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Cancer immunotherapy has been successful in patients with different types of cancers, but its efficacy in treating certain types of colorectal cancer (CRC) is limited. The aim of this study was to explore whether sea cucumber polysaccharides (SCP) could impact resistance to anti-programmed cell death-1 (anti-PD1) immunotherapy of CRC and the role of microbiota in mediating their effects. Mice inoculated with immunotherapy resistant CT-26 CRC cells were pretreated with SCP, followed by treatment with/without the anti-PD1 antibody. SCP alone exhibited no inhibitory effect on tumor growth, but they drastically enhanced the efficacy of anti-PD1 treatment, which alone showed minimal effect on tumor development. Compared to anti-PD1 only treatment, a combination of SCP and anti-PD1 increased CD8 + T cells, especially IFN-γ + cytotoxic CD8 + T cells, and decreased regulatory CD4 + T cells. SCP modulated gut microbiota and increased the relative abundance of bacteria including Bifidobacterium and Faecalibaculum . A fecal microbiota transplantation experiment showed that the sensitizing effect of SCP was at least partly mediated by microbiota. Furthermore, oral supplementation of Bifidobacterium pseudolongum or Faecalibaculum rodentium recapitulated the beneficial effect of SCP in potentiating anti-PD1 efficacy. Altogether, these findings demonstrated that SCP could be potentially developed as a dietary adjuvant to increase the efficacy of immunotherapy in CRC.

Background: Adolescent depression is increasing globally, and family conflict may contribute to its transmission across generations. However, longitudinal evidence on these dynamics remains sparse. This study examines the longitudinal associations between family conflict and adolescents' and parents' depressive symptoms from three waves of data., Methods: Data from the 2016-2020 China Family Panel Studies (CFPS) were analyzed, including 1,772 adolescents (Mean age = 12.4, SD = 1.68 in 2016) and their parents. Family conflict was measured using three questions from adolescents, while depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CESD). Multiplelinear regression, latent growth models (LGM), and cross-lagged panel models (CLPM) were employed to examine longitudinal associations between family conflict and depressive symptoms., Results: The results revealed that family conflict correlated with adolescents' depressive symptoms (r = 0.580,p < 0.001). Adolescents' depressive symptoms also exacerbated family conflict (β1 = 0.030, p < 0.05; β2 = 0.032, p < 0.01) across three waves, while family conflict had a limited contribution to parents' depressive symptoms. Mothers' depressive symptoms influenced adolescents' depressive symptoms significantly (β = 0.043,p < 0.05), while adolescents' depressive symptoms were transmitted to fathers' depressive symptoms (β = 0.080,p < 0.01) between Wave 2 and Wave 3. Moreover, the mother's education level negatively predicted adolescents' depressive symptoms (β = -0.296,p < 0.05)., Conclusions: Family conflict plays a critical role in adolescents' depressive symptoms and its intergenerational transmission. The findings underscore the pivotal role of family dynamics in mental health, especially in the development of adolescents' depressive symptoms. Interventions aimed at reducing family conflict may help mitigate depressive symptoms across generations., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The ethical sanction for conducting the survey was granted by the Biomedical Ethics·Review Committee of Peking University, under the approval code IRB00001052-14010., (© 2025. The Author(s).)

Background: The association between androgen deprivation therapy (ADT) and dementia risk is controversial, and the dose-response relationship between them remains unclear., Objective: We aim to further clarify the relationship between ADT and dementia risk., Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched up to September 2024 to identify relevant studies. A meta-analysis was conducted using hazard ratios (HR) and 95% confidence intervals (CI) as pooled indicators. The robust error meta-regression (REMR) approach was performed to explore the dose-response relationship. Heterogeneity was assessed using I² statistics, and subgroup analysis, sensitivity analysis, and meta-regressions were conducted. Publication bias was evaluated with a funnel plot and Egger's test., Results: Our meta-analysis of 21 studies involving 2,278,835 patients revealed that ADT significantly increased the risk of overall dementia (HR = 1.14, 95% CI: 1.06-1.20) and Alzheimer's disease (AD) (HR = 1.15, 95% CI: 1.06-1.23), but not non-AD dementia (HR = 1.01, 95% CI: 0.89-1.16). For ADT subtypes, anti-androgens increased the risk of overall dementia (HR = 1.27, 95% CI: 1.09-1.49), particularly for AD (HR = 1.53, 95% CI: 1.19-1.97), while Luteinizing hormone-releasing hormone therapy and bilateral orchiectomy were not linked to the risk of any dementia subtype. A bell-shaped non-linear relationship between ADT duration and dementia risk was observed, with the highest risk observed at 15.5 to 21.5 months (HR = 1.25), which was confirmed by subgroup analysis for AD., Conclusions: The risk of overall dementia and AD were found to be significantly associated with ADT in a bell-shaped dose-response effect., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) plays an important role in mitosis and is involved in tumor progression of human bladder and prostate cancer. However, its pathological effects on renal cell cancer (RCC) remain unknown. Here, we aimed to assess the impact of ESCO1 down-regulation in RCC cells and explore its role as potential prognosis biomarker for RCC., Methods: This is a retrospective study. Tumor samples from 263 RCC patients were collected, and survival data were analyzed to detect the relationship between ESCO1 expression and patient survival. For mechanistic exploration, the impact of silence ESCO1 on proliferation, migration and apoptosis were studied in ESCO1-knockdown RCC cells., Results: Significantly over-expression of ESCO1 was observed in renal tumor tissues. ESCO1 expression was related to the malignant degree and a high expression was associated with unfavorable prognosis in RCC patients. Moreover, down-regulation of ESCO1 attenuated cell proliferation and migration. The flow cytometry assay revealed that the knockdown of ESCO1 inhibited RCC cells from entering the G1 phase., Conclusions: The increased ESCO1 expression in renal tumor tissues might be a useful biomarker for prognosis of RCC patients. Knockdown of ESCO1 undermined proliferation, migration of renal cancer cells, and induced the apoptosis of renal cancer cells., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Phthalate esters (PAEs) are broadly utilized as plasticizers in industrial products, posing a significant threat to ecological security and human health. Lipase is a kind of green biocatalyst with the ability to degrade PAEs, but its application is limited due to its low stability and poor reusability. Herein, lipase from Candida rugosa (CRL) was immobilized into an organic ligand replacement MOFs (MAF-507) and cysteine modification and glutaraldehyde cross-linking were simultaneously performed to synthesize immobilized lipase (Cys-CRL@GA@MAF-507) using a one-pot method. Compared with free CRL, Cys-CRL@GA@MAF-507 not only increased its relative activity to 1.66-fold as well as improved its thermostability to 247% at 30 °C, but also constructed a synergistic system of combined adsorption and biodegradation to remove PAEs. In actual water environment, Cys-CRL@GA@MAF-507 could adsorb 88.56% of dibutyl phthalate (DBP) within 5 min and degrade 94.6% of DBP within 48 h, respectively. Therefore, this research developed an innovative bifunctional enzyme@MOFs biocomposite with synergistic adsorption and biodegradation for the efficient removal of PAEs, which provides a new platform for the elimination of pollutants in environmental remediation and industrial application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The developing foetus is particularly sensitive to neurotoxic metals. The placenta is considered an ideal tissue for biomonitoring prenatal cumulative metal exposure. Based on the Ma'anshan Birth Cohort study (MABC) in China, this study investigated associations of non-essential metals and essential metals in placenta, including arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), cobalt (Co), selenium (Se) and zinc (Zn), with cognitive development in children among 1586 mother-child pairs. Also, we explored potential interactions between the metals and modifying role of the sex. Children's cognitive development was tested at preschool age using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Analyses used multiple linear regression, Bayesian kernel machine regression (BKMR), the quantile g-computation (Qgcomp), interaction and marginal effects models, and restricted cubic spline in R and STATA. In this study, the geometric means [GMs (SD)] for placental metal concentrations were 8.10 (7.54) ng/g for As, 32.32 (29.20) ng/g for Cd, 11.89 (13.33) ng/g for Hg, 32.21 (28.24) ng/g for Pb, 15.05 (8.91) ng/g for Co, 508.82 (192.35) ng/g for Se, 18481.60 (14030.61) ng/g for Zn. In individual models, placental As levels were negatively associated with the Fluent Reasoning Index (FRI) in the overall sample. Cd levels were negatively associated with the full-scale intelligence quotient (FSIQ), the Verbal Comprehension Index (VCI) and the Visual Spatial Index (VSI). The four metal mixture (As, Cd, Hg and Pb) was negatively associated with FSIQ, VCI, VSI and FRI. Placental Cd and As were the largest contributors to the negative mixture association on the FSIQ. The negative associations of placental As, Cd and Hg with FSIQ in children were gradually attenuated with increasing Zn and Se. After stratifying by sex, the individual and mixture associations between elevated placental non-essential metal exposures and reduced cognitive scores were significant only in boys. Zn and Se were the major contributors to the positive mixture associations on the FSIQ. In summary, prenatal exposure to As, Cd and Hg has sex-specific adverse associations on children's cognitive development. A more accurate assessment of the necessity of prenatal supplementation of micronutrients including Zn and Se is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The mechanism by which coronavirus-defective viral genomes (DVGs) affect coronavirus and host cells during infection remains unclear. A variety of DVGs with different RNA structures can be synthesized from coronavirus-infected cells, and these DVGs can also encode proteins. Consequently, in the present study, we first dissected the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, and then examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions., Methods: To dissect the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, DVG 2.2 and DVG 5.1, which were previously identified in coronavirus-infected cells, and their mutants were constructed followed by transfection. Western blot and RT‒qPCR were used to detect the synthesis of protein and to quantify the synthesis of IFNβ and ISG15 mRNAs, respectively. To examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions, different naturally occurring DVGs were selected and constructed followed by transfection after or before coronavirus infection and by RT‒qPCR and hemagglutination assay., Results: These results suggested that (i) coronavirus-DVGs at the RNA, protein and combined levels have different effects on the synthesis of IFNβ and ISG15 mRNAs, (ii) coronavirus-DVGs can inhibit coronavirus replication at least partly through interferon signaling and (iii) different DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions., Conclusions: Coronavirus replication can be regulated by diverse coronavirus-derived DVGs at least partly through innate immunity. Such regulation may contribute to the pathogenesis of coronavirus. The DVG populations in coronavirus-infected cells with the ability to inhibit coronavirus replication are expected to be potential resources for the identification of antivirals at the level of RNA, protein or in combination, and the methods used in the current study can be used as a platform for this purpose., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Metal-metal bonding has played a pivotal role in advancing human technologies across various industrial sectors. As devices continue to miniaturize, there is an increasing need for efficient bonding techniques capable of achieving metal-metal bonds at smaller length scales. In this study, a facile but effective bonding technique is developed that enables the bonding of randomly oriented copper with copper nanomembranes under low temperatures and pressures. The fabricated copper nanomembranes, with a thickness of ≈50 nm and a width of 1 cm or above, exhibit a unique heterogeneous nanostructure, comprising copper nanocrystals along with nano-copper-oxide dispersions. Consequently, these copper nanomembranes display exceptional mechanical properties, including an ultra-low elastic modulus of ≈35 GPa, a remarkable yield strength of ≈1 GPa, and excellent ductility of ≈40%, overcoming the conventional strength-ductility trade-off observed in various copper alloys. Most importantly, these ultra-soft copper nanomembranes serve as metallic "glues", promoting grain growth across the bonding interface between randomly oriented copper surfaces. This process leads to an average interfacial shear strength of up to 73 MPa at room temperature, representing an approximate 35 times increase in bonding strength compared to direct copper-copper bonding achieved under identical temperature and pressure conditions., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

