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Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment,illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis.

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Objective: To observe the intervention effect of comprehensive psychological interventions on the mental health of the elderly population. Methods: 133 elderly aged 60 and above in two urban districts of Tianshui City from January 2020 to December 2020 were selected and divided into the intervention group (n=67) and the control group (n=66). The intervention group received comprehensive psychological interventions, with no intervention given to the control group. The anxiety rate, depression rate, loneliness rate and happiness rate of the two groups were collected and compared pre- and post-intervention. Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), University of California, Los Angeles Loneliness Scale (UCLA) and Memorial University of Newfoundland Scale of Happiness (MUNSH) were used to compare the psychological status of the elderly pre- and post-intervention. Results: Differences in the inter-group main effects and time-point main effects for SAS, SDS, UCLA, and MUNSH scores of the intervention group were significant (all p<0.05). The SAS, SDS, and UCLA scores of the intervention group were higher than those of the control group after intervention. Meanwhile, the SAS and SDS scores of the intervention group were lower than those of the control group after intervention (all p<0.05). Moreover, the MUNSH score of the intervention group was higher than that of the control group at 1-year follow-up post-intervention (p<0.05). Compared with pre-intervention values, the proportions of anxiety, depression loneliness, and happiness in the intervention group were improved at 1-year follow-up post-intervention (all P<0.05). Conclusion: This study provides basis and important support for further investigations and the monitoring of health indicators in a population as fragile as the elderly. Targeted comprehensive psychological interventions can improve the negative emotions of community-dwelling elderly and maintain their physical and mental health. The "community-hospital linkage" mental health service model can improve the mental health status of community-dwelling elderly.

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Forests, the largest terrestrial carbon sinks, play an important role in carbon sequestration and climate change mitigation. Although forest attributes and environmental factors have been shown to impact aboveground biomass, their influence on biomass stocks in species-rich forests in southern China, a biodiversity hotspot, has rarely been investigated. In this study, we characterized the effects of environmental factors, forest structure, and species diversity on aboveground biomass stocks of 30 plots (1 ha each) in natural forests located within seven nature reserves distributed across subtropical and marginal tropical zones in Guangxi, China. Our results indicate that forest aboveground biomass stocks in this region are lower than those in mature tropical and subtropical forests in other regions. Furthermore, we found that aboveground biomass was positively correlated with stand age, mean annual precipitation, elevation, structural attributes and species richness, although not with species evenness. When we compared stands with the same basal area, we found that aboveground biomass stock was higher in communities with a higher coefficient of variation of diameter at breast height. These findings highlight the importance of maintaining forest structural diversity and species richness to promote aboveground biomass accumulation and reveal the potential impacts of precipitation changes resulting from climate warming on the ecosystem services of subtropical and northern tropical forests in China. Notably, many natural forests in southern China are not fully stocked. Therefore, their continued growth will increase their carbon storage over time.

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Purpose: The aim of this study is to explore the interrelationships among body image perception, levels of psychological distress, and the quality of life (QOL) experienced by young breast cancer patients. Methods: This study analyzed data from 339 young female breast cancer patients aged between 18 and 40 years (mean age was 33.47 years) from August 2023 to February 2024. Data on demographic characteristics, psychological distress, body image, medical coping, and QOL of young breast cancer patients were collected. Psychological distress, body image, medical coping, and QOL were measured using the Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), Body Image Scale (BIS), Medical Coping Modes Questionnaire (MCMQ), and Functional Assessment of Cancer Therapy-Breast (FACT-B), respectively. Multiple regression analysis was conducted to examine factors influencing QOL. Results: After adjusting for covariates, significant predictors of QOL in young survivors included psychological distress (ß = -3.125; p = 0.002), anxiety and depression (ß = -4.31; p < 0.001), cognitive dimension of body image (ß = -0.218; p = 0.027), behavioral dimension of body image (ß = 0.579; p = 0.047), and confrontational dimension of medical coping (ß = -0.124; p = 0.01). Conclusion: The findings suggest that higher levels of body image concerns and psychological distress are associated with poorer QOL among young female breast cancer patients. Furthermore, breast cancer patients facing with more positive medical coping strategies predicted a higher QOL.

