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The pediatric day surgery has experienced a rapid development in recent years. This study aims to investigate the prospects of day surgery in pediatric hospitals. A total of 17,549 pediatric patients with inguinal hernia (IH) treated between July 2018 and August 2023 were included. The patients were divided into four groups: group A1 (open IH repair [OIHR] in the traditional ward), A2 (laparoscopic IH repair [LIHR] in the traditional ward), B1 (OIHR in the day ward), and B2 (LIHR in the day ward). A retrospective analysis was conducted based on clinical data, satisfaction and prognosis. The present study showed that the operative time between groups A2 and B2 showed no significant difference (p = 0.1205). However, the total time from entering to exiting the operating room was significantly longer in group A2 compared to group B2 (p < 0.0001). Hospitalization costs were significantly lower for patients in the day ward compared to the traditional ward (p < 0.0001). There was no significant difference in the recurrent IH rate between groups A2 and B2 (p = 0.977) or in incision infection rates between the day and traditional wards. The recurrent IH rate was significantly higher after OIHR compared to LIHR (p < 0.0001). The parent satisfaction in the day ward is higher than the traditional ward. The day surgery model of LIHR is a safe, reliable, and economically beneficial surgical management model that is highly recommended for pediatric hospitals., Competing Interests: Declarations. Conflict of interest: There is no conflict of interest to disclose. Compliance with Ethical Standards, Research involving human participants and/or animals: This study was approved by the Ethics Committee of The Children's Hospital, Zhejiang University School of Medicine (approval no. 2023-IRB-0313-P-01) and outlined in the Declaration of Helsinki. Informed consent: Informed consent was obtained from all participants prior to inclusion., (© 2025. The Author(s).)

Objectives: Atherosclerosis is characterized by persistent inflammatory condition, leading to various cardiovascular complications. Foam cell formation, resulting from macrophage uptake of oxidized low-density lipoprotein (ox-LDL), contributes significantly to atherosclerosis progression. This study was designed to investigate the involvement of bispecific phosphatase-6 (DUSP6) and its potential regulatory mechanisms in foam cell formation and atherosclerosis., Methods: We employed THP-1 cells to induce foam cell formation. The lipid droplet accumulation, cholesterol content, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were evaluated using Oil Red O staining, cholesterol assay, ELISA, and qRT-PCR techniques. We investigated DUSP6 ubiquitination via immunoprecipitation and western blot (WB) analysis. A bioinformatics approach identified FBXL14 as a potential E3 ligase involved in DUSP6 ubiquitination, further confirmed by siRNA and overexpression experiments. The impact of FBXL14 on the NRF2 signaling pathway was assessed using WB analysis., Results: DUSP6 interference suppressed foam cell formation and inflammatory factor secretion. Upon ox-LDL treatment, DUSP6 underwent deubiquitylation, with FBXL14 emerging as the candidate E3 ligase. FBXL14 overexpression induced DUSP6 ubiquitination, leading to the NRF2 signaling pathway activation. It counteracted with DUSP6 overexpression on foam cell formation and inflammation. In ApoE-/- mice, sh-DUSP6 adenovirus injection mitigated atherosclerotic lesion progression and improved the lipid profile, with increased the proteins expression of NQO1, HO-1, and NRF2 in aortic tissue., Conclusion: DUSP6 and FBXL14 play vital roles in modulating foam cell formation and inflammatory responses in atherosclerosis. Targeting these molecules could offer therapeutic potential in attenuating atherosclerosis-related complications., Clinical Trial Number: Not applicable.

Exceptional point (EP) is referred to degeneracies in a non-Hermitian system where two or more eigenvalues and their corresponding eigenvectors coalesce. Recently there have been significantly increased interests in harnessing EPs to enhance responsivities and achieve ultrasensitive detections in optics, electronics and acoustics, although there are few similar studies focused on using surface acoustic wave (SAW) sensing technologies, probably due to its great technical challenges. Herein, we proposed a scheme for accessing EPs in an on-chip architecture consisted of coupled-SAW-resonators system, forming a passive parity-time (PT) symmetric system. We demonstrated that by tuning additional losses in one of resonators and regulating the system in the proximity of the EP, the sensor exhibited significantly enhanced responses. As an example, we present an EP-based SAW gas sensor, which showed a much-improved sensitivity compared to that of a conventional delay-line SAW sensor. The fundamental mechanisms behind this excellent sensing performance have been elucidated., Competing Interests: Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: The concurrent presence of multiple chronic diseases, termed multimorbidity, is increasingly prevalent among patients with chronic illnesses. This phenomenon is particularly pronounced in middle-aged women, yet has not received adequate attention. The objective of this study was to investigate the pattern of multimorbidity and its changes over time in perimenopausal women., Methods: A longitudinal study was conducted on the coexistence of chronic diseases in 3990 middle-aged women aged 40-65 years. The primary analytical tools were association rule mining and cross-lagged panel modeling, applied to the comprehensive medical examination data of the cohort., Result: At the first medical examination, 77.72% of participants were diagnosed with two or more chronic diseases, a figure that rose to 86.98% by the last examination. The most frequently observed multimorbidity combination pair under strong association rules is obesity and dyslipidemia. Additionally, the findings indicated that central obesity significantly influences lipid composition., Conclusion: This study highlights the elevated prevalence of multimorbidity in perimenopausal women and the added complexity of endocrine-related disorders at this life stage. There is an urgent need to develop personalized health management strategies for this demographic and to monitor and intervene in their health status in order to achieve healthy aging for perimenopausal women.

Background: Advanced papillary thyroid carcinoma (PTC) exhibits significant heterogeneity. Understanding the gene expression programs underlying tumor heterogeneity is crucial for improving diagnostic and therapeutic strategies., Methods: We integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to explore transcriptional heterogeneity in PTC. Using consensus nonnegative matrix factorization (cNMF), we identified gene expression programs (GEPs) within malignant cells. A machine learning framework was applied to establish a lymph node metastasis (LNM) signature. Functional validation of key genes was performed through in vitro experiments, and drug screening was conducted to identify potential therapeutic candidates., Results: We identified an epithelial-mesenchymal transition (EMT)-related gene expression program, GEP3, which was strongly associated with LNM and poor clinical outcomes in PTC. Within the GEP3 high subcluster, we pinpointed ELF3 as a hub gene driving tumor invasiveness and angiogenesis. Notably, BRAF V600E mutations were associated with higher GEP3 expression levels, indicating that ELF3 may be a pivotal marker for aggressive disease progression, especially in BRAF-mutant PTC. Functional assays confirmed that ELF3 knockdown suppressed EMT and angiogenesis, reducing PTC cell migration and invasion. Regardless of whether they are positive or negative for BRAF V600E mutations, showed increased sensitivity to vemurafenib in higher ELF3 expression group., Conclusions: This study highlights the critical role of GEP and ELF3 in driving PTC progression and metastasis. Drug screening revealed that tanespimycin and vemurafenib were effective in targeting GEP3 high cells, offering therapeutic potential for aggressive PTC. These insights advance precision strategies for managing metastatic and heterogeneous PTC by targeting ELF3-driven pathways., Competing Interests: Compliance with ethical standards. Ethics approval and consent to participate: This study was approved by the Medical Ethics Committee of Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer (Approval number: 2023013). Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The past decade has seen significant progress in proton exchange membrane water electrolyzers (PEMWE), but the growing demand for cost-effective electrolytic hydrogen pushes for higher efficiency at lower costs. As a complex system, the performance of PEMWE is governed by a combination of multiscale factors. This review summarizes the latest progress from quantum to macroscopic scales. At the quantum level, electron spin configurations can be optimized to enhance catalytic activity. At the nano and meso scales, advancements in atomic structure optimization, crystal phase engineering, and heterostructure design improve catalytic performance and mass transport. At the macro scale, innovative techniques in gas bubble management and internal resistance reduction drive further efficiency gains under ampere-level operating conditions. These modifications at the quantum level cascade through meso- and macro-scales, affecting charge transfer, reaction kinetics, and gas evolution management. Unlike conventional approaches that focus solely on one scale-either at the catalyst level (e.g., atomic, or crystal modifications) or at the device level (e.g., porous transport layers design)-combining multiscale optimizations unlocks greater performance improvements. Finally, a perspective on future opportunities for multiscale engineering in PEMWE anode design toward commercial viability is offered., (© 2025 Wiley‐VCH GmbH.)