During the COVID-19 pandemic, the daily life of many patients with dermatological immune-mediated inflammatory diseases (DIMIDs), such as atopic dermatitis (AD), psoriasis, and vitiligo, was impacted by social restrictions caused by (fear of) morbidity, mortality associated with COVID-19, and vaccine hesitancy. This prospective observational, multicenter, multidisciplinary cohort study explored the impact of COVID-19 disease and vaccination on DIMIDs, specifically AD, psoriasis, and vitiligo. Data from patients with DIMIDs were collected as part of the Target2B! study (between February 2021 and October 2022). We analyzed the differences in baseline characteristics, risk of developing COVID-19, proportion of DIMIDs in patients reaching seroconversion upon vaccination per DIMID, and self-reported increase in DIMID activity by multivariable logistic regression and sensitivity analyses. A total of 424 patients with DIMID were included. COVID-19 disease commonly occurred in patients with vitiligo (51.1%), AD (42.0%), and psoriasis (34.3%) (p = 0.038). COVID-19 was not associated with the use of immunosuppressive therapy. Three patients (two with AD and one with vitiligo) were hospitalized due to COVID-19. Nearly all patients with DIMIDs exhibited effective seroconversion after regular vaccination regimens (vitiligo 100%, psoriasis 97.9%, AD 96.5%). Increased DIMID activity after COVID-19 (6.6%) or severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) vaccination (12.26%) was reported in a minority of patients, with baseline progressive disease (disease activity 3 months preceding baseline survey) being the only associated risk factor (COVID-19: odds ratio [OR], 4.27 [p = 0.02]; vaccination OR, 3.45 [p = 0.002]). In conclusion, no alarming signs were shown in this study regarding (severe) COVID-19 in patients with AD, psoriasis, or vitiligo. Vaccination against COVID-19 is advised in patients with DIMIDs. Moreover, patients with DIMIDs can safely continue their immunosuppressant therapy, since this does not increase the risk of COVID-19, while vaccination-induced humoral responses are adequate. In only a minority of patients, increased DIMID activity after COVID-19 or SARS-CoV-2 vaccination occurred., (© 2025 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

