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Overactive Bladder (OAB), characterized by urinary urgency with frequency and nocturia, affects approximately 12 % of the adult female population's quality of life. Estrogen, known for its role in modulating lower urinary tract function, is commonly prescribed to alleviate urogenital symptoms in menopausal women. However, the efficacy of oral estrogen in treating OAB remains controversial. This study explores the association between oral estrogen and OAB using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Participants were categorized based on their estrogen exposure and OAB status, with a logistic regression analysis employed to evaluate the relationship between oral estrogen and OAB, controlling for variables such as age, race, education, income, and health conditions. Additionally, network pharmacology and molecular docking were conducted to investigate the potential mechanisms underlying estrogen's effects on OAB. Our findings indicate that oral estrogen is an independent risk factor for OAB, particularly in women under 60. Moreover, the study highlights albumin and inflammation's central role in the estrogen-OAB interaction. These results suggest the need for cautious consideration of oral estrogen therapy in managing OAB and underscore the importance of personalized treatment approaches based on individual risk profiles., 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 © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Natural Xanthine oxidase (XOD) inhibitors represent promising therapeutic agents for hyperuricemia (HUA) treatment due to their potent efficacy and favorable safety profiles. This study involved the construction of a comprehensive database of 315 XOD inhibitors and development of 28 machine learning-based QSAR models. The ChemoPy light gradient boosting machine model exhibited the best performance (AUC = 0.9371 and MCC = 0.7423). This model identified three potential XOD inhibitors from the FooDB database: daphnetin, 7-hydroxycoumarin, and piceatannol. Molecular docking and dynamics simulations revealed favorable interactions, with piceatannol showing a remarkable stability through hydrogen bonding and hydrophobic interactions. ADME predictions suggested that all three compounds possess desirable drug-like properties and safety characteristics. Subsequent in vitro enzyme inhibition assays validated computational predictions, with piceatannol exhibiting the strongest inhibitory activity (IC 50  = 8.80 ± 0.05 μM). Multispectroscopic analyses revealed that piceatannol-XOD binding was predominantly mediated by hydrogen bonding and van der Waals forces, which induced conformational changes characterized by decreased α-helical content and increased proportions of β-sheets, β-turns, and random coils. This study presents an efficient strategy for the identification of natural XOD inhibitors, elucidates the molecular mechanism of piceatannol-mediated XOD inhibition, and establishes a foundation for its therapeutic application in HUA treatment., 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 © 2025 Elsevier B.V. All rights reserved.)

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm worldwide (50%-70%). Most cases of PA are straightforward diagnoses. However, the diagnosis may be challenging due to the morphological diversity of PAs, which in many cases is caused by the predominance of one of the three components or the presence of metaplastic epithelium. We present the case of a 64-year-old male with a history of prostate cancer and right submandibular gland excision 16 years ago with an unknown previous diagnosis and recent regrowth of his mass in the surgical bed. The tumour showed a predominant spindle cell morphology, cytokeratin-positivity, variable expression of myoepithelial markers in the cytology and surgical pathology specimens, and novel inversion of the chromosome 8, and LRP1B, PBRM1 and TCF3 mutations., (© 2024 John Wiley & Sons Ltd.)

Acyl CoA binding protein encoded by diazepam binding inhibitor (ACBP/DBI) is a tissue hormone that stimulates lipo-anabolic responses and inhibits autophagy, thus contributing to aging and age-related diseases. Protein expression profiling of ACBP/DBI was performed on mouse tissues to identify organs in which this major tissue hormone is expressed. Transcriptomic and proteomic data bases corroborated a high level of human-mouse interspecies conservation of ACBP/DBI expression in different organs. Single-cell RNA-seq data confirmed that ACBP/DBI was strongly expressed by parenchymatous cells from specific human and mouse organs (e.g., kidney, large intestine, liver, lung) as well as by myeloid or glial cells from other organs (e.g., adipose tissue, brain, eye) following a pattern that was conserved among the two species. We identified a panel of 44 mRNAs that are strongly co-expressed with ACBP/DBI mRNA in normal and malignant human and normal mouse tissues. Of note, 22 (50%) of these co-expressed mRNAs encode proteins localized at mitochondria, and mRNAs with metabolism-related functions are strongly overrepresented (66%). Systematic data mining was performed to identify transcription factors that regulate ACBP/DBI expression in human and mouse. Several transcription factors, including growth response 1 (EGR1), E2F Transcription Factor 1 (E2F1, which interacts with retinoblastoma, RB) and transformation-related protein 53 (TRP53, best known as p53), which are endowed with oncosuppressive effects, consistently repress ACBP/DBI expression as well as its co-expressed mRNAs across multiple datasets, suggesting a mechanistic basis for a coregulation network. Furthermore, we identified multiple transcription factors that transactivate ACBP/DBI gene expression together with its coregulation network. Altogether, this study indicates the existence of conserved mechanisms determining the expression of ACBP/DBI in specific cell types of the mammalian organism., Competing Interests: Competing interests: IM consults for Osasuna Therapeutics. GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys, and Vascage. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. GK is in the scientific advisory boards of Hevolution, Institut Servier, Longevity Vision Funds and Rejuveron Life Sciences. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. GK’s wife, Laurence Zitvogel, has held research contracts with Glaxo Smyth Kline, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9 m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. GK’s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. The funders had no role in the design of the study; in the writing of the manuscript, or in the decision to publish the results. Ethics approval and consent to participate: Human ethics approval was not needed; this study was achieved in silico with publicly available data. Mouse experiments were performed in accordance with the FELASA guidelines and under the agreement by the local Animal Experimental Ethics Committee (project number #25355-2020050715057113v4)., (© 2025. The Author(s).)

In recent decades, flash drought events have frequently occurred in the humid regions of southern China. Due to the sudden onset and rapid intensification of these droughts, they often cause severe damage to vegetation photosynthesis. However, our understanding of the spatiotemporal evolution characteristics of flash droughts across different vegetation types, as well as the response regularity of photosynthesis to flash droughts, especially early responses, remains limited. This study analyzes the spatiotemporal evolution characteristics of flash droughts for different vegetation types in the Middle and Lower Reaches of the Yangtze River Basin from 2000 to 2023. It uses solar-induced chlorophyll fluorescence (SIF) and fluorescence yield ([Formula: see text]) to explore the response regularity of vegetation photosynthesis to flash droughts, with a systematic analysis of the 2013 flash drought event. The results show that, over the past 24 years, the frequency of flash droughts for different vegetation types in the Middle and Lower Reaches of the Yangtze River Basin has decreased, but the total duration has increased, with forests experiencing the highest frequency of flash droughts, while cropland experiences the least. Cropland photosynthesis is the most sensitive to flash drought, showing an early response 8-16 days after the onset and reaching a negative anomaly between 24 and 32 days. Forests mainly show an early response between 16 and 24 days and a negative anomaly response between 32 and 40 days. During the 2013 flash drought, cropland showed an early response on the 10th day after the onset and a negative anomaly on the 26th day, while forest responses were later, with early responses on the 20th day and negative anomalies on the 36th day. These results align with long-term statistical data. This study contributes to a deeper understanding of vegetation photosynthesis response regularity to flash droughts and provides insights for developing effective flash drought management strategies., Competing Interests: Declarations. Ethical approval: Informed consent. Competing interests: The authors declare no competing interests., (© 2025. The Author(s) under exclusive licence to International Society of Biometeorology.)

Neural hyperexcitability has been clinically associated with amyloid-β (Aβ) pathology and cognitive impairment in Alzheimer's disease (AD). Here, we show that decreased GABA A receptor (GABA A R) currents are linked to hippocampal granule cell hyperexcitability in the AD mouse model APP23. Elevated levels of β-secretase (BACE1), the β-secretase responsible for generating Aβ peptides, lead to aberrant cleavage of GABA A R β1/2/3 subunits in the brains of APP23 mice and AD patients. Moreover, BACE1-dependent cleavage of the β subunits leads to a decrease in GABA A R-mediated inhibitory currents in BACE1 transgenic mice. Finally, we show that the neural hyperexcitability, Aβ load, and spatial memory deficit phenotypes of APP23 mice are significantly reduced upon the granule cell expression of a non-cleavable β3 subunit mutant. Collectively, our study establishes that BACE1-dependent cleavage of GABA A R β subunits promotes the pathological hyperexcitability known to drive neurodegeneration and cognitive impairment in the AD brain, suggesting that prevention of the cleavage could slow disease progression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Herein, we report novel p -TSA·H 2 O-catalyzed ring-opening reactions of isatins with N -alkylureas, allowing access to spiro-quinazolines with excellent substrate scope and good yields. Introducing N , N -dialkylureas, 2,4-thiazolidinedione, or rhodamine into the reactions leads to a distinct set of three-component reactions, yielding innovative spiro-quinazolines incorporating sulfur atoms. Notably, the protocol achieves a superior level of atomic economy, with water as the sole byproduct.

