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Revenues from hydropower generation often depend on the operator's ability to provide firm power in the presence of uncertain inflows. The primary options available for optimizing revenue are negotiation of a firm power contract before operations begin and adjustment of the reservoir release during operations. Contract and release strategy optimization are closely coupled and most appropriately analyzed with stochastic real-time control methods. Here we use an ensemble-based approach to stochastic optimization that provides a convenient way to construct nonparametric revenue probability distributions to explore the implications of uncertainty. The firm power contract is a simplified bilateral fixed price agreement that partially insulates operator and buyer from price fluctuations. The release control laws and firm energy target are jointly optimized to maximize the operator's expected revenue. Revenue probability distributions and related spill performance statistics indicate that predictive operating strategies such as stochastic dynamic programming and model predictive control can give significantly better performance than standard deterministic operating rules. The performance obtained from batch optimization with perfect inflow information establishes a convenient upper bound on potential revenue and provides a baseline for assessing the significance of differences between real-time operating strategies. Sensitivity analysis indicates that the benefits of predictive operational strategies are greatest for reservoirs with medium nondimensional residence times and less important for reservoirs with large residence times. Overall, probabilistic analysis of the coupled hydropower contract-operations problem provides a realistic way to assess revenue and risk for reservoirs that must provide firm power when inflows are uncertain.

Heterochromatin enforces transcriptional gene silencing and can be epigenetically inherited, but the underlying mechanisms remain unclear. Here, we show that histone deacetylation, a conserved feature of heterochromatin domains, blocks SWI/SNF subfamily remodelers involved in chromatin unraveling, thereby stabilizing modified nucleosomes that preserve gene silencing. Histone hyperacetylation, resulting from either the loss of histone deacetylase (HDAC) activity or the direct targeting of a histone acetyltransferase to heterochromatin, permits remodeler access, leading to silencing defects. The requirement for HDAC in heterochromatin silencing can be bypassed by impeding SWI/SNF activity. Highlighting the crucial role of remodelers, merely targeting SWI/SNF to heterochromatin, even in cells with functional HDAC, increases nucleosome turnover, causing defective gene silencing and compromised epigenetic inheritance. This study elucidates a fundamental mechanism whereby histone hypoacetylation, maintained by high HDAC levels in heterochromatic regions, ensures stable gene silencing and epigenetic inheritance, providing insights into genome regulatory mechanisms relevant to human diseases., Competing Interests: Declaration of interests S.I.S.G. is a member of the advisory board of Molecular Cell., (Published by Elsevier Inc.)

Background: Obesity is a burgeoning global health problem with an escalating prevalence and severe implications for public health. New evidence indicates that long non-coding RNAs (lncRNAs) may play a pivotal role in regulating adipose tissue function and energy homeostasis across various species. However, the molecular mechanisms underlying obesity remain elusive., Scope of Review: This review discusses obesity and fat metabolism in general, highlighting the emerging importance of lncRNAs in modulating adipogenesis. It describes the regulatory networks, latest tools, techniques, and approaches to enhance our understanding of obesity and its lncRNA-mediated epigenetic regulation in humans and Drosophila ., Major Conclusions: This review analyses large datasets of human and Drosophila lncRNAs from published databases and literature with experimental evidence supporting lncRNAs role in fat metabolism. It concludes that lncRNAs play a crucial role in obesity-related metabolism. Cross-species comparisons highlight the relevance of Drosophila findings to human obesity, emphasizing their potential role in adipose tissue biology. Furthermore, it discusses how recent technological advancements and multi-omics data integration enhance our capacity to characterize lncRNAs and their function. Additionally, this review briefly touches upon innovative methodologies like experimental evolution and advanced sequencing technologies for identifying novel genes and lncRNA regulators in Drosophila , which can potentially contribute to obesity research., Competing Interests: There are no financial, professional, or personal affiliations that could be perceived as influencing the research presented in this review manuscript., (© 2024 Published by Elsevier Ltd.)

Background: Delirious mania (DM) is a severe psychiatric condition having rapid onset of delirium, mania, and psychosis. It is an emergency condition as it has acute onset and is characterized by extreme hyperactivity. Catatonic signs may also be present. Very few cases have been reported from India, hence making it imperative to study its clinical characteristics and possible treatment, which can help in providing care to such patients in emergency settings., Clinical Cases Description: This paper describes four cases with a diagnosis of DM - demography, clinical features, investigations, treatment. All the patients had an acute onset and rapid progression of symptoms, with clinical symptoms of talkativeness, increased psychomotor activity, decreased need for sleep, aggressive and violent behavior, increased libido, increased appetite with delusion of grandiosity, disorientation to time/place/person, impaired memory of recent events, impaired attention with fluctuating course, negativism, echolalia, and echopraxia., Conclusion: There is a high likelihood of misdiagnosing DM in the absence of diagnostic guidelines. There should be an active search for the underlying aetiology in all cases of DM. Atypical antipsychotics and mood stabilizers may be used to treat less severe forms of DM. Modified electric convulsive treatment and intravenous benzodiazepines elicit a good response., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (© Authors, 2024.)