The clinical application of biodegradable ureteral stents holds significant potential. There is an urgent need to develop new materials for ureteral stents to address the limitations related to performance degradation and antibacterial properties observed in current designs. Here, we developed a Polycaprolactone (PCL)/Poly (L-lactide-co- ϵ -caprolactone) (PLCL) composite ureteral stent by three-dimensional (3D) printing, which exhibits biodegradable and antibacterial properties. Silver nanoparticles (AgNPs) were bonded to the surface of the stent through the polymerization of dopamine (PDA) and coating with type I collagen (Col I). The ureteral stent (PP-PDA-Ag-Col) had a densely spiraled structure and higher hydrophilicity. The release behavior of silver ions from the stent was found to be slow and continuous when coated with AgNPs, which can enable long-term antibacterial effects after being implanted in vivo . Additionally, in vitro degradation experiments demonstrated that the different ratios of ureteral stents degraded slowly in artificial urine over 6 weeks without compromising functionality. The stent exhibits excellent hemocompatibility and cell compatibility. The subcutaneous implantation experiment in Sprague-Dawley rats showed that the PP-PDA-Ag-Col stent degraded slowly in vivo and had good biocompatibility. The stent PCL5/PLCL5 was the most promising ureteral stent regarding antibacterial, mechanical properties, and degradation. The novel 3D-printed PP-PDA-Ag-Col stent exhibits biocompatibility for safe in vivo transplantation and antibacterial properties that reduce reliance on antibiotics. Additionally, its biodegradability eliminates the need for secondary surgical removal, making it a promising option for the clinical application of ureteral stents., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective. Computed tomography (CT) is a crucial medical imaging technique which uses x-ray radiation to identify cancer tissues. Since radiation poses a significant health risk, low dose acquisition procedures need to be adopted. However, low-dose CT (LDCT) can cause higher noise and artifacts which massively degrade the diagnosis. Approach. To denoise LDCT images more effectively, this paper proposes a deep learning method based on U-Net with multiple lightweight attention-based modules and residual reinforcement (MLAR-UNet). We integrate a U-Net architecture with several advanced modules, including Convolutional Block Attention Module (CBAM), Cross Residual Module (CR), Attention Cross Reinforcement Module (ACRM), and Convolution and Transformer Cross Attention Module (CTCAM). Among these modules, CBAM applies channel and spatial attention mechanisms to enhance local feature representation. However, serious detail loss caused by incorrect embedding of CBAM for LDCT denoising is verified in this study. To relieve this, we introduce CR to reduce information loss in deeper layers, preserving features more effectively. To address the excessive local attention of CBAM, we design ACRM, which incorporates Transformer to adjust the attention weights. Furthermore, we design CTCAM, which leverages a complex combination of Transformer and convolution to capture multi-scale information and compute more accurate attention weights. Results. Experiments verify the embedding rationality and validity of each module and show that the proposed MLAR-UNet denoises LDCT images more effectively and preserves more details than many state-of-the-art methods on clinical chest and abdominal CT datasets. Significance. The proposed MLAR-UNet not only demonstrates superior LDCT image denoising capability but also highlights the strong detail comprehension and negligible overheads of our designed ACRM and CTCAM. These findings provide a novel approach to integrating Transformer more efficiently in image processing., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective: Combination therapy with rituximab and belimumab is a novel treatment strategy for severe SLE and lupus nephritis. Phase II studies have shown promising results, although long-term data are currently lacking. To address this, we analysed outcomes of patients with severe treatment-refractory SLE who previously participated in the phase II Synbiose Study, with a particular focus on immunological parameters., Methods: Eight patients continued belimumab treatment beyond the 2-year duration of the original trial. We conducted a descriptive study to evaluate the course of treatment and immunological parameters over an extended follow-up. Our analyses include blood cell counts, immunoglobulins, autoantibodies, complement markers and clinical disease activity parameters. Additionally, we examined long-term effects on the B cell compartment employing high-sensitivity flow cytometry., Results: Over a median follow-up period of 6.8 years, six out of eight previously treatment-refractory patients maintained long-term clinical remission, while two experienced a major flare. Among those in remission, two patients achieved immunosuppression-free remission, and four continued belimumab. Long-term effects on humoral (auto-)immunity were a persistent decrease in IgM levels, while IgG normalised. Most patients maintained low autoantibody titres, and complement markers remained normal. On the cellular level, belimumab treatment after rituximab prevented B cell repopulation. Notably, patients exhibited a stable reduction of double-negative (DN) B cells, irrespective of continuing or stopping belimumab., Conclusions: Long-lasting remission was observed in patients with SLE following combination treatment with rituximab and belimumab. We observed no significant hypogammaglobulinaemia and, notably, persistent reduction of DN B cells., Competing Interests: Competing interests: YKOT received consultancy fees from GlaxoSmithKline., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a prototypic autoimmune disease, with a subset of AAV patients manifesting anti-myeloperoxidase (MPO) IgG. Patients with AAV respond positively to B cell-targeting and complement-targeting therapies, but disease flares are not uncommon. Here, by comparing samples from healthy individuals and MPO + AVV patients, we show that B cell autoreactivity against MPO in the circulation of patients is dominated by CD27 + IgM + B cells whereas MPO-specific IgG + cells are infrequent. Additionally, while naive anti-MPO-IgM B cells are present in both patients and controls and produce anti-MPO IgM upon stimulation, anti-MPO-IgM memory B cells and serum anti-MPO IgM are features of patients. Our results thus hint that defective elimination of B cell reactivity to MPO in the human repertoire, the presence of activated IgM + anti-MPO B cells in disease, and a dominant role for anti-MPO IgM in complement activation, may all contribute to MPO + AAV etiology and thereby serve as potential target for therapy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Most of studies have mainly paid attention to the removal efficiency of a water treatment technology, while often overlooking the environmental and ecological toxicity. However, are water treatment technologies really environmental-/eco-friendly? If the as-generated chemicals are more toxic, it may lead to more severe secondary pollution. In this work, two novel integrated systems of Vis/Cu 2 O/H 2 O 2 (visible light-excited H 2 O 2 activation) and Vis/Cu 2 O/PS (visible light-excited persulfate (PS, Na 2 S 2 O 8 activation) were designed and investigated fully, in which rhodamine B (RhB) was selected as the representative organic wastewater pollutant to assure the technology feasibility, although it has been studied widely. It is found that H 2 O 2 and PS significantly enhance the degradation efficiency of RhB, and the degradation efficiencies of RhB for the Vis/O-Cu 2 O/H 2 O 2 and Vis/O-Cu 2 O/PS systems have increased by 43.2 and 98.7 times than that of conventional Vis/O-Cu 2 O system (O-Cu 2 O, octahedral Cu 2 O). Furthermore, considering the incomplete mineralization, the degradation by-products are analyzed and their toxicity to grass carp and bacteria is evaluated. It is found that due to the production of the nitro- and chlorine-containing chemicals, the degradation by-products showed a higher toxicity to bacteria and grass carp, compared to RhB. This work warns us that it is crucial to completely mineralize the organic pollutants for all the present clean technologies, otherwise secondary pollution will be more dangerous to ecosystem., Competing Interests: Declaration of Competing Interest √ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

The focus of cancer immunotherapy has traditionally been on immune cells and tumor cells themselves, often overlooking the tumor secretome. This review provides a comprehensive overview of the intricate relationship between tumor cells and the immune response in cancer progression. It highlights the pivotal role of the tumor secretome - a diverse set of molecules secreted by tumor cells - in significantly influencing immune modulation, promoting immunosuppression, and facilitating tumor survival. In addition to elucidating these complex interactions, this review discusses current clinical trials targeting the tumor secretome and highlights their potential to advance personalized medicine strategies. These trials aim to overcome the challenges of the tumor microenvironment by designing therapies tailored to the secretome profiles of individual cancer patients. In addition, advances in proteomic techniques are highlighted as essential tools for unraveling the complexity of the tumor secretome, paving the way for improved cancer treatment outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Competing Interests: Funding Support and Author Disclosures Dr Enta is a clinical proctor at Abbott Medical Japan. Dr Munehisa is a clinical proctor at Abbott Medical Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

A definition of "disease modification" for kidney disease is long overdue. Here, we propose three key criteria for disease modification in immune-mediated glomerulonephritis and podocytopathies: minimizing disease activity, preventing loss of kidney structure and function, and reducing treatment-related toxicity. To be considered a DMAND, a drug must fulfil all three criteria hence, the DMAND status of a drug may not be clear at the time of regulatory approval. Notably, the aspect of CKD in immune-mediated kidney diseases must be considered and treated separately, e.g., RASi is a DMAND for the CKD aspect but not for the immune disease itself. Defining DMANDs is an ambitious goal but one which may help to set the priorities for future treatment strategies in immune-mediated kidney disease. This may mean much more rapid tapering or even avoidance of unselective, non-targeted immunosuppressive agents, which carry considerable short (teratogenicity) and long term risks (malignancies). The criteria proposed here set a high bar for "disease modification" in immune-mediated kidney disease. Inevitably, this must dictate altered priorities with the focus for new therapeutic agents and strategies shifting from solely reduction of proteinuria to preservation of GFR and attenuation of decline, whilst also eliminating long term toxicity., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

