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Abstract Disease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.

Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci. eQTL in IBD tissue were enriched for IBD GWAS loci colocalizations, provided novel evidence for IBD-associated genes such as ABO and TNFRSF14 , and identified additional target genes compared to non-IBD tissue eQTL. IBD-associated eQTL unique to diseased tissue had distinct regulatory and functional characteristics with increased effect sizes. Together, these highlight the importance of eQTL studies in diseased tissue for understanding functional consequences of genetic variants, and elucidating molecular mechanisms and regulation of key genes involved in IBD., Competing Interests: Competing interests The authors declare no competing interests.

This review approach is divided into two scopes to focus the pollution threats. We cover the applications of nanomaterials to curtail the pollution induced by fossil fuel combustion, and textile dye effluents. Toxic emissions released from automobile exhaust that comprise of NO X . SO X and PAHs compile to harsh breathing and respiratory troubles. The effluents generated from the mammoth textile and leather industry is potential threat to beget massive health issues to human life, and environmental problem. Part I projects the broad envisage on role of nano materials in production of alternative biofuels. In addition, green sources for synthesizing nanomaterials are given special importance. Nano catalyst's utilization in bio-derived fuels such as biogas, bio-oil, bioethanol, and biodiesel are catered to this article. Part II cover the current statistics of textile effluent pollution level in India and its steps in confronting the risks of pollution are discussed. A clear picture of the nano techniques in pre-treatment, and the recent nano related trends pursued in industries to eliminate the dyes and chemicals from the discharges is discussed. The substantial aspect of nano catalysis in achieving emission-free fuel and toxic-free effluents and the augmentation in this field is conferred. This review portrays the dependency on nano materials & technology for sustainable future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

CD47 is a ubiquitously expressed cell surface receptor, which is widely known for preventing macrophage-mediated phagocytosis by interacting with signal regulatory protein α (SIRPα) on the surface of macrophages. In addition to its role in phagocytosis, emerging studies have reported numerous noncanonical functions of CD47 that include regulation of various cellular processes such as proliferation, migration, apoptosis, differentiation, stress responses, and metabolism. Despite lacking an extensive cytoplasmic signaling domain, CD47 binds to several cytoplasmic proteins, particularly upon engaging with its secreted matricellular ligand, thrombospondin 1. Indeed, the regulatory functions of CD47 are greatly influenced by its interacting partners. These interactions are often cell- and context-specific, adding a further level of complexity. This review addresses the downstream cell-intrinsic signaling pathways regulated by CD47 in various cell types and environments. Some of the key pathways modulated by this receptor include the PI3K/AKT, MAPK/ERK, and nitric oxide signaling pathways, as well as those implicated in glucose, lipid, and mitochondrial metabolism. These pathways play vital roles in maintaining tissue homeostasis, highlighting the importance of understanding the phagocytosis-independent functions of CD47. Given that CD47 expression is dysregulated in a variety of cancers, improving our understanding of the cell-intrinsic signals regulated by this molecule will help advance the development of CD47-targeted therapies., (© 2024. The Author(s).)

While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Disease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome., (© 2024. The Author(s).)