Modern nanostructures must fulfill a wide range of functions to be valuable, leading to the combination of various nano-objects into hierarchical assemblies. Hybrid Nanoparticles (HNPs), comprised of multiple types of nanoparticles, are emerging as nanoscale structures with versatile applications. HNPs offer enhanced medical benefits compared to basic combinations of distinct components. They address the limitations of traditional nanoparticle delivery systems, such as poor water solubility, nonspecific targeting, and suboptimal therapeutic outcomes. HNPs also facilitate the transition from anatomical to molecular imaging in lung cancer diagnosis, ensuring precision. In clinical settings, the selection of nanoplatforms with superior reproducibility, cost-effectiveness, easy preparation, and advanced functional and structural characteristics is paramount. This study aims toextensively examine hybrid nanoparticles, focusing on their classification, drug delivery mechanisms, properties of hybrid inorganic nanoparticles, advancements in hybrid nanoparticle technology, and their biomedical applications, particularly emphasizing the utilization of smart hybrid nanoparticles. PHNPs enable the delivery of numerous anticancer, anti-leishmanial, and antifungal drugs, enhancing cellular absorption, bioavailability, and targeted drug delivery while reducing toxic side effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background  The keystone design perforator island flap (KDPIF) is unique among local flaps because of its high potential for adaptation. We describe our experience with the use of the keystone flap for the reconstruction of a variety of defects in different regions of the body concerning its versatility, surgical outcomes, complications, postoperative pain, operative time, and esthetic outcomes. Methods  A prospective observational study was conducted at our institute from June 2021 to June 2023 where the use of KDPIFs in resurfacing soft tissue defects of different etiopathogenesis was evaluated and the data were analyzed. Results  Forty-four patients were included in the study with soft tissue defects of various etiologies and at different locations. The largest flap raised was 18 × 10 cm and the smallest was 4 × 2 cm. The average intraoperative time for completion of the procedure was 74.86 minutes (range: 45-120 minutes). The success rate of flap survivability was 95.45% with two patients having total flap loss necessitating another reconstructive option. Partial flap dehiscence which healed secondarily was observed in two patients. Postoperative pain showed a significant fall of 83.7% from baseline and 82.9% of cases were extremely satisfied with the esthetic outcome. Conclusion  The keystone flap is a valuable reconstructive tool in the armamentarium of a plastic surgeon. It is technically reproducible, suitable to be done in resource-limited settings, and provides contiguous tissue with good vascularity and fewer complications., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells., Methods: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay., Results: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer., Conclusions: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells., (© 2024. The Author(s).)

Groundwater resources play an important role for irrigation, particularly in arid and semi-arid regions, where groundwater depletion poses a critical threat to agricultural production and associated local livelihoods. However, the relationship between groundwater use, farming, and poverty, particularly with regards to informal mechanisms of resources management, remains poorly understood. Here, we assess this relationship by developing a behavioural model of groundwater user groups, empirically grounded in the politically fragile context of Tunisia. The model integrates biophysical aquifer dynamics, institutional governance, and farmer decision-making, all of which are co-occurring under conditions of aquifer depletion and illicit groundwater extraction. The paper examines how community-level norms drive distributional outcomes of farmer behaviours and traces pathways of local system collapse - whether hydrogeological or financial. Through this model, we explore how varying levels of trust and leadership, ecological conditions, and agricultural strategies can delay or avoid collapse of the social-ecological system. Results indicate limits to collective action under path-dependent aquifer depletion, which ultimately leads to the hydrogeological collapse of groundwater user groups independent of social and institutional norms. Despite this inevitable hydrogeological collapse of user groups, the most common cause of water user group failure is bankruptcy, which is linked to the erosion of social norms regarding fee payment. Social and institutional norms, however, can serve to delay the financial collapse of user groups. In the politically fragile system of Tunisia, low levels of trust in government result in low social penalties for illicit water withdrawals. In the absence of alternative irrigation sources, this serves as a temporary buffer against income-poverty. These results highlight the need for polycentric coordination at the aquifer-level as well as income diversification beyond agriculture to sustain local livelihoods., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

β-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with β-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with β-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate β-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of β-carotene-loaded solid lipid nanoparticles were compared with intact β-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of β-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard β-carotene, β-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like β-carotene., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We have no conflict of interest If there are other authors, they 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 Published by Elsevier Ltd.)