By integrating polyvinyl alcohol (PVA)-borate-tannic acid (TA)-sodium sulfate into cellulosic wood matrices, a novel wood-basedPVA-borate-TA-sodium sulfate (WPBTS) hydrogel is successfully synthesized. Through a multicomponent synergistic design combining natural lignocellulose, PVA, borax, TA, and sodium sulfate, multiple dynamic cross-linking mechanisms-dynamic borate bonding, hydrogen bonding, and metal-ligand interactions-are established, resulting in WPBTS hydrogels with exceptional mechanical properties and self-healing capabilities. The mechanical strength of the WPBTS hydrogel reached an impressive 19.8 MPa, a 45-fold increase compared to PVA-borax-tannic acid (PBTS) hydrogels. Furthermore, the assembled WPBTS hydrogel-based flexible sensor demonstrates a remarkably fast response time of just 20 ms and maintains excellent performance in challenging simulated saline environments. This innovation represents a significant advancement in sensor technology and highlights the potential for transformative applications in complex and demanding scenarios., (© 2025 The Author(s). Small published by Wiley‐VCH GmbH.)

Sarcoidosis, a multisystemic granulomatous disease with unknown etiology, is characterized by formation of noncaseating granulomas, which can affect all organs. Recent studies have made outstanding achievement in understanding the pathology, etiology, genetics, and immune dysregulation involved in granuloma formation of sarcoidosis. Antigen stimulation in genetically predisposed individuals enhances the phagocytic activity of antigen-presenting cells, including macrophages and dendritic cells. CD4 + T cells initiate dysregulated immune responses and secrete significant quantities of inflammatory cytokines, including interleukin (IL)-2 and interferon-gamma (IFN-γ), which play a crucial role in modulating the aggregation and fusion of macrophages to form granulomas. The current therapeutic strategies focus on blocking the formation and spread of granulomas to protect organ function and alleviate symptoms. The efficacy of traditional treatments, such as glucocorticoids and immunosuppressants, has been confirmed in the management of sarcoidosis. Promising therapeutic agents encompass inhibitors of cytokines, like those targeting tumor necrosis factor (TNF)-α, as well as inhibitors of signaling pathways, such as Janus kinase (JAK) inhibitors, which exhibit favorable prospects for application. Although there has been progress in the identification of biomarkers for the diagnosis, prognosis, activity and severity of sarcoidosis, specific and sensitive biomarkers have yet to be identified. This review outlines recent advancements in the molecular mechanisms and therapeutic strategies for the sarcoidosis., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors have declared that no competing interest exists., (© 2025. The Author(s).)

Detecting β-lactoglobulin (β-Lg) with high sensitivity and selectivity is an urgent requirement due to nearly 80% of milk anaphylaxis, such as respiratory tract, skin urticaria, and gastrointestinal disorders, being caused by β-Lg. An ultrasensitive β-Lg electrochemical aptasensor utilizing core-satellite gold nanoparticle@silver nanocluster (AuNPs@AgNCs) nanohybrids as electrocatalysts was developed. First, β-Lg aptamer was anchored on gold electrodes and AuNPs to obtain high selectivity. Aptamer-cDNA-AuNPs conjugation was attached to the functionalized electrode with β-Lg as a "bridge" through the target-ligand interaction. Second, DNA-templated AgNCs were introduced via the hybridization of DNA templates oligonucleotide with cDNA anchored on AuNPs. The formed AuNPs@AgNCs nanohybrids showed enhanced catalytic performance toward the silver deposition reaction. This strategy is demonstrated by determining the oxidation current of produced silver nanoparticles (AgNPs) surrounding AuNPs by β-Lg. A detection limit of 0.87 fg/mL and a linear range of 0.001-1000 pg/mL were obtained. Finally, β-Lg content in food products was analyzed successfully, and RSD of 2.44-8.33% was obtained. The recovery of 87.54-113.70% and RSD of 0.95-9.29% was obtained for standard addition experiments. This proposed aptasensor exhibits excellent sensitivity, selectivity, reproducibility, and stability and has good practical application capability for complex food matrices.

Aim: Equivalence between HLX02 and trastuzumab sourced from the European Union (EU-trastuzumab), in combination with docetaxel, was demonstrated in a phase III study. This study aimed to evaluate the long-term efficacy and safety data after 3 years of follow-up., Methods: Patients with previously untreated, HER2-positive metastatic breast cancer received intravenous HLX02 or EU-trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel. Primary endpoint was the overall response rate up to week 24 (ORR 24 ). Secondary endpoints including updated overall survival (OS), progression-free survival (PFS), safety and immunogenicity are reported in this long-term follow-up analysis., Results: After a median follow-up duration of 35.0 months, 270 out of the 649 enrolled patients had died; 128 (39.5 %) in the HLX02 and 142 (43.7 %) in the EU-trastuzumab group. Median OS was 37.3 (95 % CI 36.2, not evaluable [NE]) months and not reached (95 % CI 34.2, NE) (stratified HR 0.86 [95 % CI 0.68, 1.10]; p = 0.229), with a 3-year OS rate of 57.5 % and 54.0 %, respectively. Median PFS at this long-term follow-up assessment was 11.7 (95 % CI 11.5, 12.1) months for the HLX02 group and 10.6 (95 % CI 9.5, 11.7) months for the EU-trastuzumab group (stratified HR 0.86 [95 % CI 0.69, 1.06]; p = 0.158). No new safety concerns were reported until the end of the survival follow-up., Conclusion: Long-term efficacy and safety were consistent with the previous findings. No clinically meaningful differences between HLX02 and reference trastuzumab were demonstrated., Clinical Trial Registration: Chinadrugtrials.org CTR20160526 (September 12, 2016), ClinicalTrials.gov NCT03084237 (March 20, 2017), EudraCT 2016-000206-10 (April 27, 2017)., Competing Interests: Declaration of competing interest Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang and Jun Zhu are employees of Shanghai Henlius Biotech, Inc. All other authors have no competing interests to declare., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid (DHA). An increased level of circulating DHA inhibits PD-L1 expression in tumor cells by binding the PD-L1 promoter and subsequently prevents c-myc-initiated transcription of PD-L1. Colonization of germ-free male mice with gut bacteria from anti-PD-L1 non-responding patients supplemented with DHA enhances the efficacy of anti-PD-L1 therapy compared to controls. Our findings reveal a previously unknown mechanistic impact of PNP on human tumor immunotherapy by modulating gut bacterial metabolic pathways., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aims: The presence of ductal carcinoma in situ (DCIS) alongside invasive ductal carcinoma (IDC) of the breast is common in clinical practice and affects clinical outcomes and treatment strategies. This study aimed to compare the clinicopathological characteristics and prognosis of patients with IDC coexisting with DCIS versus pure IDC after neoadjuvant therapy (NAT) and to explore the risk factors for residual DCIS following NAT., Material and Methods: Patients with Stage II-III IDC who underwent NAT followed by radical surgery between January 2015 and December 2022 were included. Baseline data, clinical characteristics, preoperative treatment, surgical approach, pathological outcomes, and prognostic information were collected and analysed., Results: A total of 852 patients were enrolled in this study, with 279 and 573 patients in the IDC + DCIS and IDC groups, respectively. Compared with patients in the IDC group, those in the IDC + DCIS group had a lower proportion of triple-negative molecular type (15.1% vs. 33.9%, P < 0.001), better histological grade (52.0% vs. 37.7%, P < 0.001), and higher residual rate of DCIS (71.3% vs. 38.7%, P < 0.001). The 5-year disease-free survival (DFS) (85.2% vs. 82.4%, P = 0.188) and overall survival (OS) (93.2% vs. 93.0%, P = 0.810) rates of patients in the IDC + DCIS group were similar to those in the IDC group. However, in the triple-negative breast cancer population, the DFS (88.6% vs. 75.8%, P = 0.032) of patients with IDC + DCIS was significantly better than that of patients with IDC. For patients with IDC + DCIS, age ≥40 years (odds ratio [OR] = 0.421; 95% confidence interval [CI], 0.163-0.889, P = 0.035) and HR+/HER2-molecular subtype (OR=3.347; 95% CI, 1.237-6.577, P = 0.047) were independent preoperative predictors for residual DCIS after NAT., Conclusion: The presence of DCIS in IDC demonstrated less tumour aggressiveness than pure IDC. However, a survival benefit was only observed in patients with triple-negative IDC combined with DCIS after NAT. Furthermore, patients with IDC + DCIS have a higher risk of residual DCIS after NAT, and age <40 years and the luminal subtype are risk factors for residual DCIS after NAT in patients with IDC + DCIS., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The co-culture system of Chlorella sorokiniana and Aspergillus oryzae has demonstrated exceptional tolerance and efficiency in the removal of pollutants from swine manure. This study evaluates the ability of the co-culture system to remove Zn(II) and estrone, while assessing the impact of these pollutants on the system's overall functionality. Results indicated that co-cultivation achieved higher biomass accumulation, peaking at 0.88 g/L after 96 h. Increasing estrone exposure concentration reduced photosynthetic activity and chlorophyll content, whereas Zn(II) exposure initially enhanced and later inhibited chlorophyll synthesis. Co-cultivation secreted extracellular polymeric substances, including protein-like and humus-like substances, to alleviate environmental stress and form algal-fungal community. After 96 h of cultivation, the removal efficiencies reached 86.44% for 1.5 mg/L Zn(II) and 84.55% for 20 mg/L estrone. The Quantitative Structure Activity Relationship model revealed a reduction in the ecotoxicity of estrone intermediate products to varying degrees. Metabolomics analysis showed that exposure to estrone and Zn(II) significantly boosted the production of Gibberellic acid, Indole-3-acetic acid, and Zeatin riboside in Chlorella sorokiniana, while reducing Abscisic Acid levels. Furthermore, the exposure led to an increase in various metabolites in the Tricarboxylic acid cycle of the co-cultivation system, influencing the synthesis and metabolism of key biochemical components like carbohydrates, lipids, and proteins. These findings elucidate the biochemical responses of Chlorella sorokiniana-Aspergillus oryzae co-culture system to pollutants and provide insights into its potential application in the treatment of wastewater containing endocrine disrupting chemicals and heavy metals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