Catalytic hydrolysis is a sustainable method for the degradation of perfluorinated compounds (PFCs) but is challenged by the high reaction temperatures required to cleave strong C-F bonds. Herein, we developed an innovative C-F activation strategy by constructing synergistic Lewis and Brønsted acid pairs over atomically dispersed Zn-O-Al sites to promote C-F bond activation for decomposition of typical PFCs, CF 4 . Density functional theory (DFT) calculations demonstrate tricoordinated Al (Al III ) sites and Zn-OH functional, respectively, as Lewis and Brønsted acid sites over Zn-O-Al, synergistically enhancing the adsorption and decomposition of CF 4 . X-ray absorption spectroscopy (XAS), pyridine infrared spectroscopy (Py-IR), and ammonia temperature-programmed desorption (NH 3 -TPD) verified the presence of both Al III and Zn-OH on the atomically dispersed Zn-O-Al sites. CF 4 -TPD and in situ infrared spectroscopy confirmed that the Zn-O-Al sites facilitate CF 4 adsorption and C-F bond activation. As a result, the Zn-O-Al sites with synergistic Lewis and Brønsted acid pairs achieved 100% CF 4 decomposition at a low temperature of 560 °C and demonstrated outstanding stability for more than 250 h.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by lipid accumulation in liver cells. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have great potential in repairing and regenerating liver diseases. However, it is still unclear whether MSC-sEV can inhibit hepatocyte lipid accumulation by regulating mitochondrial fission., Methods: We investigated the effects of MSC-sEV on mitochondrial fission and its potential mechanism in lipotoxic hepatocytes and high-fat diet (HFD)-induced MASLD mice., Results: We found that MSC-sEV can effectively inhibit the expression of the Dynamin-related protein 1 (DRP1), thereby reducing mitochondrial fission, mitochondrial damage, and lipid deposition in lipotoxic hepatocytes and livers of HFD-induced MASLD in mice. Further mechanistic studies revealed that RING finger protein 31 (RNF31) played a crucial role in mediating the inhibitory effect of MSC-sEV on DRP1 and mitochondrial fission. RNF31 can suppress DRP1 expression and mitochondrial fission, thereby improving mitochondrial dysfunction and reducing hepatocyte lipid deposition. These findings suggest that MSC-sEV may downregulate hepatocyte DRP1-mediated mitochondrial fission by transporting RNF31, ultimately inhibiting hepatocyte lipid accumulation., Conclusions: The insights from this study provide a new perspective on the mechanism of MSC-sEV in reducing lipid accumulation and offer a potential therapeutic target by targeting DRP1 to inhibit hepatocyte steatosis and the progression of MASLD., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declared no competing financial interest. Ethics approval and consent to participate: All experiments involving animals were conducted according to the ethical policies and procedures approved by the Jiangsu University ethics committee (Approval no. UJS-IACUC-AP-2020033127). This study is reported in accordance with ARRIVE guidelines for animal experiments. The commercial HepG2 cells and LO2 cells used in this study were purchased from Fenghui Biology Co., Ltd. and identified using genotyping of STR loc by Shanghai Yihe Biotechnology Co., Ltd. ( https://www.fenghbio.cn/goods.php?id=86043 , https://www.fenghbio.cn/goods.php?id=85691 ). Fenghui Biology Co., Ltd has confirmed that ethical approval has been obtained for the collection of HepG2 and LO2 cells and that the donor has signed an informed consent form. The use of human umbilical cord tissues was approved by the Jiangsu University ethics committee (2012258). This project entitled “The effect and mechanism of engineered MSC exosomes targeting LSEC autophagy to inhibit hepatic sinusoidal capillarization” was approved on March 8, 2019. Furthermore, all patients signed the approved informed consent form, and all the procedures were performed in accordance with the principles of the Declaration of Helsinki., (© 2025. The Author(s).)

Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group ( P < 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2400089257., Competing Interests: The authors declare no conflict of interest.

Aims: Drug-induced liver injury is among the most challenging liver disorders. Endoplasmic reticulum (ER) is responsible for the correct protein folding and secretion, which are highly active in hepatocytes. Failure in maintaining the proper protein folding under pathological condition or external stimuli leads to the unfolded protein response (UPR) to restore ER homeostasis or induce cell death. IRE1α pathway is the most conserved UPR branch with diverse physiological and pathological functions. This study aimed to screen for natural compounds to alleviate hepatic ER stress and liver injury by modulating IRE1α activity., Materials and Methods: ATP-competitive molecules from chemical libraries were recognized by virtual screening for targeting the IRE1α kinase domain. IRE1α activity-based XBP1s-reporter cell lines with flow cytometric analysis were employed to validate candidates from chemical libraries. Then the functions of the top candidate compound on IRE1α signaling were analyzed followed by the treatment with ER stress agonists in vitro. Finally, the candidate compound was used to treat ER stress-induced acute liver injury to evaluate its protective effect in vivo., Key Findings: Dicoumarol (DIC) was discovered as a potential inhibitor of IRE1α activation in HEK293T cells, HepG2 cells and primary hepatocytes. Particularly, DIC ameliorates tunicamycin (Tm)- and carbon tetrachloride (CCl 4 )-induced acute hepatic ER stress to protect against liver injury., Significance: This study established a drug screening strategy against IRE1α activation and identified potential new therapeutic effects of DIC in treating liver injury-related diseases., 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 chronic illness known as oral submucous fibrosis (OSF) results in tissue fibrosis, precancerous lesions, and scarring. It usually manifests itself in the buccal mucosa. It frequently occurs in the buccal mucosa. Von Hippel-Lindau (VHL) is an essential component of E3 ubiquitin ligase complex. The loss of VHL led to reduced fibrotic responses, accompanied by ameliorated fiber deposition. However, the precise impact of VHL on OSF is yet unclear. OSF tissues and normal mucosal tissues were applied to analyze the distinct expression of VHL and histone deacetylase 6 (HDAC6). Oral fibroblasts were treated to arecoline to simulate OSF in vitro, and molecular biological experiments were conducted to identify the role of VHL in buccal mucosa fibroblasts (BMFs). VHL was downregulated and HDAC6 was upregulated in OSF tissues and BMFs. Overexpression of VHL inhibited fibrosis in arecoline-treated BMFs. VHL inhibits the level of HDAC6 by inducing the ubiquitination of HDAC6. Knockdown of HDAC6 reduces the fibrogenic ability of BMFs. Furthermore, overexpression of HDAC6 contributes to the activation of NF-κB signaling in BMFs. HDAC6 selective inhibitor ACY-1215 inhibited the NF-κB signaling pathway. VHL attenuated arecoline-induced OSF by inhibiting the ubiquitination of HDAC6 and blocking NF-κB pathway. As a result, our study offers new perspectives into the discovery of novel tactics that can be employed against OSF., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: The Joint Ethics Committee of The First Affiliated Hospital of Hainan Medical University gave its approval for this study (2023-KYL-119 and HYLL-2023-437). Consent to participate: The informed consent has obtained., (© 2025. The Author(s).)

