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Ling Peng,1,2,&ast; Hong You,2,&ast; Mei-yu Xu,2 Zhou-yu Dong,2 Min Liu,2 Wen-jing Jin,2 Chao Zhou2 1Department of Critical Care Medicine, Qiannan Buyi and Miao Autonomous Prefecture People’s Hospital, Guizhou, People’s Republic of China; 2Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Zhou, Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, No. 43 DongMen Street. Pudong new District, Shanghai, 201399, People’s Republic of China, Tel +86-21-68019069, Email zhou2000sh@163.comBackground: Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD.Methods: In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD.Results: Serum lysine, glutamine, 3-hydroxybutyrate, pyruvate and glutamate levels were significantly higher, while 1-methylhistidine, isoleucine, choline, valine, alanine, histidine and leucine levels were significantly lower in AECOPD patients, compared with stable COPD patients after normalization based on the healthy controls. Moreover, eight metabolic pathways were significantly altered (P< 0.05) in the serum of AECOPD patients compared with the stable COPD population, including purine metabolism, glutamine and glutamate metabolism, arginine biosynthesis, butyrate metabolism, ketone body synthesis and degradation, and linoleic acid metabolism. In addition, the correlation analysis between metabolites and AECOPD patients demonstrated that an M-score based on a weighted sum of concentrations of four metabolites including pyruvate, isoleucine, 1-methylhistidine and glutamine were significantly associated with the acute exacerbation of pulmonary ventilation function in COPD patients.Conclusion: Altogether, the metabolite score based on a weighted sum of concentrations of four serum metabolites was associated with an increased risk of COPD developing acute exacerbation, which will provide a new insight for the understanding of COPD development.Keywords: COPD, AECOPD, acute exacerbation, metabolomics, metabolites

Restricted to the complex nature of dissolved organic matter (DOM) in various aquatic environments, the mechanisms of enhanced iodinated disinfection byproducts (I-DBPs) formation in water containing both I - and IO 3 - (designated as I - /IO 3 - in this study) during the ultraviolet (UV)-chloramine sequential disinfection process remains unclear. In this study, four machine learning (ML) models were established to predict I-DBP formation by using DOM and disinfection features as input variables. Extreme gradient boosting (XGB) algorithm outperformed the others in model development using synthetic waters and in cross-dataset generalization of surface waters. Shapley additive explanation (SHAP) analysis, partial dependence plots (PDPs), and individual conditional expectation (ICE) analysis were then employed to explain the models' workings and feature interactions, aiding in identification and quantification of underlying mechanisms. A type of DOM component (namely DC&#95;b) was found as the greatest contributor and identified as reduced quinones associated with broken-down lignin within higher plant-derived fulvic substance, serving as precursors and electron shuttles for I-DBP formation. Based on the interactional effects acquired from explanation results, the ejection of e - aq from excited DOM and pre-existing I - in the I - /IO 3 - system were identified responsible for the enhanced generation of I-DBPs compared to that in the I - or IO 3 - alone systems; extra DOM scavenged reactive iodine species (RIS), contributing to a limited enhancement. These findings and the methodology developed here together enhance our understanding of the mechanisms how DOM limitedly promotes I-DBP formation during UV-chloramine sequential disinfection of I - /IO 3 - -containing water and facilitate effective online monitoring in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Adipose tissue plays a pivotal role in systemic metabolism and maintaining bodily homeostasis. Exosomes from adipose tissues, known as AT-Exos, are recognized as important messengers in the communication between adipose tissue and other organs. Despite this, the alterations in exosome composition and the functional disparities among depot-specific AT-Exos in obesity remain elusive., Methods: In this work, we utilized lipidomics and microRNA (miRNA) sequencing to elucidate the lipid and miRNA profiles of AT-Exos in a diet-induced obesity model. We identified obesity-related miRNAs in AT-Exos and further explored their mechanisms using gain- and loss-of-function experiments. To evaluate the metabolic effects of AT-Exos on adipocytes, we conducted RNA-sequencing (RNA-seq) and confirmed our findings through Quantitative Real-time PCR (qPCR) and Western bolt analyses. Meanwhile, a mouse model with intraperitoneal injections was utilized to validate the role of exosomes derived from visceral white adipose tissue (vWAT-Exos) in obesity progression in vivo. Finally, we explored potential therapeutic intervention strategies targeting AT-Exos, particularly focusing on modulating the SIRPα-CD47 axis to enhance macrophage phagocytosis using Leptin-deficient (ob/ob) mice and SIRPα knock-out mice., Results: Our study revealed that obesity-related metabolism affects the biological processes of AT-Exos, with depot-specific secretion patterns. In obesity, the lipidome profile of AT-Exos was significantly altered, and diet can modify the miRNA content and function within these exosomes, influencing lipid metabolism and inflammatory pathways that contribute to metabolic dysregulation. Specifically, we identified that miR-200a-3p and miR-200b-3p promoted lipid accumulation in 3T3L1 cells partly through the PI3K/AKT/mTOR pathway. RNA-Seq analysis revealed that AT-Exos from different fat depots exerted distinct effects on adipocyte metabolism, with obese vWAT-Exos being notably potent in triggering inflammation and lipid accumulation in diet-induced obesity. Additionally, we found that inhibiting the SIRPα-CD47 axis can mitigate metabolic disorders induced by obese vWAT-Exos or ob/ob mice, partly due to the enhanced clearance of vWAT-Exos. Consistent with this, SIRPα-deficient mice exhibited a reduction in vWAT-Exos and displayed greater resistance to obesity., Conclusions: This study elucidates that diet-induced obesity altered the lipid and miRNA profiles of AT-Exos, which involved in modulating adipocyte inflammation and metabolic balance. The SIRPα-CD47 axis emerges as a potential therapeutic target for obesity and its associated complications., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: All authors have no conficts of interest to declare., (© 2025. The Author(s).)