In recent years, climate change and human activities have reduced various ecosystem services (ESs). Analyzing trade-offs/synergies among ESs is crucial for ecosystem sustainability and human well-being. Many studies overlook potential scale effects by focusing on a single scale. We addressed this by evaluating ESs - grain production (GP), habitat quality (HQ), carbon sequestration (CS), soil conservation (SC), and water yield (WY) - in the Yellow River Basin (YRB) from 1990 to 2020, using Bayesian belief networks to analyze their drivers and relationships across scales. The study revealed a steady increase in GP, while both CS and SC exhibited fluctuating upward trends, and HQ and WY experienced downward trends. Significant spatial heterogeneity was observed, with GP decreasing from east to west, and WY, CS, and SC decreasing from northeast to southwest. HQ values were generally high but lower in specific downstream and upstream locations. Key factors influencing these ESs included land use, slope, population, evapotranspiration, NDVI, and precipitation. As the spatial scale expanded, the influence of these factors diminished. The relationships among ESs primarily reflected synergies. However, with the spatial scale increased, trade-offs/synergies among ESs weakened, and several relationships transitioned between trade-offs and synergies. This study offers insights for optimizing ecosystem management by understanding the scale dependency of relationships among ESs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: The classification of lumbar spondylolysis varies, and there is currently no clear consensus on a standardized system. This study examines the morphological characteristics and parameter differences of the L5 vertebra in patients with isolated versus fused spondylolysis using CT measurements. It also proposes a preliminary classification system based on the separation distance at the fracture site and explores its clinical significance., Methods: A total of 117 young male patients with L5 spondylolysis related to high-intensity physical activity were enrolled. Patients with a pars interarticularis separation distance ≥ 2 mm were classified into the isolated group (Group A, 66 patients), while those with a separation distance < 1 mm were classified into the fused group (Group B, 51 patients).Additionally, 117 patients without spondylolysis but experiencing lower back pain were included as the control group (group C). Multislice spiral computed tomography (MSCT) was used to measure the morphological parameters of the L5 vertebra in all three groups, including the sagittal pedicle height (SPH), transverse pedicle width (TPW), transverse pedicle vertical length (TPVL), pedicle screw trajectory length (PSTL), pedicle angle of attack (PAA), frontal vertebral body height (FVH), posterior vertebral body height (PVH), sagittal midline intervertebral space height (SMISH), horizontal vertebral body angle (HVA), and vertical vertebral body angle (VVA). Differences in the morphological imaging parameters of the L5 vertebrae and pedicles among the three groups were compared., Results: There were no significant differences in age, height, weight, body mass index (BMI), or Pfirrmann grade among the three groups. No significant differences were observed in any of the pedicle parameters between the left and right sides within the groups. Group A showed significantly greater TPVL and PSTL values compared to Group B, while TPW and PAA were significantly lower. No significant difference in SPH was observed between Group A and Group B. When compared to Group C, Group A exhibited significant differences in SPH, TPW, TPVL, and PSTL, but not in PAA. Group B, compared to Group C, demonstrated significant differences in SPH and PAA, but no significant differences were observed in TPW, TPVL, or PSTL. Significant differences were also found in FVH, HVA, and VVA between Group A and Group B, with Group A showing a smaller PVH. No significant difference in SMISH was observed between the two groups. Compared to Group C, Group A showed significant differences in PVH, HVA, and VVA, but no significant differences were found in FVH or SMISH. In Group B, significant differences were noted in FVH and HVA compared to Group C, but no differences were observed in PVH, SMISH, or VVA., Conclusion: Differences in the sagittal morphological parameters of the pedicles and vertebral bodies can be observed between the two types of spondylolysis patients. In the isolated spondylolysis pattern, the pedicles exhibit a "thin, long, and contracted" morphology, while the vertebral bodies present a "stuffed bun" shape, both anteriorly, posteriorly, and superiorly. In contrast, the fused type is characterized by "short, thick, and expanded" pedicles, with the vertebral bodies showing a "less pronounced stuffed bun" shape in the anterior-posterior direction. These morphological differences indicate that spondylolysis separation may involve adaptive stress-induced bone remodeling. Surgeons must pay special attention when choosing surgical techniques, as isolated spondylolysis may present a tendency toward slippage. Caution is advised in performing isolated pars repair surgeries, especially during the placement of pedicle screws, where special attention must be given to the length and direction of the screws to avoid additional damage., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethics Committee of the General Hospital of Xinjiang Military Command and was carried out in accordance with the ethical standards set out in the Helsinki Declaration. Informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Blue light simultaneously enhances anthocyanin and carotenoid biosynthesis in mango (Mangifera indica L.) fruit peel and flesh, respectively, but the mechanism remains unclear. In this study, two blue light-triggered zinc-finger transcription factors, MiBBX24 and MiBBX27, that positively regulate anthocyanin and carotenoid biosynthesis in mango fruit were identified. Both MiBBXs transcriptionally activate the expression of MiMYB1, a positive regulator of anthocyanin biosynthesis. Furthermore, both MiBBXs also trigger the expression of a phytoene synthase gene (MiPSY), which is essential for carotenoid biosynthesis. Ectopic expression of MiBBX24 or MiBBX27 in Arabidopsis increased anthocyanin contents, and their positive effects on anthocyanin accumulation in mango peel were confirmed through transient overexpression and virus-induced silencing. Transient expression of MiBBX24 or MiBBX27 in tomato (Solanum lycopersicum) and mango fruit flesh increased the carotenoid content, while the virus-induced silencing of MiBBX24 or MiBBX27 in the mango fruit flesh decreased carotenoid accumulation. Overall, our study results reveal that MiBBX24 and MiBBX27 simultaneously promote the biosynthesis of anthocyanin and carotenoids biosynthesis in mango fruit peel and flesh under blue light, indicating that BBX-mediated dual effects on physiological functions contribute to mango fruit pigment accumulation. Furthermore, we herein shed new light on the simultaneous transcriptional regulatory effects of a single factor on the biosynthesis of different plant pigments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging., Competing Interests: Declarations. Ethical Approval: This study was approved by the ethics committee of Zhejiang provincial people's hospital. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This systematic review and meta-analysis aimed to evaluate the prevalence of bone destruction in patients with Talaromyces marneffei infection, examine distribution patterns of bone lesions, and assess differences between HIV-positive and HIV-negative patients., Methods: Following PRISMA guidelines, 15 studies involving 839 patients were analyzed. Random-effects meta-analysis was performed to estimate prevalence and odds ratios. Study quality was assessed using ROBINS-I., Results: The overall prevalence of bone destruction was 18% (95% CI: 10-27%). HIV-negative patients showed significantly higher odds of bone destruction (OR: 0.09, 95% CI: 0.02-0.37%). Bone lesions were widely distributed, with osseous involvement (45.7-71.4%) more prevalent than articular (7.1-66.7%). The skull, ribs, and lumbar vertebrae were commonly affected., Conclusion: Bone destruction is a significant complication in TM infection, particularly in HIV-negative patients. The diverse anatomical distribution emphasizes the need for comprehensive skeletal assessment in suspected cases., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pathological grade is a critical determinant of clinical outcomes and decision-making of follicular lymphoma (FL). This study aimed to develop a deep learning model as a digital biopsy for the non-invasive identification of FL grade., Methods: This study retrospectively included 513 FL patients from five independent hospital centers, randomly divided into training, internal validation, and external validation cohorts. A multimodal fusion Transformer model was developed integrating 3D PET tumor images with tabular data to predict FL grade. Additionally, the model is equipped with explainable modules, including Gradient-weighted Class Activation Mapping (Grad-CAM) for PET images, SHapley Additive exPlanations analysis for tabular data, and the calculation of predictive contribution ratios for both modalities, to enhance clinical interpretability and reliability. The predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC) and accuracy, and its prognostic value was also assessed., Results: The Transformer model demonstrated high accuracy in grading FL, with AUCs of 0.964-0.985 and accuracies of 90.2-96.7% in the training cohort, and similar performance in the validation cohorts (AUCs: 0.936-0.971, accuracies: 86.4-97.0%). Ablation studies confirmed that the fusion model outperformed single-modality models (AUCs: 0.974 - 0.956, accuracies: 89.8%-85.8%). Interpretability analysis revealed that PET images contributed 81-89% of the predictive value. Grad-CAM highlighted the tumor and peri-tumor regions. The model also effectively stratified patients by survival risk (P < 0.05), highlighting its prognostic value., Conclusions: Our study developed an explainable multimodal fusion Transformer model for accurate grading and prognosis of FL, with the potential to aid clinical decision-making., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the institutional review board of West China Hospital, Sichuan University. Consent to participate: For the nature of retrospective study, written informed consent was waived. Competing interests: The authors declare that they have no conflict of interest., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The prevalence of inflammatory bowel disease (IBD) among Chinese adolescents has continued to increase in recent years. Adolescents with IBD interrupted their schooling due to the diagnosis and treatment of the disease. And when the condition stabilises, they will return to school. However, as a lifelong and recurrent disease, the instability of the disease after returning to school affects normal school participation., Objective: This study aims to explore the psychological and life challenges of adolescents with IBD in the complex and intertwined situations of disease management, adolescent development and school social interactions., Methods: A qualitative descriptive study was conducted. Qualitative data were collected from adolescents aged 11-19 (n=21; 7 males and 14 females) through in-depth, semistructured interviews. Reflexive thematic analysis was employed to ensure rigour., Results: The results highlight the challenges of returning to school for adolescents with IBD. There are three emerging themes and nine subthemes (in parentheses). (1) Problems of continued disease management (occasional uncontrollable flare-ups of symptoms, regular medical checkups disrupting daily school programming and shame from medication management). (2) Difficulties of impaired school functioning (difficulty keeping up with academic study and participating in high-intensity sports activities). (3) Challenges of maintaining friendship (burden of disease disclosure, difficulty in sharing food with friends, common topics of conversation decreasing and absence of group activities)., Conclusion: We call on medical institutions and schools to strengthen cooperation and further optimise support measures for this group through the intermediary role of school health clinics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: This study aimed to construct a radiomics-based imaging biomarker for the non-invasive identification of transformed follicular lymphoma (t-FL) using PET/CT images., Methods: A total of 784 follicular lymphoma (FL), diffuse large B-cell lymphoma, and t-FL patients from 5 independent medical centers were included. The unsupervised EMFusion method was applied to fuse PET and CT images. Deep-based radiomic features were extracted from the fusion images using a deep learning model (ResNet18). These features, along with handcrafted radiomics, were utilized to construct a radiomic signature (R-signature) using automatic machine learning in the training and internal validation cohort. The R-signature was then tested for its predictive ability in the t-FL test cohort. Subsequently, this R-signature was combined with clinical parameters and SUVmax to develop a t-FL scoring system., Results: The R-signature demonstrated high accuracy, with mean AUC values as 0.994 in the training cohort and 0.976 in the internal validation cohort. In the t-FL test cohort, the R-signature achieved an AUC of 0.749, with an accuracy of 75.2%, sensitivity of 68.0%, and specificity of 77.5%. Furthermore, the t-FL scoring system, incorporating the R-signature along with clinical parameters (age, LDH, and ECOG PS) and SUVmax, achieved an AUC of 0.820, facilitating the stratification of patients into low, medium, and high transformation risk groups., Conclusions: This study offers a promising approach for identifying t-FL non-invasively by radiomics analysis on PET/CT images. The developed t-FL scoring system provides a valuable tool for clinical decision-making, potentially improving patient management and outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was conducted in accordance with ethical guidelines (Declaration of Helsinki and Istanbul) and approved by the Institutional Ethics Committee of involved centers (IRB No. 2024–1010). Informed consent was waived due to the retrospective nature of this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