Background: Pulmonary Alveolar Proteinosis (PAP) is a rare interstitial lung disease with diverse clinical manifestations and outcomes. However, there are limited data on the heterogeneity of PAP, as well as its prognosis, cause of death and genetic mechanisms. This study aims to elucidate mortality, prognostic features, and genetic mechanisms in patients with PAP., Methods: The individual patient data of clinical and mortality were obtained by summarizing the published cases series. Patients with PAP were classified using K-means clustering, and logistic regression identified prognostic factors affecting outcomes. Inheritance and related mechanism of PAP were described by summarizing PAP related genes and enrichment analysis., Findings: Our analysis included 3278 patients from 295 reports, with 88.6% diagnosed with idiopathic PAP (IPAP). Twelve major categories of cause were counted from 312 deaths (mortality: 9.5%), the most common of which were respiratory failure (45.8%) and lung infections (18.3%). Three symptom-related clusters were identified, and patients with multiple symptoms appeared to have worse mortality than those with single or no symptoms (p < 0.05). Non-secondary patterns (OR 2.87, p = 0.003), whole lung lavage (OR 0.15, p < 0.001), and effective GM-CSF therapy (OR 0.08, p < 0.001) are prognostic factors associated with decreased mortality. Additionally, 134 significant genes related to PAP development were identified, highlighting the roles of immune response and lipid metabolism., Interpretation: This study comprehensively describes the clinical characteristics cause of death, prognosis and associated factors based on the global PAP population. The significant phenotype heterogeneity highlighting the importance of long-term prognosis and individualized management for patients with PAP., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: All authors declare that they have no conflict of interest. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work., (© 2025. The Author(s).)

Background: Avian β-defensins (AvBDs) represent a key family of antimicrobial host defense peptides in birds. Accumulating evidence suggests that the evolutionary trajectory of β-defensin genes is specific to the gene, timescale, and species involved, implying that species-specific ecological and life-history differences drive divergent selective pressures on these genes. However, their evolutionary dynamics, particularly the interactions with ecological factors and life-history traits, remain insufficiently explored., Results: Through a comprehensive survey of 25 species spanning all major clades of Galliformes, 354 AvBD genes were identified. Comparative sequence analysis, genomic organization, and phylogenetic studies collectively reveal significant evolutionary diversification characterized by gene duplication, pseudogenization, and gene loss across these species. Notably, chicken AvBD3 exhibits significant differences in its coding regions, while AvBD6 and AvBD7 appear to have copy number variations, with species-specific paralogs of AvBD6 being especially prominent. Moreover, positive selection was more frequently observed in recently diverged gene lineages compared to ancestral ones. Using 70 samples from eight galliform species, the study further identified the prevalence of species-specific amino acid alleles. Phylogenetic comparative analysis demonstrated that the evolution of nine AvBD genes (AvBD2, -4, -5, -8, -9, -10, -11, -12, and -14) is significantly associated with specific ecological factors and life-history characteristics. Additionally, the evolutionary rates of these genes showed distinct relationship with inferred infection risk, likely reflecting the multifunctionality of β-defensins and potential trade-offs between immune defense and other biological functions., Conclusions: This cross-species identification and systematic evolutionary analysis of AvBDs in Galliformes deepen our understanding of the co-evolution of host defense peptides, offering valuable insights into their natural biology and evolution, and paving the way for future applications as alternatives to traditional antibiotics., Competing Interests: Declarations. Ethics approval and consent to participate: The experiment was performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals (Ministry of Science and Technology, Beijing, China, revised in June 2004) and was approved by the Institutional Animal Care and Use Committee of China West Normal University, Sichuan, China (No. CWNU2022D030). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Major depressive disorder (MDD) and type 2 diabetes (T 2 D) have been shown to be linked, but a comprehensive understanding of the underlying molecular mechanisms remains elusive. The purpose of this study was to explore the biological relationship between MDD and T 2 D and verify the functional roles of key genes. We used the Gene Expression Omnibus database to investigate the targets associated with MDD and T 2 D. Using linear models for microarray data, differentially expressed genes associated with MDD and T 2 D were identified in GSE76826 and GSE95849, respectively, and 126 shared genes were significantly upregulated. Weighted gene coexpression network analysis identified modules associated with MDD and T 2 D in the GSE38206 and GSE20966 datasets and identified 8 common genes. Functional enrichment analysis revealed that these genes were enriched in cell signaling, enzyme activity, cell structure and amino acid biosynthesis and involved in cell death pathways. Finally, combined with the CTD and GeneCards databases, lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was identified as a key gene. LPGAT1 was validated in GSE201332 and GSE182117, and the subject operating characteristic curve showed good diagnostic potential for MDD and T 2 D. Additionally, we used an in vitro model of MDD related to T 2 D to verify the expression of LPGAT1. A subsequent gene knockdown assay revealed that the downregulation of LPGAT1 improved mitochondrial function and reduced apoptosis in damaged neurons. Taken together, our results highlight the role of LPGAT1 in the connection between MDD and T 2 D, and these findings provide new insights into potential therapeutic targets for depression associated with diabetes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mature compost can reduce gaseous emissions in composting, but its regulation mechanisms via biotic and abiotic functions are largely unknown. This study used fresh and inactivated mature compost as additives in kitchen waste composting to unveil the relevant mechanisms using metagenomic analysis. Results showed that mature compost reduce gaseous emission by improving physiochemical properties and inoculating functional microbes. The abiotic function of mature compost alleviated methane and nitrous oxide emission by 20 % via enhancing air diffusion and pH to limit the activity of mcr, mtr, norB/C, and narG/H hosts. Compared to inactivated mature compost, the microbes in fresh counterpart promoted organic mineralization to slightly enhance ammonia release by 9 %, but alleviated 13 % of carbon dioxide emission through microbial humification to impel carbon sequestration. Therefore, another specialistic strategy (e.g. Calcium magnesium phosphate addition to form struvite Crystallization) should be integrated with mature compost to synergistically reduce gaseous emissions., 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.)

Radiotherapy is recognized as the primary treatment for nasopharyngeal carcinoma (NPC). Rapid and accurate dose prediction is crucial for enhancing the quality and efficiency of radiotherapy planning. However, the current dose prediction model based on 2D architecture cannot effectively learn the spatial information among slices. Although some studies have explored the incorporation of interslice features through 3D architecture, the resolution properties of medical image anisotropy significantly limit the predictive performance. To address the issues, we propose a novel deformable dose prediction network based on hybrid 2D and 3D convolution for NPC radiotherapy. Specifically, the proposed model innovatively incorporates a 2.5D architecture based on hybrid 2D and 3D convolution, and effectively utilizes the directional information within anisotropic resolutions to achieve cross-scale feature extraction. Additionally, deformable convolution is introduced into the model to enhance the receptive field and effectively handle multi-scale spatial transformations. To improve channel correlation and reduce redundant features, we design a Residual Deformable Squeeze-and-Excitation Module. We conduct extensive experiments on an internal dataset, and the results show that the proposed model outperforms other existing methods in most dosimetric criteria. The proposed model has superior dose prediction performance in NPC radiotherapy, and has important clinical significance for assisting physicists to optimize the treatment plan and improve standardization of radiotherapy planning. The source code is available at https://github.com/CDUTJ102/2.5D-Deformable-UNet ., Competing Interests: Declarations. Ethics Approval: Approval was obtained from the Ethics Committee of Sichuan Cancer Hospital, China (Ethical Approval Number: SCCHE-02-2022-003). Conflict of Interest: The authors declare no competing interests., (© 2024. International Federation for Medical and Biological Engineering.)