Psychotropic drugs rank among the most prescribed pharmaceuticals in the world. The ubiquitous occurrence of psychotropic drugs in the environment evoked rising concerns due to their various toxic effect on non-target organisms at low concentrations. However, the removal, transformation, and discharging of these drugs throughout wastewater treatment plants (WWTPs) have rarely been reported. Based on the targeted analysis and suspected screening, this study investigated the distribution of psychotropic drugs and their transformation products (TPs) within the entire treatment processes in WWTPs and their receiving rivers. The results indicated that 13 out of 47 psychotropic drugs are widely observed across wastewater, sludge, receiving river water, and sediment, respectively. The aqueous removal efficiencies of most psychotropic drugs exhibited their significant recalcitrance in wastewater treatment processes. For instance, venlafaxine (VEL) was slightly removed by 2.64 % and 10.8 % in these two WWTPs. The concentrations of oxazepam (OZP) and lamotrigine (LMT) dramatically increased after the overall treatment processes due to their metabolic conversion and regeneration processes, respectively. Given the recalcitrance of psychotropic drugs, the identified TPs generated within WWTPs were not abundant, but a wider variety of TPs were identified from human metabolites. A total of 25 TPs were identified via the suspect screening analysis, of which nine were newly identified. In receiving rivers, the risk quotient (RQ) presented OZP, sertraline (SER), and VEL posed high potential risks; the integration of the toxicological priority index (ToxPi) and the toxicity-weighted concentration (TWC) suggested TP-CIT-322 and TP-OCX-195 as the high-priority contaminants. Given the recalcitrance and environmental risks of psychotropic drugs and their TPs in WWTPs and environments, it is crucial for the further exploration of their effective treatment technologies and emission control 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 Ltd.)

Hydroxylamine (NH 2 OH) is a key intermediate in the formation of numerous high value-added organonitrogen compounds. The traditional synthesis of NH 2 OH requires the use of precious metals under high temperature conditions, which leads to high cost, high energy consumption, and environmental pollution. The NH 2 OH-mediated cascade reaction integrates the electrochemical synthesis of NH 2 OH and the chemical synthesis of organonitrogen compounds, offering a facile, green, and efficient alternative. This review presents the recent advances on electrosynthesis of high value-added organonitrogen compounds by NH 2 OH-mediated cascade reactions. We present key concepts and the transformation process of different N-species to NH 2 OH, discuss suitable substrates and electrocatalysts, and elucidate the reaction mechanisms involved in generating compounds such as amino acids, cyclohexanone oxime, urea, amine, etc.. Finally, we address current challenges and future directions in this emerging field to encourage further research effort and the development of NH 2 OH-mediated cascade reaction., (© 2025 Wiley-VCH GmbH.)