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Contaminants of emerging concern (CECs) in aquatic environments can adversely impact ecosystems and human health even at low concentrations. This study assessed the risk of 162 CECs, including neonicotinoid pesticides, triazine pesticides, carbamate pesticides, psychoactive substances, organophosphate esters, antidepressants, per- and polyfluoroalkyl substances, and antibiotics in 10 drinking water sources and two tributaries (Jialing and Wujiang Rivers) of the Upper Yangtze River in Chongqing, China. Target screening detected 156 CECs at 0.01-2218.2 ng/L, while suspect screening via LC-QTOF-MS identified 64 CECs, with 13 pesticides, 29 pharmaceuticals and personal care products, and 2 industrial chemicals reported for the first time in the Yangtze River Basin. Risk quotient-based ecological risk assessment revealed that 48 CECs posed medium to high risks (RQ > 0.1) to aquatic life, with antibiotics (n = 20) as the main contributors. Non-carcinogenic risks were below negligible levels, but carcinogenic risks from neonicotinoids, triazines, antidepressants, and antibiotics were concerning. A multi-criteria prioritization approach integrating occurrence, physico-chemical properties, and toxicological data ranked 26 CECs as high priority. This study underscores the importance of comprehensive CEC screening in rivers and provides insights for future monitoring and management strategies.

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In this study, we redefine the diagnostic landscape of diabetic ulcers (DUs), a major diabetes complication. Our research uncovers new biomarkers linked to immunogenic cell death (ICD) in DUs by utilizing RNA-sequencing data of Gene Expression Omnibus (GEO) analysis combined with a comprehensive database interrogation. Employing a random forest algorithm, we have developed a diagnostic model that demonstrates improved accuracy in distinguishing DUs from normal tissue, with satisfactory results from ROC analysis. Beyond mere diagnosis, our model categorizes DUs into novel molecular classifications, which may enhance our comprehension of their underlying pathophysiology. This study bridges the gap between molecular insights and clinical practice. It sets the stage for transformative strategies in DUs management, marking a significant step forward in personalized medicine for diabetic patients.

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Interleukin-15 (IL-15) was identified in 1994 as a T-cell growth factor with the capability to mimic the functions of IL-2. IL-15 engages with the IL-15Rα subunit expressed on the surface of antigen-presenting cells (APCs) and, through a trans-presentation mechanism, activates the IL-2/IL-15Rßγ complex receptor on the surface of natural killer (NK) cells and CD8+ T cells. This interaction initiates a cascade of downstream signaling pathways, playing a pivotal role in the activation, proliferation, and anti-apoptotic processes in NK cells, CD8+ T cells, and B cells. It provides a substantial theoretical foundation and potential therapeutic targets for tumor immunotherapy. Whether through active or passive immunotherapeutic strategies, IL-15 has emerged as a critical molecule for stimulating anti-tumor cell proliferation.

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BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

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The versatile applications of 5-aminolevulinic acid (5-ALA) across the fields of agriculture, livestock, and medicine necessitate a cost-efficient biomanufacturing process. In this study, we achieved the economic viability of biomanufacturing this compound through a systematic engineering framework. First, we obtained a 5-ALA synthase (ALAS) with superior performance by exploring its natural diversity with divergent evolution. Subsequently, using a genome-scale model, we identified and modified four key targets from distinct pathways in Escherichia coli, resulting in a final enhancement of 5-ALA titers up to 21.82 g/l in a 5-l bioreactor. Furthermore, recognizing that an imbalance of redox equivalents hindered further titer improvement, we developed a dynamic control system that effectively balances redox status and carbon flux. Ultimately, we collaboratively optimized the artificial redox homeostasis system at the transcription level with other cofactors at the feeding level, demonstrating the highest recorded performance to date with a titer of 63.39 g/l for the biomanufacturing of 5-ALA.