The purpose of the current research is to formulate a smart drug delivery system for solubility enhancement and sustained release of hydrophobic drugs. Drug solubility-related challenges constitute a significant concern for formulation scientists. To address this issue, a recent study focused on developing PEG- g -poly(MAA) copolymeric nanogels to enhance the solubility of olmesartan, a poorly soluble drug. The researchers employed a free radical polymerization technique to formulate these nanogels. Nine formulations were formulated. The newly formulated nanogels underwent comprehensive tests, including physicochemical assessments, dissolution studies, solubility evaluations, toxicity investigations, and stability examinations. Fourier transform infrared (FTIR) investigations confirmed the successful encapsulation of olmesartan within the nanogels, while thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies verified their thermal stability. Scanning electron microscopy (SEM) images revealed the presence of pores on the surface of the nanogels, facilitating water penetration and promoting rapid drug release. Moreover, powder X-ray diffraction (PXRD) studies indicated that the prepared nanogels exhibited an amorphous structure. The nanogel carrier system led to a significant enhancement in olmesartan's solubility, achieving a remarkable 12.3-fold increase at pH 1.2 and 13.29-fold rise in phosphate buffer of pH 6.8 (NGP3). Significant swelling was observed at pH 6.8 compared to pH 1.2. Moreover, the formulated nexus is nontoxic and biocompatible and depicts considerable potential for delivery of drugs and protein as well as heat-sensitive active moieties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Advanced technology innovations allow cost-effective, high-throughput profiling of biological systems. It enabled genome sequencing in days using advanced technologies (e.g., next-generation sequencing, microarrays, and mass spectrometry). Since technology has been developed, massive biological data (e.g., genomics, proteomics) has been produced cheaply, allowing the "big data" era to create new opportunities to solve medical and biological complications in many disciplines-preventive medicine, biology, Personalized Medicine, gene sequencing, healthcare, and industry. Computational biology and bioinformatics are interdisciplinary fields that develop and apply computational methods (e.g., analytical methods, mathematical modeling, and simulation) to analyze large collections of biological data, such as genetic sequences, cell populations, or protein samples, to make new predictions or discover new biology. Biological data storage, mining, and analysis have challenges because data is much more heterogeneous. In this study, the big data resources of genomics, proteomics, and metabolomics have been explored to solve biological problems using big data analysis approaches. The goal is to build a network of relationship-based gene-disease associations to prioritize phenotypes common to epilepsy and seizure disease. Through network analysis, The 10 seed genes, 22 associated genes, 132 microRNAs, and 38 transcription factors have been identified that have a direct effect on all forms of epilepsy and seizures. The majority of seed genes, according to the results of a functional analysis of seed genes, are involved in the acetylcholine-gated channel complex (10%) and the heterotrimeric G-protein complex (10%) pathways related to cellular components, followed by a role in the regulation of action potential (20%) and positive regulation of vascular endothelial growth factor production (20%) in Epilepsy and Seizures pathways related to biological processes. This study might provide insight into the workings of the disease and shows the importance of continued research into epilepsy and other conditions that can trigger seizure activity., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Four surgical treatment modalities namely cryosurgery, scalpel and blade surgery, diode LASER surgery and CO2 LASER surgery in the management of oral potentially malignant disorders (OPMDs) in terms of healing outcomes post operatively and recurrence is evaluated. The study included sixty outpatients whose biopsies revealed OPMDs (oral lichen planus, homogeneous leukoplakia, non-homogenous leukoplakia and erythroplakia). There is decrease in post-operative pain and oedema in all four treatment categories at one week follow up and two week follow up. It was observed that pain was low in cryosurgery treatment category at day of surgery as well as at one week of follow up as compared to diode LASER and CO2 LASER. Observations from the study highlights that all four surgical modalities used in this study were effective for treatment of OPMDs, and the overall summation of the results of the study showed that cryotherapy seems to offer better clinically significant results than laser therapy., (© 2023 Biomedical Informatics.)

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Krishna, Farhana, T.P., Hussain, Viswanad, Nasr, Sahu and Khan.)

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2- c ]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, β- C -glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1- C -formyl glycals were synthesized from these β- C -glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1- C -formyl galactal and 4-hydroxycoumarin. Next, 1- C -formyl galactal and 1- C -formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2- c ]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

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.