Northern China's grasslands play a pivotal role in livestock production, energy utilization, and ecosystem balance, both domestically and globally. However, they exhibit pronounced temporal variability and marked spatial heterogeneity. Since most existing studies rely on single vegetation indices and regional-scale analyses, they may introduce biases in interpreting grassland dynamics and their underlying drivers. To address this gap, we integrated both functional and structural indices - Gross Primary Productivity (GPP), solar-Induced chlorophyll fluorescence (SIF), Normalized Difference Vegetation Index (NDVI), and Leaf Area Index (LAI) - to systematically investigate spatiotemporal trends across various grassland types in northern China. Using partial derivative analysis, we quantified the relative contributions of climate change and human activities to these observed vegetation trends. Results indicated that over 70 % of grassland areas, especially temperate grasslands, showed an overall increase in vegetation indices, while a decline was observed in the southwestern alpine grasslands. Climate change was the primary driver of grassland greening (56.55 %-63.83 %), primarily through increased precipitation in temperate grasslands and rising temperatures in alpine grasslands. Human activities contributed substantially to greening (36.17 %-43.45 %), especially in desertified temperate grasslands (e.g., Mu Us Sandy Land, Gansu, Ningxia, Xinjiang) and Qinghai alpine meadows, mainly through farmland restoration and desertification control. Conversely, human activities also served as the primary driver of grassland degradation (51.70 %-69.64 %) in certain alpine regions, where overgrazing and population growth - compounded by rising temperatures and declining soil moisture - led to significant vegetation losses. Moreover, 72.66 % of temperate grasslands demonstrated strong coupling between vegetation structure and function, whereas 57.59 % of alpine grasslands exhibited increasing GPP alongside declines in both LAI and SIF. Overall, these findings underscore the spatial heterogeneity of grassland responses to climatic and anthropogenic drivers, highlighting the necessity of employing multiple vegetation indices to guide targeted and effective grassland management strategies., 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 © 2025. Published by Elsevier B.V.)

Background: Inter-fractional and intra-fractional positioning and motion monitoring based on implanted fiducials through kilovoltage (kV) imaging is a cost-effective approach to enhance intact prostate radiotherapy treatment accuracy. However, comprehensive studies for three-dimensional (3D) position extraction and the corrective action threshold are lacking., Purpose: To develop and verify a fiducial motion monitoring system with 3D position information based on triggered kV images taken during treatment delivery, and to comprehensively evaluate the recommended thresholds for corrective action during treatment., Methods: An in-house fiducial triangulation algorithm was developed to monitor fiducial positions using subsequent kV triggered images. The precision of fiducial triangulation and motion detection was validated on a pelvis phantom with four fiducial inserts. A retrospective study was conducted on prostate cancer patients who received either moderately hypofractionated radiotherapy (MHRT, n = 16) or stereotactic body radiotherapy (SBRT, n = 12), categorized by endo-rectal balloon (ERB) use. Intra-fractional positions relative to isocenter were computed, and these positions were analyzed in comparison to the original marker locations of the patient's treatment plan. A linear regression fit was used per fraction to determine correlation coefficients between motions in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions. Average fraction time (AFT) of treatment was reported based on the observed average time spent on steps in the workflow and the percentage of fiducials caught outside of the current two-dimensional (2D) tolerance threshold of 5 mm. The observed 3D offsets were used to estimate AFT for various 3D tolerance thresholds., Results: Overall, our triangulation method proved to be very precise for static cases, where phantom measurements revealed a fiducial position triangulation precision of σ = 0.37 $\sigma = 0.37$ mm for stationary targets, but had a spread of σ = 0.81 $\sigma = 0.81$ mm for targets with 1 mm of motion. Employing triangulation, true motion exceeding 5 mm was detected above 4.0 mm in magnitude 90.9% of the time, a noticeable improvement in comparison to the 28%-65% successful detection rate reported by 2D projection methods. Most detection errors were attributed to depth disparity. Similar to other reports, correlation coefficients for intra-fractional motion generally indicated no LR/SI, no LR/AP, and weak positive SI/AP correlations for MHRT and SBRT patients. Offsets beyond a 3D tolerance threshold of 5 mm were observed at a rate of 4.25%-5.25%, while the 5 mm 2D out-of-tolerance catch-rate was 1.6%. The AFT was 8.1-8.2 min using the 2D tolerance threshold of 5 mm. In comparison, the estimated AFT for the proposed 3D tolerance monitoring of offsets beyond 2-5 mm was slightly higher at 8.2-10.9 min due to the higher amount of out-of-tolerance instances for the higher precision intra-fractional motion management., Conclusions: Our study showcases a promising subsequent kV-based triangulation method for intra-fractional prostate motion monitoring. Acquiring 3D motion information results in higher out-of-tolerance catch-rates particularly in the depth dimension of the kV images, which is perpendicular to the treatment beam. Failure to properly observe and catch these offsets would result in sub-optimal conformality and accuracy of the dose delivery., (© 2025 American Association of Physicists in Medicine.)

E7766 is a novel stimulator of interferon genes (STING) agonist, capable of potent activation of immune cells and generating strong antitumor response in preclinical murine tumor models. Here we present the safety, efficacy, and biomarker results of the first-in-human phase I/Ib study of intratumoral E7766 in patients with advanced solid tumors. Eligible patients with relapsing/refractory cancers (n=24) were enrolled in dose-escalating cohorts to receive intratumoral injections of E7766 from 75 to 1000 µg. The most frequent treatment-related treatment-emergent adverse events were chills (50.0%; 85.7%), fever (40.0%; 85.7%), and fatigue (30.0%; 35.7%) in patients who received non-visceral and visceral injections, respectively. Eight patients (33.3%) achieved stable disease as their best response per modified Response Evaluation Criteria In Solid Tumors version 1.1 with variability between injected and non-injected lesions. Plasma levels of IFN-α, IFN-β, IFN-γ, TNF-α, IL-6, IP-10, MCP1, and MIP1b transiently increased in all evaluable patients within 10 hours postinjection, then dropped to baseline levels. Levels of blood and tumor gene expression increased in most interferon-related and STING genes tested. Further increases in programmed death ligand 1 and cluster of differentiation 8 expression at both the RNA and protein levels were also observed in some patients across dose levels. In total, E7766 generated on-target pharmacodynamic effects in patients with solid tumors. Further exploration in a homogeneous patient population is necessary to assess efficacy., Competing Interests: Competing interests: JJL: DSMB: AbbVie, Agenus, Immutep, Evaxion; Scientific Advisory Board: (no stock) 7 Hills, Affivant, BioCytics, Bright Peak, Exo, Fstar, Inzen, RefleXion, Xilio (stock) Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Kanaph, Mavu, NeoTx, Onc.AI, OncoNano, physIQ, Pyxis, Saros, STipe, Tempest; Consultancy with compensation: AbbVie, Agenus, Alnylam, AstraZeneca, Askgene, Atomwise, Bayer, Bristol Myers Squibb, Castle, Checkmate, Codiak, Crown, Cugene, Curadev, Day One, Eisai, EMD Serono, Endeavor, Flame, G1 Therapeutics, Genentech, Gilead, Glenmark, HotSpot, Kadmon, Ko Bio Labs, Krystal, KSQ, Janssen, Ikena, Inzen, Immatics, Immunocore, Incyte, Instil, IO Biotech, LegoChem, Macrogenics, Merck, Mersana, Nektar, Novartis, Partner, Pfizer, Pioneering Medicines, PsiOxus, Regeneron, Replimmune, Ribon, Roivant, Servier, STINGthera, Storm, Sumoitomo, Synlogic, Synthekine, Teva; Research Support: (all to institution for clinical trials unless noted) AbbVie, Astellas, AstraZeneca, Bristol Myers Squibb, Corvus, Day One, EMD Serono, Fstar, Genmab, Hot Spot, Ikena, Immatics, Incyte, Kadmon, KAHR, Macrogenics, Merck, Moderna, Nektar, Next Cure, Novartis, Numab, Palleon, Pfizer, Replimmune, Rubius, Servier, Scholar Rock, Synlogic, Takeda, Trishula, Tizona, Xencor; Patents: US-11638728 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof). DJP: lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, Falk Foundation, Incyte, Boston Scientific, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, Elevar Therapeutics, Eisai, Roche, DaVolterra, Mursla, Starpharma, Exact Sciences, and Astra Zeneca; research funding (paid to institution) from MSD, GSK, and BMS. DJ: Consulting or advisory role for AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, Vibliome Therapeutics; research funding (paid to institution) from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, Takeda; stock and other ownership interests from PIC Therapeutics, Relay Therapeutics, Vibliome Therapeutics. PL: Participation on a Data Safety Monitoring Board or Advisory Board for: AbbVie, Takeda, Agenus, IQVIA, Glaxo-Smith Kline, Pfizer, QED Therapeutics, AstraZeneca, EMD Serono, Kyowa Kirin Pharmaceutical Development, Kineta, Inc., Zentalis Pharmaceuticals, Molecular Templates, ABL Bio, STCube Pharmaceuticals, I-Mab, Seagen, imCheck, Relay Therapeutics, Stemline, Compass BADX, Mekanistic, Mersana Therapeutics, BAKX Therapeutics, Scenic Biotech, Qualigen, NeuroTrials, Actuate Therapeutics, Atreca Development, Cullinan, Amgen, DrenBio, Quanta Therapeutics, Schrodinger, Boehrigner Ingelheim; Consultant for Sotio, IDMC, I-Mab, Roivant Sciences; Member of imCORE Alliance-Roche. PJH: consultant/advisory role for Fibrogen. AMD: nothing to disclose. RH: consulting or advisory role at Merck, Eisai, Bristol Myers Squibb, AstraZeneca, GSK, EMD Serono, Bayer, Coherus Biosciences, Boehringer Ingelheim, Genmab, Galera Therapeutics, Merus, and ALX Oncology; stock and other ownership interests from Tosk; research funding from Merck, Eisai, Bristol Myers Squibb, AstraZeneca, Genentech, Pfizer, Kura, EMD Serono, and Incyte; other from Nanobiotix, ISA Pharmaceuticals, Boehringer Ingelheim, and Hookipa Pharma. MdM: nothing to disclose. AC: grants and contracts paid to institutions from Genentech, Merck Serono, Roche, Beigene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, Fibrogen, Amcure, Sierra Oncology, Astra Zeneca, Medimmune, BMS, and MSD. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck Serono, Roche, Angem, Bayer, Servier, and Foundation Medicine. Participation on a Data Safety Monitoring Board or Advisory Board for GSK, Merck Serono, Agenus, MSD, AbbVie, Roche, Beigene, Bayer, Servier, Lilly, Novartis, Takeda, and Astellas. WSK: grant/research support from Sanofi, Beigene, Boryong, Roche, Kyowa-Kirin, and Donga. AM: manuscript writing support from Eisai. Consulting and scientific advisory boards on STING for Eisai, Merck (MSD), Boehringer Ingelheim, and GSK. YZ: employee of Eisai. YR: Employee of Eisai. XY: employee of Eisai. SC: Speaking Engagement: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck KGaA, MSD, Novartis, Roche, Servier, Takeda. Principal investigator of clinical trials for: AbbVie, Amgen, Boehringer Ingelheim, Bolt Biotherapeutics, Centessa Pharmaceuticals, Cytovation, Eisai, GlaxoSmithKline, Imcheck Therapeutics, Immunocore, Molecular Partners Ag, MSD, Ose Immunotherapeutics, Pierre Fabre, Replimune, Roche, Sanofi Aventis, Seagen, Sotio A.S., Transgene. Advisory Board/Consulting: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Beigene, BioNTech, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Mariana Oncology, Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Takeda, Tatum Bioscience, Tollys, UltraHuman8; Travel and congress: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Ose Immunotherapeutics, Roche, Sotio., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Osteoporosis is a metabolic bone disease characterized by a decrease in the amount of bone tissue per unit volume and changes in bone microstructure, often resulting in bone fragility and increased susceptibility to fracture. Iron plays an important role in the normal physiological activities of human body, and its abnormal metabolism is one of the risk factors of osteoporosis. Iron overload, as an abnormality of iron metabolism, has been reported to be associated with osteoporosis in recent years. However, the mechanism of iron overload involved in the process of osteoporosis is not fully understood. In this review, we summarize what we have learned about iron overload-associated bone loss from clinical studies and animal models. Starting from the three signaling pathways of Wnt/β-catenin, BMP/SMADs, PI3K/AKT/mTOR, the mechanism of iron overload affecting the process of osteoporosis was explored, we got the conclusion that iron overload accelerates the process of osteoporosis by inhibiting normal wnt signaling, suppressing the BMP-2/SMADs pathway, down-regulating the PI3K/AKT/mTOR pathway to inhibit bone formation, and destroying the bone strength and load-bearing capacity, which providing a new direction for clinical treatment., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Recent advancements have revealed the presence of a microbiome within tumor tissues, underscoring the crucial role of the tumor microbiome in the tumor ecosystem. This review delves into the characteristics of the intratumoral microbiome, underscoring its dual role in modulating immune responses and its potential to both suppress and promote tumor growth. We examine state-of-the-art techniques for detecting and analyzing intratumoral bacteria, with a particular focus on their interactions with the immune system and the resulting implications for cancer prognosis and treatment. By elucidating the intricate crosstalk between the intratumoral microbiome and the host immune system, we aim to uncover novel therapeutic strategies that enhance the efficacy of cancer treatments. Additionally, this review addresses the existing challenges and future prospects within this burgeoning field, advocating for the integration of microbiome research into comprehensive cancer therapy frameworks., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Our manuscript does not contain data from any individual person. All authors consent for publication of this review. Competing interests: All authors declare no conflicts of interest related to this review., (© 2025. The Author(s).)