Cytoplasmic poly(A)-binding protein (PABPC; Pab1 in yeast) is thought to be involved in multiple steps of post-transcriptional control, including translation initiation, translation termination, and mRNA decay. To understand both the direct and indirect roles of PABPC in more detail, we have employed mass spectrometry to assess the abundance of the components of the yeast proteome, as well as RNA-Seq and Ribo-Seq to analyze changes in the abundance and translation of the yeast transcriptome, in cells lacking the PAB1 gene. We find that pab1Δ cells manifest drastic changes in the proteome and transcriptome, as well as defects in translation initiation and termination. Defects in translation initiation and the stabilization of specific classes of mRNAs in pab1Δ cells appear to be partly indirect consequences of reduced levels of specific initiation factors, decapping activators, and components of the deadenylation complex in addition to the general loss of Pab1's direct role in these processes. Cells devoid of Pab1 also manifested a nonsense codon readthrough phenotype indicative of a defect in translation termination. Collectively, our results indicate that, unlike the loss of simpler regulatory proteins, elimination of cellular Pab1 is profoundly pleiotropic and disruptive to numerous aspects of post-transcriptional regulation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.J. is co-founder, director, and consultant for PTC Therapeutics Inc., (Copyright: © 2024 Mangkalaphiban et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Standard of care genetic testing has undergone significant changes in recent years. The British Gynecological Cancer Society and the British Association of Gynecological Pathologists (BGCS/BAGP) has re-assembled a multidisciplinary expert consensus group to update the previous guidance with the latest standard of care for germline and tumor testing in patients with ovarian cancer. For the first time, the BGCS/BAGP guideline group has incorporated a patient advisor at the initial consensus group meeting. We have used patient focused groups to inform discussions related to reflex tumor testing - a key change in this updated guidance. This report summarizes recommendations from our consensus group deliberations and audit standards to support continual quality improvement in routine clinical settings., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer., Methods: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots., Results: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38)., Conclusion: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EM – has received grant funding from BGCS, Orion Corporation, Leicester, Leicestershire and Rutland Integrated Care Board, East Genomic Medicine Service Alliance, North East London Cancer Alliance, Intuitive Surgical Ltd, East Midlands Clinical Research Network and Medical Research Council (MRC). AT − Has received financial support to attend meetings from Merck & Co., Inc (MSD). AA − None to declare. CA − None to declare. RA − None to declare. SB – Has received grants to her institution from Astrazeneca and Glaxo Smith Kline (GSK), and consulting fees from Astrazeneca, Epsilogen, GSK, Immunogen MSD, Mersana, Myriad, Novartis, Oncxerna, Seagen, Shattuck Labs, Regeneron and Verastem. She has received honoraria payments for lectures from Abbive, Astrazeneca, GSK, Immunogen, MSD, Mersnae, Pfizer, Roche, Takeda and Novacure, and financial support for attending meetings from Astrazeneca, GSK and Verastem. She is on the Ovacome advisory board (unpaid). RB – Has received honoraria for lecturers and presentations from GSK, Astra Zeneca and EISAI; support to attend meetings from GSK and PharmaAnd. She is an advisory board member for MSD, Clovis, Astra Zeneca, and GSK.She has unpaid board roles for NCRI Gynae Deputy Lead (GTGUK), UKGOM (co-chair) and is the BGCS Medical Oncology Representative. LB – is a director of Buckley Consultants Ltd. NB – Has received financial support from RanD for travel to meetings. SC – None to declare. RE – Has received consulting fees from GSK; honoraria for lecturers from GSK and Astra Zeneca and sits on the for Advisory Board for International Rainbo Study. ME-B – None to declare. CF –Has received payments for participation on a Data Safety Monitoring Board or Advisory Board for GSK, Roche, Ethicon, Astra Zeneca, MSD. JF – Has received consulting fees from ASTELLAS ASP5354 Advisory Board and is a BGCS Council member (unpaid). RG – Has received honoraria payments for lectures from Astra Zeneca, on topics unrelated to this document. AG – has received honoraria for lectrures/presentation from GSK. LH – Has received royalties from Cambridge University Press, support from Mims and Roche and Tata Medical Center to attend meetings, and is an unpaid board member to the Royal College of Radiologists. BK – Has received funding from NIHR Imperial BRC. RM – has received research grant funding from Rosetrees Trust, Barts Charity, NHS England, NHS Innovational Accelerator, Yorkshire Cancer Research and GSK. He has received honoraria from GSK and Astrazeneca for lectures and presentations. He is Chair Trial of the Steering Committee BRCA DIRECT trial, a member NICE National Standards Quality Assurance Board for Ovarian Cancer and Topic Advisor NICE Guideline – [NG241] −- Ovarian cancer: identifying and managing familial and genetic risk. He is a scientific advisor to GO Girls, BRCA Umbrella and acted on an Expert Advisory Group NHS Jewish BRCA Programme. HM – In a trustee of GO Girsls Gynaecological Cancer Charity. AM – has received National Institute for Cancer Research (NCRI) and MERCK received research funding from MDS. She has received payment from EUSA Pharma and Clovis Oncology for advisory board roles and consulting. She has recived payment from GSK for invited lectures and manuscript writing. She has received educational support and support for meeting attendance from MSD and IPSEN. TM – Project lead for NHS transformation project to embed mainstream BRCA testing into practice for breast, ovarian cancers. Nurse advisor to The EVE APPEAL gynae cancer charity. CN – None to declare. SN – has received research grants from GSK, AstraZenenca, North Central London Cancer Alliance and BGCS via her institution. She has received consulting fees from GSK, AstraZeneca and Biontech, and honoraria payments from lectures from GSK and AstraZenca. She has received financial support for attending meetings from MSD. She is an data safety monitoring/advisory board member to AstraZeneca, GSK and Biontech. She has stock options with GSK and AstraZeneca, and she is chair of the GynaeOncology Trials Group UK (previously NCRI) (unpaid). NR – None to declare. NRy – has received grants from the Chief Scientist Office Scotland (NES/CSO Postdoctoral Clinical Lectureship Scheme) and Academy of Medical Sciences to his institution. He has received honorariao payments from GSK for lectures. He is an European Hereditary Tumour Group (EHTG) Board member (unpaid). SS – has received a research grant to University of Birmingham from AoA diagnostics. She has received consultancy fees from GSK and Immunogen, and honoraria for lecturers from Astra Zeneca, Merck and GSK. She is Surgery Lead for the National Ovarian Cancer Audit, England and Wales and Co-Chair Scientific Program, International Gynaecological Cancer Society conference 2024. KV – Councillor for British Association of Gynaecological Pathology (unpaid). AW – has received honoraria for lecturers and presentaions from GSK, Astra Zeneca and Clovis. JW – is President, British Association of Gynaecological Pathologists (unpaid). JM – has received grants to her institution from the National Institute for Health and Care Research (NIHR) and MRC. She is BGCS guidelines subgroup co-chair (unpaid), sitting on BGCS Council in this role, and a NHS Cervical Screening Research Innovation and Development Advisory Committee Member (unpaid). She was an unpaid council member to Cochrane Collaboration (2019–2023) and received financial support to attend a meeting from Cochrane.