The objective of this investigation was to fabricate nanoparticles consisting of Imatinib mesylate-poly sarcosine-loaded chitosan/carrageenan in order to attain prolonged drug release and efficacious therapy for colorectal cancer. The study involved the synthesis of nanoparticles through the utilisation of ionic complexation and nanoprecipitation techniques. The subsequent nanoparticles were subjected to an assessment of their physicochemical characteristics, anti-cancer efficacy using HCT116 cell line, and acute toxicity. The present study examined two distinct nanoparticle formulations, namely IMT-PSar-NPs and CS-CRG-IMT-NPs, with respect to their particle size, zeta potential, and morphology. Both formulations demonstrated satisfactory characteristics, as they displayed consistent and prolonged drug release for a duration of 24 h, with the highest level of release occurring at a pH of 5.5. The efficacy and safety of IMT-PSar-NPs and CS-CRG-IMT-PSar-NPs nanoparticles were evaluated through various tests including in vitro cytotoxicity, cellular uptake, apoptosis, scratch test, cell cycle analysis, MMP & ROS estimate, acute toxicity, and stability tests. The results suggest that these nanoparticles were well fabricated and have promising potential for in vivo applications. The prepared polysaccharide nanoparticles have great potential for active targeting and could potentially reduce dose-dependent toxicity in the treatment of colon cancer., Competing Interests: Declaration of competing interest Authors declare there are no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sahu, Ruhi, Jeppu, Al-Goshae, Syed, Nagdev, Widyowati, Ekasari, Khan, Bhattacharjee, Goyal, Bhattacharya and Jangde.)

Abemaciclib (Ab) and palbociclib (Pb) are CDK4/6 inhibitors used to cure advanced breast cancer (BC). However, acquired resistance is a major challenge. The molecular mechanisms and signature proteins of therapy resistance for Ab and Pb drugs need to be explored. Here we developed resistant cells for Ab and Pb drugs in MCF-7 cell lines and explored the mechanisms and signature proteins of therapy resistance in BC. Proteome profiling was performed using the label-free proteome-orbitrap-fusion-MS-MS technique. Gene ontology (GO)-terms, KEGG pathways and network analysis were performed for the proteome data. Drug-resistant cells showed increased drug tolerance, enhanced colony formation potential and an increased gap-healing tendency for the respective drug. Up-regulation of survival genes (BCL-2 and MCL-1) and down-regulation of apoptosis inducers were observed. Drug-resistance markers (MDR-1 and ABCG2 (BCRP)) along with ESR-1, CDK4, CDK6, and cyclin-D1 genes were up-regulated in resistant cells. A total of 237 and 239 proteins were found to be differentially expressed in the Ab and Pb-resistant cells, respectively. Down-regulated proteins induce apoptosis signalling and nucleotide metabolisms and restrict EGFR signalling; however, up-regulated proteins induce Erk, wnt-β-catenin, VEGFR-PI3K-AKT, glucose transportation, and hypoxia signalling pathways and regulate hydrogen peroxide signalling pathways. The panel of identified proteins associated with these pathways might have characteristics of molecular signature and new drug targets for overcoming drug resistance in breast cancer.

Lung cancer is a fatal disease caused by an abnormal proliferation of cells in the lungs. Similarly, chronic kidney disorders affect people worldwide and can lead to renal failure and impaired kidney function. Cyst development, kidney stones, and tumors are frequent diseases impairing kidney function. Since these conditions are generally asymptomatic, early, and accurate identification of lung cancer and renal conditions is necessary to prevent serious complications. Artificial Intelligence plays a vital role in the early detection of lethal diseases. In this paper, we proposed a modified Xception deep neural network-based computer-aided diagnosis model, consisting of transfer learning based image net weights of Xception model and a fine-tuned network for automatic lung and kidney computed tomography multi-class image classification. The proposed model obtained 99.39% accuracy, 99.33% precision, 98% recall, and 98.67% F1-score for lung cancer multi-class classification. Whereas, it attained 100% accuracy, F1 score, recall and precision for kidney disease multi-class classification. Also, the proposed modified Xception model outperformed the original Xception model and the existing methods. Hence, it can serve as a support tool to the radiologists and nephrologists for early detection of lung cancer and chronic kidney disease, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhattacharjee, Rabea, Bhattacharjee, Elkaeed, Murugan, Selim, Sahu, Shazly and Salem Bekhit.)

Water splitting is the process of using energy to break down water molecules into hydrogen and oxygen. The use of an aluminum catalyst in the thermochemical process can help to increase the efficiency and rate of the reaction. Furthermore, aluminum is a relatively inexpensive material that can be easily produced, making it an appealing option for use in large-scale water-splitting operations. We investigated the reaction mechanism between aluminum nanotubes and water at various temperatures using reactive molecular dynamic simulations. We found that an aluminum catalyst makes it possible to split water at temperatures higher than T > 600 K. It was also observed that the yield of H 2 evolution is dependent on the diameter of the Al nanotube and decreases with increasing size. During the process of splitting water, the inner surfaces of the aluminum nanotubes are seen to be severely eroded, as shown by changes in the aspect ratio and solvent-accessible surface area. In order to compare the H 2 evolution efficiency of water with other solvents, we also split a variety of solvents, including methanol, ethanol, and formic acid. We presume that our study will give researchers enough knowledge to create hydrogen through thermochemical process in the presence of an aluminum catalyst by dissociating water and other solvent molecules.