Transmembrane B cell lymphoma 2-associated X protein inhibitor motif-containing (TMBIM) 6, also known as Bax Inhibitor-1 (BI-1), has been heavily researched for its cytoprotective functions. TMBIM6 functional diversity includes modulating cell survival, stress, metabolism, cytoskeletal dynamics, organelle function, regulating cytosolic acidification, calcium, and reactive oxygen species (ROS). Clinical research shows TMBIM6 plays a key role in many of the world's top diseases/injuries (i.e., Alzheimer's, Parkinson's, diabetes, obesity, brain injury, liver disease, heart disease, aging, etc.), including cancer, where TMBIM6 expression impacts patient survival, chemoresistance, cancer progression, and metastasis. We show TMBIM6 is activated by, and undergoes, different conformational changes that dictate its function following a significant change in the cell's IntraCellular Environment (ICE). TMBIM6 agonism, following ICE change, can help the cell overcome multiple stresses including toxin exposure, viral infection, wound healing, and excitotoxicity. However, in cancer cells TMBIM6 agonism results in rapid paraptotic induction irrespective of the cancer type, sub-type, genotype or phenotype. Furthermore, the level of TMBIM6 expression in cancer did not dictate the level of paraptotic induction; however, it did dictate the rate at which paraptosis occurred. TMBIM6 agonism did not induce paraptosis in cancer via canonical routes involving p38 MAPK, JNK, ERK, UPR, autophagy, proteasomes, or Caspase-9. Instead, TMBIM6 agonism in cancer upregulates cytosolic Ca2+ and ROS, activates lysosome biogenesis, and induces paraptosis via ERAD II mechanisms. In xenograft models, we show TMBIM6 agonism induces rapid cancer cell death with no toxicity, even at high doses of TMBIM6 agonist (>450 mg/kg). In summary, this study shows TMBIM6's functional diversity is only activated by severe ICE change in diseased/injured cells, highlighting its transformative potential as a therapeutic target across various diseases and injuries, including cancer., Competing Interests: Competing interests: Authors are interested in the development of therapeutics for the TMBIM family, one of which is described in this article. Although MicroQuin has a commercial interest in MQT, MicroQuin’s lead therapeutics are small molecules and not peptides. MicroQuin’s small molecules act akin to MQT, but the data presented in this article is that of the peptide drug MQT. Several patents have been filed and are pending in relation to the activities of these products and the data presented in this article. Ethics approval and consent to participate: All methods were performed in accordance with relevant guidelines, regulations, and best practices. For in vivo studies financed by CDMRP approval was sought from the USAMRDC Animal Care and Use Review Office (ACURO). Labcorp Early Development Laboratories Limited (formerly Covance) – Huntingdon (UK) F16-00136 (A5616-01) was used for in vitro anti-viral studies. LabCorp (formerly Covance) Ann Arbor, Michigan (USA) D16-00871 (A4671-01) and WuXi AppTec (Shanghai, China) Co., Ltd. F16-00281 (A5969-01) were used for in vivo studies. Human data regarding TMBIM6 expression in patient biopsies was obtained from ProteinAtlas and NCI GEO databases. Informed consent was obtained from all patients for tissue samples to be used and analyzed. No images or identifiable information is provided or alluded to in this article about any participants., (© 2024. The Author(s).)

Weakly supervised temporal action localization (TAL) aims to localize the action instances in untrimmed videos using only video-level action labels. Without snippet-level labels, this task should be hard to distinguish all snippets with accurate action/background categories. The main difficulties are the large variations brought by the unconstraint background snippets and multiple subactions in action snippets. The existing prototype model focuses on describing snippets by covering them with clusters (defined as prototypes). In this work, we argue that the clustered prototype covering snippets with simple variations still suffers from the misclassification of the snippets with large variations. We propose an ensemble prototype network (EPNet), which ensembles prototypes learned with consensus-aware clustering. The network stacks a consensus prototype learning (CPL) module and an ensemble snippet weight learning (ESWL) module as one stage and extends one stage to multiple stages in an ensemble learning way. The CPL module learns the consensus matrix by estimating the similarity of clustering labels between two successive clustering generations. The consensus matrix optimizes the clustering to learn consensus prototypes, which can predict the snippets with consensus labels. The ESWL module estimates the weights of the misclassified snippets using the snippet-level loss. The weights update the posterior probabilities of the snippets in the clustering to learn prototypes in the next stage. We use multiple stages to learn multiple prototypes, which can cover the snippets with large variations for accurate snippet classification. Extensive experiments show that our method achieves the state-of-the-art weakly supervised TAL methods on two benchmark datasets, that is, THUMOS'14, ActivityNet v1.2, and ActivityNet v1.3 datasets.

The complexity of serum constituents and the lack of knowledge on biomarkers bring obstacles for reliable cancer screening with the limited information obtained by surface-enhanced Raman scattering (SERS) on a single substrate. We report here an extremely high-accurate approach for cancer screening by biomarker-free serum-SERS technique which employs three principal SERS substrates that are of specially designed surface properties. With three substrates rich information on serum can be obtained from SERS spectra, of which quadratic discriminant analysis (QDA) yields excellent classifications of serum samples independently. Diagnosis with an accuracy of ∼100% can be achieved based on the three independent QDA classifications, by the unanimity principle. In this study, a screening accuracy of 100% was achieved by this approach for 122 diagnosed out of the 194 serum samples. The mechanism for the extremely high accuracy of this approach was also theoretically investigated. The three-principal-substrate approach opens up a path towards highly accurate biomarker-free cancer screening by serum-SERS technique., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tiller is an important factor in determining rice yield. Currently, researches mainly focus on the outgrowth of low-order tiller (LOT), while the regulation mechanism of high-order tiller (HOT) outgrowth has remained unknown. In this study, we detected one OsNL1 mutant, nl1, exhibiting HOT numbers increase, and found that OsNL1 interacts with OsTOPLESS2, which was mediated by the core motif of nine amino acids VDCTLSLGT within the HAN domain of OsNL1. The topless2 mutant exhibits similar HOT number increase as in the nl1. Through ChIP-seq analysis, we revealed that OsNL1 recruits OsTOPLESS2 to conduct histone deacetylation in the promoters of OsMOC1 and OsMOC3 to regulate HOT outgrowth. Moreover, we showed that the HAN domain is essential for OsNL1 function as a repressor. In summary, our study reveals partial mechanism of HOT outgrowth in rice and deciphers the molecular biology function of the HAN domain. This will contribute to the comprehensive understanding of tiller outgrowth and the role of HAN-domain-containing genes., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Objectives: To develop a predicted algorithm for drug-resistant epilepsy (DRE) in newly diagnosed temporal lobe epilepsy (TLE) patients., Methods: A total of 139 newly diagnosed TLE patients were prospectively enrolled, and long-term video EEG monitoring was recorded. Clinical evaluations, including seizure frequency and antiseizure medications (ASMs) usage, were collected and prospectively followed up for 24 months. Interictal EEG data were used for feature extraction, identifying 216 EEG network features. Traditional machine learning and ensemble learning techniques were employed to predict DRE outcomes., Results: Over two years, TLE patients with DRE exhibited significant EEG differences, particularly in frontotemporal θ-band networks, characterized by increased connectivity metrics such as phase lag index (P = 0.000), etc. The predictive algorithm based on EEG features achieved accuracies between 59.2 %-84.6 % (AUC: 0.60-0.87). When compared to the whole brain, EEG features of the frontotemporal network showed improved classification performance in Naïve Bayes (P = 0.032), Tree Bagger (P = 0.021), and Subspace Discriminant (P = 0.022) models. The ensemble learning technique (Tree Bagger) delivered the best prediction results, achieving 91.5 % accuracy, 97 % sensitivity, 81 % specificity, and AUC of 0.92., Conclusions: Increased frontotemporal EEG connectivity was observed in TLE patients with 2-year DRE. A predictive model based on routine EEG provides an accessible method for forecasting ASMs efficacy., Significance: This study highlights the clinical utility of EEG-based algorithms in identifying DRE early, aiding personalized treatment strategies and improving patient outcomes., 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. Conflict of interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2025 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Arthrospira platensis (spirulina) is pivotal to the global microalgae industry, valued for its nutritional and bioactive properties. However, its sustainable production is challenged by freshwater scarcity and biological contaminants. This study introduces a salinity-biostimulants strategy to adapt a freshwater spirulina strain, CBD05, to near-seawater salinity (3 %). Exogenous glycine betaine (GB) and nitric oxide (NO), typical salinity enhancers, improved biomass productivity (0.36 g L - 1 d - 1), C-phycocyanin (C-PC) yield (83 mg L - 1 d - 1), and the economic output-to-input ratio was significantly enhanced. Metabolomic analysis linked salt tolerance to elevated amino acid accumulation, protein synthesis, and glycolysis, while transcriptional evidence highlighted enhanced carbon fixation and nitrogen assimilation towards C-PC synthesis upon addition of GB and NO. This strategy also demonstrated high resistance to Microcystis aeruginosa, a common contaminant in open systems. It provides a sustainable and cost-effective approach for industry-oriented spirulina production in freshwater-limited regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