Endo-β-N-acetylglucosaminidases (ENGases) are essential enzymes for hydrolyzing N-glycans, with applications in protein N-glycosylation analysis and glycoprotein synthesis. In this study, a novel GH18 family ENGase, Endo-LB, was identified from Listeria booriae FSL A5-0281. Composed of 593 amino acids (65.78 kDa), Endo-LB features with two domains: an Endo S-like catalytic domain and a mucin-binding protein (MucBP) domain. Recombinant Endo-LB, expressed in Escherichia coli BL21 (DE3) pLysS, exhibited a specific activity of 198.25 U/mg and hydrolyzed high mannose-type N-glycans at a temperature from 4 °C to 60 °C with optimal activity at 37 °C and pH 6.0 (range 3.0 to 10.0), making it versatile for various environmental conditions. The MucBP domain does not affect soluble Endo-LB activity but influences interaction with mucin on cell surface, suggesting potential application in targeting specific glycoproteins in complex biological environments. To address the heterogeneity of N-glycans in Pichia pastoris (Komagataella phaffii) expression, Endo-LB was further expressed in the Golgi of P. pastoris, efficiently producing glycoproteins, such as Erythropoietin (EPO) (37 mg/L) and Darbepoetin α (53 mg/L) with nearly complete N-glycans truncation, which can be further extended to generate diverse N-glycan structures. These findings highlight the versatility and potential utility of Endo-LB in glycoprotein engineering and biotechnological applications., 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. Published by Elsevier Inc.)

Dual single-atom catalysts have attracted considerable research interest due to their higher metal atom loading and more flexible active sites compared to single-atom catalysts (SACs). We pioneered the one-step synthesis of sheets copper-cobalt graphitic carbon nitride dual single-atom (S-Cu/Co-g-C 3 N 4 ) using folding fan-shaped aluminum foil as a template, and used them as catalysts in the epoxidation of styrene respectively. Through XAFS (X-ray Absorption Fine Structure) and other characterizations, it is found that Cu and Co single atoms are stabilized separately on g-C 3 N 4 via coordination with nitrogen (N), hindered the ordered growth of sheets, and formed more pore structures, which not only increased more catalytically active sites, but also effectively prevented the flakes re-aggregate during the catalytic process. And the synergistic effect between Cu and Co changes the energy band structure of the material and facilitates electron transfer during catalysis, hence an excellent catalytic effect of 89 % styrene conversion and 85 % styrene oxide selectivity was achieved when S-Cu/Co-g-C 3 N 4 -1 : 1 was applied in the epoxidation of styrene. Furthermore, the mechanisms of the epoxidation of styrene with S-Cu/Co-g-C 3 N 4 -1 : 1 was probed by the density functional theory (DFT) based on the slab model., (© 2025 Wiley-VCH GmbH.)

Overcoming the intrinsic low activity of most photoinduced oxidase mimics has been extremely challenging. In this work, we developed a methyl viologen (MV 2+ ) mediated strategy to enhance the oxidase-like activity of fluorescein. The presence of MV 2+ gives it a high affinity for TMB with a low Michaelis-Menten constant (K m ) of 0.053 mM, which is about 2.8 times lower than that of fluorescein and with a remarkable catalytic constant (K cat ) as 0.2490 s -1 , which is 3 times as high as that of fluorescein. Fluorescein diacetate (FDA) without oxidase-like activity can be hydrolyzed in situ to produce fluorescein in the presence of carboxylesterases (CaE). Based on the inhibition of CaE activity by organophosphorus pesticides (OP), a novel colorimetric signal biosensor was established with a wide linear range from 1.0 to 200 ng/mL. This work not only provides a convenient and feasible strategy for enhancing the activity of photoinduced oxidase mimics but also blazes a new pathway for the sensitive detection of OP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Constipation causes significant morbidity in Cystic Fibrosis (CF) patients. Using CF patient (F508del) derived ex vivo ileal and distal colonic/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis. CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated and then mature villus cells . While there was no FIS response in undifferentiated (crypt enterocytes) F508del-CF enteroids, partially differentiated F508del-CF enteroids had a swelling response to forskolin (cAMP) and linaclotide (cGMP) which was ∼48%, and ∼67% of the response in healthy enteroids, respectively and was prevented by a CFTR inhibitor. Also, linaclotide and a general PDE inhibitor independently enhanced combined CFTR-modulator-induced FIS response from partially differentiated F508del-CF enteroids. These findings demonstrate that partially differentiated ileal and distal colonic F508del-CFTR enteroids can be stimulated to secrete fluid by cAMP and cGMP.

The escalating needs in information protection underscore the urgency of developing advanced encryption strategies. Herein we report a novel chemical approach that enables information encryption by on-paper electrochemiluminescence (ECL). Dendritic porous silica nanospheres modified with polyetherimide and bovine serum albumin were prepared as the chemical ink to write the secret message on a paper. Attaching the paper to an electrode, immersing it in a solution containing tris(2,2'-bipyridyl)ruthenium (Ru(bpy) 3 2+ ) and then applying a suitable voltage, a remote "catalytic route" electrochemical reaction produces ECL that functions as the key to decrypt and visualize the message by imaging. In addition, proteins can be also used as the biological ink to write the secret message, which is then decrypted by a combined use of immunochemistry and ECL imaging as two keys. We believe the ECL-based strategy holds great promise in high-safety and multilevel information encryption, as it is protected not only by encoding, like conventional invisible inks, but also by the unique ECL decoding approach., (© 2024 Wiley-VCH GmbH.)