Radical prostatectomy with pelvic lymph node dissection is the best treatment for intermediate- to high-risk localized prostate cancer (PCa). However, conventional white light surgery has difficulties in identifying tumor boundary and micrometastases intraoperatively. Fluorescence guided surgery (FGS) can solve the above difficulties, but lacks tumor-specific near-infrared fluorescent (NIRF) probes in PCa. STEAP1 was an ideal target in PCa treatment and imaging. Here, we constructed a PCa specific fluorescent probe based on extracellular vesicles targeting STEAP1 (AS-EVs) loaded with NIRF dye S0456 and evaluated its preclinical profiles. In vitro and in vivo studies both showed S0456@AS-EVs was safe and showed strong targeting ability to PCa in various mice xenograft models. S0456@AS-EVs could clear rapidly from blood (half-time of 4.29 h) and retain in the STEAP1 positive tumor tissues for more than 72 h with the highest tumor background ratio (TBR) of 3:1, which was superior to ICG, free S0456, ICG@Ctrl-EVs and S0456@Ctrl-EVs (p < 0.01). Finally, S0456@AS-EVs was applied in FGS on intramuscular model, and the tumors were resected under white light and fluorescence respectively. Compared with white light surgery, mice undergoing FGS had lower positive margin rate and better postoperative survival (p = 0.0342)., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Background: Post-operative recurrence for patients with intermediate and high-risk non-muscular invasive bladder cancer (NMIBC) is common. This study aims to evaluate the potential factors of tumor recurrence, and construct a novel nomogram to predict the probability of tumor recurrence., Methods: We retrospectively enrolled patients with intermediate and high-risk NMIBC who received thulium laser resection of bladder tumors (TmLRBT) or transurethral resection of the bladder tumor (TURBT) followed by intravesical bacille Calmette-Guérin (BCG) immunotherapy. The risk factors were screened by the least absolute shrinkage and selection operator (LASSO) regression method. And multivariate logistic regression was applied to recognize the independent risk factors of bladder cancer recurrence. A nomogram was established, and the recurrence probability was calculated based on the model scores., Results: A total of 90 patients with intermediate and high-risk NMIBC were included in this study, of whom 53 underwent TURBT and 37 underwent TmLRBT. During the follow-up period, 22 patients (24.4%) experienced bladder cancer recurrence. Three variables were screened out in the LASSO regression. The multivariate logistic analysis suggested that surgery of TURBT [odds ratio (OR) =6.86760; 95% confidence interval (CI): 1.5048-31.34300] and previous bladder tumor (OR =14.73600; 95% CI: 2.81180-77.23000) were independent risk factors of recurrence, while more BCG treatment sessions (OR =0.26504; 95% CI: 0.12455-0.56398) was independent protective factor of recurrence., Conclusions: Patients with TURBT and previous bladder tumor history were more likely to develop recurrent bladder cancer, while more BCG treatment sessions was independent protective factor of recurrence., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-535/coif). The authors have no conflicts of interest to declare., (Copyright © 2025 AME Publishing Company. All rights reserved.)

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO&#95;4·2H&#95;2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO&#95;4·2H&#95;2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO&#95;4·2H&#95;2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO&#95;4·2H&#95;2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO&#95;4·2H&#95;2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO&#95;4·2H&#95;2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO&#95;4·2H&#95;2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO&#95;4·2H&#95;2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO&#95;4·2H&#95;2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO&#95;4·2H&#95;2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO&#95;4·2H&#95;2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO&#95;4·2H&#95;2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.

In this study, we reported a new approach to activate the C-F bond of trifluoromethylarenes to achieve the hydro-difluoroalkylation of arylethylenes using photoexcited Hantzsch esters (HEs) anions. A wide range of α,α-difluoroalkanes was synthesized. Late-stage functionalization of drug molecules and synthesis of bioactive molecule bioisostere were also presented. Mechanistic studies revealed that the dual-single electron transfer (SET) process of HEs anion was the key to this reaction., (© 2024 Wiley-VCH GmbH.)

Background: Cholesterol metabolism is essential for the development and progression of prostate cancer (PCa). Our previous study provided a new insight of cholesterol metabolism in the systematic management of PCa. However, the comprehensive role of cholesterol metabolism in PCa remains unclear., Methods: Using the cholesterol metabolism related genes (CMRGs) downloaded from the MSigDB database, and gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a cholesterol risk index by the least absolute shrinkage and selection operator (LASSO) model, and correlated the risk index with prognosis, tumor mutation burden (TMB), tumor microenvironment (TME) infiltration and response to chemotherapy and immunotherapy. RT-qPCR, western blot, immunohistochemistry, cell proliferation assays by CCK-8 and EdU assays, and cell apoptosis assays by flow cytometry analysis were also performed., Results: We found PCa was tightly correlated with the cholesterol metabolism pathways. The cholesterol risk index was an excellent and independent predictor of prognosis for PCa. A nomogram involving the risk index and other clinical factors (age, T stage) was established to explore the clinical value of risk index. We found high-risk index group was associated with worse prognosis, higher TMB, lower infiltration level of CD8 + T cells and a worse response to chemotherapy and immunotherapy. RT-qPCR, western blot and immunohistochemical staining validated the expression level of important CMRGs in PCa. In vitro experiments revealed downregulation of cholesterol metabolism could inhibit the proliferation of PCa cells and promoted their apoptosis., Conclusions: We demonstrated the comprehensive role of cholesterol metabolism in PCa. Using the risk index, we could predict the prognosis, TME infiltration and response to chemotherapy/immunotherapy of PCa. Better understanding and evaluating the cholesterol metabolism could aid in precision medicine and promoting prognosis of PCa., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Metal-organic frameworks (MOFs) are promising catalysts for the electrochemical oxygen evolution reaction (OER) due to their high surface area, tunable pore structures, and abundant active sites. Ligand engineering is an important strategy to optimize their performance. Here, we report the synthesis of NiFe-MOFs based on three different ligands: 1,4-terephthalic acid (BDC), 2,4-thiophene dicarboxylic acid (TDC), and 2,5-furandicarboxylic acid (FDC), to investigate the effects of heteroatom-based aromatic rings on OER performance. It is revealed that by incorporating electronegative sulfur and oxygen atoms into the ligands, the electron density at the metal sites is reduced, leading to enhanced metal-oxygen covalency and improved charge transfer kinetics. The NiFe-FDC/NF catalyst demonstrates an overpotential of 189 mV at 10 mA·cm-2 and stable performance over 1300 hours at 1 A·cm-2. In situ infrared spectroscopy reveal minimal structural reconstruction in NiFe-FDC/NF, contributing to its superior stability. The NiFe-FDC/NF were then subjected to 3600 hours of OER operation and it's metal elution was monitored. These findings offer a novel approach to ligand design for high-performance MOF-based OER catalysts, highlighting the potential of furan-based ligands for MOF ligand engineering., (© 2024 Wiley‐VCH GmbH.)

Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence., Competing Interests: Declaration of Competing Interest All authors declare no financial and personal relationships., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Since silver nanoparticles (AgNPs) and polystyrene microplastics (PS-MP) share common environmental niches, their interactions can modulate their hazard impacts. Herein, we assessed the developmental toxicity of 1 mg/L PS-MP, 0.5 mg/L AgNPs and the mixtures of AgNPs and PS-MP on embryo-larval zebrafish. We found that AgNPs co-exposure with PS-MP remarkably decreased mortality rates, malformation rates, heart rates and yolk sac area, while it increased hatching rates and eye size compared to the AgNPs group. These phenomena revealed that the cell cycle, oxidative stress, apoptosis, lipid metabolism, ferroptosis and p53 signalling pathway were obviously affected by single AgNPs exposure at 96 hpf (hours post fertilization). Interestingly, all these effects were effectively ameliorated by co-exposure with PS-MP. The combination of transcriptomic and metabolomic analyses showed that the imbalance of DEGs (differentially expressed genes) and DEMs (differentially expressed metabolites) (PI, phosphatidylinositol and TAG-FA, triacylglycerol-fatty acid) disturbed both the cell cycle and lipid metabolism following single AgNPs exposure and co-exposure with PS-MP. These findings suggest that PS-MP attenuates the developmental toxicity of AgNPs on embryo-larval zebrafish. Overall, this study provides important insight into understanding the transcriptional responses and mechanisms of AgNPs alone or in combination with PS-MPs on embryo-larval zebrafish, providing a reference for ecological risk assessment of combined exposure to PS-MP and metal nanoparticles., 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.)

Background . Fatty acids are essential components in breast milk with mutable characteristics. The fatty acid profiles of breast milk varied with lactating women's intake of long-chain polyunsaturated fatty acids (LCPUFAs) including DHA, EPA, and ALA. Objective . This study aimed to investigate the correlation between dietary n-3 PUFA supplementation and the hourly variation of the fatty acid compositions in breast milk. Materials and methods . The fatty acid profiles were analyzed in 600 human milk samples from 8 hospitals in 8 different Chinese areas. Blood and breast milk samples were obtained from a group of seventy-five lactating mothers, all within 6 to 9 months postpartum. Each mother collected 8 dried milk samples (DMSs) within 2 days: half an hour before breakfast; 2 and 3 hours after breakfast every day; and 2 and 3 hours after lunch on day 1. One fingertip blood sample was collected 10 minutes before the breakfast on the first day. The mothers took supplements containing about 3 grams of n-3 PUFAs at 10 minutes before the breakfast on day 2. Results . (1) In breast milk, oleic acid (C18:1n9c, OA) was the most abundant fatty acid (35.55%) followed by C18:2n6c (linoleic acid, LA, 24.45%); (2) the breast milk DHA of the inland participants (0.26%) was lower than that from coastal participants (0.57%), but compensated with much higher ALA (inland 3.19% vs. coastal 2.21%), and thus provided higher total milk n-3 PUFAs (inland 3.88% vs. coastal 3.28%); (3) the breast milk EPA and DHA increased from the baseline (EPA 0.17% and DHA 0.44%) after supplementation in 2 hours (EPA 0.18% and DHA 0.44%) and 3 hours (EPA 0.19% and DHA 0.46%). Conclusions . Dietary supplementation of n-3 PUFAs had an immediate impact on the breast milk fatty acid composition. The concentration of ALA, LA and OA was strengthened in breast milk compared to that in maternal blood.

