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Abstract Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4+ T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC.

Abstract The Qinghai-Tibet Plateau is a valuable genetic resource pool, and the high-altitude adaptation of Tibetan pigs is a classic example of the adaptive evolution of domestic animals. Here, we report the presence of Darwinian positive selection signatures in Tibetan pigs (TBPs) using 348 genome-wide datasets (127 whole-genome sequence datasets (WGSs) and 221 whole-genome single-nucleotide polymorphism (SNP) chip datasets). We characterized a high-confidence list of genetic signatures related response to high-altitude adaptation in Tibetan pigs, including 4,598 candidate SNPs and 131 candidate genes. Functional annotation and enrichment analysis revealed that 131 candidate genes are related to multiple systems and organs in Tibetan pigs. Notably, eight of the top ten novel genes, RALB, NBEA, LIFR, CLEC17A, PRIM2, CDH7, GK5 and FAM83B, were highlighted and associated with improved adaptive heart functions in Tibetan pigs high-altitude adaptation. Moreover, genome-wide association analysis revealed that 29 SNPs were involved in 13 candidate genes associated with at least one adaptive trait. In particular, among the top ten candidate genes, CLEC17A is related to a reduction in hemoglobin (HGB) in Tibetan pigs. Overall, our study provides a robust SNP/gene list involving genetic adaptation for Tibetan pig high-altitude adaptation, and it will be a valuable resource for future Tibetan pig studies.

Abstract Dysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients’ clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells’ glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase β-transducin repeat-containing protein (β-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the β-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A–C (1–3), with distinctive C–C and C–O–C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

IntroductionResveratrol (Res), a natural plant antitoxin polyphenol, is widely used in animal husbandry due to its antioxidant and anti-inflammatory properties, and current research has focused on humans, sows, and female mice. This study aimed to analyze the effects of dietary Res supplementation in ewes on antioxidant activity, immune responses, hormone levels, rumen microbiota and metabolites across various reproductive stages (estrus, pregnancy, and lactation).MethodsTwenty-four healthy ewe lambs (Hu sheep, 2 months old) with a similar body weight (BW) (mean: 21.79 ± 2.09 kg) were selected and randomly divided into two groups: the control group (Con) and the Res group (Res). The Res group received 10 mg/kg Res (based on BW) in addition to their basal diet.ResultsRes increased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in ewes at sexual maturity (p < 0.05). Additionally, Res supplementation induced significant increases in serum glutathione peroxidase (GSH-Px), IgG, FSH, and LH levels during estrus (p < 0.05); serum IgA, IgG and IgM during pregnancy and lactation (p < 0.05); and serum LH, glucose, GSH-Px, and catalase (CAT) levels during lactation (p < 0.05). Meanwhile, serum interleukin 1β (IL-1β) (p =0.005) and cholesterol levels (p = 0.041) during the lactation stage decreased following Res supplementation. Notably, colostrum IgA, IgG, and fat concentrations were significantly higher in the Res group than in the Con group (p < 0.05). Moreover, Res altered the rumen microbiota in ewes. Specifically, the relative abundance of Prevotella (p < 0.05) during pregnancy and Rikenellaceae_RC9_gut_group (p < 0.001) during lactation were significantly increased in ewes under Res treatment. The abundance of Rikenellaceae_RC9_gut_group was positively correlated with the levels of Ig A, Ig M, E2, FSH, LH, GSH-PX, and CAT. Additionally, Res altered the activity of metabolic pathways such as progesterone-mediated oocyte maturation, the estrogen signaling pathway, ovarian steroidogenesis, and the AMPK signaling pathway, and the levels of AICAR and 2-hydroxyestradiol metabolites, both during pregnancy and lactation.DiscussionThere findings show that Res can improve health, antioxidant status, and immune activity throughout the reproductive cycle in ewes by regulating rumen microorganisms and metabolites.

Chinese multinational enterprises (CMNEs) are increasingly initiating risky mergers and acquisitions (M&As) in developed markets to obtain strategic assets, which necessitates long-term integration that often takes years. Drawing on knowledge management literature, this study explores CMNEs’ dynamic post-merger integration (PMI) changes, the role of knowledge, and coevolutionary relationships. Based on 41 conversations concerning five Chinese acquisitions in Germany, this study develops a spiral-forward framework, determining that CMNEs’ PMI changes proceed through three phases of access, adjustment, and growth, moving from autonomy to systemic integration to business integration in a forward spiral with evolving knowledge needs. The efficiency of previous integration and knowledge needs has an influence in the following periods’ degree of integration via balanced integration, over-integration, or delayed integration. This study stresses the crucial role of knowledge types and knowledge processes in CMNEs’ PMI changes, offering a valuable framework for understanding CMNEs’ PMI dynamics and the role of knowledge management.