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Neuroinflammation has been considered involved in the process of cerebral ischemia-reperfusion injury (CIRI). Transcription factors play a crucial role in regulating gene transcription and the expressions of specific proteins during the progression of various neurological diseases. Evidence showed that transcription factor nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as Nrf1) possessed strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in CIRI remain unclear. In our study, we observed a significant elevation of Nrf1 in the cerebral cortex following cerebral ischemia-reperfusion in rats. The Nrf1 downregulation markedly raised COX-2, TNF-α, IL-1ß, and IL-6 protein levels during middle cerebral artery occlusion/reperfusion in rats, which led to worsened neurological deficits, higher cerebral infarct volume, and intensified cortical histopathological damage. In subsequent in vitro studies, the expression of Nrf1 protein increased following oxygen-glucose deprivation/reperfusion treatment on neurons. Subsequently, Nrf1 knockdown resulted in a significant upregulation of inflammatory factors, leading to a substantial increase in the cell death rate. Through analyzing the alterations in the expression of inflammatory factors under diverse interventions, it is indicated that Nrf1 possesses the capacity to discern variations in inflammatory factors via specific structural domains. Our findings demonstrate the translocation of the Nrf1 protein from the cytoplasm to the nucleus, thereby modulating the protein expression of IL-6/TNF-α and subsequently reducing the expression of multiple inflammatory factors. This study signifies, for the first time, that during cerebral ischemia-reperfusion, Nrf1 translocases to the nucleus to regulate the protein expression of IL-6/TNF-α, consequently suppressing COX-2 expression and governing cellular inflammation, ultimately upholding cellular homeostasis.

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Deoxynivalenol (DON) is a mycotoxin produced by Fusarium fungi widespread in wheat, corn, barley and other grain crops, posing the potential for being toxic to human and animal health, especially in the small intestine, which is the primary target organ for defense against the invasion of toxins. This study firstly investigated DON contamination in a local area of a wheat production district in China. Subsequently, the mechanism of DON toxicity was analyzed through cellular molecular biology combining with intestinal flora and gene transcription analysis; the results indicated that DON exposure can decrease IPEC-J2 cell viability and antioxidant capacity, stimulate the secretion and expression of proinflammatory factors, destroy the gut microbiota and affect normal functions of the body. It is illustrated that DON could induce intestinal damage through structural damage, functional injury and even intestinal internal environment disturbance, and, also, these intestinal toxicity effects are intrinsically interrelated. This study may provide multifaceted information for the treatment of intestinal injury induced by DON.

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Psoriasis is a skin disease that is inflammatory and persistent, causing a high rate of recurrence, poor quality of life, and significant socioeconomic burden. Its main pathological manifestations are abnormal activation and infiltration of T cells and excessive proliferation of keratinocytes (KCs). The great majority of patients with psoriasis will relapse after remission. It usually lasts a lifetime and necessitates long-term treatment strategies. During periods of activity and remission, one of the main cell types in psoriasis is memory T cells, which include tissue-resident memory T (TRM) cells, central memory T (TCM) cells, and effector memory T (TEM) cells. They work by releasing inflammatory factors, cytotoxic particles, or altering cell subpopulations, leading to increased inflammation or recurrence. This review summarizes the role of memory T cells in the pathology and treatment of psoriasis, with a view to potential novel therapies and therapeutic targets.

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Unveiling inherent interactions among solvents, Li+ ions, and anions are crucial in dictating solvation-desolvation kinetics at the electrode/electrolyte interface. Developing an electrolyte with a low ion-transport barrier and minimal solvent coordination in its interfacial solvation structure is essential for forming an anion-derived solid-electrolyte interface, a key component for high-performance Li-metal batteries. In this study, we harness electric dipole-dipole synergistic interactions to formulate an electrolyte with significantly reduced interfacial solvent coordination. Operando characterization and theoretical analysis reveal that 2-fluoropyridine (FPy) with high dipole preferentially adsorbs onto the Li metal surface. The adsorbed FPy molecule squeezes succinonitrile in the primary solvation sheath through steric hindrance, leading to the formation of an inorganic-rich interphase. Consequently, the introduction of FPy enhances the reversible capacity of the LiCoO2||Li cell, which maintains a capacity of 143 mAh g-1 after 500 cycles at a 1C rate. Moreover, the cycle life of LiCoO2 batteries with a limited supply of lithium extends from 120 cycles to over 200 cycles. These findings offer a strategy that can be applied broadly to design interfacial solvation structures for various metal-ion/metal-based batteries.