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhattacharjee, Syeda, Rynjah, Hussain, Chandra Bora, Pegu, Sahu and Khan.)

Purpose: Seroepidemiology and genomic surveillance are valuable tools to investigate infection transmission during a pandemic. North East (NE) India is a strategically important region being the gateway connecting the country with Southeast Asia. Here, we examined the spread of SARS-CoV-2 in NE India during the first and second waves of COVID-19 using serological and whole genome sequencing approaches., Methods: qRT-PCR analysis was performed on a selected population (n ​= ​16,295) from June 2020 to July 2021, and metadata was collected. Immunoassays were studied (n ​= ​2026) at three-time points (August 2020, February 2021, and June 2021) and in a cohort (n ​= ​35) for a year. SARS-CoV-2 whole genomes (n ​= ​914) were sequenced and analyzed with those obtained from the databases., Results: Test positivity rates (TPR) in the first and second waves were 6.34% and 6.64% in Assam, respectively, and a similar pattern was observed in other NE states. Seropositivity in the three time points was 10.63%, 40.3%, and 46.33%, respectively, and neutralizing antibody prevalence was 90.91%, 52.14%, and 69.30%, respectively. Persistence of pan-IgG-N SARS-CoV-2 antibody for over a year was observed among three subjects in the cohort group. Normal variants dominated the first wave, while B.1.617.2 and AY-sublineages dominated the second wave in the region. The prevalence of the variants co-related well with high TPR and seropositivity rate in the region and identified mostly among vaccinated individuals., Conclusion: The COVID-19 first wave in the region witnessed low transmission with the evolution of diverse variants. Seropositivity increased during the study period with over half of the individuals carrying neutralizing antibodies against SARS-CoV-2. High infection and seroprevalence in NE India during the second wave were associated with the dominant emergence of variants of concern., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

The outbreak of COVID-19 has caused great havoc and affected many parts of the world. It has imposed a great challenge to the medical and health fraternity with its ability to continue mutating and increasing the transmission rate. Some challenges include the availability of current knowledge of active drugs against the virus, mode of delivery of the medicaments, its diagnosis, which are relatively limited and do not suffice for further prognosis. One recently developed drug delivery system called nanoparticles is currently being utilized in combating COVID-19. This article highlights the existing methods for diagnosis of COVID-19 such as computed tomography scan, reverse transcription-polymerase chain reaction, nucleic acid sequencing, immunoassay, point-of-care test, detection from breath, nanotechnology-based bio-sensors, viral antigen detection, microfluidic device, magnetic nanosensor, magnetic resonance platform and internet-of-things biosensors. The latest detection strategy based on nanotechnology, biosensor, is said to produce satisfactory results in recognizing SARS-CoV-2 virus. It also highlights the successes in the research and development of COVID-19 treatments and vaccines that are already in use. In addition, there are a number of nanovaccines and nanomedicines currently in clinical trials that have the potential to target COVID-19., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Institute of Chemistry, Slovak Academy of Sciences 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. It has been observed that the blood-brain barrier (BBB) limits the distribution of drugs into the tumour environment, which complicates the oncological therapy of malignant brain tumours. Numerous studies have found that nanocarriers have demonstrated significant therapeutic efficacy in brain diseases. This review, based on a non-systematic search of the existing literature, provides an update on the existing knowledge of the types of dendrimers, synthesis methods, and mechanisms of action in relation to brain tumours. It also discusses the use of dendrimers in the diagnosis and treatment of brain tumours and the future possibilities of dendrimers. Dendrimers are of particular interest in the diagnosis and treatment of brain tumours because they can transport biochemical agents across the BBB to the tumour and into the brain after systemic administration. Dendrimers are being used to develop novel therapeutics such as prolonged release of drugs, immunotherapy, and antineoplastic effects. The use of PAMAM, PPI, PLL and surface engineered dendrimers has proven revolutionary in the effective diagnosis and treatment of brain tumours., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kaurav, Ruhi, Al-Goshae, Jeppu, Ramachandran, Sahu, Sarkar, Khan and Ashif Ikbal.)

