds and is more effective in processing white seeds than the red and black varieties.

Background: NTRK1, NTRK2, and NTRK3 are members of the neurotrophic receptor tyrosine kinases (NTRK) family, which encode TrkA, TrkB, and TrkC receptors, respectively. Hematologic cancers are also linked to point mutations in the NTRK gene's kinase domain. Trk fusions are the most common genetic change associated with oncogenic activity in Trk-driven liquid tumors. Thus, point mutations in NTRK genes may also play a role in tumorigenesis. The structural and functional effect of mutations in Trk-B & Trk-C proteins remains unclear. Methods: In this research, Homology (threading-based approach) modeling and the all-atom molecular dynamics simulations approaches are applied to examine the structural and functional behavior of native and mutant Trk-B and Trk-C proteins at the molecular level. Results: The result of this study reveals how the mutations in Trk-B (A203T & R458G) and Trk-C (E176D & L449F) proteins lost their stability and native conformations. The Trk-B mutant A203T became more flexible than the native protein, whereas the R458G mutation became more rigid than the native conformation of the Trk-B protein. Also, the Trk-C mutations (E176D & L449F) become more rigid compared to the native structure. Conclusions: This structural transition may interrupt the function of Trk-B and Trk-C proteins. Observing the impact of NTRK-2/3 gene alterations at the atomic level could aid in discovering a viable treatment for Trk-related leukemias.