Proteolysis Targeting Chimera (PROTAC) is an emerging and evolving technology based on targeted protein degradation (TPD). Small molecule PROTACs have shown great efficacy in degrading disease-specific proteins in preclinical and clinical studies, but also showed various limitations. In recent years, new technologies and advances in TPD have provided additional optimized strategies based on conventional PROTACs that can overcome the shortcomings of conventional PROTACs in terms of undruggable targets, bioavailability, tissue-specificity, spatiotemporal control, and degradation scope. In addition, some designs of special targeting chimeras and applications based on multidisciplinary science have shed light on novel therapeutic modalities and drug design. However, each improvement has its own advantages, disadvantages and application conditions. In this review, we summarize the exploration of PROTAC elements, depict a landscape of improvements and derived concepts of PROTACs, and expect to provide perspectives for technological innovations, combinations and applications in future targeting chimera design., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE -/- ) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg -1 ·d -1 , i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 μM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE -/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Taste and odor (T&O) are among the most frequently encountered aesthetic issues in drinking water. While fungi have been reported to produce offensive odors, their contribution to T&O in drinking water remains understudied and often overlooked. In this study, the profiles of fungal community and odorants produced by 10 native fungal isolates were investigated in 36 samples collected from two drinking water treatment plants and a premise plumbing system. A total of 17 odorants were identified with Penicillium , Aspergillus , Paecilomyces , and Alternaria genera exhibiting the highest odorant yields. Significant concentrations of musty/earthy compounds were produced by these fungal isolates, such as 2-methylisoborneol (2-MIB) (26-256 ng/L), geosmin (10-13 ng/L), and 2-isobutyl-3-methoxy-pyrazine (IBMP) (3-13 ng/L). The high odor activity value of the odorants primarily occurred within 4 d, while toxicity continued to increase during the 8 d incubation. UV treatment in premise plumbing significantly ( p < 0.05) reduced the gene read counts of Ascomycota phylum, Aspergillus spp., Fusarium spp., Rhizopus spp., and Trichoderma spp., by 2.3-4.0 times. These findings underscore the previously underestimated role of fungi in contributing to T&O issues in drinking water and corresponding risks to consumers and indicate UV as a promising strategy for fungal control in drinking water.

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment., (© 2024. The Author(s).)

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI 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 © 2024 Elsevier B.V. All rights reserved.)

As robot-assisted laparoscopic techniques continue to advance, becoming increasingly complex and refined, there has been significant progress in the minimally invasive treatment of ureteral strictures. This abstract aims to provide an overview and description of various surgical techniques that utilize robots for repairing ureteral strictures. We have summarized the progression of these surgical methods and highlighted the latest advancements in the procedures. When compared to open surgery, robot-assisted reconstruction techniques demonstrate superior functional outcomes, fewer postoperative complications, and a faster recovery in the treatment of ureteral strictures. This abstract aims to provide an overview and description of various surgical techniques utilizing robots to repair ureteral strictures. Robotic ureteral stricture correction has emerged as a valuable therapeutic option, particularly when endoscopic procedures are not feasible. Compared to traditional open surgery, robotic methods exhibit superior therapeutic effectiveness, fewer postoperative complications, and accelerated recovery. Reconstructive procedures such as reimplantation, psoas hitch, Boari flap, ureter-to-ureter anastomosis, appendix graft, buccal mucosa graft (BMG), ileal transplantation, or kidney autotransplantation can be performed depending on the extent and location of the stricture. Robotic surgical techniques also offer advantages, such as an expanded field of vision and the incorporation of supplementary technologies such as FireflyTM, indocyanine green (ICG), and near-infrared fluorescence (NIRF) imaging. However, further long-term, multicenter investigations are necessary to validate the positive findings reported in existing case series. Compared with open surgery, robot-assisted reconstruction techniques yield superior functional outcomes, fewer postoperative complications, and accelerated recovery for the treatment of ureteral strictures., (© 2024. The Author(s).)

