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Abstract Extracellular vesicles (EVs) carry a variety of bioactive molecules and are becoming a promising alternative to cell therapy. Scale-up EV isolation is necessary for their functional studies and biological applications, while the traditional methods are challenged by low throughput, low yield, and potential damage. Herein, we developed an ion osmolarity-driven sequential concentration-enrichment strategy (IOSCE) for the EV isolation. IOSCE is composed of a novel superabsorbent polymers (SAPs) for EV concentration and a charged polymer for EV enrichment. Based on the driving force of ionic osmotic pressure, IOSCE can isolate EVs on a large scale from cell culture medium. The saturated water absorption capacity of IOSCE is 13.62 times higher than that of commercial SAPs. Compared with the ultracentrifugation method, IOSCE exhibited a 2.64 times higher yield (6.33 × 108 particles/mL). Moreover, the mesenchymal stem cell-derived EVs isolated using IOSCE demonstrate strong biological activity and can reduce neuroinflammation by affecting RNA metabolism and translation processes. IOSCE provides a cost-effective, high-throughput, and low-damage method for the scale up EV isolation, which is promising for disease diagnosis and treatment. Graphical Abstract

Abstract Colorectal cancer (CRC) is a common malignant tumor with the third and second highest incidence and mortality rates among various malignant tumors. Despite significant advancements in the present therapy for CRC, the majority of CRC cases feature proficient mismatch repair/microsatellite stability and have no response to immunotherapy. Therefore, the search for new treatment options holds immense importance in the diagnosis and treatment of CRC. In recent years, clinical research on immunotherapy combined with epigenetic therapy has gradually increased, which may bring hope for these patients. This review explores the role of epigenetic regulation in exerting antitumor effects through its action on immune cell function and highlights the potential of certain epigenetic genes that can be used as markers of immunotherapy to predict therapeutic efficacy. We also discuss the application of epigenetic drug sensitization immunotherapy to develop new treatment options combining epigenetic therapy and immunotherapy.

Abstract Background This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. Methods A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). Results In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. Conclusion This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society.

Implant surface designs have advanced to address challenges in oral rehabilitation for healthy and compromised bone. Several studies have analyzed the effects of altering material surfaces on osteogenic differentiation. However, the crucial role of osteoclasts in osseointegration has often been overlooked. Overactive osteoclasts can compromise implant stability. In this study, we employed a silanization method to alter pure titanium to produce a surface loaded with the antimicrobial peptide GL13K that enhanced biocompatibility. Pure titanium (Ti), silanization-modified titanium, and GL13K-modified titanium (GL13K-Ti) were co-cultured with macrophages. Our findings indicated that GL13K-Ti partially inhibited osteoclastogenesis and expression of osteoclast-related genes and proteins by limiting the formation of the actin ring, an important structure for osteoclast bone resorption. Our subsequent experiments confirmed the epigenetic role in regulating this process. GL13K-Ti was found to impact the degree of methylation modifications of H3K27 in the NFATc1 promoter region following RANKL-induced osteoclastic differentiation. In conclusion, our study unveils the potential mechanism of methylation modifications, a type of epigenetic regulatory modality, on osteoclastogenesis and activity on the surface of a material. This presents novel concepts and ideas for further broadening the clinical indications of oral implants and targeting the design of implant surfaces.

IntroductionThis study explores the effectiveness of music therapy in repairing psychological trauma in bereaved families, aiming to provide a comprehensive understanding of its potential therapeutic impact. It begins with an analysis of the current situation faced by bereaved families, identifying the psychological challenges they experience.MethodsThe research design included the recruitment of participants from bereaved families, who were then divided into an experimental group and a control group. An optimized Long Short-Term Memory (LSTM) network model was constructed to analyze music therapy data, tailored specifically to capture the nuances of this therapeutic process. The experimental procedure detailed the specific operations involved in the music therapy sessions and established a clear comparison framework between the two groups.ResultsThe performance of the proposed LSTM model demonstrated high accuracy (0.85), precision (0.86), recall (0.84), and F1-score (0.85), indicating its effectiveness in predicting treatment outcomes. When compared to the Self-Reporting Inventory-90 (SCL-90) scale, the model captured the trend of treatment effects with a high level of accuracy and reliability. Notably, participants numbered 2, 6, and 8 in the experimental group showed substantial improvement rates of 67.21%, 71.45%, and 75.67%, respectively, in their psychological health issues.DiscussionThe comparative analysis between the experimental and control groups confirmed that the music therapy approach, as guided by the proposed LSTM model, led to a more significant improvement in psychological health issues for bereaved families. This suggests that the model offers a promising avenue for enhancing the effectiveness of music therapy in this context.

IntroductionWith the growing interest in the psychological basis of language learning, this study aims to validate the Chinese version of the Language Mindset Inventory (LMI) among Chinese university students.MethodsA sample of 476 students from various universities in mainland China was used. The translation process followed the forward-backward method. Confirmatory factor analyses (CFAs) were conducted to evaluate the factor structure. The internal consistency of the LMI was assessed using Cronbach's alpha, and convergent validity was examined through correlations with established mindset measures.ResultsCompared with the one-factor model, the two-factor model which distinguishes between fixed and growth mindsets, showed an acceptable and better fit index. The overall Cronbach's alpha for the full scale was 0.954, with 0.929 for the fixed mindset dimension and 0.903 for the growth mindset dimension. AVE values for the fixed and growth dimensions were 0.597 and 0.510, respectively. Correlations showed that the growth mindset dimension was significantly positively associated with the 8-Item Growth Mindset Scale (r = 0.186, p < 0.01) and the Mindset Scale for Learning English (r = 0.149, p < 0.01), while the fixed mindset dimension was negatively associated with both scales (r = −0.228 and r = −0.169, p < 0.01).DiscussionThis study confirms the reliability and validity of the Chinese version of the LMI, making it a relevant tool for assessing language learning mindsets among Chinese university students. The findings support the integration of LMI into educational strategies to promote resilience and adaptability, enhancing language education outcomes.

The article Study on Dynamic Response Characteristics of Offshore Floating Wind Turbine Pitch System has been retracted at the request of EAI's Research Integrity Committee on the grounds of plagiarism.

IntroductionThis study investigates the experiences of leading Chinese companies in environmental conservation under varying extreme climate conditions, focusing on the role of artificial intelligence (AI) and governmental assistance.MethodsA survey was conducted involving 200 participants to assess recognition and endorsement of AI’s role in environmental protection and to explore the adoption of AI technologies by firms for enhancing environmental management practices.ResultsThe survey revealed widespread recognition of Tencent’s green initiatives and strong support for AI’s role in environmental protection. Many firms are considering adopting AI technologies to optimize energy management, deploy intelligent HVAC systems, and improve the operations of data centers and smart lighting systems.DiscussionThe findings highlight a strong belief in AI’s potential to advance environmental protection efforts, with a call for increased governmental support to foster this development. The study underscores the importance of a partnership between businesses and governments to leverage AI for environmental sustainability, contributing significantly to conservation efforts.