Lithium-ion batteries (LIBs) are the mainstream of the energy storage device market. Efficient and environmentally friendly separators are beneficial for LIBs. Here, we prepared a regenerated cellulose (RC) aerogel with three-dimensional (3D) pores, which was used as the separators of LIBs. Under the effects of homogeneous pore structure and excellent specific surface area, LIBs that use 3 wt% RC aerogel membrane as a separator showed the initial specific capacity of 101.3 mAh g -1 at 1C, 74.3 % capacity retention rate after 110 cycles, which were higher than that of the commercial Celgard 2340 separator-based battery. In addition, the stability and wettability of the RC aerogel membranes as separators were also studied. These results indicated that the RC aerogel membranes can be used as efficient and environmentally friendly cellulose-based separators for LIBs., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) significantly impacts human health due to its tendency to develop multi-drug resistance. Regarding the treatment of HCC, galactosylated conjugates can target drug delivery. Bacterial N-glycosyltransferases (NGTs) catalyze glucosylation or galactosylation of the Asn residue motif Asn 0 -X +1 -Ser/Thr +2 (X ≠ P). However, the limited utilization of the sugar donor UDP-Gal by NGTs severely restricts the potential applications in the development of glycol-drugs and vaccines. In this study, we rationally designed an NGT derived from Aggregatibacter aphrophilus and generated a mutant called AaFQ, which has a catalytic activity 18.8 times greater than that of wild-type towards UDP-Gal. AaFQ could rapidly synthesize Gal-modified peptides, which have been demonstrated to possess high targeting activity for HCC cells HepG2. Moreover, AaFQ exhibited a marked affinity for sugar donors with an equatorial bond-linked hydroxyl group at the C-2 position in monosaccharides. The mutant led to a significantly enhanced binding of K440 to the hydroxyl group at the C-2 position, which might be a major factor contributing to the significantly increased ability to utilize UDP-Gal. This work provides a crucial enzymatic synthetic tool for the targeted therapy of HCC and also offers a new perspective for the engineering modification and application of NGTs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The developmental competence and epigenetic progression of oocytes gradually become dysregulated with increasing maternal age. However, the mechanisms underlying age-related epigenetic regulation in oocytes remain poorly understood. Zygote arrest proteins 1 and 2 (ZAR1/2) are two maternal factors with partially redundant roles in maintaining oocyte quality, mainly known by regulating mRNA stability. In addition to this known function, it is found that ZAR1/2 is required for oocyte epigenetic maturation and zygotic reprogramming. Zar1/2-deleted oocytes exhibited reduced levels of multiple histone modifications and of the expression of corresponding histone modifiers, along with over-condensed chromatin, leading to compromised minor zygotic genome activation and deficient embryo development following fertilization. Cytoplasmic ZAR1/2 participated in intranuclear epigenetic maturation by binding the transcripts encoding histone modifiers and regulating their stability and translational activity. Moreover, oocytes from aged mice exhibited similar histone-modification deficiencies as the Zar1/2-deleted oocytes. ZAR1/2 mRNA and protein levels are downregulated in oocytes from mice and women with advanced ages, suggesting ZAR1/2 as regulators of epigenetic changes with reproductive aging. This study presents a new nucleo-cytoplasmic interaction mechanism that is involved in preventing oocyte epigenetic aging. Further, ZAR1/2 represents potential gene targets for diagnosis and clinical interventions in age-associated deficiencies in oocyte and embryo development., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The abrupt and substantial elevation of intraocular pressure (IOP) in acute glaucoma induces retinal ischemia/reperfusion (I/R) injury, resulting in progressive retinal ganglion cell (RGC) death and irreversible visual impairment. PANoptosis, a form of regulated cell death consisting of pyroptosis, apoptosis and necroptosis, is reported to be involved in high IOP-induced RGC death. However, the precise mechanisms of RGC death remain unclear, and neuroinflammation is considered to play a vital role. TAT-N24, a synthetic inhibitor targeting the p55 regulatory subunit of phosphatidylinositol 3-kinase (p55PIK) signaling, demonstrates anti-inflammatory effect in uveitis and may have certain neuroprotective effects. Therefore, we investigated whether TAT-N24 could shield RGCs from immunoinflammatory damage in an acute glaucoma mouse model and explored the potential mechanism associated with PANoptosis. A mouse model of acute ocular hypertension (AOH) was established. Intravitreal injection of TAT-N24 was conducted to evaluate its impact on RGC death. The expression levels of key components in PANoptosis were analyzed using RT-qPCR and Western blotting. Immunohistochemistry and immunofluorescence staining on eyeball sections were employed to assess the expression of p55PIK, Brn3a, and ionized calcium binding adaptor molecule 1 (Iba1). Retinal structure was examined by H&E staining, while cell apoptosis was evaluated by TdT-mediated dUTP nick end labeling (TUNEL). The results showed that intravitreal injection of TAT-N24 effectively alleviated RGC death and retinal damage induced by AOH injury. The key components in PANoptosis were markedly upregulated after AOH injury, while these components were significantly inhibited after TAT-N24 treatment. Moreover, the expression levels of Z-DNA-binding protein 1 (ZBP1)-PANoptosome (ZBP1, RIPK1, RIPK3, and Caspase-8), NLR family pyrin domain-containing protein 3 (NLRP3), and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes were notably elevated after AOH injury, which was significantly suppressed by TAT-N24. In conclusion, PANoptosis was involved in AOH-induced RGC death and retinal damage. TAT-N24 exhibited an anti-PANoptotic effect, protecting RGCs by inhibiting ZBP1-PANoptosome as well as NLRP3 and NLRC4 inflammasomes after AOH injury., Competing Interests: Declaration of competing interest None., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Direct visualization and monitoring of volatile organic compounds (VOCs) sensing processes via portable colorimetric sensors are highly desired but challenging targets. The key challenge resides in the development of efficient sensing systems with high sensitivity, selectivity, humidity resistance, and profuse color change. Herein, a strategy is reported for the direct visualization of VOCs sensing by mimicking human olfactory function and integrating colorimetric COF-on-MOF sensors with artificial intelligence (AI)-assisted data analysis techniques. The Dye@Zeolitic Imidazolate Framework@Covalent Organic Framework (Dye@ZIF-8@COF) sensor takes advantage of the highly porous structure of MOF core and hydrophobic nature of the COF shell, enabling highly sensitive colorimetric sensing of trace number of VOCs. The Dye@ZIF-8@COF sensor exhibits exceptional sensitivity to VOCs at sub-parts per million levels and demonstrates excellent humidity resistance (under 20-90% relative humidity), showing great promise for practical applications. Importantly, AI-assisted information fusion and perceptual analysis greatly promote the accuracy of the VOCs sensing processes, enabling direct visualization and classification of seven stages of matcha drying processes with a superior accuracy of 95.74%. This work paves the way for the direct visualization of sensing processes of VOCs via the integration of advanced humidity-resistant sensing materials and AI-assisted data analyzing techniques., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The impact of chirality on immune response has attracted great interest in cancer vaccine research recently. However, the study of chiral synthetic polypeptide hydrogels as cancer vaccines as well as of the impact of biomaterials themselves for antitumor immunotherapy has rarely been reported. Here, we show the key role of residue chirality of polypeptide hydrogels in antitumor immunity and local immune microenvironment regulation. Compared to poly(γ-ethyl-L-glutamate)-based hydrogels (L-Gel), poly(γ-ethyl-D-glutamate)-based hydrogels (D-Gel) induces enhanced level of immune cell infiltration. However, D-Gel causes higher levels of suppressive markers on antigen-presenting cells and even induces stronger T cell exhaustion than L-Gel. Finally, D-Gel establishes a local chronic inflammatory and immunosuppressive microenvironment and shows insufficient anti-tumor effects. Conversely, the milder host immune responses induced by L-Gel leads to more effective tumor inhibition. This study provides insights on the role of residue chirality in the regulation of local immune microenvironment and affecting antitumor immune response., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

During the operation of the reactor, a mixture of oxygen, hydrogen, nitrogen, and radioactive gases is produced and stored under pressure in a decay chamber. This review uses numerical simulation methods to study the accumulation and explosion of hydrogen in these mixed gases during storage. The results show that when the initial volume concentration of hydrogen is 0.2%, the maximum volume concentration of hydrogen in the decay box is about 4% after about 1.61 h, the maximum concentration of hydrogen in the decay box is 30% after about 16.79 h, and the concentration is highest at the top of the decay box. As the operating pressure of the decay chamber increases, the maximum explosion pressure of hydrogen gas significantly increases, reaching up to 7.110 MPa., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)

Context: SiGe nanotubes (SiGeNTs) hold significant promise for applications in nanosolar cells, optoelectronic systems, and interconnects, where thermal conductivity is critical to performance. This study investigates the effects of length, diameter, temperature, and axial strain on the thermal conductivity of armchair and zigzag SiGeNTs through molecular dynamics simulations. Results indicate that thermal conductivity increases with sample length due to ballistic heat transport and decreases with temperature as phonon scattering intensifies. Axial strain transitions from compression to tension enhance phonon propagation, improving conductivity. Chirality affects conductivity, with zigzag SiGeNTs consistently outperforming armchair structures, while diameter exhibits negligible impact., Methods: Non-equilibrium molecular dynamics simulations were conducted using the LAMMPS package with the Tersoff potential to model Si-Ge interactions. Thermal conductivity was computed via Fourier's law, with the system divided into regions for controlled heat input and dissipation. Lengths, diameters, temperatures (100-500 K), and axial strains (- 6% to + 9%) were varied systematically. Phonon spectrum analysis was performed using Fourier transforms of velocity autocorrelation functions to compute., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This white paper examines the potential of pioneering technologies and artificial intelligence-driven solutions in advancing clinical trials involving radiation therapy. As the field of radiation therapy evolves, the integration of cutting-edge approaches such as radiopharmaceutical dosimetry, FLASH radiation therapy, image guided radiation therapy, and artificial intelligence promises to improve treatment planning, patient care, and outcomes. Additionally, recent advancements in quantum science, linear energy transfer/relative biological effect, and the combination of radiation therapy and immunotherapy create new avenues for innovation in clinical trials. The paper aims to provide an overview of these emerging technologies and discuss their challenges and opportunities in shaping the future of radiation oncology clinical trials. By synthesizing knowledge from experts across various disciplines, this white paper aims to present a foundation for the successful integration of these innovations into radiation therapy research and practice, ultimately enhancing patient outcomes and revolutionizing cancer care., (Published by Elsevier Inc.)