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BACKGROUND: It is common to see patients who need orthodontic treatment but with insufficient alveolar bone volume. However, safe and effective tooth movement requires sufficient alveolar bone width and height. The aim of this study is to compare the bone augmentation efficacy of Autologous Partially Demineralized Dentin Matrix (APDDM) and Deproteinized Bovine Bone Mineral (DBBM) in orthodontic patients with insufficient bone by using a randomized controlled clinical trial approach. MATERIALS AND METHODS: Twenty-seven orthodontic patients involving 40 posterior teeth alveolar sites (n = 40) with insufficient alveolar bone volume were randomly divided into a control group (n = 20) and an experimental group (n = 20). The patients in the experimental group were treated with APDDM, and those in the control group were treated with DBBM. After surgery, the adjacent teeth are moved toward the bone grafting sites according to the orthodontic treatment plan. Patients completed a postoperative response questionnaire by the Visual Analogue Scale (VAS) score to indicate pain and swelling in the bone grafted area at the time of suture removal; and CBCT scans were conducted before surgery, 6 months and 2 years after surgery to assess changes in buccal and central alveolar heights, as well as widths at the alveolar ridge apex and 3 mm, 5 mm below the apex, respectively. The CBCT image sequences were imported into Mimics 21.0 software in DICOM format. The data of the patients in both groups were collected and analyzed by SPSS 25.0. RESULTS: The VAS scores were significantly lower in the APDDM group than in the DBBM group (p < 0.05). Significant increases were observed in alveolar bone height and width at 6 months and 2 years postoperative (p < 0.05); At 2 years, the APDDM group exhibited a reduction in buccal crest height and in 3 mm, 5 mm width below alveolar ridge apex, relative to 6 months (p < 0.05), while the DBBM group showed a decrease only in the central height of the alveolar bone (p < 0.05). There was a significant bone augmentation increase found only 3 mm below the alveolar ridge apex in the APDDM group compared with the DBBM group among all 6 months group comparison (p < 0.05). At 2 years, the augmentation effects were similar across both groups (p > 0.05). CONCLUSION: Radiomics analysis indicates that APDDM serves as a viable bone augmentation material for orthodontic patients with insufficient alveolar bone volume, achieving comparable clinical efficacy to DBBM. Additionally, APDDM is associated with a milder postoperative response than DBBM. THE REGISTRATION NUMBER (TRN): ChiCTR2400084607.

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BACKGROUND: Psoriasis (PSO) poses a global health threat. The current research challenge in PSO is relapse. Liquiritin (LIQ), a major active compound from Glycyrrhiza inflata Batalin, has multiple pharmacological properties, including anti-inflammatory and anti-proliferative. Nonetheless, the precise mechanisms underlying LIQ's therapeutic actions in PSO and prevention abilities remain elusive. PURPOSE: The present study aimed to delve into the potential to treat and prevent PSO and the mechanism of LIQ. METHODS: The anti-inflammatory and anti-proliferative effects of LIQ were studied in vitro with the HaCaT cell line. Then, Transcriptional analysis and bioinformatic analysis were used to determine the internal associations of the target set. Subsequently, functional experiment, luciferase report assay, ChIP-PCR, and immunohistochemical validation of clinical samples were performed to investigate the mechanism of LIQ. Finally, the anti-psoriatic effects and prevention abilities of LIQ were verified in vivo with imiquimod (IMQ)-induced PSO-like mouse models. RESULTS: Here, we identified differentially expressed genes in LIQ-stimulated HaCaT cells and Retinol-Binding Protein 3 (RBP3) as the core target, whereas YY1 was a predicted upstream transcription factor of RBP3. The YY1/RBP3 axis was obviously altered after administering LIQ at optimal doses of 20 µM in vitro and 100 µg/ml in vivo. LIQ can significantly inhibit the progression of PSO in vivo. Notably, LIQ also prevented the relapse of psoriatic lesions induced by the second round of low-dose IMQ. Mechanistically, we observed that LIQ could increase the promotion of YY1 for RBP3 by enhancing the binding affinity between them. CONCLUSION: These findings revealed that the YY1/RBP3 axis is a potential psoriatic target, and LIQ is a promising and innovative therapeutic candidate for the treatment and prevention of PSO.