Abstract As one of the most attractive next‐generation probiotics, mucin‐degrading Akkermansia muciniphila has emerged as an essential and integral factor in maintaining human health and affecting pathological outcomes. Its abundance is inversely associated with various metabolic diseases (e.g., obesity and type 2 diabetes), cardiovascular diseases, and intestinal inflammation. Supplementing A. muciniphila to restore the gut microbiota ecosystem is a promising approach for treating metabolic disorders. However, the direct utilization of this probiotic is limited by technological and regulatory hurdles, such as the in vitro bulk culture of A. muciniphila and the need for expensive animal‐derived materials. Therefore, enrichment of A. muciniphila using nutraceutical supplements is a feasible strategy. Dietary supplements, especially medicinal herbs, offer a vast and valuable resource as potential prebiotics for promoting the growth of A. muciniphila in the gut, ensuring reliable safety and efficacy. In this study, we first systemically reviewed the dietary substances and medicinal foods known to promote A. muciniphila from over 100 literature sources, aiming to establish a candidate basis for future exploration of prebiotics targeting A. muciniphila. Furthermore, we summarized and discussed the major regulatory factors and mechanisms responsible for the beneficial effect of A. muciniphila on metabolic disorders, hoping to open up exciting directions for in‐depth research on the pharmacological mechanism of A. muciniphila and pave the way for its clinical therapeutics.

Adipokine chemerin plays important roles in disorders of glucose and lipid metabolism of obesity and obesity-related diseases, and exercise-induced improvement of glucose and lipid metabolism is closely related to the decrease of chemerin, but the mechanisms by which chemerin regulates glucose and lipid metabolism remain unclarified. Hypotestosterone induces male obesity and disorders of glucose and lipid metabolism through androgen receptor (AR) and its target genes: glucose and lipid metabolism-related molecules (including FOXO1, PEPCK, PGC-1α, and SCD1). Recently, the link between them has been reported that chemerin modulated the secretion of androgen. In this study, global chemerin knockout (chemerin (−/−)) mice were established to demonstrate the roles of chemerin in regulating blood glucose and blood lipid of mice under diet (high-fat (HFD) and normal diet) and exercise interventions and then to explore its mechanisms (AR – glucose and lipid metabolism enzymes). We found that the blood lipid and adipocyte size were low accompanied by the improvements in the levels of serum testosterone, gastrocnemius AR, and gastrocnemius FOXO1, SCD1, and PGC-1α in HFD chemerin (−/−) mice, but exercise-induced improvements of these indicators in HFD WT mice were attenuated or abolished in HFD chemerin (−/−) mice. In conclusion, the decrease of chemerin improved the blood lipid profile of HFD male mice at sedentary and exercise states, mediated partly by the increases of testosterone and AR to regulate glucose and lipid metabolism enzymes. To our knowledge, it is the first report that chemerin’s regulation of glucose and lipid metabolism might be mediated by testosterone and AR in vivo.

Abstract Oxidative stress and the immune microenvironment both contribute to the pathogenesis of esophageal squamous cell carcinoma (ESCC). However, their interrelationships remain poorly understood. We aimed to examine the status of key molecules involved in oxidative stress and the immune microenvironment, as well as their relationships with each other and with clinicopathological features and prognosis in ESCC. The expression of programmed death‐ligand 1 (PD‐L1), CD8, nuclear factor erythroid‐2 related factor‐2 (NRF2), and NAD(P)H quinone oxidoreductase 1 (NQO1) was detected using immunohistochemistry in tissue samples from 176 patients with ESCC. We employed both combined positive score (CPS) and tumor proportion score (TPS) to evaluate PD‐L1 expression and found a positive correlation between CPS and TPS. Notably, PD‐L1 expression, as assessed by either CPS or TPS, was positively correlated with both NRF2 nuclear score and NQO1 score in stage II–IV ESCC. We also observed a positive correlation between the density of CD8+ T cells and PD‐L1 expression. Furthermore, high levels of PD‐L1 CPS, but not TPS, were associated with advanced TNM stage and lymph node metastases. Moreover, both PD‐L1 CPS and the nuclear expression of NRF2 were found to be predictive of shorter overall survival in stage II–IV ESCC. By using the Mandard‐tumor regression grading (TRG) system to evaluate the pathological response of tumors to neoadjuvant chemotherapy (NACT), we found that the TRG‐5 group had higher NRF2 nuclear score, PD‐L1 CPS, and TPS in pre‐NACT biopsy samples compared with the TRG‐3 + 4 group. The NQO1 scores of post‐NACT surgical specimens were significantly higher in the TRG‐5 group than in the TRG 3 + 4 group. In conclusion, the expression of PD‐L1 is associated with aberrant NRF2 signaling pathway, advanced TNM stage, lymph node metastases, and unfavorable prognosis. The dysregulation of PD‐L1 and aberrant activation of the NRF2 signaling pathway are implicated in resistance to NACT. Our findings shed light on the complex interrelationships between oxidative stress and the immune microenvironment in ESCC, which may have implications for personalized therapies and improved patient outcomes.

Background: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment. Methods: We retrospectively analysed patients with stage IIIA–IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST. Findings: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS. Interpretation: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.