Background: The common diagnostic methods for tuberculosis have been showing reduced sensitivity among chronic obstructive pulmonary disease patients. This study was conducted to evaluate and analyse the diagnostic value of an interferon-γ release assay in COPD patients complicated with pulmonary tuberculosis., Methods: A nested case-control study was conducted on 123 COPD patients hospitalized at the Fifth Hospital of Shijiazhuang, Hebei Province, from January 2019 to June 2021. Thirty-one patients with active pulmonary tuberculosis complicated with COPD composed the observation group (Group A), 31 patients with nonactive pulmonary tuberculosis complicated with COPD composed the COPD control group (Group B), and 31 patients with active pulmonary tuberculosis not complicated with COPD composed the non-COPD control group (Group C). An interferon-γ release assay, a purified protein derivative of tuberculin (PPD) test, an anti-tuberculosis antibody test, a test of Mycobacterium tuberculosis by sputum smear microscopy and a test of Mycobacterium tuberculosis by PCR method were used to test patients in each group. The positive detection rates generated from the five test methods were compared and analysed., Results: In COPD patients complicated with active pulmonary tuberculosis, the differences in the percentage of patients with positive interferon-γ release between the PPD test, anti-tuberculosis antibody test, Mycobacterium tuberculosis by sputum smear microscopy and PCR test results were statistically significant., Conclusion: In patients with COPD complicated with active pulmonary tuberculosis, the percentage of patients who were positive according to the interferon-γ release assay was higher than that according to the sputum smear microscopy, PCR detection of Mycobacterium tuberculosis in sputum specimen, and detection of anti-tuberculosis antibodies. COPD-related complications did not affect the T-SPOT; the greater the T-SPOT value was, the greater the likelihood of active TB. For patients who are T-SPOT positive but clinically considered to have inactive tuberculosis, regular follow-ups should be performed to observe changes in the patient's condition., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Ethics Management Committee of Fifth Hospital of Shijiazhuang. And owing to the retrospective study design, the need for informed consent was waived. Consent for publication: Not required. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Bacterial vaginosis (BV) is an abnormal gynecological condition caused by the overgrowth of specific bacteria in the vagina. This study aims to develop a novel method for BV detection by integrating surface-enhanced Raman scattering (SERS) with machine learning (ML) algorithms. Vaginal fluid samples were classified as BV positive or BV negative using the BVBlue Test and clinical microscopy, followed by SERS spectral acquisition to construct the data set. Preliminary SERS spectral analysis revealed notable disparities in characteristic peak features. Multiple ML models were constructed and optimized, with the convolutional neural network (CNN) model achieving the highest prediction accuracy at 99%. Gradient-weighted class activation mapping (Grad-CAM) was used to highlight important regions in the images for prediction. Moreover, the CNN model was blindly tested on SERS spectra of vaginal fluid samples collected from 40 participants with unknown BV infection status, achieving a prediction accuracy of 90.75% compared with the results of the BVBlue Test combined with clinical microscopy. This novel technique is simple, cheap, and rapid in accurately diagnosing bacterial vaginosis, potentially complementing current diagnostic methods in clinical laboratories., Importance: The accurate and rapid diagnosis of bacterial vaginosis (BV) is crucial due to its high prevalence and association with serious health complications, including increased risk of sexually transmitted infections and adverse pregnancy outcomes. Although widely used, traditional diagnostic methods have significant limitations in subjectivity, complexity, and cost. The development of a novel diagnostic approach that integrates SERS with ML offers a promising solution. The CNN model's high prediction accuracy, cost-effectiveness, and extraordinary rapidity underscore its significant potential to enhance the diagnosis of BV in clinical settings. This method not only addresses the limitations of current diagnostic tools but also provides a more accessible and reliable option for healthcare providers, ultimately enhancing patient care and health outcomes., Competing Interests: The authors declare no conflict of interest.

Puerarin, a flavonoid compound present in the roots of radix puerariae , contributes to the development of tissues such as bone and nerve, but its role in skeletal muscle regeneration remains unclear. In this study, we employed C2C12 myoblasts and barium chloride (BaCl 2 )-based muscle injury models to investigate the effects of puerarin on myogenesis. Our study showed that puerarin stimulated the migration and differentiation of myoblasts in vitro. For the mechanism study, we found that puerarin's influence on cell migration was associated with the activation of FAK signaling; additionally, puerarin induced myoblast differentiation by upregulating the PI3K/AKT pathway. We also found that puerarin treatment could improve muscle regeneration following muscle injury. Taken together, our data indicate that puerarin facilitated myogenesis by promoting migration and differentiation, which suggests puerarin as a new candidate drug for the treatment of muscle loss diseases.

Strategies that can introduce catalytic auxiliary into electrocatalysts to boost the performance of electrocatalytic CO 2 reduction reaction (CO 2 RR) are meaningful in exploring hybrid electrocatalytic systems. Here, a series of hybrid electrocatalysts (Cu NCs@MOF-545-M, M=Fe, Co and Ni) have been prepared by assembly Cu NCs with MOF-545-M (M=Fe, Co and Ni) and successfully applied in electrocatalytic CO 2 RR. In the obtained MOF-545-M (M=Fe, Co and Ni), the integration of Cu NCs with MOF-545-M (M=Fe, Co and Ni) can create a hybrid electrocatalytic system that enhances the charge transfer efficiency and electrocatalytic CO 2 RR activity. Specifically, the optimal Cu NCs@MOF-545-Co presents remarkable FE CO over a wide potential range (-0.7 V to -1.0 V), high CO generation rate (8.2 mol m -2  h -1 ) and excellent maximum energy efficiency (69 %, -0.7 V), which is superior to Cu NCs and MOF-545-Co, and represented to be one of the best performances to date. This work demonstrates a facile approach to significantly improve the FE CO by loading metal nanoclusters into MOFs, providing a valuable reference for future studies on hybridization strategies to enhance the performance of electrocatalysts., (© 2024 Wiley-VCH GmbH.)