A surfactant is an efficient and common additive used to enhance the spreading of droplets on hydrophobic surfaces. However, a high surfactant concentration is required to achieve the desired performance, resulting in environmental pollution and increased costs. Additionally, the pesticide loading capacity of surfactants at low concentrations (below their critical micelle concentrations) is a concern. Thus, in this study, we developed a strategy to enhance pesticide loading and droplet deposition by mixing small amounts of sodium dodecyl sulfate (SDS) (0.1 wt %) and cationically modified cellulose nanocrystals (PCNC). The reduced surface tension, increased viscosity and adhesion, and electrostatic and hydrogen interactions resulted in a low retraction velocity, excellent spreading, and resistance to air turbulence. The improved loading content was facilitated by the hydrophobic domains of PCNC and SDS micelles.

Background: Nursing undergraduates receive inadequate training in death and end-of-life care within the education system, resulting in feelings of unpreparedness and inadequacy when confronted with their first death event in clinical practice, as well as a low willingness to engage in end-of-life care., Objective: To explore the cognitive and emotional experiences of nursing undergraduate students participating in the simulated death graded exposure programme, and to evaluate the educational significance of the programme., Design: A qualitative descriptive study design., Setting: A comprehensive university in Jiangsu Province, China., Participants: In October 2023, twenty-eight (age range, 19-21 years; 21 [75 %] female;) first-year nursing undergraduates were recruited to participate in the simulated death graded exposure programme., Methods: The research team developed and implemented a systematic simulated death graded exposure programme, consisting of four parts: end-of-life farewell role-playing, simulated funeral experience, post-simulation recovery and death reflection. Semi-structured interviews were conducted after the experience, and the interview data were analysed using content analysis., Results: The nursing students' experiences in the simulated death graded exposure programme could be divided into three phases through a longitudinal process: approaching death (dying), immersing in the world of death (death), and initiating the transformation of life's meaning (rebirth). In the first phase, participants felt integrated into the simulated roles, experienced the complex emotions of approaching death, and ultimately accepted the declaration of death. In the second phase, participants experienced a highly realistic simulation of death, guiding physical symptoms and emotional reactions. Additionally, their awareness of death began to awaken and disperse, leading to profound reflections on death. In the third phase, participants engaged in a process of self-examination which culminated in a self-proclaimed healing process from the experience of the simulated death. Through deep reflection, they were reacquainted with their values and professional mission., Conclusions: The simulated death graded exposure programme enhances nursing students' psychological preparedness and emotional adjustment helping to prepare them for experiencing death in a clinical context, and deepens their understanding of life and death. This programme provides a practical example of nursing professionals' training and education in end-of-life care., Competing Interests: Declaration of competing interest We have nothing to declare., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Purpose: The systemic immune-inflammation index (SII) has been found to be associated with various inflammatory and neoplastic diseases. The aim of this study was to investigate the relationship between the SII and colorectal polyps (CPs) in Chinese patients., Methods: This was a cross-sectional study. We retrospectively collected data from 3,028 Chinese patients who underwent physical examinations, including colonoscopy, from 2018 to 2022. We conducted a comparative analysis of patient characteristics among those with adenomatous polyps, non-adenomatous polyps, and individuals without CPs using descriptive statistics. We calculated the SII for each group and assessed the relationship between SII values and the presence of CPs., Results: Our study included 3,028 individuals, of whom 1,432 (47.29%) had colorectal polyps. After adjusting for confounding variables, the natural logarithm of the SII (Ln-SII) was significantly associated with the prevalence of adenomatous polyps in both males and females, with an odds ratio (OR) of 0.76 [95% confidence interval (CI): 0.65-0.88, p  = 0.0003]. An inverted U-shaped relationship was observed between Ln-SII and the prevalence of colorectal polyps, including both adenomatous and non-adenomatous polyps, with a cut-off point at 5.78 (5.39 for adenomatous polyps and 5.79 for non-adenomatous polyps). Below this cut-off point, a significant association with colorectal polyps was identified, with an OR of 1.73 (95% CI: 1.25-2.40, p  = 0.0009). Specifically, for adenomatous polyps, the OR was 2.91 (95% CI: 1.03-8.20, p  = 0.0437), and for non-adenomatous polyps, the OR was 1.86 (95% CI: 1.31-2.65, p  = 0.0006). Beyond the cut-off point, the association between Ln-SII and colorectal polyps remained significant, with an OR of 0.56 (95% CI: 0.46-0.68, p  < 0.0001). In the adenomatous polyps group, the OR was 0.57 (95% CI: 0.43-0.74, p  < 0.0001), and in the non-adenomatous polyps group, the OR was 0.57 (95% CI: 0.46-0.70, p  < 0.0001)., Conclusion: The inverted U-shaped association between Ln-SII and the risk of colorectal polyps highlights the potential relevance of monitoring variations in SII and suggests that SII may be a promising predictor for colorectal polyp development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Bao, Teng, Yang and Wang.)

Objectives: To explore the factors influencing medication adherence and the medication needs of patients with schizophrenia when living in a community in China., Design: A qualitative study., Setting: Community and psychiatric ward in Zhuhai city, Guangdong province., Participants: Patients with schizophrenia and (or) their primary caregivers., Primary and Secondary Outcome Measures: Facilitators and barriers of medication adherence and the medication needs., Results: A total of 20 patients with schizophrenia and 12 primary caregivers participated in the study. Based on the Health Ecology Model, the analysis identified four levels of factors influencing medication adherence, categorised as individual (facilitators: effective treatment, positive expectation, establishing a routine and assistive tools; barriers: side effects, inadequate knowledge, forgetfulness and irregular daily schedule), interpersonal (facilitators: caregiver assistance and psychiatrist's recommendation; barriers: lack of social support), community (facilitators: community mental health services and reducing medication use frequency; barriers: limited medication accessibility and affordability) and policy and culture related (facilitators: collectivist culture and social security policy; barriers: stigma). Additionally, five medication needs (managing side effects, applying for social security, improving medication accessibility, transitioning to long-acting injections and getting health education) were recognised., Conclusions: These findings offer valuable insights for healthcare providers and policymakers, underscoring the need for targeted interventions to enhance medication adherence among patients with schizophrenia in China., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and significantly improved outcomes for patients with certain malignancies. However, immunotherapy with ICIs is only effective in a subset of patients and the gut microbiota have been identified as an important factor associated with response to ICI therapy. Polysaccharides from sea cucumber ( Stichopus japonicus ) (SCP) have been shown to modulate the gut microbiota and exhibit beneficial health functions, but whether SCP could synergize with anti-PD1 immunotherapy remains unexplored. In this study, mice with ICI-sensitive MC38 tumors were treated with anti-PD1 antibody after supplementation with or without SCP to examine the potential impact of SCP on the efficacy of immunotherapy. SCP strongly amplified the anti-tumor activity of anti-PD1 in MC38 tumor-bearing mice. Flow cytometry and immunohistological staining demonstrated that SCP treatment increased cytotoxic CD8 + T lymphocytes while decreasing regulatory Foxp3 + CD4 + T lymphocytes. Gut microbiota and metabolomic analysis revealed that SCP modulated the microbiota and increased the abundance of certain metabolites such as indole-3-carboxylic acid. Furthermore, fecal microbiota transplantation experiments justified that the synergistic effect of SCP with anti-PD1 was partially mediated through the gut microbiota. Mice receiving microbiota from SCP-treated mice showed a boosted response to anti-PD1, along with enhanced anti-tumor immunity. These findings indicate that SCP could be utilized as a dietary strategy combined with anti-PD1 therapy to achieve improved outcomes in patients.

The performance and reliability of an aviation engine, as a core component of an aircraft, is of paramount importance to flight safety. Scholars worldwide have contributed to the design and research of aviation engines, and these advancements and contributions embody the relentless efforts and innovative spirit of scholars and engineers in the field of aviation engine design research. In recent studies, researchers have proposed various vibration control methods to address friction issues in aviation engines, offering corresponding control strategies for the aspects of materials, lubrication, and structural design. However, how to reduce the loss of service life and the safety risks caused by friction in aircraft engines has become an urgent issue that needs to be addressed in the aviation sector. This paper briefly analyzes the current development status regarding vibration and friction reduction in aircraft engines, explores key technologies and research progress in addressing this challenge, and provides insights and prospects for future developments. With advancements in technology, research into vibration and friction in aviation engines will continue to deepen, providing strong support for the development of the aviation industry.