Background: Due to frequent and high-risk sports activities, the elbow joint is susceptible to injury, especially to cartilage tissue, which can cause pain, limited movement and even loss of joint function., Aim: To evaluate magnetic resonance imaging (MRI) multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury., Methods: A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study. We analyzed the accuracy of conventional MRI sequences (T1-weighted imaging, T2-weighted imaging, proton density weighted imaging, and T2 star weighted image) and Three-Dimensional Coronary Imaging by Spiral Scanning (3D-CISS) in the diagnosis of elbow cartilage injury. Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy., Results: The diagnostic accuracy of 3D-CISS sequence was 89.34% ± 4.98%, the sensitivity was 90%, and the specificity was 88.33%, which showed the best performance among all sequences ( P < 0.05). The combined application of the whole sequence had the highest accuracy in all sequence combinations, the accuracy of mild injury was 91.30%, the accuracy of moderate injury was 96.15%, and the accuracy of severe injury was 93.33% ( P < 0.05). Compared with arthroscopy, the combination of all MRI sequences had the highest consistency of 91.67%, and the kappa value reached 0.890 ( P < 0.001)., Conclusion: Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults. Multisequence MRI is recommended to ensure the best diagnosis and treatment., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Bioelectrochemical reactions using whole-cell biocatalysts are promising carbon-neutral approaches because of their easy operation, low cost, and sustainability. Bidirectional (outward or inward) electron transfer via exoelectrogens plays the main role in driving bioelectrochemical reactions. However, the low electron transfer efficiency seriously inhibits bioelectrochemical reaction kinetics. Here, a three dimensional and artificial nanoparticles-constituent inverse opal-indium tin oxide (IO-ITO) electrode is fabricated and employed to connect with exoelectrogens (Shewanella loihica PV-4). The above electrode collected 128-fold higher cell density and exhibited a maximum current output approaching 1.5 mA cm -2 within 24 h at anode mode. By changing the IO-ITO electrode to cathode mode, the exoelectrogens exhibited the attractive ability of extracellular electron uptake to reduce fumarate and 16 times higher reverse current than the commercial carbon electrode. Notably, Fe-containing oxide nanoparticles are biologically synthesized at both sides of the outer cell membrane and probably contributed to direct electron transfer with the transmembrane c-type cytochromes. Owing to the efficient electron exchange via artificial and biosynthetic nanoparticles, bioelectrochemical CO 2 reduction is also realized at the cathode. This work not only explored the possibility of augmenting bidirectional electron transfer but also provided a new strategy to boost bioelectrochemical reactions by introducing biohybrid nanoparticles., (© 2024 Wiley‐VCH GmbH.)

Bidirectional electron transfer is about that exoelectrogens produce bioelectricity via extracellular electron transfer at anode and drive cytoplasmic biochemical reactions via extracellular electron uptake at cathode. The key factor to determine above bioelectrochemical performances is the electron transfer efficiency under biocompatible abiotic/biotic interface. Here, a graphene/polyaniline (GO/PANI) nanocomposite electrode specially interfacing exoelectrogens (Shewanella loihica) and augmenting bidirectional electron transfer was conducted by in-situ electrochemical modification on carbon paper (CP). Impressively, the GO/PANI@CP electrode tremendously improved the performance of exoelectrogens at anode for wastewater treatment and bioelectricity generation (about 54 folds increase of power density compared to blank CP electrode). The bacteria on electrode surface not only showed fast electron release but also exhibited high electricity density of extracellular electron uptake through the proposed direct electron transfer pathway. Thus, the cathode applications of microbial electrosynthesis and bio-denitrification were developed via GO/PANI@CP electrode, which assisted the close contact between microbial outer-membrane cytochromes and nanocomposite electrode for efficient nitrate removal (0.333 mM/h). Overall, nanocomposite modified electrode with biocompatible interfaces has great potential to enhance bioelectrochemical reactions with exoelectrogens., 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.)

Iodinated X-ray contrast media (ICM) are ubiquitously present in water sources and challenging to eliminate using conventional processes, posing a significant risk to aquatic ecosystems. Ultraviolet light-emitting diodes (UV-LED) emerge as a promising technology for transforming micropollutants in water, boasting advantages such as diverse wavelengths, elimination of chemical additives, and no induction of microorganisms' resistance to disinfectants. The research reveals that iohexol (IOX) degradation escalates as UV wavelength decreases, attributed to enhanced photon utilization efficiency. Pseudo-first-order rate constants (k obs ) were determined as 3.70, 2.60, 1.31 and 0.65 cm 2 J -1 at UV-LED wavelengths of 255, 265, 275 and 285 nm, respectively. The optical properties of dissolved organic matter (DOM) and anions undeniably influence the UV-LED photolysis process through photon competition and the generation of reactive substances. The influence of Cl - on IOX degradation was insignificant at UV-LED 255, but it promoted IOX degradation at 265, 275 and 285 nm. IOX degradation was accelerated by ClO 2 - , NO 3 - and HA due to the formation of various reactive species. In the presence of NO 3 - , the k obs of IOX followed the order: 265 > 255 > 275 > 285 nm. Photosensitizers altered the spectral dependence of IOX, and the intermediate photoactivity products were detected using electron spin resonance. The transformation pathways of IOX were determined through density functional theory calculations and experiments. Disinfection by-products (DBPs) yields of IOX during UV-LED irradiation decreased as the wavelength increased: 255 > 265 > 275 > 285 nm. The cytotoxicity index value decreased as the UV-LED wavelength increased from 255 to 285 nm. These findings are crucial for selecting the most efficient wavelength for UV-LED degradation of ICM and will benefit future water purification design., 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 Ltd.)

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa., Method: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis., Results: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots., Conclusion: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8 + T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study., (© 2024. The Author(s).)

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy., (© 2024. The Author(s).)