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Background: Cervical cancer (CC) stands as a significant health threat to women globally, with high-risk human papillomaviruses as major etiologic agents. The DNA damage repair (DDR) protein topoisomerase I (TOP1) has been linked to various cancers, yet its distinct roles and mechanisms in CC are not fully elucidated. Methods: We investigated TOP1 expression in cervical intraepithelial neoplasia (CIN) and CC tissues utilizing qRT-PCR and IHC, correlating findings with patient prognosis. Subsequent knockdown studies were performed in vitro and in vivo to evaluate the influence of TOP1 on tumor growth, DNA repair, and inflammatory responses. Results: TOP1 was highly expressed in CIN and CC, negatively correlating with patient prognosis. Inhibition of TOP1 impeded CC cell growth and disrupted DNA repair. TOP1 was shown to regulate tumor-promoting inflammation and programmed death-ligand 1 (PD-L1) production in a cGAS-dependent manner. HPV oncoproteins E6 and E7 upregulated TOP1 and activated the cGAS-PD-L1 pathway. Conclusions: TOP1 acts as a DNA repair mediator, promoting CC development and immune evasion. Targeting the TOP1-cGAS-PD-L1 axis could be a potential therapeutic strategy for CC.

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OBJECTIVE: Preeclampsia (PE) poses a significant threat to maternal and perinatal health, so its early prediction, prevention, and management are of paramount importance to mitigate adverse pregnancy outcomes. This article provides a brief review spanning epidemiology, etiology, pathophysiology, and risk factors associated with PE, mainly discussing the emerging role of Artificial Intelligence (AI) deep learning (DL) technology in predicting PE, to advance the understanding of PE and foster the clinical application of early prediction methods. METHODS: Our narrative review comprehensively examines the PE epidemiology, etiology, pathophysiology, risk factors and predictive approaches, including traditional models and AI deep learning technology. RESULTS: Preeclampsia involves a wide range of biological and biochemical risk factors, among which poor uterine artery remodeling, excessive immune response, endothelial dysfunction, and imbalanced angiogenesis play important roles. Traditional PE prediction models exhibit significant limitations in sensitivity and specificity, particularly in predicting late-onset PE, with detection rates ranging from only 30% to 50%. AI models have exhibited a notable level of predictive accuracy and value across various populations and datasets, achieving detection rates of approximately 70%. Particularly, they have shown superior predictive capabilities for late-onset PE, thereby presenting novel opportunities for early screening and management of the condition. CONCLUSION: AI DL technology holds promise in revolutionizing the prediction and management of PE. AI-based approaches offer a pathway toward more effective risk assessment methods by addressing the shortcomings of traditional prediction models. Ongoing research efforts should focus on expanding databases and validating the performance of AI in diverse populations, leading to the development of more sophisticated prediction models with improved accuracy.