Background: Identifying markers or genes crucial for growth traits in Zhongwei goats is pivotal for breeding. Pinpointing genetic factors linked to body size gain enhances breeding efficiency and economic value. In this study, we used the MGISEQ-T7 platform to re-sequence 240 Zhongwei goats (133 male; 107 female) belonging to 5 metrics of growth traits at different growth stages (40 days and 6 months, here in after referred to as 40d and 6 m), namely, Body Weight (BW), Body Height (BH), Body Length (BL), Chest Circumference (CC), Tube Circumference (TC) were examined. A Genome-wide association study (GWAS) was conducted to identify candidate genes associated with the five indicators of body conformation traits, thereby establishing a foundation for subsequent investigations into the biological functions of these genes., Results: A total of 19.89 Tb of raw data was generated with an average sequencing depth of about 20×. After quality control, 15,958,716 SNPs were available for the analysis. A total of 342 genome-wide significant SNPs were obtained. Among them, in the two physiological stages of 40d and 6 m, 147 and 32 SNPs were significantly associated with BW; 1 and 4 SNPs were significantly associated with BH; 19 and 6 SNPs were significantly associated with BL; 33 and 64 SNPs were significantly associated with CC, 34 and 2 SNPs were significantly associated with TC. These SNPs were annotated to 425 candidate genes. Finally, A total of 39 candidate genes are closely related to biological processes such as skeletal muscle development, skeletal formation, carcass quality, and embryonic development, where ADIPOQ, CCDD39, PTPRT, ZNF215, VRTN, ABCD4, DLST, ADAMTS2, ROBO1, AKAP13, AQPI, SOX2, and AHSG were identified as an important component of the genetic framework that may control somatic conformational traits in Zhongwei goats. which warrants further investigation and review. We verified the polymorphism of 11 SNPs by KASP, and found that Chr13&#95;g.11,700,438 A > G, Chr15&#95;g.37,120,328 A > G, Chr6&#95;g.7,209,383 C > T, Chr20&#95;g.51277932T > A, Chr19&#95;g.17,078,199 A > G, and Chr1&#95;g.79,943,276 C > T were significantly genotyped in verified populations (P < 0.001)., Conclution: It is the first GWAS study to analyze genomic data from 40d and 6 m of Zhongwei goats to understand the molecular genetic mechanisms of growth. Our research identified a series of SNPs and candidate genes associated with growth traits, which could assist us in developing the meat production trait in Zhongwei goats., Competing Interests: Declarations. Ethics approval and consent to participate: All samples were collected in accordance with the International Guiding Principles for Biomedical Research involving animals and approved by the Special Committee on Scientific Research and Academic Ethics of Inner Mongolia Agricultural University, responsible for the approval of Biomedical Research Ethics of Inner Mongolia Agricultural University [Approval No. (2020) 056]. No specific permissions were required for these activities, and no endangered or protected species were involved. These activities were performed under the informed consent from all owners. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Autophagy, a conserved catabolic process implicated in a diverse array of human diseases, requires efficient fusion between autophagosomes and lysosomes to function effectively. Recently, SNAP47 has been identified as a key component of the dual-purpose SNARE complex mediating autophagosome-lysosome fusion in both bulk and selective autophagy. However, the spatiotemporal regulatory mechanisms of this SNARE complex remain unknown. In this study, we found that SNAP47 undergoes acetylation followed by deacetylation during bulk autophagy and mitophagy. The acetylation status of SNAP47 is regulated by the acetyltransferase CBP and the deacetylase HDAC2. Notably, the spatiotemporal regulatory dynamics of SNAP47 acetylation differ between bulk autophagy and mitophagy due to distinct regulation on the activity of acetyltransferase and deacetylase. Acetylated SNAP47 inhibits autophagosome-lysosome fusion by indirectly impeding SNARE complex assembly. Mechanistically, deacetylated SNAP47 recruits HOPS components to autophagic vacuoles independently of STX17 and STX17-SNAP47 interaction, while acetylated SNAP47 inhibits this recruitment, consequently leading to the failure of SNARE complex assembly. Taken together, our study uncovers a SNAP47 acetylation-dependent regulatory mechanism governing autophagosome-lysosome fusion by modulating the recruitment of HOPS to autophagic vacuoles without involving STX17, SNAP47-STX17 interaction and ternary SNARE complex formation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Tin-lead perovskites provide an ideal bandgap for narrow-bandgap perovskites in all-perovskite tandem solar cells, fundamentally improving power conversion efficiency. However, light-induced degradation in ambient air is a major issue that can hinder the long-term operational stability of these devices. Understanding the specifics of what occurs during this pathway provides the direction for improving device stability. In this study, we investigate the long-term stability problem of tin-lead perovskites under irradiation, counterintuitively discovering an irreversible phase reconstruction process. In-situ photoluminescence spectroscopy is used to monitor the reconstruction process, which involves the reaction of oxygen with photoexcited electrons to form superoxide. It is proposed that Pb-rich regions appear on the surface after Sn 2+ oxidation, and these Pb-rich regions are reconstituted from the yellow phase of formamidinium lead iodide to the black phase with prolonged irradiation. This study highlights the phase reconstruction process during the degradation of tin-lead perovskites, providing valuable insights into the superoxide degradation mechanism and guiding further stability improvements for narrow-bandgap tin-lead perovskites and tandem solar cells., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by inflammation and ulceration of the digestive tract., Methods: Photodynamic therapy (PDT) with a novel photosensitizer LD 4 was used to treat UC rat models to explore the therapeutic effect and mechanism of LD 4 -PDT on UC. 16S ribosomal RNA was used to detect the composition of Gut microbiota., Results: Our findings indicate that LD 4 -PDT could protect the integrity of the colonic mucosa, alleviate the inflammatory response and promote the healing of colonic mucosa. Mechanism studies demonstrated that LD 4 -PDT could inhibit the NF-κB signaling pathway, downregulated the expression of the inflammatory factors' tumor necrosis factor-α (TNF-α), interleukin-6 ( IL-6 ) and myeloperoxidase ( MPO ), increased the contents of glutathione (GSH) and superoxide dismutase ( SOD ) and decreased the content of malondialdehyde (MDA). Additionally, analysis of gut microbiota revealed that LD 4 -PDT treatment could decrease the abundance of the Proteobacteria phylum in fecal samples, while no significant differences were observed in the Firmicutes, Bacteroidetes, or Actinobacteria phyla among the three groups using 16S rRNA analysis., Discussion: In summary, our data suggested that LD 4 -PDT could inhibit DSS-induced UC in rats via the NF-κB signaling pathway, indicating its potential as a novel photosensitizer for the treatment of UC., 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 © 2025 Rong, Zhu, Wang, Zhang and Liu.)

Oocytes are the largest cell type in multicellular animals. Here, we show that mRNA transporter 4 (MTR4) is indispensable for oocyte growth and functions as part of the RNA surveillance mechanism, which is responsible for nuclear waste RNA clearance. MTR4 ensures the normal post-transcriptional processing of maternal RNAs, their nuclear export to the cytoplasm, and the accumulation of properly processed transcripts. Oocytes with Mtr4 knockout fail to accumulate sufficient and normal transcripts in the cytoplasm and cannot grow to normal sizes. MTR4-dependent RNA surveillance has a previously unrecognized function in maintaining a stable nuclear environment for the establishment of non-canonical histone H3 lysine-4 trimethylation and chromatin reorganization, which is necessary to form a nucleolus-like structure in oocytes. In conclusion, MTR4-dependent RNA surveillance activity is a checkpoint that allows oocytes to grow to a normal size, undergo nuclear and cytoplasmic maturation, and acquire developmental competence., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Flexible thermoelectric systems capable of converting human body heat or solar heat into sustainable electricity are crucial for the development of self-powered wearable electronics. However, challenges persist in maintaining a stable temperature gradient and enabling scalable fabrication for their commercialization. Herein, we present a facile approach involving the screen printing of large-scale carbon nanotube (CNT)-based thermoelectric arrays on conventional textile. These arrays were integrated with the radiation-modulated thermoelectric fabrics of electrospun poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) membranes for the low-cost and high-performance wearable self-power application. Combined with the excellent photothermal properties of CNTs, the resulting thermoelectric fabric (0.2 square meters) achieves a substantial Δ T of 37 kelvin under a solar intensity of ~800 watt per square meter, yielding a peak power density of 0.20 milliwatt per square meter. This study offers a pragmatic pathway to simultaneously address thermal management and electricity generation in self-powered wearable applications by efficiently harvesting solar energy.

Clinical Relevance: It is particularly important to perform reasonable and effective optical correction to enable visual development after primary lens removal surgery for congenital cataracts. Aphakic infants need a suitable addition power of prescription (ADD) to help them focus on close visual objects., Background: It is challenging to obtain appropriate ADD power for infants due to poor cooperation and lack of subjective feedback. We aimed to determine the appropriate ADD for aphakic infants using a recently developed smart wearable device called Clouclip., Methods: The study was a cross-sectional, observational pilot study. Twenty-three aphakic infants (aged from 6 months to 3.5 years) were invited to wear a smart wearable device for 7 days consecutively to monitor the near viewing distance in real life. Viewing habits and its associations with the possible influencing factors were investigated based on the data obtained from the device., Results: The average proportion of near viewing time was 77.9% (95% confidence interval (CI) 72.1-83.7%). The average of the median near viewing distance was 23.8 cm (95% CI 20.6 cm-27.0 cm), which corresponded to an ADD of +4.25 D (95% CI + 3.75 D - +4.75 D) spectacle prescription. The height of the child was found to be positively correlated with the median of near viewing distance ( r  = 0.646, p  = 0.001). Age, current ADD, age of cataract extraction surgery and bilaterality or monocularity of the aphakic eyes showed no significant correlation with the aforementioned viewing habits (all p  > 0.05)., Conclusion: By using the novel wearable device, we found the suitable ADD of spectacle prescription for aphakic infants is about +4.25 D. The height of the child was an influencing factor for ADD.