Abstract Background Neoadjuvant immunochemotherapy (NICT) plus esophagectomy has emerged as a promising treatment option for locally advanced esophageal squamous cell carcinoma (LA-ESCC). Pathologic complete response (pCR) is a key indicator associated with great efficacy and overall survival (OS). However, there are insufficient indicators for the reliable assessment of pCR. Methods 192 patients with LA-ESCC treated with NICT from December 2019 to October 2023 were recruited. According to pCR status, patients were categorized into pCR group (22.92%) and non-pCR group (77.08%). Radiological features of pretreatment and preoperative CT images were extracted. Logistic and COX regressions were trained to predict pathological response and prognosis, respectively. Results Four of the selected radiological features were combined to construct an ESCC preoperative imaging score (ECPI-Score). Logistic models revealed independent associations of ECPI-Score and vascular sign with pCR, with AUC of 0.918 in the training set and 0.862 in the validation set, respectively. After grouping by ECPI-Score, a higher proportion of pCR was observed among the high-ECPI group and negative vascular sign. Kaplan Meier analysis demonstrated that recurrence-free survival (RFS) with negative vascular sign was significantly better than those with positive (P = 0.038), but not for OS (P = 0.310). Conclusions This study demonstrates dynamic radiological features are independent predictors of pCR for LA-ESCC treated with NICT. It will guide clinicians to make accurate treatment plans.

Abstract Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

Abstract Objective AT-rich interaction domain 1A (ARID1A) mutant tumors show active anti-tumor immune response, which is the potential indication of immunotherapy. However, the relationship between the heterogeneous ARID1A expression and the immune response and immunotherapy efficacy in colorectal cancer (CRC) is still unclear. Methods We collected 1113 cases of patients with stage I-IV CRC who underwent primary resection at Harbin Medical University Cancer Hospital. ARID1A expression in CRC tissues was assessed via immunohistochemistry (IHC). CD8, CD163 and FOXP3 were stained by IHC to identify the immune landscape. Clinicopathological features of patients were compared using statistical tests like the Wilcoxon-Mann–Whitney test or χ2 tests. Kaplan–Meier survival analysis with log-rank tests were employed. Results Heterogeneous ARID1A expression was categorized into integrity expression, complete expression deficiency (cd-ARID1A), partial expression deficiency (pd-ARID1A), and clonal expression deficiency (cld-ARID1A). ARID1A-deficient expression was significant association with dMMR (P value

The production of reactive oxygen species (ROS) is susceptible to external excitation or insufficient supply of related participants (e.g., hydrogen peroxide (H2O2) and sensitizer), liming ROS-driven tumor treatment. Additionally, the lysosomal retention effect severely hinders the utilization of ROS-based nanosystems and severely restricted the therapeutic effect of tumors. Therefore, first reported herein an intelligent nanocatalyst, TCPP-Cu@MnOx ((MnII)1(MnIII)2.1(MnIV)2.6O9.35), and proposed a programmed ROS amplification strategy to treat tumors. Initially, the acidity-unlocked nanocatalyst was voluntarily triggered to generate abundant singlet oxygen (1O2) to mediate acid lysosomal ablation to assist nanocatalyst escape and partially induce lysosomal death, a stage known as lysosome-driven therapy. More unexpectedly, the high-yielding production of 1O2 in acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Subsequently, the escaping nanocatalyst further activated H2O2-mediated 1O2 and hydroxyl radical (•OH) generation and glutathione (GSH) consumption for further accentuation tumor therapy efficiency, which is based on the Fenton-like reaction and Russell reaction mechanisms. Therefore, in this system, a program-activatable TCPP-Cu@MnOx nanocatalyst, was proposed to efficiently destruct organelle-lysosome via 1O2 inducing, and stimulated H2O2 conversion into highly toxic 1O2 and •OH in cytoplasm, constituting an attractive method to overcome limitations of current ROS treatment.

α-Methyl groups play significant roles in the regulation of water molecules within both small molecular systems and bio-macromolecular systems. Systematically studying the influence of α-methyl on the dynamics of water molecules within hydrogel systems is therefore worthwhile. In this study, we prepared a series of hydrogen-bonded (H-bonded) hydrogels with varying densities of α-methyl groups by copolymerizing methacrylamide (MAm) with its α-methyl-absent analogue, acrylamide (Am). Introducing a small amount of Am (≤6 mol%) into the polymer chain resulted in significant shifts in the viscoelasticity of the hydrogels. The hydrogels exhibit a “time-temperature-α-methyl equivalence”, meaning that introduction of α-methyl-absent monomer has effects similar to elevating temperature and prolonging observation time on the dynamic properties. Based on low-field nuclear magnetic resonance spectroscopy and Raman scattering, a “hydrophilic defects-assisted H-bonds dissociation” mechanism is proposed, depicting that the α-methyl-absent monomer can disturb the rearrangement of water molecules surrounding the polymer chain and accelerate chain dissociation. These findings enabled the copolymer hydrogels with functions such as fast self-healing and tunable interface adhesion.

Aim To examine the associations of healthy lifestyles with risk of all-cause and cause-specific mortality among adults with metabolic dysfunction-associated steatotic liver disease (MASLD), and whether the association was mediated by systemic immune-inflammatory biomarkers (SIIBs).Methods The study included 10,347 subjects with MASLD, who were enrolled in the Dongfeng-Tongji cohort study. The healthy lifestyles referred to non-smoking, being physically active (≥7.5 metabolic equivalents-hours/week), low-risk alcohol consumption (1–14 g/day for women and 1–28 g/day for men), and optimal sleep duration (≥6 to ≤8 h/day). Cox proportional hazard models were used to examine the relationship between each lifestyle and SIIBs with the risk of all-cause and cause-specific mortality. A mediation analysis was conducted to investigate the role of SIIBs on the association between healthy lifestyles and mortality.Results There were 418 MASLD subjects dead till the follow-up of 2018, including 259 deaths from cardiovascular disease (CVD). Compared to MASLD participants with 0–1 healthy lifestyle score (HLS), those with 3-4 HLS had the lowest risk of all-cause mortality [hazard ratio (HR), 0.46; 95% CI, (0.36–0.60)], and CVD mortality [HR (95%CI), 0.41 (0.29–0.58)]. Mediation analyses indicated that SIIBs mediated the association between healthy lifestyles and mortality, with proportions ranging from 2.5% to 6.1%.Conclusions These findings suggest that adherence to healthy lifestyles can significantly reduce mortality for MASLD patients, and the decreased SIIBs may partially explain the protection mechanism of healthy lifestyles.

Abstract The unique physical tumor microenvironment (TME) and aberrant immune metabolic status are two obstacles that must be overcome in cancer immunotherapy to improve clinical outcomes. Here, an in situ mechano‐immunometabolic therapy involving the injection of a biomimetic hydrogel is presented with sequential release of the anti‐fibrotic agent pirfenidone, which softens the stiff extracellular matrix, and small interfering RNA IDO1, which disrupts kynurenine‐mediated immunosuppressive metabolic pathways, together with the multi‐kinase inhibitor sorafenib, which induces immunogenic cell death. This combination synergistically augmented tumor immunogenicity and induced anti‐tumor immunity. In mouse models of clear cell renal cell carcinoma, a single‐dose peritumoral injection of a biomimetic hydrogel facilitated the perioperative TME toward a more immunostimulatory landscape, which prevented tumor relapse post‐surgery and prolonged mouse survival. Additionally, the systemic anti‐tumor surveillance effect induced by local treatment decreased lung metastasis by inhibiting epithelial‐mesenchymal transition conversion. The versatile localized mechano‐immunometabolic therapy can serve as a universal strategy for conferring efficient tumoricidal immunity in “cold” tumor postoperative interventions.