Chronic disease can cause tissue and organ damage constituting the largest obstacle to therapy which, in turn, reduces patients' quality-adjusted life-year. Degenerative diseases such as osteoporosis, Alzheimer's disease, Parkinson's disease, and infectious conditions such as hepatitis, cause physical injury to organs. Moreover, damage resulting from chronic conditions such as diabetes can also culminate in the loss of organ function. In these cases, organ transplantation constitutes the therapy of choice, despite the associated problems of immunological rejection, potential disease transmission, and high morbidity rates. Tissue regeneration has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to treat disabilities. Stem cell use represents an unprecedented strategy for these therapies. However, product availability and mass production remain challenges. A novel therapeutic alternative involving amniotic mesenchymal stem cell metabolite products (AMSC-MP) has been developed using metabolites from stem cells which contain cytokines and growth factors. Its potential role in regenerative therapy has recently been explored, enabling broad pharmacological applications including various gastrointestinal, lung, bladder and renal conditions, as well as the treatment of bone wounds, regeneration and skin aging due to its low immunogenicity and anti-inflammatory effects. The various kinds of growth factors present in AMSC-MP, namely bFGF, VEGF, TGF-β, EGF and KGF, have their respective functions and activities. Each growth factor is formed by different proteins resulting in molecules with various physicochemical properties and levels of stability. This knowledge will assist in the manufacture and application of AMSC-MP as a therapeutic agent., (© 2023. The Author(s).)

Background  The morbidity of donor finger in a cross-finger flap has not received as much importance as the outcomes of the flap itself. The sensory, functional, and aesthetic morbidity of donor fingers, reported by various authors, are often contradictory to each other. In this study, objective parameters for the sensory recovery, stiffness, cold intolerance, cosmetic outcome, and other complications in the donor fingers, reported in the previous studies, are systematically evaluated. Methods  This systematic review is reported using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and was registered with the International prospective register of systematic reviews (PROSPERO registration no. CRD42020213721). Literature search was done using "cross-finger," "heterodigital," "donor finger," and "transdigital" words. Data regarding demography, patients' number and age, follow-up duration and outcomes of donor finger, including 2-point discrimination, range of motion (ROM), cold intolerance, questionnaires, etc. were extracted from included studies. Meta-analysis was performed using MetaXL and risk of bias was evaluated using Cochrane risk of bias tool. Results  Out of the total 16 included studies, 279 patients were objectively evaluated for donor finger morbidity. Middle finger was most frequently used as donor. Static two-point discrimination seemed to be impaired in donor finger in comparison to contralateral finger. Meta-analysis of ROM suggested that statistically there is no significant difference in ROM of interphalangeal joints in donor and control fingers (pooled weighted mean difference: -12.10; 95% confidence interval: -28.59, 4.39; I2 = 81%, n  = 6 studies). One-third of donor fingers had cold intolerance. Conclusion  There is no significant effect on ROM of donor finger. However, the impairment that seems to be in sensory recovery and aesthetic outcomes needs to be further evaluated objectively., Competing Interests: Conflict of Interest Statement The authors declare that they have no conflict of interest., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Different studies performed on nasal subunit reconstruction by either the nasolabial flap or the paramedian forehead flap have reported contradictory outcomes and complications, claiming one flap or the other as superior. This inconsistency has led to a gap in existing literature regarding the preferable flap for nasal reconstruction. Our aim was to statistically evaluate and compare these two flaps for nasal reconstruction, in terms of subunit preference, complications, and outcomes, using data from previous studies., Methods: This systematic review is reported using PRISMA protocol and was registered with the International prospective register of systematic reviews. The literature search was done using "paramedian forehead flap", "nasolabial flap", "melolabial flap", "nasal reconstruction". Data regarding demography of study and population, subunit reconstructed, complications, and aesthetic outcomes were extracted. Meta-analysis was performed using MetaXL and summary of findings using GRADEpro GDT., Results: Thirty-eight studies were included, and data from 2036 followed-up patients were extracted for the review. Meta-analysis was done on data from nine studies. Difference in alar reconstruction by forehead versus nasolabial flap is statistically significant [pooled odds ratio (OR) 0.3; 95% CI 0.01, 0.92; p = 0.72; I 2  = 0%, n = 6 studies], while for dorsum and columella reconstruction the difference is not statistically significant. Risk of alar notching is marginally more in forehead flap, however difference in incidence of partial/complete flap necrosis, alar notching and hematoma/bleeding among the flaps is not statistically significant., Conclusion: Alar reconstruction is preferred by nasolabial flap. Complications are similar in both groups. Comparison of aesthetic outcome needs further exploration., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Competing Interests: There are no conflicts of interest.