Aim: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status., Methods: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K 1 , K 2 ) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups., Results: Both SE and AL were greater in the LCC group ( P =0.013, P <0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group ( P <0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P <0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group., Conclusion: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia., Competing Interests: Conflicts of Interest: He SY, None; He T, None; Xu MY, None; Ni YJ, None; Hong CY, None; Shen T, None., (International Journal of Ophthalmology Press.)

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes., 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 © 2024 Xu, Xia, Sun, Liu, An, Xu, Zhang, Zhong, Zeng, Ma, He, Wang and Xia.)

In this study, a series of enantioenriched sp 3 -Ge/B bimetallic modules were successfully synthesized via an enantioselective copper-catalyzed hydroboration of carbagermatrane (Ge)-containing alkenes. Orthogonal cross-coupling selectivity under different Pd-catalyzed conditions was achieved in an enantiospecific manner. Notably, the chiral secondary Ge exhibited a remarkable transmetallation ability prior to primary or secondary Bpin. The effectiveness of this Ge/B bimetallic strategy was further demonstrated through the development of new functional small molecules with Aggregation-Induced Emission (AIE) and Circularly Polarized Luminescence (CPL) performance. This represents the first successful example of synthesis of enantioenriched alkylgermanium reagents that permit enantiospecific cross-coupling reactions., (© 2024 Wiley‐VCH GmbH.)

The efficient removal of 2-Methylisoborneol (2-MIB), a typical odour component, in water treatment plants (WTPs), poses a great challenge to conventional water treatment technology due to its chemical stability. In this study, the combination of ultraviolet light-emitting diode (UV-LED) and chlorine (UV-LED/chlorine) was exploited for 2-MIB removal, and the role of ultraviolet (UV) wavelength was investigated systematically. The results showed that UV or chlorination alone did not degrade 2-MIB effectively, and the UV/chlorine process could degrade 2-MIB efficiently, following the pseudo-first-order kinetic model. The 275 nm UV exhibited higher 2-MIB degradation efficiency in this UV-LED/chlorine system than 254 nm UV, 265 nm UV and 285 nm UV due to the highest mole adsorption coefficient and quantum yield of chlorine in 275 nm UV. ·OH and ·Cl produced in the 275 nm UV/chlorine system played major roles in 2-MIB degradation. HCO 3 - and Natural organic matter (NOM), prevalent in water, consumed ·OH and ·Cl, thus inhibiting the 2-MIB degradation by UV-LED/chlorine. In addition, NOM and 2-MIB could form a photonic competition effect. The degradation of 2-MIB by UV-LED/chlorine was done mainly through dehydration and demethylation, and odorous intermediates, such as camphor, were produced. 2-MIB was degraded through the α bond fracture and six-membered ring opening to form saturated or unsaturated hydrocarbons and aldehydes. Four DBPs, chloroform (CF), trichloroacetaldehyde (TCE), trichloroacetone (TCP) and dichloroacetone (DCP), were mainly generated, and CF was the most significant by-product.

Aim: To understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH)., Methods: We profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit + -LSECs were determined using coculture and bone marrow transplantation (BMT) methods., Results: Three special clusters of single-LSEC were differentiated. C-Kit + -LSECs of cluster 0, Msr1 + -LSECs of cluster 1 and Bmp4 + Selp + -VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH. The number of C-Kit + -primary LSECs isolated from MCD mice was lower than control mice. Immunofluorescence co-staining of CD31 and C-KIT showed C-Kit + -LSECs located in hepatic sinusoid were also reduced in NASH patients and MCD mice, compared to AIH patients and control mice respectively. Interestingly, lipotoxic hepatocytes/HSCs cocultured with C-Kit + -LSECs or the livers of MCD mice receipting of C-Kit + -BMCs (bone marrow cells) showed less steatosis, inflammation and fibrosis, higher expression of prolipolytic FXR and PPAR-α, lower expression of TNF-α and α-SMA. Furthermore, coculturing or BMT of C-Kit + -endothelial derived cells could increase the levels of hepatic mitochondrial LC3B, decrease the degree of mitochondrial damage and ROS production through activating Pink1-mediated mitophagy pathway in NASH., Conclusions: Hence, a novel transcriptomic view of LSECs was revealed to have heterogeneity and complexity in NASH. Importantly, a cluster of C-Kit + -LSECs was confirmed to recovery Pink1-related mitophagy and NASH progression., (© 2024. The Author(s).)

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM 2.5 were analyzed in Xinxiang city, Henan Province. PM 2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM 2.5 . The average seasonal concentrations of WSIIs ranged from 19.62-72.15 μg·m -3 , accounting for more than 60% of PM 2.5 , demonstrating that WSIIs were the major components of PM 2.5 . The annual concentration value of NO 3 - /SO 4 2- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH 4 + ]/[NO 3 - ] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca 2+ and Mg 2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity ( T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures ( T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH 4 NO 3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status., (© 2024. The Author(s).)