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods.Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes.Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = −1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13–11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52–18.90).Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively.

Biomimetic damping materials have emerged as promising candidates for various applications due to their ability to mimic the exceptional damping properties observed in biological systems. This review provides a comprehensive overview of recent advances in the field of biomimetic damping gel materials. The conceptual framework of biomimetic damping materials is discussed, the synthesis methods inspired by biological principles are elucidated, and key considerations in material selection are highlighted. The latest research findings on the mechanical properties, biocompatibility and practical applications of these materials are synthesized and insights into the future directions of biomimetic damping gel materials are offered.

Objective: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. Methods: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. Results: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standard deviation increase in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer’s disease (AD), but no significant modification effects are found for sleep patterns or smoking status. Conclusion: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.

Introduction: Eplerenone is approved for the treatment of hypertension as well as symptomatic heart failure with reduced ejection fraction (HFrEF) following an acute myocardial infarction. However, the adverse events (AEs) have not been systematically analyzed. The aim of this study was to identify adverse drug reactions (ADRs) related to eplerenone using the FDA Adverse Event Reporting System (FAERS) database. By identifying previously unreported AEs, the study could potentially contribute to updating the drug’s label.Methods: In order to find significant AEs, four algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM), were used to analyze the signal strength of the ADRs connected to eplerenone that were gathered from the FAERS database over the previous 20 years.Results: From 2004Q1 to 2023Q4, a total of 20, 629, 811 reported cases were gathered from the FAERS database for this study. After processing the data and filtering, 1,874 case reports were analyzed. Of these cases, 1,070 AEs were identified, 128 of which were eplerenone-related ADRs. We investigated the occurrence of ADRs induced by eplerenone in 27 organ systems. Our study showed that the AEs listed in the medication’s package insert correspond with those listed in the literature, including hyperkalemia and increased creatinine. Additionally, the prescription label for eplerenone does not include all system organ class (SOC) terms, like Vascular disorders, hepatobiliary Disorders, etc.Discussion: The study used multiple algorithms to quantify the signal strength and then identified any previously unrecognized ADRs, further studies are needed to confirm the association of ADRs with eplerenone. The findings of this study may provide important insights into the safety profile of eplerenone, ensure that healthcare providers have up-to-date information about their potential risks and help guide them in the correct use of the drug.

Abstract Background Although numerous studies have indicated that activated pyroptosis can enhance the efficacy of antitumour therapy in several tumours, the precise mechanism of pyroptosis in colorectal cancer (CRC) remains unclear. Methods Pyroptosis in CRC cells treated with antitumour agents was assessed using various techniques, including Western blotting, lactate dehydrogenase release assay and microscopy analysis. To uncover the epigenetic mechanisms that regulate NLRP3, chromatin changes and NLRP3 promoter histone modifications were assessed using Assay for Transposase‐Accessible Chromatin using sequencing and RNA sequencing. Chromatin immunoprecipitation‒quantitative polymerase chain reaction was used to investigate the NLRP3 transcriptional regulatory mechanism. Additionally, xenograft and patient‐derived xenograft models were constructed to validate the effects of the drug combinations. Results As the core molecule of the inflammasome, NLRP3 expression was silenced in CRC, thereby limiting gasdermin D (GSDMD)‐mediated pyroptosis. Supplementation with NLRP3 can rescue pyroptosis induced by antitumour therapy. Overexpression of HDAC2 in CRC silences NLRP3 via epigenetic regulation. Mechanistically, HDAC2 suppressed chromatin accessibility by eliminating H3K27 acetylation. HDAC2 knockout promotes H3K27ac‐mediated recruitment of the BRD4‐p‐P65 complex to enhance NLRP3 transcription. Inhibiting HDAC2 by Santacruzamate A in combination with classic antitumour agents (5‐fluorouracil or regorafenib) in CRC xenograft‐bearing animals markedly activated pyroptosis and achieved a significant therapeutic effect. Clinically, HDAC2 is inversely correlated with H3K27ac/p‐P65/NLRP3 and is a prognostic factor for CRC patients. Conclusion Collectively, our data revealed a crucial role for HDAC2 in inhibiting NLRP3/GSDMD‐mediated pyroptosis in CRC cells and highlighted HDAC2 as a potential therapeutic target for antitumour therapy. Highlights Silencing of NLRP3 limits the GSDMD‐dependent pyroptosis in colorectal cancer. HDAC2‐mediated histone deacetylation leads to epigenetic silencing of NLRP3. HDAC2 suppresses the NLRP3 transcription by inhibiting the formation of H3K27ac/BRD4/p‐P65 complex. Targeting HDAC2 activates pyroptosis and enhances therapeutic effect.

With the proposal of dual carbon goals, enhancing carbon sinks and reducing carbon emissions has become a critical issue. Fisheries, as a component of agriculture, possess the dual attributes of being a “carbon sink” (biological carbon fixation) and a “carbon source” (the carbon emissions from fishing vessels). Therefore, it is necessary to assess the carbon sink and carbon emission levels of fisheries. The northern marine economic circle, which includes Liaoning, Hebei, Tianjin, and Shandong, is an important site for fisheries in China, characterized by abundant aquatic resources. However, a comprehensive assessment of the carbon budget for fisheries in this region is still unclear. This study calculated the carbon sinks, carbon emissions, and net carbon emissions associated with fisheries in the region from 2013 to 2020. Additionally, we used sensitivity analysis and scenario simulation to explore the factors influencing the net carbon emissions. The results revealed that the carbon budget of the northern marine economic circle was in a carbon deficit (the amount of carbon emissions was higher than that of carbon sinks) from 2013 to 2020. However, a downward trend in the net carbon emissions was observed, indicating the potential of achieving carbon neutrality. From the perspective of provinces, significant differences among provinces (cities) were found in terms of carbon sinks, carbon emissions, and net carbon emissions, with Shandong having the largest net carbon emissions. Furthermore, the production of clams and the use of seawater trawl net have a significant impact on the net carbon emissions. Increasing the production of clams while reducing the power of trawling operations can significantly decrease net carbon emissions. Based on these results, this study provides relevant suggestions to enhance the carbon sink capacity and decrease the carbon emissions of fisheries in the northern marine economic circle.