To date, RNA-targeted chemical matter is under explored due to a lack of robust screening assays. In this study, we present a novel RNA-targeted small molecule screening approach using a specialized DNA-encoded library (DEL). Our findings reveal that the specialized DEL library, called "DEL Zipper", can significantly reduce single-stranded DNA-RNA region interaction signals during various kinds of RNA selection. By performing the selection against both G-quadruplex, we have identified novel hits that interact with RNA targets and the results are validated through binding. This study demonstrates that the "DEL Zipper" method is a robust screening assay that has potential for discovering small molecule ligands for diverse RNA targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Osteoarthritis (OA) is a common degenerative bone and joint disease with an unclear pathogenesis. Our study identified that the histone acetyltransferase encoded by Kat7 is upregulated in the affected articular cartilage of OA patients and in a mice model of medial meniscal instability-induced OA. Chondrocyte-specific knockdown of Kat7 expression exhibited a protective effect on articular cartilage integrity. In vitro experiments demonstrated that KAT7 promotes cartilage catabolism, inhibits cartilage anabolism, and induces chondrocyte senescence and apoptosis. Conversely, knocking down Kat7 was shown to protect chondrocyte function. Corresponding in vivo results indicated that silencing Kat7 effectively enhances cartilage anabolism, prevents articular cartilage damage, and significantly slows OA progression. Mechanistically, KAT7 activates the TLR4/NF-κB signaling pathway, and inhibition of this pathway reverses the catabolic effects and restores anabolic activity in the presence of Kat7 overexpression. Collectively, these findings confirm the critical role of KAT7 in the pathogenesis of OA and suggest that Kat7 represents a potential therapeutic target for OA treatment. KEY MESSAGES: There is a lack of clinically effective drugs for the treatment of osteoarthritis (OA). Kat7 plays a key role in the development of OA. Knocking down Kat7 expression can alleviate the progression of OA. Kat7 accelerates the progression of OA by activating the TLR4/NF-KB signaling pathway., Competing Interests: Declarations. Ethics approval: This study was approved and granted by the Ethics Committee of The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1a and b. Conflicts of interest: The authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemotherapy is important in the systemic therapy for breast cancer. However, after chemotherapy, the left living tumour cells are more progressive. There is an urgent need to study the underlying mechanism which is still unclear to further improve the therapeutic efficacy of chemotherapy in breast cancer. Here we find a pro-tumour effect of the apoptotic cells induced by the chemotherapy, which is mediated by a new subset of macrophages undergoing LC3-associated phagocytosis (LAP). By transferring exosomal S100A11 into the living tumour cells after chemotherapy, the macrophage exhibits a more pro-tumour phenotype than classic M2-type macrophages. Moreover, S100A11 binds to IFITM3, inducing Akt phosphorylation of living tumour cells after chemotherapy, which promotes tumour progression. Of note, Akt inhibitor can enhance the therapeutic effcicay of chemotherapy in breast cancer. This study provides a novel mechanistic link between tumour-associated macrophages and breast cancer, uncovering Akt as a potential therapeutic target to improve chemotherapy efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Extreme droughts generally decrease productivity in grassland ecosystems 1-3 with negative consequences for nature's contribution to people 4-7 . The extent to which this negative effect varies among grassland types and over time in response to multi-year extreme drought remains unclear. Here, using a coordinated distributed experiment that simulated four years of growing-season drought (around 66% rainfall reduction), we compared drought sensitivity within and among six representative grasslands spanning broad precipitation gradients in each of Eurasia and North America-two of the Northern Hemisphere's largest grass-dominated regions. Aboveground plant production declined substantially with drought in the Eurasian grasslands and the effects accumulated over time, while the declines were less severe and more muted over time in the North American grasslands. Drought effects on species richness shifted from positive to negative in Eurasia, but from negative to positive in North America over time. The differing responses of plant production in these grasslands were accompanied by less common (subordinate) plant species declining in Eurasian grasslands but increasing in North American grasslands. Our findings demonstrate the high production sensitivity of Eurasian compared with North American grasslands to extreme drought (43.6% versus 25.2% reduction), and the key role of subordinate species in determining impacts of extreme drought on grassland productivity., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Study Objective: Difficult airway management is a significant challenge in clinical anesthesia, critical care, and emergency medicine. Inadequate management can lead to severe complications including organ damage and death. This study assessed the variability in difficult airway management across China and focused on how patient and operator factors influenced outcomes in operating rooms., Design: A multicenter observational cross-sectional study., Setting: This study was conducted from November 2022 to November 2023 and included 25 secondary and tertiary hospitals across various regions in China., Patients: In the total of 181,399 general anesthesia patients, 384 (0.21 %) were identified as having difficult airways., Interventions: Data were gathered from a specialized questionnaire comprising four sections with 27 questions and analyzed using logistic regression in SPSS to identify key factors that influenced effective management of difficult airways., Measurements: This study focused on preoperative assessment, anesthesia selection, intubation attempts, and contingency planning for difficult airway management practices among anesthesiologists., Main Results: In anticipated difficult airways, rapid sequence induction was used in 51.7 % of the cases, maintaining spontaneous breathing under general anesthesia in 11.1 %, and awake intubation in 36 %. For unanticipated difficult airways, 95.9 % of the anesthesiologists opted for rapid sequence induction. Limited mouth opening was the most common cause of difficult airways and obesity and ankylosing spondylitis were identified as significant factors. The logistic regression analysis identified the type of difficult airway, anesthesiologist experience, and assessment methods as key factors influencing the first attempt intubation success., Conclusions: The accuracy of difficult airway assessment and first attempt intubation success is influenced by both patient-related factors and the anesthesiologist's expertise. Regional and institutional variability in decision-making and tool selection underscores the critical need for standardized guidelines and comprehensive training to enhance airway management outcomes across diverse clinical settings in China., 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 Inc. All rights reserved.)

Objective: To summarise and compare the applications and effectiveness of virtual reality in cultivating clinical thinking among nursing students and to further analyse the active ingredients of virtual reality applications., Design: Systematic review., Review Methods: A systematic and comprehensive search of PubMed, Web of Science, Cochrane, Scopus, Embase, and CINAHL was conducted from the inception until 5th of February 2024. The standardised JBI critical appraisal tools for randomised controlled trials (RCTs) and quasiexperimental studies were used to assess the quality of the selected studies., Results: After screening, 17 articles were ultimately included, including 5 RCTs and 12 quasiexperimental studies. The findings reveal that different applications of virtual reality have varying impacts on nursing students' clinical thinking. The analysis of active ingredients reveals a number of key factors that enhance learning in virtual reality applications. A hybrid approach benefits development across critical thinking, clinical judgement, and clinical decision-making. Nonimmersive virtual reality appears to be active and effective for critical thinking, whereas immersive virtual reality proves to be effective for problem solving. Shorter simulation running times enhance clinical judgement. Shorter prebriefing sessions, fewer simulation scenarios, and structured debriefing centred on the algorithm of the scenario contribute positively to clinical reasoning. Individual operation of the virtual reality system, immediate scenario-embedded feedback, and instructor-led debriefing support clinical decision-making., Conclusions: Nurse educators should consider integrating virtual reality technology with other teaching methods to increase the effectiveness of the development of clinical thinking among students. The prebriefing time and debriefing structure should be tailored to specific contexts and objectives. To maintain students' attention during the simulations, allowing students to operate the system independently and shortening the simulation cycles are advisable while limiting the number of scenarios to reduce the cognitive load. For effective reflection, combining scenario-embedded feedback within the virtual reality system with teacher-led debriefing is essential. Additionally, a sensible design of the level of immersion is necessary due to differences in accessibility, the complexity of the learning environment, and the costs between nonimmersive and immersive virtual reality., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Primary Familial Brain Calcification (PFBC) can manifest clinically with a complex and heterogeneous array of symptoms, including parkinsonism, dysarthria, and cognitive impairment. However, the distinct presentations of PFBC in Asian and European populations remain unclear., Methods: We conducted a systematic search of PubMed for studies involving genetically confirmed PFBC patients. Demographic data, genetic information, radiological examinations, and clinical characteristics were extracted for each case., Results: The study included 120 publications and 564 genetically confirmed PFBC patients. Asian and European PFBC populations represented 54 % and 37 % of global patients, respectively. While calcification patterns showed no significant differences between Asian and European PFBC patients, European autosomal dominant PFBC variant carriers were more likely to exhibit clinical symptoms compared to their Asian counterparts (OR = 2.90, 95 % CI 1.55-5.60) and had an earlier estimated age of onset (median age 42 vs 58)., Conclusion: The interaction between regional differences and genetically determined calcification severity may collectively influence PFBC symptom progression. Future research should further explore the potential roles of gene modifiers, ethnic background, socioeconomic and environmental exposure factors underlying regional differences in PFBC progression., 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.)