This study aims to explore the food management strategies among caregivers/family members of children with Prader-Willi Syndrome (PWS) using the lens of 'familialisation' of a health problem and the sociology of food socialization. Food intake among individuals with PWS is a main concern for parents, caregivers, and medical practitioners as it affects their physical, mental, and social well-being throughout their lives. Earlier studies on PWS and food intake centered around dietary management, dietary intake and growth, nutritional treatment and pharmacological approaches, nutritional phases, and weight gain. However, little has been done to understand the challenges of managing children with PWS from the sociological lens of food management strategies and socialization among families in Malaysia. This study is based on an investigation involving eight children with PWS and 46 family members and caregivers through lab observations and reflexive interviews. Ten food management strategies were identified that were adopted by the caregivers and families, which were influenced by cultural factors, family norms, and formal and informal support systems. The findings will influence future behavioral interventions to ensure the empowerment and well-being of individuals with PWS and their families., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Heart Failure (HF) is a life-threatening condition. It affects more than 64 million people worldwide. Early diagnosis of HF is extremely crucial. In this study, we propose utilization of machine learning (ML) models to predict severity of HF from primary Electronic Health Records (EHRs). We used a public dataset of 2008 HF patients for the study. Gaussian Naive Bayes, Random Forest and CatBoost methods were used for prediction. The study shows that CatBoost works best for the goal. In addition to that, the largest contributors for tree-based models harmonize well with clinically important parameters, which exhibits the trustworthiness of these models. Hence, we conclude that utilization of ML methods on primary EHRs is a promising step for time-efficient diagnosis of HF patients.