Abstract Tin‐based perovskite solar cells (PSCs) are promising environmentally friendly alternatives to their lead‐based counterparts, yet they currently suffer from much lower device performance. Due to variations in the chemical properties of lead (II) and tin (II) ions, similar treatments may yield distinct effects resulting from differences in underlying mechanisms. In this work, a surface treatment on tin‐based perovskite is conducted with a commonly employed ligand, iso‐butylammonium iodide (iso‐BAI). Unlike the passivation effects previously observed in lead‐based perovskites, such treatment leads to the recrystallization of the surface, driven by the higher solubility of tin‐based perovskite in common solvents. By carefully designing the solvent composition, the perovskite surface is effectively modified while preserving the integrity of the bulk. The treatment led to enhanced surface crystallinity, reduced surface strain and defects, and improved charge transport. Consequently, the best‐performing power conversion efficiency of FASnI3 PSCs increases from 11.8% to 14.2%. This work not only distinguishes the mechanism of surface treatments in tin‐based perovskites from that of lead‐based counterparts, but also underscores the critical role in designing tailor‐made strategies for fabricating efficient tin‐based PSCs.

IntroductionTo enhance the precision of evaluating the impact of urban environments on resident health, this study introduces a novel fuzzy intelligent computing model designed to address health risk concerns using multi-media environmental monitoring data.MethodsThree cities were selected for the study: Beijing (B City), Kunming (K City), and Wuxi (W City), representing high, low, and moderate pollution levels, respectively. The study employs a Fuzzy Inference System (FIS) as the chosen fuzzy intelligent computing model, synthesizing multi-media environmental monitoring data for the purpose of urban health risk assessment.Results(1) The model reliably estimates health risks across diverse cities and environmental conditions. (2) There is a positive correlation between PM2.5 concentrations and health risks, though the impact of noise levels varies by city. In cities B, K, and W, the respective correlation coefficients are 0.65, 0.55, and 0.7. (3) The Root Mean Square Error (RMSE) values for cities B, K, and W, are 0.0132, 0.0125, and 0.0118, respectively, indicating that the model has high accuracy. The R2 values for the three cities are 0.8963, 0.9127, and 0.9254, respectively, demonstrating the model’s high explanatory power. The residual values for the three cities are 0.0087, 0.0075, and 0.0069, respectively, indicating small residuals and demonstrating robustness and adaptability. (4) The model’s p-values for the Indoor Air Quality Index (IAQI), Thermal Comfort Index (TCI), and Noise Pollution Index (NPI) all satisfy p < 0.05 for the three cities, affirming the model’s credibility in estimating health risks under varied urban environments.DiscussionThese results showcase the model’s ability to adapt to diverse geographical conditions and aid in the accurate assessment of existing risks in urban settings. This study significantly advances environmental health risk assessment by integrating multidimensional data, enhancing the formulation of comprehensive environmental protection and health management strategies, and providing scientific support for sustainable urban planning.

Abstract We perform a high-precision computation of the three-loop three-point form factor of the stress-tensor supermultiplet in N $$ \mathcal{N} $$ = 4 SYM. Both the leading-color and sub-leading-color form factors are expanded in terms of simple integrals. We compute the complete set of integrals at a special kinematic point with very high precision using AMFlow. The high-precision leading-color result enables us to obtain the analytic form of a numerical constant in the three-loop BDS ansatz, which is previously known only numerically. The high-precision values of the non-leading-color finite remainder as well as all integrals are also presented, which can be valuable for future use.

Abstract Endoscopic optical coherence tomography (OCT) is a valuable tool for providing diagnostic images of internal organs and guiding interventions in real time. Miniaturized OCT endoscopes are essential for imaging small and convoluted luminal organs while minimizing invasiveness. However, current methods for fabricating miniature fiber probes have limited ability to correct optical aberrations, leading to suboptimal imaging performance. Here we introduce a liquid shaping technique for the rapid and scalable fabrication of ultrathin and high-performance OCT microendoscopes suitable for minimally invasive clinical applications. This technique enables the flexible customization of freeform microlenses with sub-nanometer optical surface roughness by regulating the minimum energy state of curable optical liquid on a wettability-modified substrate and precisely controlling the liquid volume and physical boundary on a substrate. Using this technique, we simultaneously fabricated 800-nm OCT microendoscopes with a diameter of approximately 0.6 mm and evaluated their ultrahigh-resolution imaging performance in the esophagus of rats and the aorta and brain of mice.

Rural e-commerce, as a new form of digital economy, is of great significance in promoting the income of rural households and realizing common prosperity. Based on the 2021 China Rural Revitalization Survey (CRRS), the impact of rural e-commerce on farmers’ income and the intra-rural income gap is explored using quantile regression. The results found that (1) rural e-commerce can effectively promote the level of farm household income and alleviate the intra-rural income disparity, with this finding still holding after addressing the potential endogeneity problem and conducting robust-type tests. (2) Rural e-commerce has the most pronounced income-generating effect on low-income households in the southern region; participation in rural e-commerce has a more “center-expanding” effect on households in the secondary education and high material capital groups. (3) Saving production and operation costs, shortening the product circulation chain, and improving access to information are channels through which rural e-commerce affects households’ income. It is recommended to actively promote the deep integration and development of rural e-commerce in rural areas, establish a sound mechanism for bridging the “digital divide”, encourage e-commerce “leaders” to build a perfect industrial chain, and guide smallholders to integrate into the rural e-commerce industrial chain to enjoy the digital dividend.

Computer-assisted preparation of porcelain laminate veneers (PLVs) using stereolithographic templates has been developed to enhance the accuracy of tooth preparation. However, the digital workflows involved in guided PLV preparation remain inconsistently defined across various practices. Therefore, this scoping review aimed to examine publications on computer-assisted PLV preparation to identify the key stage of digital workflows involved in designing and fabricating stereolithographic templates, as well as to highlight the limitations of various template designs. This scoping review aimed to identify publications on digital workflows for designing and fabricating stereolithographic templates in computer-assisted porcelain laminate veneer preparation. A systematic search on MEDLINE/PubMed, Web of Science and Scopus identified English-language articles published from 2014 to March 2024. Eligible articles focused on digitally designed and fabricated tooth reduction templates for porcelain laminate veneers, excluding conventional tooth preparation procedures for tooth reduction assessment. Seven clinical reports were included, demonstrating various 3D data acquisition techniques for virtual patient generation. All articles described virtual diagnostic wax-ups on digital casts, with two using a virtual articulator. Only five articles documented chair-side mock-ups with resin trial restorations to evaluate planned dental esthetics. Additionally, virtual tooth preparation prior to templates design was included in only four articles. The templates were designed using different software and ranged from simple designs with access windows to complex stacked templates with rotary instrument sleeved windows. Each template design had limitations affecting tooth reduction accuracy. All articles reported printing templates in clear acrylic resin using different technologies. In conclusion, the review highlights a lack of standardization in the digital workflow for designing stereolithographic templates for PLVs. Establishing a sound protocol for designing the tooth reduction templates is essential to ensure the accuracy and consistency of veneer preparation.

This paper explores methodologies to enhance the integration of a green supply chain circular economy within smart cities by incorporating machine learning technology. To refine the precision and effectiveness of the prediction model, the gravitational algorithm is introduced to optimize parameter selection in the support vector machine model. A nationwide prediction model for green supply chain economic development efficiency is meticulously constructed by leveraging public economic, environmental, and demographic data. A comprehensive empirical analysis follows, revealing a noteworthy reduction in mean squared error and root mean squared error with increasing iterations, reaching a minimum of 0.007 and 0.103, respectively—figures that are the lowest among all considered machine learning models. Moreover, the mean absolute percentage error value is remarkably low at 0.0923. The data illustrate a gradual decline in average prediction error and standard deviation throughout the model optimization process, indicative of both model convergence and heightened prediction accuracy. These results underscore the significant potential of machine learning technology in optimizing supply chain and circular economy management. The paper provides valuable insights for decision-makers and researchers navigating the landscape of sustainable development.