Study Question: What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)?, Summary Answer: Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels., What Is Known Already: Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development., Study Design, Size, Duration: This is a cross-sectional study aimed to elucidate the molecular mechanisms underlying the impact of OEM on follicular development. Initially, miRNA expression profiles in follicular fluid (FF) samples were sequenced from patients with infertility related to OEM (N = 3) and male factor (MF) infertility (N = 3), with the latter serving as the control group. Differentially expressed miRNAs were validated in additional samples from each group (N = 55 in OEM group and N = 45 in MF group) to confirm candidate miRNAs. The study also investigated indicators associated with GCs dysfunction in vitro on rat GCs. Subsequently, rat models of OEM were established through endometrial allogeneic transplantation, and fertility experiments were conducted to assess the let-7/IGF1R axis response to OEM in vivo. Patient samples were collected between May 2018 and April 2019, and the mechanistic study was conducted over the subsequent three years., Participants/materials, Setting, Methods: FF and GC samples were obtained from infertile patients undergoing IVF treatment for OEM and MF related infertility. miRNA expression profiles in FF samples were analyzed using second-generation high-throughput sequencing technology, and candidate miRNAs were validated through quantitative PCR (qPCR). In the in vitro experiments conducted with rat GCs, cell proliferation was assessed using the CCK-8 assay, while steroid hormone concentrations were measured using chemiluminescence. ATP content was determined with an ATP assay kit, and levels of ROS were quantified using flow cytometry. A dual luciferase reporter gene assay was employed to identify the target gene of let-7 based on the construction of a IGF1R reporter gene plasmid using 293T cells. Western blotting was utilized to evaluate the expression of IGF1R in GCs, as well as its downstream proteins, and changes in signaling pathways following let-7 agomir/antagomir transfection and/or Igf1r silencing. In the in vivo OEM rat models, alterations in ovarian structure and cyst morphology were observed using hematoxylin and eosin staining. The expressions of let-7 and Igf1r in GCs were evaluated through qPCR, while variations in IGF1R expression were investigated with immunohistochemistry., Main Results and the Role of Chance: The cohort of patients with ovarian OEM in this study exhibited significantly decreased antral follicle counts, oocyte retrieval numbers, and normal fertilization rates compared to the control group with MF. The expression of the let-7 miRNA family was markedly upregulated in the FF and GCs of OEM patients. Transfection of rat GCs with let-7 agonists diminished the functions of GCs, including disrupted cell proliferation, mitochondrial oxidative phosphorylation, and steroid hormone secretion, while transfection of rat GCs with let-7 antagonists caused the opposite effects. Luciferase reporter gene experiments confirmed that let-7 complementarily bound to the 3'-untranslated regions of IGF1R. Stimulation of let-7 expression in rat GCs led to a significant decrease in IGF1R expression, while inhibition of let-7 increased IGF1R expression. The expression of IGF1R in the GCs of OEM patients was also significantly reduced compared to MF patients. Silencing of Igf1r led to the dysfunction of GCs, similar to the effects of let-7 agonization, as demonstrated by the downregulation of key proteins involved in cell proliferation (CCND2 and CCND3) and oestradiol synthesis, as well as an increase in progesterone synthesis (StAR), while implicating the PI3K-Akt and MAPK signaling pathways. The antagonistic effect of let-7 on GCs was ineffective when Igf1r was silenced. Conversely, the agonistic effect of let-7 on GCs could be reversed by stimulation with the IGF1R ligand IGF-1. These findings suggested that let-7 regulated the proliferation, differentiation, and ATP synthesis of GCs through targeting IGF1R. The OEM rat model demonstrated alterations in ovarian morphology and structure, along with reduced fertility. Let-7 expression was significantly upregulated in GCs of OEM rats compared to normal rats, while Igf1r and IGF1R expression in pre-ovulatory follicular GCs were notably downregulated, supporting the notion that elevated let-7 expression in the follicular microenvironment of OEM inhibited IGF1R, leading to abnormal GC function and impacting fertility at the molecular level., Large Scale Data: N/A., Limitations, Reasons for Caution: The synthesis and secretion mechanisms of steroid hormones are intricate and complex. Some enzymes that regulate oestrogen synthesis also play a role in progesterone synthesis. Moreover, certain receptors can respond to multiple hormone signals. Therefore, in this study, the expression patterns of key enzymes such as CYP17A, CYP11A1, HSD3B2, StAR, and receptors including AR, LHCGR, FSHR, ESR2, might be influenced by various factors and might not demonstrate complete consistency., Wider Implications of the Findings: Future research will concentrate on investigating the potential impact of ovarian stromal cells on the external microenvironment of follicle growth. Additionally, screening for small molecule drugs that target let-7 and IGF1R actions can be conducted to intervene and modify the ovarian microenvironment, ultimately enhancing ovarian function., Study Funding/competing Interest(s): This study received funding from the National Natural Science Foundation of China (grant number 82301851 to L.B.S., grant numbers U23A20403 and U20A20349 to S.Y.Z., and grant number 82371637 to Y.D.D.) and the Natural Science Foundation of Zhejiang Province (grant LTGY23H040010 to F.Z.). The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Magnetic resonance imaging (MRI) is considered the gold standard for prostate segmentation. Computed tomography (CT)-based segmentation is prone to observer bias, potentially overestimating the prostate volume by ∼ 30 % compared to MRI. However, MRI accessibility is challenging for patients with contraindications or in rural areas globally with limited clinical resources., Purpose: This study investigates the possibility of achieving MRI-level prostate auto-segmentation accuracy using CT-only input via a deep learning (DL) model trained with CT-MRI registered segmentation., Methods and Materials: A cohort of 111 definitive prostate radiotherapy patients with both CT and MRI images was retrospectively grouped into training (n = 37) and validation (n = 20) (where reference contours were derived from CT-MRI registration), and testing (n = 54) sets. Two commercial DL models were benchmarked against the reference contours in the training and validation sets. A custom DL model was incrementally retrained using the training dataset, quantitatively evaluated on the validation dataset, and qualitatively assessed by two different physician groups on the validation and testing datasets. A contour quality assurance (QA) model, established from the proposed model on the validation dataset, was applied to the test group to identify potential errors, confirmed by human visual inspection., Results: Two commercial models exhibited large deviations in the prostate apex with CT-only input (median: 0.77/0.78 for Dice similarity coefficient (DSC), and 0.80 cm/0.83 cm for 95 % directed Hausdorff Distance (HD95), respectively). The proposed model demonstrated superior geometric similarity compared to commercial models, particularly in the apex region, with improvements of 0.05/0.17 cm and 0.06/0.25 cm in median DSC/HD95, respectively. Physician evaluation on MRI-CT registration data rated 69 %-78 % of the proposed model's contours as clinically acceptable without modifications. Additionally, 73 % of cases flagged by the contour quality assurance (QA) model were confirmed via visual inspection., Conclusions: The proposed incremental learning strategy based on CT-MRI registration information enhances prostate segmentation accuracy when MRI availability is limited clinically., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Quan Chen is co-founder of Carina Medical LLC]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: A critical aspect affecting the quality of life in Traumatic spinal cord injury (TSCI) patients is bladder dysfunction. Metabolities in arachidonic acid are crucial lipid signaling molecules involved innumerous physiological processes. In this study, We are the first use eicosanoid metabolomics detrusor contraction examine, to assess the effect of the arachidonic acid metabolic in bladder dysfunction following TSCI. In additon, we explore the time of inflammatory and function changes in bladder tissue., Methods: Adult male Sprague-Dawley rats were subjected to improved Weight Drop method surgeries. Detrusor contraction examination, urodynamic examination, eicosanoid metabolomics, transmission electron microscopy, Elisa and histological staining were performed to assess the change of inflammatory, metabolic and function variation over time after TSCI., Results: Following TSCI, before the variations of bladder function, inflammatory changes including the increase of inflammatory factors, mitochondrial damage, and slight lipid peroxidation, occurred in bladder tissue. And the inflammatory changes gradually decreases over time. However, From the third day after TSCI, secondary lesions appeared in bladder tissue. Not only did inflammation-related indexes increase again, the degree of mitochondrial damage and lipid peroxidation increased, but also the contractility of detrusor began to change significantly. We also found that the content of metabolites in arachidonic acid metabolic pathway and the degree of detrusor contractility change showed a strong correlation. In addition, we found that rats had moved beyond the spinal shock stage on the seventh day after TSCI., Conclusion: Altogether, we are the first to demonstrate that abnormal arachidonic acid metabolism plays an important role in bladder dysfunction after TSCI. We also demonstrate that 3d is a critical juncture for changes in rat bladder tissue, which indicates it is an important juncture in the treatment of neurogenic bladder., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Published by Elsevier Inc.)

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment are lacking. We asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound (CDDO-EA) mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received CDDO-EA (400 μg/g of food) or a control diet (vehicle, Veh) for 5 days and Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: (1) location discrimination reversal (tests behavior pattern separation and cognitive flexibility, abilities reliant on the dentate gyrus) and (2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment's end (14.25-month post-IRR), an index relevant to neurogenesis was quantified (doublecortin-immunoreactive [DCX+] dentate gyrus immature neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. One radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had slower stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice showed normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change relevant to neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Aim: Radiofrequency (RF) catheter ablation (CA) is a mainstay treatment for atrial fibrillation (AF). RF catheters with contact force (CF) sensing technology and electroanatomical mapping systems enable real-time assessment of catheter tip-tissue interface CF, facilitating individualized and precise CA. This study examined inpatient hospital readmissions in patients with AF treated with THERMOCOOL™ ST/ THERMOCOOL™ STSF catheter with the CARTO™ 3 System versus TactiCath™ catheter with the EnSite™ System. Materials & methods: Patients undergoing CA for AF between 1 July 2019 to 30 November 2021 were identified from the Premier Healthcare Database and grouped based on use of THERMOCOOL ST/STSF or TactiCath™. Study outcomes were all-cause, cardiovascular (CV)-, and AF-related inpatient readmission at 91-365-day post-CA. Inverse probability of treatment weighting of propensity scores balanced baseline patient, comorbidity and hospital characteristics. A weighted generalized estimating equation (GEE) model examined differences in readmission outcomes. Results: A total of 15,518 patients met inclusion criteria (THERMOCOOL ST/STSF, n = 13,001; TactiCath™, n = 2517). Patient characteristics were generally well-balanced after weighting. Patients treated with THERMOCOOL ST/STSF + CARTO 3 had a 20% lower likelihood of all-cause inpatient readmissions (7.8 vs 9.3%, chi-square p = 0.041; odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.66-0.96, GEE p = 0.019) and a 21% lower likelihood of CV-related inpatient readmission (5.2 vs 6.2%, chi-square p = 0.133, OR: 0.79, 95% CI: 0.62-0.99, GEE p = 0.043) in 91-365-days post-CA versus those treated with TactiCath™ + Ensite. No significant differences were observed for AF-related readmissions. Conclusion: Patients undergoing CA for AF treated with THERMOCOOL ST/STSF + CARTO 3 had a significantly lower risk of all-cause and CV-related inpatient hospital readmission versus those treated with TactiCath™ + Ensite.

Hepatocellular carcinoma (HCC) poses a significant global health burden, with escalating incidence rates and substantial mortality. The predominant etiological factors include liver cirrhosis (LC) and chronic hepatitis B infections (CHB). Surveillance primarily relies on ultrasound and Alpha-fetoprotein (AFP), yet their efficacy, particularly in early HCC detection, is limited. Hence, there is a critical need for accurate non-invasive biomarkers to enhance surveillance and early diagnosis. Extracellular vesicles (EVs) hold promises as stable carriers of signaling molecules, offering potential in tumor diagnosis. Our study developed a novel tidal microfluidic chip for label-free EV isolation, enabling rapid and efficient enrichment from small plasma volumes. Through transcriptome sequencing and single-cell analysis, we identified HMMR and B4GALT2 as promising HCC-associated biomarkers in EVs. In a comprehensive clinical evaluation, bi-mRNAs in EVs exhibited superior diagnostic performance over AFP, particularly in distinguishing early-stage HCC or AFP-negative cases from high-risk individuals (CHB/LC). Notably, our study demonstrated the potential of bi-mRNAs to complement imaging examinations, enabling early detection of HCC lesions. In conclusion, the tidal microfluidic chip offers a practical solution for EV isolation, with the integration of EV-based biomarkers presenting opportunities for improved early detection and management of HCC in clinical practice., 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 © 2025. Published by Elsevier B.V.)