Uterine sarcomas are rare; most are either smooth muscle or endometrial stromal in origin. Recent molecular advances have identified several, genetically defined entities with specific morphologic, clinicopathological associations, and therapeutic options. We report 3 cases of uterine neurotrophic tyrosine receptor kinase ( NTRK )-rearranged spindle cell neoplasms," currently classified as "emerging entities" in the WHO Classification of Female Genital Tract Tumors, 2020, Fifth Edition. The affected patients were 32, 34, and 42 years of age. Two patients presented with vaginal bleeding; the third presented with a cervical mass found incidentally during laparoscopy for an ectopic gestation. All 3 tumors were polypoid masses that distorted the cervix. Microscopically, they comprised cellular, fascicular, and storiform, plump spindle cells, with occasional rounded cells, and frequent mitoses (4-48/10 high power fields) in a myxoid stroma. All 3 cases showed entrapment of benign cervical glands. Inflammatory cell infiltrates, including plasma cells, were noted in all 3 tumors. One case had tumor cell necrosis, osteoid-like material, and osteoclast-like giant cells and showed lymphovascular invasion. Immunohistochemically, our cases showed patchy S100 (2/3) and CD34 (3/3) positivity. CD10 was positive in 2/3 cases. 3/3 cases showed pan-tropomyosin receptor kinase positivity (cytoplasmic). The NTRK -translocations demonstrated were: NTRK1::TMP3, NTRK1::TPR, and NTRK3::SPECC1L . Two of the patients had extensive disease and underwent chemotherapy. Larotrectinib was approved for one patient who demonstrated a striking reduction in tumor volume upon initiation of this treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance 1-10 . After activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, resulting in translation repression 11-15 . However, the catalytic activity of isolated angiogenin is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle 3,16-23 . Here we identify these mechanisms using biochemical assays and cryogenic electron microscopy (cryo-EM). Our study reveals that the cytosolic ribosome is the activator of angiogenin. A cryo-EM structure features angiogenin bound in the A site of the 80S ribosome. The C-terminal tail of angiogenin is rearranged by interactions with the ribosome to activate the RNase catalytic centre, making the enzyme several orders of magnitude more efficient in tRNA cleavage. Additional 80S-angiogenin structures capture how tRNA substrate is directed by the ribosome into angiogenin's active site, demonstrating that the ribosome acts as the specificity factor. Our findings therefore suggest that angiogenin is activated by ribosomes with a vacant A site, the abundance of which increases during cellular stress 24-27 . These results may facilitate the development of therapeutics to treat cancer and neurodegenerative diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A differential scanning calorimeter was designed to study the thermal analysis of the materials for the nuclear reactor/allied facilities. The hardware and software were developed for measuring the calorimetric signals and had various features for the thermal analysis of the material. The processing of calorimetric signals was carried out by a programmable system-on-chip. Using a programmed temperature profile, the differential scanning calorimeter setup was tested, calibrated, and validated with standard aluminum and indium metal samples. It was found that the obtained results agree with the literature values. The methodology for the experiment was optimized. Various experiments were carried out, and the thermal analysis of different materials for nuclear reactors was investigated and studied. The instrumentation is also compact, accurate, reliable, and cost-effective for the thermal analysis of materials., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background and Aim: The prevalence and severity of alcoholic liver disease (ALD) are increasing. The incidence of alcohol-related cirrhosis has risen up to 2.5%. This study aimed to identify novel metabolite mechanisms involved in the development of ALD in patients. The use of gut microbiome-derived metabolites is increasing in targeted therapies. Identifying metabolic compounds is challenging due to the complex patterns that have long-term effects on ALD. We investigated the specific metabolite signatures in ALD patients., Methods: This study included 247 patients (heathy control, HC: n = 62, alcoholic fatty liver, AFL; n = 25, alcoholic hepatitis, AH; n = 80, and alcoholic cirrhosis, AC, n = 80) identified, and stool samples were collected. 16S rRNA sequencing and metabolomics were performed with MiSeq sequencer and liquid chromatography coupled to time-of-flight-mass spectrometry (LC-TOF-MS), respectively. The untargeted metabolites in AFL, AH, and AC samples were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Metabolic network classifiers were used to predict the pathway expression of the AFL, AH, and AC stages., Results: The relative abundance of Proteobacteria was increased and the abundance of Bacteroides was decreased in ALD samples (p = 0.001) compared with that in HC samples. Fusobacteria levels were higher in AH samples (p = 0.0001) than in HC samples. Untargeted metabolomics was applied to quantitatively screen 103 metabolites from each stool sample. Indole-3-propionic acid levels are significantly lower in AH and AC (vs. HC, p = 0.001). Indole-3-lactic acid (ILA: p = 0.04) levels were increased in AC samples. AC group showed an increase in indole-3-lactic acid (vs. HC, p = 0.040) level. Compared with that in HC samples, the levels of short-chain fatty acids (SCFAs: acetic acid, butyric acid, propionic acid, iso-butyric acid, and iso-valeric acid) and bile acids (lithocholic acids) were significantly decreased in AC. The pathways of linoleic acid metabolism, indole compounds, histidine metabolism, fatty acid degradation, and glutamate metabolism were closely associated with ALD metabolism., Conclusions: This study identified that microbial metabolic dysbiosis is associated with ALD-related metabolic dysfunction. The SCFAs, bile acids, and indole compounds were depleted during ALD progression., Clinical Trial: Clinicaltrials.gov, number NCT04339725., (© 2023. Asian Pacific Association for the Study of the Liver.)