IntroductionThis paper aims to explore the intersection of corporate social responsibility (CSR) and public health within the context of digital platforms. Specifically, the paper explores the impact of digital platforms on the sustainable development practices of enterprises, seeking to comprehend how these platforms influence the implementation of environmental protection policies, resource management, and social responsibility initiatives.MethodsTo assess the impact of digital platforms on corporate environmental behavior, we conducted a questionnaire survey targeting employees in private enterprises. This survey aimed to evaluate the relationship between the adoption of digital platforms and the implementation of environmental protection policies and practices.ResultsAnalysis of the survey responses revealed a significant positive correlation between the use of digital platforms and the environmental protection behavior of enterprises (r=0.523;p

Due to its special working conditions, offshore wind turbine will bear large direct and indirect loads under the combined action of air flow and wave flow. In this paper, a variable pitch system composed of variablepitch motorand variable pitch bearing is improved, and the characteristics of system's bending moment, torque, vibration and other physical quantities under the action of multiple physical loads are verified, and the mechanical response characteristics of floating wind turbine under the control of unified variable pitch and independent variable pitch are studied under the running conditions at sea. The results show that mechanical structure of uniform pitch is compared with that of independent pitch, the independent variable pitch structure can effectively reduce the mean oscillation value of wind turbine tower in the parallel direction of air flow by optimizing control strategy, and reduce the thrust at the hub of wind turbine and the bending moment at the root of tower, but increase the vibration frequency and fatigue load of offshore wind turbine tower along parallel direction of air flow. Reduce the fatigue life of equipment. The research results can be used as a reference to reduce the variable pitch control and vibration suppression of offshore wind turbines and improve the reliability of wind turbines.

INTRODUCTION: As a renewable and clean use of energy, wind power generation has a very important role in the new energy generation industry. For the many parts of various wind turbines, the safety and reliability of wind turbine blades are very important. OBJECTIVES: The energy spectrum simulation algorithm included in the wavelet analysis method is used to simulate and analyzewind turbine blade damage, to verify the correctness and validity of wind turbine blade damage analysis. METHODS: Matlab simulation is used to introduce the experiments related to the static and dynamic detection of fiber grating sensors, analyze the signal characteristics of the wind turbine blade when it is damaged by the impact, and provide a basis for the analysis of the external damage of large wind turbine blade. RESULTS: The main results obtained in this paper are the following. By analyzing the decomposition of wavelet packets, the gradient change of wavelet impact energy spectrum before and after the wavelet damage was obtained and compared with the histogram, and the impact energy spectrum of each three-dimensional wavelet energy packet in the image was compared and analyzed, which can well realize the recognition of wavelet damage gradient for solid composite materials. CONCLUSION: With the help of Matlab simulation to collect the impact response signal, using the wavelet packet energy spectrum method to analyze the signal, can derive the characteristics of wind turbine blade damage.

In the era of information technology advancement, big data analysis has emerged as a crucial tool for government governance. Despite this, corruption remains a challenge at the grass-roots level, primarily attributed to information asymmetry. To enhance the efficacy of corruption prevention and control in grass-roots government, this study introduces the concept of data platform management and integrates it with the “5W” (Who, What, When, Where, Why) analysis framework. The research is motivated by the observation that existing studies on corruption prevention primarily concentrate on the formulation of laws and regulations, neglecting the potential improvement in actual effectiveness through the utilization of data platforms and analytical frameworks. The research employs methodologies grounded in the Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis framework, the Plan, Do, Check, Act (PDCA) cycle analysis framework, and the 5W analysis framework. Throughout the iterative process of implementing data platform management, various timeframes are established, and the impact of the three models is evaluated using indicators such as public participation and government satisfaction. The research reveals that the SWOT framework can formulate targeted strategies, the PDCA framework continuously optimizes work processes, and the 5W framework profoundly explores the root causes of corruption. The outcomes indicate a 10.76% increase in the public participation level score with the 5W model, rising from 71.67%, and a 23.24% increase in the governance efficiency score, reaching 66.12%. The SWOT model excels in case handling prescription and corruption reporting rate. The synergistic application of the three models demonstrates a positive impact. In conclusion, the amalgamation of data platform management and a multi-model approach effectively enhances the corruption prevention capabilities of grass-roots governments, offering insights for the establishment of transparent and efficient grass-roots governance.

Abstract Objective The aim of this article is to evaluate the cost-effectiveness of abemaciclib plus endocrine therapy (ABE + ET) vs. ET as adjuvant treatment for high-risk hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) early breast cancer in China. Methods From the perspective of the Chinese health care system, a 5-state Markov model was developed with a lifetime horizon. Data of the monarchE phase III clinical trial were used to model the invasive disease-free survival (iDFS) and standard parameters models were used for data extrapolation. Costs were obtained from national data sources, expert opinions and published literature using 2023 US dollars and discounted by 5%. The results were evaluated in terms of life-years (LYs) and quality-adjusted life-years (QALYs). Sensitivity analyses and scenario analyses were performed to test the robustness of the basic results. Results In the base-case analysis result, the model projected improved outcomes (by 0.65 LYs and 0.72 QALYs) and increased costs (by $16,057.72) for incremental cost-effectiveness ratios (ICERs) of $24,841/LY and $22,385/QALY for ABE + ET vs. ET patients. The results in scenario analysis estimated the ICERs of ABE + ET treatment to be $16,959/LY and $15,264/QALY in a mixture cure model, and $13,560/LY and $12,191/QALY in a non-mixture cure model. The model was sensitive to outcome discount rate and utility of iDFS. Conclusion ABE + ET might not have an economic advantage over ET at a willingness-to-pay (WTP) threshold of one time the per capita GDP in China, but was expected to be more cost-effective at a WTP threshold of three times the per capita GDP. Further analysis will be conducted once data from longer-term studies become available.