Background: Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown., Results: This study uncovers three novel mutations (c.1201G > T, c.1284delA and c.1613 + 2&#95;1613 + 3insGT) and three reported mutations (c.1204 C > T, c.1271T > C, c.223 - 14&#95;223-2delCCCTCCTGTTCCA) in the PATL2 gene across five unrelated individuals exhibiting OMD, oocyte death, and early embryonic arrest. RNA sequencing revealed that PATL2 mutations decreased mRNA storage in human germinal vesicle (GV) oocytes and impeded mRNA decay during maturation and in early embryos. We demonstrate that PATL2 interacts with CPEB1 and TUT7 in human oocytes to maintain mRNA homeostasis. Additionally, we observed a reduction in CCNB1 and CCNE1 mRNA levels in PATL2-mutant GV oocytes, which may be linked to GV arrest. Employing both wild-type and mutated PATL2 V401F/R402W variants, we characterized the protein interactome of PATL2, identifying disruptions of PATL2 V401F/R402W variants predominantly affecting cell cycle-related proteins, including CDC23, APC1 and MAD2L1. PATL2's interaction with and stabilization of CDC23 in oocytes may elucidate the mechanisms behind the mutation-induced MI arrest. PALT2 is required for the efficient mRNA translation and it maintains the protein level of CDC23, APC1 and MAD2L1 in mouse GV oocyte., Conclusion: PATL2 plays a critical role in regulating mRNA accumulation and decay in human oocytes, potentially through interactions with CPEB1 and TUT7, respectively. Mutations in PATL2 lead to oocyte meiosis defects by affecting the mRNA accumulation, mRNA translation, and direct binding to and stabilizing proteins related to cell cycle regulation, such as CCNB1 and CDC23. This study expands the mutational spectrum of PATL2 and provides new insights into the molecular mechanisms underlying PATL2 mutation-associated oocyte maturation disorders., Competing Interests: Declarations. Ethics approval and consent to participate: The animal study protocol was approved by the Animal Care and Use Committee of Zhejiang University (ZJU20220464). Studies of human subjects were approved by the Ethics Committee of Sir Run Run Shaw Hospital (NO. 20220461). Informed consent was obtained from each participant as adhering to tenets of the Declarations of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare they have no conflict of interest., (© 2024. The Author(s).)

Background: Neurological complications are a significant concern of Coronavirus Disease 2019 (COVID-19). However, the pathogenic mechanism of neurological symptoms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is poorly understood., Methods: We used Drosophila as a model to systematically analyze SARS-CoV-2 genes encoding structural and accessory proteins and identified the membrane protein (M) that disrupted mitochondrial functions in vivo. The M protein was stereotaxically injected to further assess its effects in the brains of wild-type (WT) and 5 × FAD mice. Omics technologies, including RNA sequencing and interactome analysis, were performed to explore the mechanisms of the effects of M protein both in vitro and in vivo., Results: Systematic analysis of SARS-CoV-2 structural and accessory proteins in Drosophila identified that the M protein induces mitochondrial fragmentation and dysfunction, leading to reduced ATP production, ROS overproduction, and eventually cell death in the indirect flight muscles. In WT mice, M caused hippocampal atrophy, neural apoptosis, glial activation, and mitochondrial damage. These changes were further aggravated in 5 × FAD mice. M was localized to the Golgi apparatus and genetically interacted with four wheel drive (FWD, a Drosophila homolog of mammalian PI4KIIIβ) to regulate Golgi functions in flies. Fwd RNAi, but not PI4KIIIα RNAi, reversed the M-induced Golgi abnormality, mitochondrial fragmentation, and ATP reduction. Inhibition of PI4KIIIβ activity suppressed the M-induced neuronal cell death. Therefore, M induced mitochondrial fragmentation and apoptosis likely through disruption of Golgi-derived PI(4)P-containing vesicles., Conclusions: M disturbs the distribution and function of Golgi, leading to mitochondrial abnormality and eventually neurodegeneration via a PI4KIIIβ-mediated mechanism. This study reveals a potential mechanism for COVID-19 neurological symptoms and opens a new avenue for development of therapeutic strategies targeting SARS-CoV-2 M or mitochondria., Competing Interests: Declarations. Ethics approval and consent to participate: All animal studies had complied with all relevant ethical regulations for the animal testing and research, and were approved by the Animal Care and Use Committee of Xiangya Hospital, Central South University. Consent for publication: All authors read and approved the final manuscript. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Uterine adenomyosis causing attention to the abnormal smooth muscle layer has recently received increasing attention, which has created the need for a method that can efficiently collect high purity uterine smooth muscle cells (USMC) in a laboratory setting. In this study, we explored the composition ratios of the digestion solution to obtain the optimal digestion solution (DM4). Furthermore, we tested the superiority of the two methods of obtaining adenomyotic uterine smooth muscle by comparing DM4 with the conventional tissue adhesion method by growth rate, single-cell RNA sequencing, and purity of fluorescence identification. The results demonstrated that USMCs produced by the DM4 digestion method exhibited significantly higher rates of proliferation and were more effective in generating mature smooth muscle cells of high purity compared to those obtained using tissue adherence methods, which is more inclined to isolate the progenitor cell population. This study presents a reliable method for isolating USMCs and provides a solid foundation for future studies on the etiology and mechanism of adenomyosis., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Conventional approaches for emergent or expedited palliative radiotherapy (RT) involve the application of cumbersome vendor-provided solutions and/or multiple patient appointments to complete the RT workflow within a compressed timeframe., Purpose: This report delineates the clinical development of an in-house, semi-automated Cone-beam computed tomography (CBCT)-based simulation-free platform for expedited palliative RT on conventional linacs, intended to supplant existing techniques employed at this institution., Methods: The internal software, termed SimFree Wizard (SFW), was engineered utilizing a C#-based application programming interface integrated within the treatment planning system (TPS). Generated scripts were compiled as stand-alone executables, with a graphical user interface (GUI) customized via an integrated development environment. The platform was conceived as a framework for accelerated CBCT-based RT, bypassing the requirement for standard simulation imaging. SFW employs full automation where feasible to minimize user intervention, supplemented by graphical instructions for tasks requiring manual execution. During development, relevant temporal metrics from 10 end-to-end tests for palliative spine RT were quantified. User feedback was solicited via a simple questionnaire assessing the overall platform usability. Automated in-house secondary verification software was developed for validation of the TPS-calculated monitor units (MUs)., Results: The mean duration for workflow execution was 41:42 ± 3:18 [mm:ss] (range ∼37-46 min). SFW satisfactorily generated simple, multi-field CBCT-based 3D treatment plans within seconds following delineation of the desired treatment area. User feedback indicated enhanced usability compared to previously employed solutions. Validation of the secondary verification software demonstrated accurate results for palliative spine RT and other simple cases wherein the dose calculation point resides in a predominantly homogenous medium., Conclusion: A novel in-house solution for expedited CBCT-based RT was successfully developed, facilitating completion of the entire workflow within approximately 1-hour or less for simple palliative/emergent scenarios. Overall, this application is expected to improve the quality and safety of palliative RT while greatly reducing workflow duration, thereby improving access to palliative care., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Different species of sea cucumbers in various regions have diverse preferred habitats and feeding habits. However, detailed research on the correlation between food selection and habitat preference of sea cucumbers, as well as their adaptive adjustments to specific habitat types, is still lacking., Methods: A field study was carried out to explore the relationship between food selection and habitat preference, as well as the adaptation process, of the tropical sea cucumber Stichopus chloronotus, which has specific food preferences. This was achieved using an in situ mesocosm method with three single habitat types: sandy, broken coral branches, and reef. Changes is the prokaryotic community structure of gut contents, revealed by high-throughput sequencing analysis of the 16S rRNA gene, were used as the biomarker. Tax4Fun assessed the metabolic pathways of samples, and FAPROTAX evaluated the biogeochemical cycling processes., Results: Alpha diversity, PCoA, and UPGMA tree analyses consistently revealed that bacterial community structures in the gut contents of S. chloronotus in reef bottom cages (GRee) are closely related to those of wild S. chloronotus collected in September (GWS) and October (GWO) than those from the sandy bottom (GSan) and broken coral branches bottom (GBra) cages. The relative abundance of Ruegeria is one of the dominant genera in the control groups (GWS and GWO), while Synechococcus CC9902 is among the predominant genera in the treatment groups (GSan, GBra and GRee). Functional prediction outcomes from Tax4Fun and FAPROTAX also indicate that the metabolic pathways in the gut contents of the treatment groups are distinct from those of the control groups., Conclusions: Compared with S. chloronotus in single habitat types, wild S. chloronotus showed stronger feeding selectivity and ingested actively larger proportion of Ruegeria sp. For this picky species, hard-substrate habitats that can keep it away from strong waves seem to be more important to than those with good sedimentary food. Inappropriate habitats without stable substrate for attachment may cause an unusual change in food preference of S. chloronotus. Tax4Fun and FAPROTAX functional annotation also confirmed that the adaptive adjustment of S. chloronotus can be completed within a month., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Our research did not involve human participants or samples. No specific permits were required for the described field studies. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)