Leaf disease detection holds significant application value in the agricultural domain, as timely and accurate detection of crop leaf disease targets is crucial for improving crop yield and quality. To handle varying crop leaf disease target sizes, occlusion issues, and detection errors in complex environments, the YOLOv8 structure has been enhanced. Firstly, to tackle the issues of target diversity and loss of image features, this paper designs the GOCR-ELAN lightweight module to replace some of the C2f modules in the Backbone, thereby reducing the parameters in the model and enhancing the network's feature extraction capability. Secondly, replacing the CBS convolution in the network with the ADown downsampling module effectively addresses issues such as feature selection and preservation in occluded scenes, further reducing the algorithm's parameter count. Finally, to tackle missed detections and false alarms in complex environments, this paper introduces the WSIoU loss function optimization algorithm to enhance both convergence speed and localization accuracy. Averaged experimental results suggest that, relative to the original YOLOv8 algorithm, parameters have been reduced by 28.7 %, the GFLOPs metric has decreased by 43.2 %, MAP50 has increased from 86 % to 87.7 %, and MAP50-95 has risen from 67 % to 68.9 %, achieving both lightweight model construction and improved detection performance. The trained model is just 4.55 MB, smaller than the lightest YOLOv5 model, and remains highly competitive in detection accuracy compared to larger models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aim: The relationship between the systemic inflammatory response index (SIRI) and carotid atherosclerosis has not yet been assessed in a longitudinal investigation. Our current study aimed to investigate whether SIRI is related to an increased risk of incident carotid plaque., Methods and Results: Our study included individuals who did not have carotid atherosclerosis and had undergone yearly health check-ups at the Department of Health Management of Nanfang Hospital between 2011 and 2018 (total n = 3927). SIRI was computed by a composite value of neutrophils, monocytes, and lymphocytes. Over a median follow-up time of 4.42 years, 872 (22.21 %) participants developed carotid plaque in the entire cohort. The adjusted hazard ratio (HR) for the continuous SIRI was 1.093 (95 % CI: 1.021-1.223) in our present study. In the general population, individuals belonging to the highest quartile of SIRI had an elevated risk of carotid plaque, as compared to those within the lowest quartile (HR 1.122, 95 % CI: 1.011-1.391, P for trend = 0.041). Furthermore, this trend was even more pronounced among participants without hypertension, diabetes and hyperlipidemia in the highest SIRI quartile, who demonstrated a markedly increased risk of carotid plaque when contrasted with those in the lowest quartile (HR 1.277, 95 % CI: 1.041-1.568, P for trend = 0.006)., Conclusions: Our research findings suggest an association between increased SIRI levels and a higher incidence of carotid atherosclerosis, especially among the people without a history of hypertension, diabetes and hyperlipidemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess vestibular function, video head impulse test (vHIT) is taken as the gold standard by evaluating the vestibulo-ocular reflex (VOR). However, vHIT requires the patient to wear a specialized head-mounted goggle equipment that needs to be calibrated before each use. For this, we proposed an intelligent head impulse test (iHIT) setting with a monocular infrared camera instead of the head-mounted goggle and contributed correspondingly a video classification approach with deep learning to vestibular function determination., Methods: Within the iHIT framework, a monocular infrared camera was set in front of the patient to capture test videos, based on which a dataset DiHIT of HIT video clips was set up. We then proposed a two-stage multi-modal video classification network, trained on the dataset DiHIT, that took as input the eye motion and head motion data extracted from the facial keypoints via HIT clips and outputted the identification of the semicircular canal (SCC) being tested (SCC identification) and determination of VOR abnormality (SCC qualitation)., Results: Experiments on this dataset DiHIT showed that it achieved the accuracy of 100% in prediction of SCC identification. Furthermore, it attained predictive accuracies of 84.1% in horizontal and 79.0% in vertical SCC qualitation., Conclusions: Compared with existing video-based HIT, iHIT eliminates goggles, does not require equipment calibration, and achieves complete automation. Furthermore, iHIT will bring more benefits to users due to its low cost and ease of operation. Codes and use case pipeline are available at: https://github.com/dec1st2023/iHIT., Level of Evidence: 3 Laryngoscope, 135:1161-1168, 2025., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Recommending suitable exercises and providing the reasons for these recommendations is a highly valuable task, as it can significantly improve students' learning efficiency. Nevertheless, the extensive range of exercise resources and the diverse learning capacities of students present a notable difficulty in recommending exercises. Collaborative filtering approaches frequently have difficulties in recommending suitable exercises, whereas deep learning methods lack explanation, which restricts their practical use. To address these issue, this paper proposes KG4EER, an explainable exercise recommendation with a knowledge graph. KG4EER facilitates the matching of various students with suitable exercises and offers explanations for its recommendations. More precisely, a feature extraction module is introduced to represent students' learning features, and a knowledge graph is constructed to recommend exercises. This knowledge graph, which includes three primary entities - knowledge concepts, students, and exercises - and their interrelationships, serves to recommend suitable exercises. Extensive experiments conducted on three real-world datasets, coupled with expert interviews, establish the superiority of KG4EER over existing baseline methods and underscore its robust explainability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1) is caused by (TTTTA)exp(TTTCA)exp repeat expansions in SAMD12, while pure (TTTTA)exp is polymorphic. Our investigation focused on the origin and evolution of pure (TTTTA)exp and (TTTTA)exp(TTTCA)exp at this locus. We observed a founder effect between them. The phylogenetic analysis suggested that the (TTTTA)exp(TTTCA)exp might be generated from pure (TTTTA)exp through infrequent transformation events. Long-read sequencing revealed somatic generation of (TTTTA)exp(TTTCA)exp from pure (TTTTA)exp, likely via long segment (TTTCA) repeats insertion. Our findings indicate close relationships between the non-pathogenic (TTTTA)exp and the pathogenic (TTTTA)exp(TTTCA)exp, with dynamic interconversions. This sheds light on the genesis of pathogenic repeat expansions from ancestral premutation alleles. Our results may guide future studies in detecting novel repeat expansion disorders and elucidating repeat expansion mutational processes, thereby enhancing our understanding of human genomic variation., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: The ethics was approved in the Second Affiliated Hospital, Zhejiang University School of Medicine (I2019001151). Written informed consent was obtained from all participants following the Declaration of Helsinki., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Multiple sclerosis (MS) is an immune-mediated disease in the central nervous system that is characterized by demyelination, axonal degeneration, and progressive neurological disability and is so far incurable. Current medications are predominantly immune-targeted but fail to prevent disease progression due to their inability to actively promote remyelination. Small molecules have been reported to promote myelin regeneration but their therapeutic efficacy is limited by insufficient immune modulation. Thus, the strategies achieving both immunomodulation and active myelin regeneration are highly desired. Here, we investigated a combination therapy (CT) for MS designed to simultaneously modulate immune responses and promote oligodendrocyte precursor cell (OPC) differentiation and in situ remyelination in an experimental autoimmune encephalomyelitis (EAE) mouse model. Remarkably, CT suppressed acute inflammatory activity, activated the signaling pathways for myelin development, induced the expression of myelin-related genes, and significantly promoted remyelination and the recovery of motor performance. Furthermore, a reduced immunomodulator dosage or shorter treatment duration with small-molecule drugs achieved comparable symptom reversal. Our findings demonstrate the potential of CT to address complex pathobiology and lay a foundation for developing novel therapeutic strategies for MS., (© The Author(s) 2025. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.)