Abstract Background This study aimed to assess the methodological quality of the systematic reviews/meta-analyses (SRs/MAs) of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using A Measurement Tool to Assess systematic Reviews (AMSTAR2) and to explore the potential influencing factors. Methods PubMed, EMBASE and Cochrane Library databases were searched for relevant studies. AMSTAR2 was used for evaluating the methodological quality of eligible SRs/MAs. Differences between methodological characteristics of SRs/MAs were compared using chi-square tests. The intra-class correlation coefficient (ICC) was used to assess reviewer agreement in the pre-experiment. Multivariate regression analysis was used to identify potential factors affecting methodological quality. Results A total of 45 SRs/MAs were included. After AMSTAR2 evaluation, only two (4.4%) of 45 SRs/MAs were moderate, three (6.7%) were rated as low quality, and the remainder 40 (88.9%) were rated as critically low quality. Among the 16 items of AMSTAR2, item 3 and item 10 had the poorest adherence. Item 4 received the most significant number of "Partial Yes" responses. Univariable analysis indicated that there were significant differences in methodological quality in SRs between different continents (P = 0.027) as well as between preregistered SRs and those that were not (P = 0.004). However, in multivariate analysis, there was no significant association between methodological quality and the following research characteristics: publication year, continent, whether reporting followed Preferred Reporting Items for Systematic Reviews (PRISMA), preregistration, funding support, randomized controlled trials (RCT) enrollment, whether SR was published in the Cochrane Database of Systematic Reviews (CDSR), and whether with meta-analysis. Additionally, subgroup analysis based on interventional SRs/MAs showed that continent was independently associated with the methodological quality of SRs/MAs of CP/CPPS via univariable and multivariate analysis. Conclusions Our study demonstrates that the methodological quality of SRs/MAs of CP/CPPS was generally poor. SRs/MAs of CP/CPPS should adopt the AMSTAR2 to enhance their methodological quality.

Background and objective Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2. Methods Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2. Results The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2. Conclusion miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.

Abstract Secukinumab is effective in treating patients with moderate‐to‐severe plaque psoriasis. However, most studies assessing its effectiveness in routine clinical settings in China are mostly single‐center studies with a limited sample size. The objective of this study was to assess secukinumab's efficacy, treatment patterns, and characteristics in patients with moderate‐to‐severe plaque psoriasis. This 24‐week, multicenter (n = 5) retrospective study analyzed the data of Chinese adult patients with moderate‐to‐severe plaque psoriasis who initiated secukinumab treatment between May 2019 and March 2020. The Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator's Global Assessment Modified 2011 (IGA mod 2011), and Dermatology Life Quality Index (DLQI) were assessed. Dermatologists documented the treatment dosage and modification reasons. Of the 244 secukinumab‐naïve patients, most were men (73.4%, 179/244) and weighed 60–90 kg (72.8%, 177/243). The mean (SD) age at secukinumab initiation was 38.1 (11.6) years, and the disease duration was 13.5 (7.9) years. Most patients (97.1%, 237/244) received secukinumab 300 mg. At weeks 4, 12, 16, and 24, the proportion of patients achieving PASI 75 (≥75% reduction from baseline) was 40.0%, 92.1%, 88.4%, and 88.9%, respectively; PASI 90 was 15.0%, 73.7%, 81.4%, and 68.3%, respectively; and PASI 100 was 8.7%, 40.8%, 58.1%, and 41.3%, respectively. During the same periods, BSA and IGA mod 2011 showed similar improvement trends. An increasing proportion of patients achieved DLQI of 0–1 (21.6%, 65.7%, 75.0%, and 80.3%, respectively). Treatment modification was highest at week 12. The average interval between two administrations after week 4 was 62.95 days. Secukinumab was highly effective in improving the PASI, IGA, BSA, and DLQI in Chinese patients with moderate‐to‐severe plaque psoriasis throughout the first 24 weeks. The treatment pattern for Chinese patients differs from that in the clinical guidelines.

Abstract Background Multitarget tyrosine kinase inhibitors (mTKIs) such as Regorafenib and Sorafenib have already been approved for the treatment of many solid tumours. However, the efficacy of mTKIs in colorectal cancer (CRC) is limited; the underlined mechanism remains largely elusive. Our study was aimed to find out the resistance mechanism of mTKIs in CRC. Methods RNA sequencing was used to identify the expression of Activin A receptor-like type 1 (ACVRL1) under the treatment of mTKIs. Gain/loss-of-function experiments were performed to assess the biological function of ACVRL1 in resistance to mTKIs. The underlying mechanisms of ACVRL1-mediated mTKI resistance were investigated by using liquid chromatography-mass spectrometry assays (LC-MS), co-immunoprecipitation assays (Co-IP), chromatin immunoprecipitation assays, ubiquitination assays, dual luciferase reporter assays, etc. Results RNA sequencing identified the activation of ACVRL1 under the treatment of mTKIs in CRC cells. ACVRL1 knockdown and overexpression significantly affects the sensitivity of CRC cells to mTKIs both in vitro and vivo. Mechanistically, we found the β-catenin/TCF-1-KCNQ1OT1/miR-7-5p axis mediated the activation of ACVRL1. Furthermore, LC-MS assays indicated the interaction between ACVRL1 and glutathione peroxidase 2(GPX2) protein. IP assay defined ACVRL1 truncation (282–503aa) could be responsible for interacting with GPX2, and rescue experiments with ACVRL1 truncations confirmed the importance of this interaction in driving mTKI resistance. Co-IP assays confirmed that ACVRL1 associates with ubiquitin-specific peptidase 15(USP15) which directly deubiquinates GPX2 at the K187(K, lysine) site, leading to the accumulation of GPX2 protein. Rescue experiments performed with the lysine mutants in GPX2 CRISPR knockout cell model confirmed the importance of GPX2 K187 mutant. As a result, the increased ROS clearance and decreased cell apoptosis eventually lead to mTKI resistance in CRC. Conclusions Our results demonstrate that the Wnt/β-catenin/KCNQ1OT1/miR-7-5p/ACVRL1/GPX2 biological axis plays a vital role in CRC, targeting which may be an effective approach for overcoming mTKI resistance.

Abstract Background Although WD repeat and high-mobility group box DNA binding protein 1 (WDHD1) played an essential role in DNA replication, chromosome stability, and DNA damage repair, the panoramic picture of WDHD1 in human tumors remains unclear. Hence, this study aims to comprehensively characterize WDHD1 across 33 human cancers. Methods Based on publicly available databases such as TCGA, GTEx, and HPA, we used a bioinformatics approach to systematically explore the genomic features and biological functions of WDHD1 in pan-cancer. Results WDHD1 mRNA levels were significantly increased in more than 20 types of tumor tissues. Elevated WDHD1 expression was associated with significantly shorter overall survival (OS) in 10 tumors. Furthermore, in uterine corpus endometrial carcinoma (UCEC) and liver hepatocellular carcinoma (LIHC), WDHD1 expression was significantly associated with higher histological grades and pathological stages. In addition, WDHD1 had a high diagnostic value among 16 tumors (area under the ROC curve [AUC] > 0.9). Functional enrichment analyses suggested that WDHD1 probably participated in many oncogenic pathways such as E2F and MYC targets (false discovery rate [FDR]

Abstract Tumors have evolved in various mechanisms to evade the immune system, hindering the antitumor immune response and facilitating tumor progression. Immunotherapy has become a potential treatment strategy specific to different cancer types by utilizing multifarious molecular mechanisms to enhance the immune response against tumors. Among these mechanisms, the ubiquitin–proteasome system (UPS) is a significant non-lysosomal pathway specific to protein degradation, regulated by deubiquitinating enzymes (DUBs) that counterbalance ubiquitin signaling. Ubiquitin-specific proteases (USPs), the largest DUB family with the strongest variety, play critical roles in modulating immune cell function, regulating immune response, and participating in antigen processing and presentation during tumor progression. According to recent studies, the expressions of some USP family members in tumor cells are involved in tumor immune escape and immune microenvironment. This review explores the potential of targeting USPs as a new approach for cancer immunotherapy, highlighting recent basic and preclinical studies investigating the applications of USP inhibitors. By providing insights into the structure and function of USPs in cancer immunity, this review aims at assisting in developing new therapeutic approaches for enhancing the immunotherapy efficacy.