Background: Long non-coding RNAs (lncRNAs) in extracellular vesicles (EVs) have been confirmed as effective non-invasive biomarkers for multiple diseases. However, their expression and clinical value in gastric cancer (GC) remain poorly understood., Materials and Methods: Serum EV RNA was extracted from four patients with GC and four healthy controls, followed by high-throughput RNA sequencing. LncRNAs were further validated in training and validation sets using quantitative real-time reverse transcription polymerase chain reaction., Results: A total of 37,684 lncRNAs were obtained, and 10 lncRNAs were selected based on the criteria ( P < 0.05 and |log 2 FoldChange| ≥1). Serum EV lncRNA RMRP, RPPH1, and linc-ROR were significantly higher in patients with GC than in those with chronic gastritis, atypical hyperplasia, or healthy control (all P < 0.05). Three lncRNAs were also significantly correlated with tumor diameter, lymphatic metastasis, distal metastasis, and TNM stage (all P < 0.05). The area under the curve (AUC) values for lncRNA RMRP, RPPH1, and linc-ROR were 0.727, 0.774, and 0.811, respectively. Corresponding sensitivity and specificity were 63.4% and 85.4%, 50.7% and 89.6%, and 78.5% and 66.7%. The combination of these three lncRNAs with carcinoembryonic antigen (CEA) yielded an AUC of 0.909, with a sensitivity and specificity of 83.3% each. Furthermore, high EV linc-ROR and RMRP expression levels were associated with worse disease-free survival and overall survival (OS). Univariate and multivariate Cox regression analyses confirmed that linc-ROR was the only independent prognostic factor for GC. Finally, the lncRNA-miRNA-mRNA network showed that three lncRNAs were predicted to interact with 15 miRNAs and 69 mRNAs. In addition, lncRNA RMRP and linc-ROR were correlated with immune cell infiltration, including neutrophils, central memory CD4 T cells, macrophage, and natural kill T cells., Conclusion: EV lncRNAs are prospective biomarker and correlated with immune cell infiltration in GC. It provides a foundation for the development of serum EV-targeted novel biomarkers and immunotherapy targets of GC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Ding, Teng, Cui, Liu, Xiao, Dong, Zhang and Xu.)

Craniofacial bone defect healing in periodontitis patients with diabetes background has long been difficult due to increased blood glucose levels which cause overproduction of reactive oxygen species (ROS) and a low pH environment. These conditions negatively affect the function of macrophages, worsen inflammation and oxidative stress, and ultimately, hinder osteoblasts' bone repair potential. In this study, we for the first time found that annexin A1 (ANXA1) expression in macrophages was reduced in a diabetic periodontitis (DP) environment, with the activation of the NLRP3/Caspase-1/GSDMD signaling pathway, and, eventually, increased macrophage pyroptosis. Next, we have developed a new GPPG intelligent hydrogel system which was ROS and pH responsive, and loaded with Ac2-26, an ANXA1 bioactive peptide, and osteogenic peptide OGP as well. We found that Ac2-26/OGP/GPPG can effectively reduce ROS, mitigates macrophage pyroptosis via the ANXA1/NLRP3/Caspase-1/GSDMD pathway and enhanced osteogenic differentiation. The effect of Ac2-26/OGP/GPPG in regulation of pyroptosis and bone defect repair was also further validated by animal experiments on periodontitis-induced tooth loss model in diabetic rats. To conclude, our study unveils the effect of ANXA1 on macrophage pyroptosis in periodontitis patients with diabetes, based on which we introduced a promising innovative hydrogel system for improvement of bone defects repair in DP patients via targeting macrophage pyroptosis and enhancing osteogenic potential., (Creative Commons Attribution license.)

Intervertebral disc degeneration (IVDD) is a major contributor to chronic back pain and disability, with limited effective therapeutic options. Current treatment options, including conservative management and surgical interventions, often fail to effectively halt disease progression and come with notable side effects. IVDD is characterized by the breakdown of the extracellular matrix (ECM) and the infiltration of inflammatory cells, which exacerbate disc degeneration. This study presents a novel therapeutic strategy aimed at addressing the dual challenges of inflammation and ECM degradation in IVDD. We developed a gelatin methacryloyl (GelMA) hydrogel system loaded with interleukin-10 (IL-10), an anti-inflammatory cytokine, and kartogenin (KGN), a small-molecule compound known for its regenerative properties. The KGN + IL-10@GelMA hydrogel was designed to deliver these agents in a controlled manner directly to the degenerated disc, targeting both the inflammatory microenvironment and the promotion of nucleus pulposus (NP) tissue regeneration. In a puncture-induced IVDD model, this hydrogel system effectively delayed the degenerative progression and facilitated NP regeneration. Our findings suggest that the KGN + IL-10@GelMA hydrogel holds significant potential as a nonsurgical treatment option for IVDD, offering a promising approach to mitigate the progression of IVDD and enhance disc repair.

Dendrobium is divided into ornamental and medicinal varieties due to ornamental and medicinal values. However, current research mainly focuses on medicinal Dendrobium, with less study on the medicinal value of ornamental Dendrobium. We analyzed the microstructures, active components of the stems from twelve ornamental Dendrobium, and explored the biosynthetic networks of these active components based on transcriptome sequencing. This study found the Dendrobium with the highest content of polysaccharide, alkaloid, and flavonoid was Dendrobium aphyllum (53.89 %), Dendrobium thyrsiflorum (2.11 %) and Dendrobium loddigesii (7.21 %). Further research revealed 9 DEGs associated with polysaccharide biosynthesis were highly expressed in D. aphyllum; 4 DEGs related to alkaloid biosynthesis were highly expressed in D. thyrsiflorum; 8 DEGs associated with flavonoid biosynthesis were highly expressed in D. loddigesii. This study revealed the potential medicinal value of ornamental Dendrobium and the synthetic mechanisms of its medicinal components, providing a foundation for the medical applications of ornamental Dendrobium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

This study developed and validated a deep learning network using baseline magnetic resonance imaging (MRI) to predict Ki-67 status in meningioma patients. A total of 1239 patients were retrospectively recruited from three hospitals between January 2010 and December 2023, forming training, internal validation, and two external validation cohorts. A representation learning framework was utilized for modeling, and performance was assessed against existing methods. Furthermore, Kaplan-Meier survival analysis was conducted to investigate whether the model could be used for tumor growth prediction. The model achieved superior results, with areas under the curve (AUCs) of 0.797 for internal testing and 0.808 for generalization, alongside 0.756 and 0.727 for 3- and 5-year tumor growth predictions, respectively. The prediction was significantly associated with the growth of asymptomatic small meningiomas. Overall, the model provides an effective tool for early prediction of Ki-67 and tumor volume growth, aiding in individualized patient management., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Protein arginine methyltransferases (PRMTs) play crucial roles in gene regulation, signal transduction, mRNA splicing, DNA repair, cell differentiation, and embryonic development. Due to its significant impact, PRMTs is a target for the prevention and treatment of various diseases. Among the PRMT family, PRMT1 is the most abundant and ubiquitously expressed in the human body. Although extensive research has been conducted on PRMT1, the reported inhibitors have not successfully passed clinical trials. In this study, deep learning was employed to analyze the characteristics of existing PRMTs inhibitors and to construct a classification model for PRMT1 inhibitors. Through a classification model and molecular docking, a series of potential PRMT1 inhibitors were identified. The representative compound (compound 156) demonstrates stable binding to the PRMT1 protein by molecular hybridization, molecular dynamics simulations, and binding free energy analyses. The study discovered novel scaffolds for potential PRMT1 inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhang, Ren, Teng, Wu, Xue, Chen, Song, Li, Zhou, Pang and Wang.)