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OBJECTIVES: The aim of this study was to determine the strength of the association between frailty and adverse outcomes in patients undergoing maintenance hemodialysis. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients aged ≥18 years who were undergoing maintenance hemodialysis. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, Scopus, the China Knowledge Resource Integrated Database, the Wanfang Database and the Weipu Database were searched from inception until 11 April 2024. The reviewers independently selected the studies, extracted the data and evaluated the quality of the studies. Stata 15.1 software was used to perform the meta-analysis. RESULTS: A total of 36 articles were included in this study, including 56,867 patients. The primary outcome events in this study were mortality, hospitalization, and vascular access events. The secondary outcomes were depression, cognitive impairment, falls, fracture, sleep disturbances, and quality of life. This study suggested that frailty was associated with mortality in patients undergoing maintenance hemodialysis [hazard ratio (HR), 1.97; 95% CI, 1.62-2.40]. Frailty increased the risk of mortality in patients [odds ratio (OR), 2.33; 95% CI, 1.47-3.68]. In addition, we found that frailty was significantly associated with hospitalization in patients undergoing maintenance hemodialysis (OR, 2.47; 95% CI, 1.52-4.03). Patients who were undergoing maintenance hemodialysis and who were frail had a greater risk of hospitalization [RR, 1.47; 95% CI, 1.05-2.08] and emergency visits (RR, 2.28; 95% CI, 1.78-2.92). The results of this study also suggested that frailty was associated with a greater risk of vascular access events (HR, 1.72; 95% CI, 1.50-1.97). Finally, frailty increased the risk of depression (OR, 4.31; 95% CI, 1.83-10.18), falls and fractures, and reduced quality of life. CONCLUSIONS: The findings of this study suggested that frailty was an important predictor of adverse outcomes in patients undergoing maintenance hemodialysis. In the future, medical staff should regularly evaluate signs of weakness, formulate individual diagnosis and treatment plans, adjust dialysis plans according to the patient's condition, and reduce the occurrence of adverse events. REGISTRATION: The study protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023486239).

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Meniscal injuries are highly correlated with osteoarthritis (OA) onset and progression. Although meniscal allograft transplantation (MAT) is a therapeutic option to restore meniscal anatomy, a shortage of donor material and the donor-derived infectious risk may be concerns in clinics. This review summarizes the literature reporting meniscus repair status in preclinical models and clinical practice using allografts or synthetic grafts. The advantages and limitations of biodegradable polymer-based meniscal scaffolds, applied in preclinical studies, are discussed. Then, the long-term treatment outcomes of patients with allografts or commercial synthetic scaffolds are compared. A total of 47 studies are included in our network meta-analysis. Compared with the meniscal allografts, the commercial synthetic products significantly improved clinical treatment outcomes in terms of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analog Scale (VAS) scores, and Lysholm scores. In addition, development strategies for the next generation of novel synthetic scaffolds are proposed through optimization of structural design and fabrication, and selection of cell sources, external stimuli, and active ingredients. This review may inspire researchers and surgeons to design and fabricate clinic-orientated grafts with improved treatment outcomes.

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Background and Aims: Hepatic fibrosis (HF) is a critical step in the progression of hepatocellular carcinoma (HCC). Gene associated with retinoid-IFN-induced mortality 19 (GRIM19), an essential component of mitochondrial respiratory chain complex I, is frequently attenuated in various human cancers, including HCC. Here, we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis. Methods: GRIM19 expression was evaluated in normal liver tissues, hepatitis, hepatic cirrhosis, and HCC using human liver disease spectrum tissue microarrays. We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo. We performed flow cytometry, immunofluorescence, immunohistochemistry, western blotting, and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF. Results: Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues, including hepatitis, cirrhosis, and HCC tissues. Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice. In addition, GRIM19 loss caused chronic liver injury through reactive oxygen species (ROS)-mediated oxidative stress, resulting in aberrant NF-кB activation via an IKK/IкB partner in hepatocytes. Furthermore, GRIM19 loss activated NLRP3-mediated IL33 signaling via the ROS/NF-кB pathway in hepatocytes. Intraperitoneal administration of the NLRP3 inhibitor MCC950 dramatically alleviated GRIM19 loss-driven HF in vivo. Conclusions: The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-кB signaling, providing potential therapeutic approaches for earlier HF prevention.