Diarrhea, a common gastrointestinal symptom in health problems, is highly associated with gut dysbiosis. The purpose of this study is to demonstrate the effect of multistrain probiotics (Sensi-Biome) on diarrhea from the perspective of the microbiome-neuron axis. Sensi-Biome (Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, Streptococcus thermophilus, Bifidobacterium bifidum, and Lactococcus lactis) was administered in a 4% acetic acid-induced diarrhea rat model at concentrations of 1 × 10 8 (G1), 1 × 10 9 (G2), and 1 × 10 10  CFU/0.5 mL (G3). Diarrhea-related parameters, inflammation-related cytokines, and stool microbiota analysis by 16S rRNA were evaluated. A targeted and untargeted metabolomics approach was used to analyze the cecum samples using liquid chromatography and orbitrap mass spectrometry. The stool moisture content (p < 0.001), intestinal movement rate (p < 0.05), and pH (p < 0.05) were significantly recovered in G3. Serotonin levels were decreased in the multistrain probiotics groups. The inflammatory cytokines, serotonin, and tryptophan hydroxylase expression were improved in the Sensi-Biome groups. At the phylum level, Sensi-Biome showed the highest relative abundance of Firmicutes. Short-chain fatty acids including butyrate, iso-butyrate, propionate, and iso-valeric acid were significantly modified in the Sensi-Biome groups. Equol and oleamide were significantly improved in the multistrain probiotics groups. In conclusion, Sensi-Biome effectively controls diarrhea by modulating metabolites and the serotonin pathway., (© 2024. The Author(s).)

While ultrafine gold nanosystems (UGNs) are being extensively studied for their antimicrobial activities, hitherto, no report is available on their propensity towards mitigating bacterial resuscitation-a potential factor contributing to the antimicrobial resistance. The investigations herein with two categories of gold nanosystems-modulated for their stability and surface accessibility through glutathione capping-have provided insights into overcoming resuscitation. Additionally, the study cautions that even moderate resistance development in bacteria exposed to nanosystems can result in significant cross-resistance against conventional antibiotics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti-OB efficacy of the non-fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein-protein interaction (PPI), PAF-signaling pathways-targets-compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti-OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1-gamma-tocopherol, PPARA-fucosterol, PPARD-stigmasterol, (PPARG)-fucosterol, (NR1H3)-campesterol, and ILK-alpha-tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps. As a novel and adaptable strategy, we hypothesized that well-established non-responsive polymeric micelles could be augmented with a pH-trigger via the co-encapsulation of cytocompatible oligoelectrolytes, which would allow rapid cargo release in the endosome, leading to increased cytotoxicity. Herein, we demonstrate how this strategy can be applied to render non-responsive micelles pH-responsive, resulting in abrupt cargo release at specific and tunable pH values compatible with endosomal delivery, which significantly increased their cytotoxicity up to 3-fold in an ovarian adenocarcinoma (SKOV-3) cell line compared to non-responsive micelles. In comparison, the oligoelectrolyte-loaded micelles were significantly less toxic to healthy 3T3 fibroblasts, indicating a selective cargo release in cancer cell lines. Oligoelectrolytes can be co-encapsulated in the micelles along with drugs at high encapsulation efficiency percentages, which are both ejected from the micelle core upon oligoelectrolyte ionization. Mechanistically, the increase in cytotoxicity appears to also result from the accelerated endosomal escape of the cargo caused by disruption of the endosomal membrane by the simultaneous release of the oligoelectrolytes from the micelles. Furthermore, we show how this approach is broadly applicable to non-responsive micelles regardless of their composition and various classes of hydrophobic chemotherapeutics. The preliminary studies presented here reveal the versatility and wide scope of oligoelectrolyte-mediated, pH-triggered drug release as a compelling and powerful strategy to enhance the cytotoxicity of non-responsive polymeric micelles.