Bound states in the continuum (BICs), which are characterized by their high-quality factor, have become a focal point in modern optical research. This study investigates BICs within a periodic array of dielectric resonators, specifically composed of a silicon rectangular bar coupled with four silicon rectangular blocks. Through the analysis of mode coupling, we demonstrate that the interaction between the blocks significantly modulates the eigenmodes of the bar, causing a redshift in all modes and enabling the formation of electromagnetically induced transparency based on BICs (EIT-BIC). Unlike typical EIT mechanisms, this EIT-BIC arises from the coupling of “bright” and “dark” modes both from the rectangular bar, offering novel insights for nanophotonic and photonic device design. Further, our systematic exploration of BIC formation mechanisms and their sensing properties by breaking structural symmetries and changing environmental refractive indices has shed light on the underlying physics. This research not only consolidates a robust theoretical framework for understanding BIC behavior but also paves the way for high-quality factor resonator and sensor development, as well as the precise control of photonic states. The findings significantly deepen our understanding of these phenomena and hold substantial promise for future photonic applications.

The impact of frequent water deficits on dominant tree species in boreal forests has received increased attention, particularly towards addressing the global climate change scenarios. However, the impacts of coupled light intensity and water deficit in the regeneration and growth of Larix gmelinii seedlings, a dominant species in China’s boreal forests, are still unclear. We conducted a dual-factor controlled experiment with four light intensities (natural sunlight, 50% shading, 75% shading, and 90% shading) and three soil water conditions (80%, 60%, and 40% soil saturated water content). The results showed that the coupling of light and water has a significant effect on the growth and development of Larix gmelinii seedlings. In 40% of the saturated soil moisture content, net photosynthetic rate, transpiration rate, chlorophyll a, and total phenol—leaf were significantly lower than the same light conditions under 80% soil saturated water content. Under the coupling treatment of 60% soil saturated water content and 50% shading treatment, the plant height increment, net photosynthetic rate, stomatal conductance, transpiration rate, chlorophyll a, and phenolic compound content were significantly higher than those of other coupling treatments; however, more than 75% shading inhibited photosynthetic parameters, chlorophyll a, total flavonoid—leaf, and total flavonoid—branch. Our results have important implications for forest management practices; they provide a scientific reference for the early growth of Larix gmelinii seedlings under the coupling of light and water and promote the survival and growth of seedlings.

The oceans and seas are vital resources for human life and fundamental to global economic growth. With the expansion of globalization and increasing demand for resource exploitation, the ocean economy has emerged as a critical support for economic growth and a significant concern for many. However, the exploitation of marine resources often leads to ecological damage and environmental pollution, seriously threatening the long-term viability of the marine economy. Measures must be implemented to balance ecological protection and economic development for sustainable growth in the marine sector. This investigation synthesizes over a decade’s worth of data from various coastal cities, incorporating insights from national databases, international reports, and scholarly articles, resulting in an analysis of more than 500 data points. Through the application of a rigorous quantitative approach and a dual fixed-effect model, the study delves into the dynamics between ocean governance and economic development. By analyzing a broad and representative dataset, the research provides an exhaustive overview of global ocean governance frameworks and the current state of the marine economy. The statistical analyses unveil the complexity and diversity of factors influencing the development and governance of marine economies. This paper explores the interplay between marine economic development and ocean governance, evaluating the impact of governance on marine economic progression within the context of environmental optimization. Furthermore, it proposes policy interventions aimed at fostering the sustainable growth of marine economies, ensuring the conservation of marine ecosystems, and pursuing overarching long-term global growth ambitions.

We aimed to explore the anti-obesity mechanism from the microbiome, metabolome, and transcriptome viewpoints, focusing on the sulfated polysaccharides found in the cooking liquid of Apostichopus japonicus (CLSPAJ) to explore the potential mediators of the anti-obesity effects in mice fed a high-fat diet (HFD). The mice treated with CLSPAJ showed a decrease in obesity and blood lipid levels. Gut microbiome dysbiosis caused by the HFD was reversed after CLSPAJ supplementation, along with increased levels of indole-3-ethanol, N-2-succinyl-L-glutamic acid 5-semialdehyde, and urocanic acid. These increases were positively related to the increased Akkermansia, Lactobacillus, Roseburia, and Phascolarctobacterium. Transcriptome analysis showed that B cell receptor signaling and cytochrome P450 xenobiotic metabolism were the main contributors to the improvement in obesity. Metabolome–transcriptome analysis revealed that CLSPAJ reversal of obesity was mainly due to amino acid metabolism. These findings suggest that CLSPAJ could be a valuable prebiotic preparation for preventing obesity-related diseases.

Accurate segmentation of brain tumors from magnetic resonance images is the key to the clinical diagnosis and rational treatment of brain tumor diseases. Recently, convolutional neural networks have been widely used in biomedical image processing. 3D U-Net is sought after because of its excellent segmentation effect; however, the feature map supplemented by the skip connection is the output feature map after the encoder feature extraction, and the loss of original detail information in this process is ignored. In the 3D U-Net design, after each layer of convolution, regularization, and activation function processing, the detailed information contained in the feature map will deviate from the original detailed information. For skip connections, the essence of this design is to supplement the detailed information of the original features to the decoder; that is, in the decoder stage, the more original the skip connection-supplemented feature maps are, the more easily the decoder can achieve a better segmentation effect. To address this problem, this paper proposes the concept of a front-skip connection. That is, the starting point of the skip connection is adjusted to the front to improve the network performance. On the basis of this idea, we design a front-skip connection inverted residual U-shaped network (FS Inv-Res U-Net). First, the front-skip connections are applied to three typical networks, DMF Net, HDC Net, and 3D U-Net, to verify their effectiveness and generalization. Applying our proposed front-skip connection concept on these three networks improves the network performance, indicating that the idea of a front-skip connection is simple but powerful and has out-of-the-box characteristics. Second, 3D U-Net is enhanced using the front-skip connection concept and the inverted residual structure of MobileNet, and then FS Inv-Res U-Net is proposed based on these two ideas. Additionally, ablation experiments are conducted on FS Inv-Res U-Net. After adding the front-skip connection and the inverted residual module to the backbone network 3D U-Net, the segmentation performance of the proposed network is greatly improved, indicating that the front-skip connection and the inverted residual module help our brain tumor segmentation network. Finally, the proposed network is validated on the validation dataset of the public datasets BraTS 2018 and BraTS 2019. The Dice scores of the validation results on the enhanced tumor, whole tumor, and tumor core were 80.23%, 90.30%, and 85.45% and 78.38%, 89.78%, and 83.01%, respectively; the hausdorff95 distances were 2.35, 4.77, and 5.50 mm and 4, 5.57, and 6.37 mm, respectively. The above results show that the FS Inv-Res U-Net proposed in this paper achieves the same evaluation indicators as advanced networks and provides accurate brain tumor segmentations.