Pre-oxidation and powdered activate carbon (PAC) are usually used to remove algae and odorants in drinking waterworks. However, the influence of interaction between oxidants and PAC on the treatment performance are scarcely known. This study systematically investigated the combination schemes of four oxidants (KMnO 4 , NaClO, ClO 2 , and O 3 ) and PAC on the inactivation of Microcystis aeruginosa cells and removal of four frequently detected odorants in raw water (diethyl disulfide (DEDS), 2,2'-oxybis(1chloropropane) (DCIP), 2-methylisoborneol (2-MIB) and geosmin (GSM)). O 3 showed highest pseudo-first-order removal rate for all four compounds and NaClO exhibited highest inactivation rates for the cell viability and Chlorophyll a (Chl-a). The Freundlich model fitted well for the adsorption of DEDS and DCIP by PAC. When treated by combined oxidation/PAC, the removal ratio of algae cells and odorants were lower (at least 1.6 times) than the sum of removal ratios obtained in oxidation or PAC adsorption alone. Among these four oxidants, the highest synchronous control efficiency of odorants (52 %) and algae (66 %) was achieved by NaClO/PAC. Prolonging the dosage time interval promoted the removal rates. The pre-PAC/post-oxidation processes possessed comparable efficiency for the removal of odorants and algae cells comparing with pre-oxidation/post-PAC process, but significantly inhibited formation of disinfection byproducts (DBPs), especially for the formation of C-DBPs (for NaClO and ClO 2 ), bromate (for O 3 ) and chlorate/chlorite (for ClO 2 ). This study could provide a better understanding of improving in-situ operation of the combined pre-treatments of oxidation and PAC for source water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The causative implications remain ambiguous. Consequently, this study aims to evaluate the putative causal relationship between gut microbiota and Esophageal cancer (EC)., Methods: The genome-wide association study (GWAS) pertaining to the microbiome, derived from the MiBioGen consortium-which consolidates 18,340 samples across 24 population-based cohorts-was utilized as the exposure dataset. Employing the GWAS summary statistics specific to EC patients sourced from the GWAS Catalog and leveraging the two-sample Mendelian randomization (MR) methodology, the principal analytical method applied was the inverse variance weighted (IVW) technique. Cochran's Q statistic was utilized to discern heterogeneity inherent in the data set. Subsequently, a reverse MR analysis was executed., Results: Findings derived from the IVW technique elucidated that the Family Porphyromonadaceae (P = 0.048) and Genus Candidatus Soleaferrea (P = 0.048) function as deterrents against EC development. In contrast, the Genus Catenibacterium (P = 0.044), Genus Eubacterium coprostanoligenes group (P = 0.038), Genus Marvinbryantia (P = 0.049), Genus Ruminococcaceae UCG010 (P = 0.034), Genus Ruminococcus1 (P = 0.047), and Genus Sutterella (P = 0.012) emerged as prospective risk contributors for EC. To assess reverse causal effect, we used EC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between EC and seven different types of gut microbiota. The robustness of the MR findings was substantiated through comprehensive heterogeneity and pleiotropy evaluations., Conclusions: This research identified certain microbial taxa as either protective or detrimental elements for EC, potentially offering valuable biomarkers for asymptomatic diagnosis and prospective therapeutic interventions for EC.

Objective: To study the complete genome characterization of Human Astrovirus (HAstV) in Shandong Province. Methods: Stool samples from acute flaccid paralysis (AFP) surveillance in Shandong Province from 2020 to 2022 were collected, and HAstV nucleic acid was examined by real-time quantitative PCR (qPCR). Next-generation sequencing (NGS) was conducted for the positive samples to obtain complete genome sequences and identify the genotype. Homology comparison and phylogenetic analysis were performed by using BioEdit and Mega software. Results: A total of 667 samples were examined by qPCR, of which 14 were HAstV-positive (2.1%), including HAstV-1 ( n =6), MLB1 ( n =6), MLB2 ( n =1), and VA2 ( n =1). The complete genome sequences were obtained from 11 samples. The six HAstV-1 sequences of this study had 98.2% to 99.9% nt similarities with each other and 87.6% to 98.6% with those from other regions. The four MLB1 sequences of this study had 99.1% to 99.9% nt similarities with each other and 92.2% to 99.4% with those from other regions. The VA2 sequence of this study had 96.0% to 96.3% nt similarities with those from other regions. Phylogenetic analysis based on ORF2 region showed that the local HAstV-1 sequences were most closely related to Japanese strains, and had distinct topology with phylogenies based on ORF1a and ORF1b regions. Conclusion: The complete genome sequences of 11 HAstV strains are obtained, and the VA2 complete genome is found.