Background  Defining cut-off values of flap glucose levels in diagnosing free flap vascular compromise, without taking patients' glucose levels into account, does not hold good in all circumstances, especially in cases of high fluctuations in patients' capillary blood glucose and in diabetic patients. The aim of our study was to establish the role of capillary blood glucose measurements of the flap in relation to patients' fingertip, as an objective tool for postoperative free flap monitoring. Methods  A total of 76 free flaps underwent postoperative monitoring with reference test (clinical parameters) and simultaneously with our index test (difference between capillary blood glucose of free flap and the patient), in non-diabetic and diabetic patients. Patients' demography and flap characteristics were also recorded. An ROC curve was plotted to determine diagnostic accuracy and cut-offs of the index test in diagnosing free flap vascular compromise. Results  Our Index test has a cut-off value of 24.5 mg/dL with 68.75% sensitivity and 93% specificity, with an accuracy of 91.54%. Conclusion  The difference between capillary blood glucose of free flap and the patient is simple, feasible, and inexpensive, and can be done by any health care professional and does not require any specialized facilities or training. It has an excellent diagnostic accuracy to detect impending free flap vascular compromise, especially in non-diabetics. Although in diabetics, this test becomes less accurate. Being an observer-independent objective test, the difference in capillary blood glucose of patient and flap measurement can be used as a highly reliable tool for postoperative free flap monitoring., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Context: Effects of coronavirus disease 2019 (COVID-19) pandemic lockdown on road traffic accidents (RTAs) in Chhattisgarh, India., Background: Most neurosurgical emergencies are from brain and spine trauma. RTA is the leading cause of such injuries. While the nationwide lockdown was an extreme measure to control the COVID pandemic, it influenced the overall road traffic dynamics and neurotrauma., Objective: This study aims to assess the impact of the lockdown on neurotrauma., Methods and Materials: This retrospective study included all patients with brain and spine injuries who were admitted between January 17 th and May 31 st , 2020. The study population was divided into prelockdown (PL) and lockdown (L) groups., Results: Of the 668 patients, 436 were placed in the PL and 232 in the L group. The mean ages were 36.34 (SD = 17.96) and 35.98 (SD = 16.93), respectively. Male to female ratios were 82.3:17.7 in the PL group and 79.7:20.3 for the L group. RTA-related injuries were significantly lower during the lockdown period (n = 335 PL vs. 162 L [P = 0.048]). During the lockdown, there were more mild injuries (25.91% PL vs. 36.63% L) and less severe injuries (33.25% PL vs. 18.96% L [P = 0.0002]). Mortality was significantly less (P = 0.029) during the lockdown (n = 48 L vs. 124 PL). The proportion of RTA-related neurotrauma cases increased (33.33% L1, 57.14% L2, 73.13% L3, and 80.39% L4) with each phase of lockdown (L1-L4)., Conclusions: During the lockdown period, the number of trauma cases had decreased, with a significant decrease in RTA-related admissions, along with their severity and mortality. The number of trauma cases and their severity increased gradually with each phase of lockdown., Competing Interests: None

Objective: Fabrication and analyses of mucoadhesive patches made from chitosan oligosaccharide for the purpose of oromucosal drug delivery., Significance: The mucosal epithelium in the oral cavity, consisting of buccal and sublingual epithelium, has gained significant attention in the last decade as an alternative anatomical site for systemic drug delivery that could potentially minimize the challenges of solid oral dosage and parenteral delivery. In this study, we have fabricated and tested drug-loaded chitosan oligosaccharide-based patches for the oromucosal drug delivery., Methods: The chitosan oligosaccharide (with and without alginate) based patches were fabricated using the conventional solvent casting method and were analyzed for their swelling capacity, hydrophilicity, anti-cancer activity, in vitro drug release, and in vivo drug release activity. The in-house developed artificial saliva was used for the swelling study., Results: Alginate-containing patches showed lesser swelling ability compared to the bare chitosan oligosaccharide-based patches. The former was also found to be more hydrophobic compared to the latter one. Both the unloaded patches restricted the growth of epithelial cancer cells indicating their anti-cancer behavior. In vitro drug release indicated a super case II release pattern while in vivo study demonstrated the release of drug from the patch into the plasma indicating the purpose of the fabricated patch., Conclusions: The chitosan oligosaccharide-based mucoadhesive hydrogel patch fabricated in this study can be highly suitable for possible translational purpose s .

Infantile (fetal and neonatal) megakaryocytes (Mks) have a distinct phenotype consisting of hyperproliferation, limited morphogenesis, and low platelet production capacity. These properties contribute to clinical problems that include thrombocytopenia in neonates, delayed platelet engraftment in recipients of cord blood stem cell transplants, and inefficient ex vivo platelet production from pluripotent stem cell-derived Mks. The infantile phenotype results from deficiency of the actin-regulated coactivator, MKL1, which programs cytoskeletal changes driving morphogenesis. As a strategy to complement this molecular defect, we screened pathways with the potential to affect MKL1 function and found that DYRK1A inhibition dramatically enhanced Mk morphogenesis in vitro and in vivo. Dyrk1 inhibitors rescued enlargement, polyploidization, and thrombopoiesis in human neonatal Mks. Mks derived from induced pluripotent stem cells responded in a similar manner. Progenitors undergoing Dyrk1 inhibition demonstrated filamentous actin assembly, MKL1 nuclear translocation, and modulation of MKL1 target genes. Loss-of-function studies confirmed MKL1 involvement in this morphogenetic pathway. Expression of Ablim2, a stabilizer of filamentous actin, increased with Dyrk1 inhibition, and Ablim2 knockdown abrogated the actin, MKL1, and morphogenetic responses to Dyrk1 inhibition. These results delineate a pharmacologically tractable morphogenetic pathway whose manipulation may alleviate clinical problems associated with the limited thrombopoietic capacity of infantile Mks.