Herein, we have synthesized pristine and g-C 3 N 4 -assisted Ce 2 (WO 4 ) 3 via a facile hydrothermal method. The structure was confirmed with the standard JCPDS card. g-C 3 N 4 encapsulated the crystal and reduced the size. The Raman spectra revealed the presence of Ce-O, W-O stretching and bending vibrations. Electron hole transfer facilitation and controllable recombination were altered by g-C 3 N 4 heterojunction with cerium tungstate. Ce 2 (WO 4 ) 3 possessed a larger band gap. As g-C 3 N 4 was assisted, the band gap was reduced which facilitates Ce 2 (WO 4 ) 3 to utilize more visible light. The prepared photocatalysts were used to investigate the model pollutant removal with visible light. The pure Janus Green B sample showed lesser efficiency, as it does not show self-degradation under light. As Ce 2 (WO 4 ) 3 was added, it slightly improved the efficiency as it possesses lower electron hole transfer and high recombination. Thus, g-C 3 N 4 was composited with Ce 2 (WO 4 ) 3 to make heterojunctions which will enhance the photo-excited electron and hole transfer and decrease e - /h + recombination. The rate constant values of the photocatalysts were calculated, and the system follows the first-order pseudo-kinetic model. Ciprofloxacin, a well-known antibiotic, was also used to degrade under visible light. The pure sample showed lower efficiency, and the antibiotic was reduced well with the addition of prepared photocatalysts. The modification of Ce 2 (WO 4 ) 3 with the optimum-level g-C 3 N 4 facilitated electron hole charge transfer, and numerous adsorbed dye molecules on the photocatalyst surface made 0.1 g g-C 3 N 4 -Ce 2 (WO 4 ) 3 a plausible photocatalyst for the water remediation process., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy., 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 B.V. All rights reserved.)

Introduction: Endometrial carcinoma (EC) is the commonest gynecological cancer affecting women in Western populations. To predict patient risk, the 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract stressed the importance of integrated histo-molecular classification of the disease. This survey analysis poses attention on the most frequently used immunohistochemical and molecular markers adopted in daily categorization of ECs in European laboratories., Methods: We analyzed data collected through questionnaires administered to 40 Italian, 20 Spanish, 3 Swiss and 6 United Kingdom (UK) laboratories. We collected information regarding daily practice in EC evaluation, specifically concerning mismatch repair status (MMR) and microsatellite instability (MSI). Summary and descriptive statistical analyses were carried out to evaluate the current practice of each laboratory., Results: The results show that MMR status is mainly evaluated by using immunohistochemistry (IHC) on most EC samples. The most frequent approach for the analysis of MMR status is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular methods is uncommon but useful as a supplemental tool in specific conditions. MLH1 promoter hypermethylation and BRAF V600 mutations analysis are performed in case of negative expression of MLH1/PMS2. Other markers (mainly p53 followed by POLE and PTEN) are investigated in particular in Spain and Switzerland in a consistent number of cases., Conclusion: Guidelines consultation and standardization of laboratory procedures are efficient means for EC prognostic risk stratification and improving the quality of care., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Silica nanoparticles (SNPs) are widely explored as drug carriers, gene delivery vehicles, and as nanoparticles intended for bone and tissue engineering. SNPs are highly evident through various clinical trials for a wide range of biomedical applications. SNPs are biocompatible and promising nanoparticles for next-generation therapeutics. However, despite the well-established importance of SNPs, metabolomics methods for the SNPs remain elusive which renders its maximal clinical translation. We applied 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy to investigate the metabolomics profile in Zebrafish (Danio rerio) exposed to SNPs. Zebrafish were exposed to the SNPs (10.0, 25.0, and 50.0 μg/mL) for 72 h and whole-body samples were subjected for targeted profiling. Pattern recognition of 1 H NMR spectral data depicted alterations in the metabolomic profiles between control and SNPs exposed zebrafish. We found that tryptophane, lysine, methionine, phenylalanine, tyrosine, sn-glycero-3-phosphocholine (G3PC), and o-phosphocholine were decreased. The metabolic expression of niacinamide, nicotinamide adenine dinucleotide (NAD+), citrate, adenosine triphosphate (ATP), and xanthine were increased in zebrafish with SNPs treatment. We are report for the first time on metabolite alterations and phenotypic expression in zebrafish via 1 H NMR. These results demonstrate that SNPs can adversely affect the significant metabolic pathways involved in energy, amino acids, cellular membrane, lipids, and fatty acid metabolisms. Metabolomics profiling may be able to detect metabolic dysregulation in SNPs-treated zebrafish and establish a foundation for further toxicological studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