Abstract Since the handover of the sovereignty of Hong Kong from Britain to China in 1997, convergence between Mainland China and Hong Kong has gradually emerged. During this process, young people have engaged in demonstrations to express their dissatisfaction with government policies and limited socio-economic progression. However, the underlying reasons for their dissatisfaction have not been fully investigated. This study investigates their perceived challenges and opportunities during the convergence, with the objective of identifying the factors affecting the Mainland China–Hong Kong convergence and examining young people’s perceived challenges and opportunities during the convergence. Mixed research methods of focus groups and a survey were adopted. Ten focus groups with 83 participants were conducted to collect qualitative data on the factors relating to convergence. Based on the qualitative data, a questionnaire was constructed to investigate young people’s perceived challenges and opportunities during the convergence, using a sample of 1253 young people. Ordinary least-squares regression was applied to analyse the relationships among identified factors. The study found that Hong Kong’s youth tended to regard the Mainland China–Hong Kong convergence as an opportunity for socio-economic progression, and they identified three challenges during the convergence. It also revealed that young people’s higher education, perceived housing challenges, and perceived socio-economic challenges are negatively related to the convergence, whereas their perceived challenges associated with entrepreneurship and innovation are positively related to the convergence. The development of more well-balanced and mutually beneficial policies that satisfy the needs of young people will lead to a higher acceptance of the convergence. As such, young people will be more willing to embrace the opportunities and face the challenges brought about by the convergence, resulting in a more harmonious society and socio-economic progression.

Fibroblasts are important components of animal tissues such as muscle and skin, as they are the major producers of various matrix proteins. Matrix proteins such as collagen play an important role in meat products by providing unique nutrition, texture, and flavor. Cultured meat is an innovative meat alternative produced by culturing animal cells, but currently, relatively few studies have been conducted using fibroblasts as seed cells for cultured meat manufacturing. In this work, we first developed an innovative digestion-friction method for isolating fibroblasts from porcine skin efficiently and cost-effectively. After optimizing the enzymatic digestion and physical friction conditions, 2.39 ± 0.28 × 105 fibroblasts were obtained from 1 cm2 of porcine skin tissue, which was about 9 times higher than the conventional tissue explant method. In addition, we identified an edible bio-ink composed of gelatin and chitosan that has good printing properties and supports fibroblast adhesion and growth. Furthermore, we fabricated fibroblast-based cultured meat by 3D printing with an initial cell density of 1.0 × 107 mL−1 and evaluated its texture and nutritional properties. This work provides valuable insights and references for introducing fibroblasts into the production of cultured meat that is more comparable to structured animal meat.

In order to enhance the operational efficiency of the healthcare industry, this paper investigates a medical information diagnostic platform through the application of swarm and evolutionary algorithms. This paper begins with an analysis of the current development status of medical information diagnostic platforms based on Chat Generative Pre-trained Transformer (ChatGPT) and Internet of Things (IoT) technology. Subsequently, a comprehensive exploration of the advantages and disadvantages of swarm and evolutionary algorithms within the medical information diagnostic platform is presented. Further, the optimization of the swarm algorithm is achieved through reverse learning and Gaussian functions. The rationality and effectiveness of the proposed optimization algorithm are validated through horizontal comparative experiments. Experimental results demonstrate that the optimized model achieves favorable performance at the levels of minimum, average, and maximum algorithm fitness values. Additionally, preprocessing data in a 10 * 10 server configuration enhances the algorithm’s fitness values. The minimum fitness value obtained by the optimized algorithm is 3.56, representing a 3 % improvement compared to the minimum value without sorting. In comparative experiments on algorithm stability, the optimized algorithm exhibits the best stability, with further enhancement observed when using sorting algorithms. Therefore, this paper not only provides a new perspective for the field of medical information diagnostics but also offers effective technical support for practical applications in medical information processing.

Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P

Background: As commonly used harvest residue management practices in subtropical plantations, stem only harvesting (SOH) and whole tree harvesting (WTH) are expected to affect soil organic carbon (SOC) content. However, knowledge on how SOC and its fractions (POC: particulate organic carbon; MAOC: mineral-associated organic carbon) respond to different harvest residue managements is limited. Methods: In this study, a randomized block experiment containing SOH and WTH was conducted in a Chinese fir (Cunninghamia lanceolata) plantation. The effect of harvest residue management on SOC and its fractions in topsoil (0–10 ​cm) and subsoil (20–40 ​cm) was determined. Plant inputs (harvest residue retaining mass and fine root biomass) and microbial and mineral properties were also measured. Results: The responses of SOC and its fractions to different harvest residue managements varied with soil depth. Specifically, SOH enhanced the content of SOC and POC in topsoil with increases of 15.9% and 29.8%, respectively, compared with WTH. However, SOH had no significant effects on MAOC in topsoil and SOC and its fractions in subsoil. These results indicated that the increase in POC induced by the retention of harvest residue was the primary contributor to SOC accumulation, especially in topsoil. The harvest residue managements affected SOC and its fractions through different pathways in topsoil and subsoil. The plant inputs (the increase in fine root biomass induced by SOH) exerted a principal role in the SOC accumulation in topsoil, whereas mineral and microbial properties played a more important role in regulating SOC dynamics than plants inputs in subsoil. Conclusion: The retention of harvest residues can promote SOC accumulation by increasing POC, and is thus suggested as an effective technology to enhance the soil carbon sink for mitigating climate change in plantation management.

IntroductionThe Omicron variant has rapidly spread throughout the world compared to the Delta variant and poses a great threat to global healthcare systems due to its immune evasion and rapid spread. Sex has been identified as a factor significantly associated with COVID-19 mortality, but it remains unclear which clinical indicators could be identified as risk factors in each sex group and which sex-specific risk factors might shape the worse clinical outcome, especially for Omicrons. This study aimed to confirm the relationship between sex and the progression of the Omicron variant and to explore its sex-biased risk factors.MethodsWe conducted a retrospective study including 1,132 hospitalized patients with the COVID-19 Omicron variant from 5 December 2022 to 25 January 2023 at Shanghai General Hospital, and the medical history data and clinical index data of the inpatients for possible sex differences were compared and analyzed. Then, a sex-specific Lasso regression was performed to select the variables significantly associated with critical illness, including intensive care unit admission, invasive mechanical ventilation, or death. A logistic regression was used to construct a sex-specific predictive model distinctively for the critical illness outcome using selected covariates.ResultsAmong the collected 115 clinical indicators, up to 72 showed significant sex differences, including the difference in merit and the proportion of people with abnormalities. More importantly, males had greater critical illness (28.4% vs. 19.9%) and a significantly higher intensive care unit occupancy (20.96% vs. 14.49%) and mortality (13.2% vs. 4.9%), and males over 80 showed worse outcomes than females. Predictive models (AUC: 0.861 for males and 0.898 for females) showed 12 risk factors for males and 10 for females. Through a comprehensive sex-stratified analysis of a large cohort of hospitalized Omicron-infected patients, we identified the specific risk factors for critical illness by developing prediction models.DiscussionSex disparities and the identified risk factors should be considered, especially in the personalized prevention and treatment of the COVID-19 Omicron variant.