Background: The standard (dorsal) cross-finger flap (CFF) is one of the common flaps used for fingertip reconstruction. There is little consensus regarding the sensory outcomes associated with this flap. In this systematic review, we evaluated objective sensory outcome parameters of patients who underwent CFF reconstruction. Methods: This systematic review is reported using the PRISMA protocol and was registered with the International Prospective Register of Systematic Reviews. Literature search was done using the terms 'cross-finger flap', 'heterodigital', 'finger-tip' and 'transdigital'. Data regarding the number of patients, follow-up duration and sensory outcomes, including 2-point discrimination (2-PD) were extracted from included studies. The analysis was performed using Microsoft Excel with MetaXL add-in software. Certainty assessment and summary of findings table was created using GRADEpro GDT. Results: This review includes 14 studies with 301 patients. We found a statistically significant difference in static 2-PD of recipient and control fingers (pooled weighted mean difference [WMD]: 1.66; 95%CI: 0.03, 3.29; p = 0.00; I 2 =92%, n = 7 studies). Conclusions: Dorsal CFF reconstruction for fingertip defect does not provide adequate sensory recovery. Level of Evidence: Level III (Therapeutic).

Micromachining of difficult-to-machine materials is of prime focus nowadays. One such material is Titanium, which has numerous applications in aerospace, chemical, and biomedical industries. The micromachining of Titanium has become the need of the day because of its exhilarating properties. This investigation employs a tailor-made electrolyte sonicated micro-electrochemical discharge machining (ES-µ-ECDM) system to generate microholes in a commercially pure titanium plate with a thickness of 1000 µm. The machining chamber is the ultrasonication unit (36 kHz) with process parameters voltage (V), concentration (wt%), and duty factor (DF) chosen at three levels. The FCC-RSM-based DOE is selected for experimentation to study the machining characteristics like material removal rate, overcut, and circularity. Through holes were achieved at parameters of 80 V, 25 wt%, and 60% DF and 80 V, 30 wt%, and 50% DF. The incorporation of ultrasonication into the system enhanced electrolyte replenishment and evacuation of the debris at the machining vicinity. The assistance technique improved the gas film stabilization around the tool enabling uniform machining. The multi-response optimization is performed using the MOJAYA algorithm to obtain Pareto optimal solutions, and the MADM (R-method) is employed to obtain the optimal parameter. The optimal parameter was found to be 69 V, 30 wt%, and 50% DF, at which the machined microhole was found to have a circularity of 0.9615 with minimal surface defects., (© 2022. The Author(s).)

Sauropus androgynus (L.) Merr., in the Indonesian local name known as "Katuk," is a tropical shrub plant of the family Euphorbiaceae. Based on genus and chemotaxonomic approaches, as well as in vitro testing of Plasmodium falciparum , leaves of S. androgynus are presumed to have an active compound content as an antimalarial. The current study aims to investigate the antimalarial activity of 96% ethanol extract and fractions of S. androgynus leaves. The ethanolic extract was fractionated using the vacuum liquid chromatography (VLC) method with three solvents of different polarities (n-hexane, chloroform, and 96% ethanol). The fraction obtained was then evaluated for antimalarial activity against P. falciparum 3D7 strain. The ethanolic extract was evaluated for antimalarial suppressive and prophylactic activity against P. berghei -infected mice, as well as inhibitory activity against the heme detoxification process in vitro. Fractionation of ethanolic extract resulted in seven combined fractions, with the most active fraction being FV (50% inhibitory concentration (IC 50 ) = 2.042  µ g/mL). The ethanolic extract showed good parasitic suppressive (therapeutic) activity with a median effective dose (ED 50 ) value of 15.35 mg/kg body weight. In a prophylactic test, ethanolic extract showed parasite growth inhibitory activity of 67.74 ± 9.21% after the administration of 400 mg/kg body weight for 4 days before infection, and 65.30 ± 10.44% after the administration of 200 mg/kg body weight for 8 consecutive days (4 days before and after infection). The ethanolic extract also showed an effect in inhibiting the formation of β -hematin of about 26.87-79.36% at a concentration of 0.1-4 mg/mL and an IC 50 value of 0.479 mg/mL. The S. androgynus leaves were shown to have antimalarial activity in vitro and in vivo, where ethanolic extract were more active compared with the fraction obtained. The antimalarial properties of the extract showed a higher suppressive activity than prophylactic activity., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Wiwied Ekasari et al.)