Patients with complex coronary artery disease (CAD) often have poor clinical outcomes. This study aimed to develop a predictive model for assessing the 1-year risk of major adverse cardiovascular events (MACE) in patients with stable complex CAD, using retrospective data collected from January 2020 to September 2023 at Guangzhou Red Cross Hospital. The goal was to enable early risk stratification and intervention to improve clinical outcomes. A total of 369 patients were included and randomly divided into a training set (70%) for model development and a validation set (30%) for performance evaluation. Predictive factors were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by logistic regression to construct the model and create a nomogram. Seven independent predictors were identified: functional SYNTAX score (OR 1.257, 95% CI 1.159-1.375), low-density lipoprotein cholesterol (LDL-C, OR 1.487, 95% CI 1.147-1.963, /1mmol/L), left ventricular ejection fraction (LVEF, OR 0.934, 95% CI 0.882-0.985, /1%), albumin (OR 0.889, 95% CI 0.809-0.974, /1g/L), pulse pressure ≥ 72 mmHg (OR 3.358, 95% CI 1.621-7.118), angiotensin-converting enzyme 2 (ACE2) ≥ 27.5 U/L (OR 2.503, 95% CI 1.290-5.014), and diabetes (OR 2.261, 95% CI 1.186-4.397). Among these, the functional SYNTAX score was the strongest predictor. The area under the receiver operating characteristic curve (AUC) was 0.843 for the training set and 0.844 for the validation set, with Youden indices of 0.561 and 0.601, respectively. Calibration curves and decision curve analysis demonstrated good predictive accuracy and clinical utility of the model. These findings suggest that the developed model has strong predictive performance for 1-year MACE risk in patients with complex CAD, and early risk stratification and intervention based on this model may improve clinical outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Accurate and efficient sorting of single target cells is crucial for downstream single-cell analysis, such as RNA sequencing, to uncover cellular heterogeneity and functional characteristics. However, conventional single-cell sorting techniques, such as manual micromanipulation or fluorescence-activated cell sorting, do not match current demands and are limited by low throughput, low sorting efficiency and precision, or limited cell viability. Here, we report an automated, highly efficient single-cell sorter, integrating laser-induced forward transfer (LIFT) with a high-throughput picoliter micropore array. The micropore array was surface-functionalized to manipulate liquid surface tension, facilitating the formation of single-cell picoliter droplets in the micropores to realize automated and highly efficient (>80%) single-cell isolation. Using an in-house built microscopic system, rare target cells were identified and automatically retrieved by LIFT with precise sorting efficiency (about 100%) for downstream single-cell analysis while maintaining high cell viability (about 80%). As a case demonstration, we demonstrated the accurate sorting of rare transfected PC-9 cells and post-transfection cell culture, minimizing cell loss and the risk of contamination. Furthermore, we performed single-cell RNA sequencing and showed that high-quality single-cell transcriptome information was efficiently and reliably obtained during cell sorting, preventing additional costs due to low sorting accuracy. The single-cell sorter will become invaluable for single-cell analysis, laying the foundation for multiomics analysis and precision medicine research.

Aim: This retrospective study was aimed to evaluate the diagnostic value of a combination of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-II) in pancreatic cancer., Methods: Clinical data were collected from 111 pancreatic cancer patients and 158 patients with benign pancreatic diseases (BPD). Serum CA19-9, CEA and PIVKA-II were subjected to receiver operating characteristic curve (ROC) analysis alone and in combination for the diagnosis of pancreatic cancer., Results: Serum CA19-9, CEA, and PIVKA-II were higher in pancreatic cancer patients than in BPD patients (P < 0.001). ROC analysis indicated that the cutoff values were 99.390 for CA19-9, 3.065 for CEA, and 42.965 for PIVKA-II, at which the positive rate in pancreatic cancer was 78.38 % for CA19-9, 43.24 % for CEA and 48.65 % for PIVKA-Ⅱ. When serum CA19-9, CEA, and PIVKA-II were used alone, the areas under the curves (AUC), sensitivity and specificity were 0.821, 68.47 % and 89.24 % for CA19-9, 0.763, 61.26 % and 85.44 % for CEA, and 0.681, 45.95 % and 87.34 % for PIVKA-II. When serum CA19-9, CEA, and PIVKA-II were used in combination, the positivity rate was 94.59 % in pancreatic cancer with AUC of 0.903, sensitivity of 81.10 % and specificity of 88.00 %., Conclusion: PIVKA-II is a potential serum marker of pancreatic cancer and the combination of CA19-9, CEA, and PIVKA-II is a novel panel of serum markers with promising diagnostic value for pancreatic cancer., 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 Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Current treatments for bone injuries face notable limitations such as adverse reactions to implant materials and increased risks of infection. There is an essential need for a therapeutic that will address these issues and decrease recovery times. Herein, a multifunctional nanohybrid zinc-based metal-organic framework integrated with gold nanoparticles (Au@ZIF-8) is synthesized to promote antibacterial and osteogenic benefits. Au@ZIF-8 is capable of converting light energy into heat and has demonstrated its ability to increase the surrounding temperature by ≈30 °C. As a result, Au@ZIF-8 has exhibited bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) upon exposure to near-infrared (NIR) irradiation. Concurrently, Au@ZIF-8 sustains the release of zinc ions from the nanohybrid for the potential of bone repair. When combined with a gelatin-based hydrogel, Au@ZIF-8 significantly elevated osteogenic gene expression and promoted preosteoclast differentiation through the sustained zinc ion release, as opposed to a gel-only control. The potential of the multifunctional nanohybrid is further demonstrated as a coating material for titanium orthopedic implants to introduce antibacterial properties and promote osteogenic differentiation of preosteoblasts for bone healing. Given its excellent antibacterial in response to NIR irradiation and osteogenic abilities, Au@ZIF-8 is a promising photothermal therapy for bone injuries., (© 2025 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Acute liver injury (ALI) is associated with high mortality rates. Despite its severity, there are currently no effective interventions, underscoring the urgent need for research on the mechanisms driving ALI progression. Irisin, a hormone derived from its precursor FNDC5, has been shown to play a critical role in some chronic liver diseases. In this study we investigated the role of hepatic FNDC5/Irisin in a mouse model of AILI induced by acetaminophen (APAP, 400 mg/kg, i.p.). The mice were euthanized at 6, 12 and 24 h after APAP injection, then the blood and liver tissues were collected for analyses. By conducting transcriptome sequencing, we identified that both the expression and release of FNDC5/Irisin were significantly increased and highly correlated with AILI. We showed that knockout of Irisin significantly improved APAP-induced tissue damage and hepatocyte death in mouse liver. Conversely, preinjection of recombinant Irisin protein (1 mg·kg -1 ·d - 1 , i.p., for 3 days) exacerbated the AILI in FNDC5 knockout mice. RNA-seq analysis revealed that knockout of FNDC5/Irisin reduced inflammatory responses and JNK/NF-κB activation in APAP-treated mouse liver, while exogenous Irisin administration aggravated JNK/NF-κB-mediated inflammation. In primary mouse hepatocytes treated with APAP (15 mM), application of Irisin (100 ng/mL) activated the integrin αV/JNK/NF-κB axis, driving inflammation and oxidative stress. In summary, this study highlights Irisin as a critical regulator in AILI progression. Circulating Irisin could be a novel biomarker for AILI diagnosis, and targeting FNDC5/Irisin could hold promise for the development of novel treatments for AILI., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Extracellular signal-regulated kinases (ERKs) are pivotal signaling molecules in the RAS-RAF-MEK-ERK signaling pathway and have emerged as potential antitumor targets, providing a promising strategy for tumor therapy. Therefore, the development of antitumor drugs targeting ERK protein has received extensive attention. Here, we developed a compound library based on a series of novel aromatic urea-imidazole salt derivatives and conducted phenotypic screening against various cancer cell lines. Notably, 21y exhibited high efficacy against MCF-7 cells (IC 50 = 0.67 μM). Furthermore, label-free drug affinity responsive target stability (DARTS) and LC-MS/MS proteomics techniques revealed that 21y directly targets ERK1/2. Mechanistically, 21y induced cell apoptosis and autophagy-related cell death. In vivo studies confirmed that 21y strongly inhibited tumor growth and lung metastasis in breast cancer. Taken together, 21y targets ERK1/2 as a promising therapeutic agent for breast cancer therapy.