TFEB is a master regulator of autophagy, lysosome biogenesis, mitochondrial metabolism, and immunity that works primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomics analysis reveals extensive TFEB co-immunoprecipitation with several mitochondrial proteins, whose interactions are disrupted upon infection with S. Typhimurium. High resolution confocal microscopy and biochemistry confirms TFEB localization in the mitochondrial matrix. TFEB translocation depends on a conserved N-terminal TOMM20-binding motif and is enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis., (© 2024. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM - None to declare. PB - None to declare. LH - None to declare. AA- None to declare. LB- Works for Perci Health Ltd, 1 Vincent Square, London, SW1P 2PN and director of Buckley Consultants Ltd. KE- Royal College of Obstetricians and Gynaecologists Workforce Fellow Jan 2022-Dec 2022. Paid for 8 h/week via her organisation. CF – Has received payments for participation on a Data Safety Monitoring Board or Advisory Board for Glaxo Smith Klein, Roche, Ethicon, Astra Zeneca MSD (Merck & Co., Inc). RG – Has received payments for lectures from Astra Zeneca, Oncoinvent and MSD. AT - Has received financial support to attend meetings and for participation on a Data Safety Monitoring Board or Advisory Board from MSD.

Thin film coatings with potent antibacterial properties find critical applications in diverse domains such as medical devices, frequently touched surfaces, and food packaging for combating microbial proliferation across diverse scenarios. Two-dimensional photocatalytic antimicrobial coatings, offering a substantial actual-to-apparent surface ratio, hold immense potential for achieving this objective. However, realizing antibacterial performance not just under light but also in dark conditions remains a challenge. To address this, we present AgBr-coated vertically aligned ZnO nanorods (NRs) thin film architecture, employing a unique surfactant-mediated solution-phase spin-coating approach for achieving uniform deposition of AgBr onto ZnO NRs. The resulting ZnO NRs/AgBr heterojunction architectures have been characterized for their microstructural, morphological, elemental, optical, and wettability attributes. The studies have ascertained the tunability of AgBr content by modulating the concentration of its surfactant-based precursor solution. Further, valence band (VB) analyses revealed an increase in the electron density near to the VB edge. The dual role of AgBr as an antimicrobial agent and a photosensitizer, effectively enhancing the visible-light photodisinfection efficacy of ZnO NRs, has been evident through the dark-light dual mode antibacterial studies. Electron paramagnetic resonance measurements have shown hydroxyl radicals being majorly responsible for the visible-light photodisinfection performance. Encouragingly, reusability assessments showcase significant promise, while artificial sweat-wiping studies on the structures unveil heightened photodisinfection efficacy. This enhancement could be attributed to components like urea and lactic acid, speculated to augment the photocatalytic efficiency by minimizing charge recombination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)