To elucidate the characteristic aroma of Hainan Dayezhong black tea, GC-MS, GC-olfactometry, and electronic nose analyses were used to examine the changes in volatile compounds. A total of 527 volatiles were identified and quantified, of which 80 compounds with relative odor activity values exceeding 1 in dried tea samples were selected as biomarkers. Floral and sweet-associated volatiles, including damascenone, benzaldehyde, and linalool, were proposed to be responsible for the characteristic aroma. Our results indicated that multiple stresses occurring during withering, rolling, and fermentation contributed to the distinctive floral aroma, while the thermal effects of drying enhanced sweet odors by volatilizing certain fragrant compounds, thereby improving the final quality of the dried tea. These findings provide a foundation for quality control in practical manufacturing and will contribute to the development of standard operating procedures for producing Hainan Dayezhong black tea with desirable aromas., 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.)

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide. The prognosis of patients has been significantly improved by chemotherapy, but acquired drug resistance remains a major obstacle to NSCLC treatment. Circular RNAs (circRNAs), which act as miRNA or protein sponges, are critically associated with the development and chemotherapy resistance of NSCLC., Methods: CircRNA sequencing was performed to analyze the differential expression of circRNAs between A549 and A549-GR cells. Chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) technologies were used to detect the expression of hsa&#95;circ&#95;0125356, miR-582-5p,and FGF9 in NSCLC tissues and para-carcinoma tissues. Fluorescence in situ hybridization (FISH), dual-luciferase reporter assays and RNA immunoprecipitation (RIP) were conducted to evaluate the expression and regulation of hsa&#95;circ&#95;0125356, miR-582-5p, and FGF9. Furthermore, the regulation of hsa&#95;circ&#95;0125356/miR-582-5p/FGF9 on gemcitabine sensitivity was confirmed by TUNEL, Transwell, EdU, CCK8 and immunohistochemistry., Results: We identified a novel hsa&#95;circ&#95;0125356 as a therapeutic target against gemcitabine resistance. Hsa&#95;circ&#95;0125356 was significantly elevated in clinical samples of patients with NSCLC. Moreover, hsa&#95;circ&#95;0125356 overexpression promoted gemcitabine resistance to NSCLC by upregulating FGF9 via sponging miR-582-5p in vivo and in vitro. Notably, WNT canonical (ERK/GSK3β/β-catenin) and non-canonical (Daam1/RhoA/ROCK2) signaling pathways were activated due to hsa&#95;circ&#95;0125356 acting as an endogenous miR-582-5p sponge to regulate the expression of FGF9, and thereby enhancing gemcitabine resistance via promoting DNA damage repair and inhibition of apoptosis. The results were further confirmed by two small molecule antagonists, WAY 316606 and XAV-939,which could inhibit the activation of WNT signaling pathway induced by hsa&#95;circ&#95;0125356., Conclusion: We first demonstrated that hsa&#95;circ&#95;0125356 was significantly upregulated and served as a biomarker for gemcitabine resistance in NSCLC by sponging miR-582-5p/FGF9 axis to regulate the WNT canonical and non-canonical signaling pathways, which provided a new direction for identification of therapeutic targets for the treatment of gemcitabine resistance of NSCLC., Competing Interests: Declarations. Consent for publication: All authors agreed to the publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Exercise is acknowledged for its beneficial effects on brain health; however, the intricate underlying molecular mechanisms remain poorly understood., Aims: This study aimed to explore aerobic exercise-induced metabolic alterations in the brain., Methods: We conducted an eight-week treadmill running exercise program in two-month-old male C57/BL6J mice. Body weight, serum lipid, glucose levels, and spatial cognition were measured. Spatial metabolomic analysis was performed to compare the metabolomic profiles across different brain regions. Immunohistochemical methods were used to compare the expression of carnitine palmitoyltransferase 1c (CPT1c)., Results: Exercise induced significant changes in the analysed metabolomic profiles. There were 904 differentially expressed metabolites (DEMs) detected in the whole brain section. Notable alterations in lipid profiles were observed, and among the 292 lipids detected, there were 74 (25.34 %), 85 (29.11 %), and 78 (26.71 %) lipids differentially expressed in the hippocampus, thalamus, and hypothalamus of the Exe group, respectively. Lipid metabolism related pathways and enzymes were also altered, with L-carnitine and CPT1c upregulated in the three regions (p<0.05), and epinephrine levels decreased in the hippocampus (p<0.05). Furthermore, the vitamin B6 metabolism pathway was altered in the hypothalamus., Conclusions: This study highlighted the significant changes in lipid metabolism induced by involuntary exercise in the brains of young male mice. Exercise also altered epinephrine levels and the vitamin B12 metabolic pathway in specific brain regions, which indicated the multifaceted effects of exercise on the brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atherosclerotic cardiovascular diseases can lead to myocardial infarction and stroke, which are linked to elevated rates of mortality. Morin is a flavonoid compound that can be extracted from mulberries and possesses anti-inflammatory and antioxidant properties. The objective of this research is to elucidate Morin's impact on atherosclerosis. The ApoE -/- mice were divided into three groups: control group, HFD group and HFD + Morin group. The mice in control group received a normal diet (ND). To create an atherosclerosis model, ApoE -/- mice were subjected to a high-fat diet (HFD) for 8 weeks. The mice were assigned to two distinct categories at random based on whether Morin intervention was administered: one serving as the HFD group and the other as the HFD + Morin group. The mice received Morin for 4 weeks at a dosage of 50 mg/kg orally in the model + Morin group. Subsequently, ORO staining assay was performed to evaluate the formation of aortic plaques. ELISA was used to measure IFN-γ and TNF-α levels in plasma of the mice. In vitro, mouse macrophages RAW264.7 were cultured and treated with IFN-γ for 24 h, followed by Morin treatment for another 24 h. Western blotting was conducted to analyze changes in macrophage polarization markers CD86 and CD206, as well as P-STAT1 levels. DCFH-DA was used to detect changes in intracellular ROS levels. Subsequently, RAW264.7 cells were treated with the STAT1 inhibitor Lenvatinib to further investigate changes in CD86 and CD206, as well as ROS levels. In vivo data showed that Morin markedly diminished the size of aortic plaques and suppressed the secretion of IFN-γ and TNF-α. In vitro data indicated that Morin reduced M1 polarization and intracellular ROS levels through inhibiting the STAT1 pathway activation in RAW264.7 cells, ultimately suppressing inflammation., 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 Inc. All rights reserved.)