BackgroundCD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).MethodsFive suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 “mAb-trap” platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.ResultsUsing hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a “mAb-trap” platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605–26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605–12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605–12C10 efficiently eradicated all established tumors in all mice.ConclusionA panel of BsAbs targeting CD38 and CD47 developed based on the “mAb-tarp” platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Abstract Inferior air stability is a primary barrier for large‐scale applications of garnet electrolytes in energy storage systems. Herein, a deeply hydrated hydrogarnet electrolyte generated by a simple ion‐exchange‐induced phase transition from conventional garnet, realizing a record‐long air stability of more than two years when exposed to ambient air is proposed. Benefited from the elimination of air‐sensitive lithium ions at 96 h/48e sites and unobstructed lithium conduction path along tetragonal sites (12a) and vacancies (12b), the hydrogarnet electrolyte exhibits intrinsic air stability and comparable ion conductivity to that of traditional garnet. Moreover, the unique properties of hydrogarnet pave the way for a brand‐new aqueous route to prepare lithium metal stable composite electrolyte on a large‐scale, with high ionic conductivity (8.04 × 10−4 S cm−1), wide electrochemical windows (4.95 V), and a high lithium transference number (0.43). When applied in solid‐state lithium batteries (SSLBs), the batteries present impressive capacity and cycle life (164 mAh g−1 with capacity retention of 89.6% after 180 cycles at 1.0C under 50 °C). This work not only designs a new sort of hydrogarnet electrolyte, which is stable to both air and lithium metal but also provides an eco‐friendly and large‐scale fabrication route for SSLBs.

This study analyzes the performance degradation of traditional hybrid wind turbines under high blade-tip-speed ratio conditions and proposes solutions through two-dimensional Computational Fluid Dynamics (CFD) simulations. It also introduces the design of two innovative asynchronous-hybrid dual-rotor wind turbines. The results indicate a remarkable 98.5% enhancement in torque performance at low blade-tip-speed ratios with the hybrid wind turbine model. However, as the blade-tip-speed ratio increases, it leads to negative torque generation within the inner rotor of the conventional design, resulting in a reduction of the power coefficient by up to 13.1%. The introduction of the new wind turbine design addresses this challenge by eliminating negative torque at high blade-tip-speed ratios through adjustments in the inner rotor’s operating range. This modification not only rectifies the negative torque issue but also enhances the performance of the outer rotor in the leeward region, consequently boosting the overall power coefficient. Moreover, the optimized inner rotor configuration effectively disrupts and shortens the wake length by 16.7%, with this effect intensifying as the rotational speed increases. This optimization is pivotal for enhancing the efficiency of multi-machine operations within wind farms.

Aquatic animals frequently undergo feed deprivation and starvation stress. It is well-known that the gut microbiota and the gut–brain short neuropeptide F (sNPF) play essential roles in diet restriction. Therefore, investigating the responses of the gut microbiota and sNPF can enhance our understanding of physiological adaptations to feed deprivation and starvation stress. In this study, we examined the alterations in the gut microbiota of juvenile mud crabs under feed deprivation and starvation conditions. The results reveal differences in the richness and diversity of gut microbiota among the satisfied, half food, and starvation groups. Moreover, the microbial composition was affected by starvation stress, and more than 30 bacterial taxa exhibited significantly different abundances among the three feeding conditions. These results indicate that the diversity and composition of the gut microbiota are influenced by diet restriction, potentially involving interactions with the gut–brain sNPF. Subsequently, we detected the location of sNPF in the brains and guts of mud crabs through immunofluorescence and investigated the expression profile of sNPF under different feeding conditions. The results suggest that sNPF is located in both the brains and guts of mud crabs and shows increased expression levels among different degrees of diet restriction during a 96 h period. This study suggested a potential role for sNPF in regulating digestive activities and immunity through interactions with the gut microbiota. In conclusion, these findings significantly contribute to our understanding of the dynamic changes in gut microbiota and sNPF, highlighting their interplay in response to diet restriction.

Examining dual vertical-axis wind turbines (VAWTs) across various turbulence scenarios is crucial for advancing the efficiency of urban energy generation and promoting sustainable development. This study introduces a novel approach by employing two-dimensional numerical analysis through computational fluid dynamics (CFD) software to investigate the performance of VAWTs under varying turbulence intensity conditions, a topic that has been relatively unexplored in existing research. The analysis focuses on the self-starting capabilities and the effective utilization of wind energy, which are key factors in urban wind turbine deployment. The results reveal that while the impact of increased turbulence intensity on the self-starting performance of VAWTs is modest, there is a significant improvement in wind energy utilization within a specific turbulence range, leading to an average power increase of 1.41%. This phenomenon is attributed to the more complex flow field induced by heightened turbulence intensity, which delays the onset of dynamic stall through non-uniform aerodynamic excitation of the blade boundary layer. Additionally, the inherent interaction among VAWTs contributes to enhanced turbine output power. However, this study also highlights the trade-off between increased power and the potential for significant fatigue issues in the turbine rotor. These findings provide new insights into the optimal deployment of VAWTs in urban environments, offering practical recommendations for maximizing energy efficiency while mitigating fatigue-related risks.

Unmanned sailboats can convert wind energy with sails to provide power for navigation, which can independently plan routes and collect data without human intervention. They have received increasing attention in recent years due to their low power consumption and strong self-sustainability. Due to the greater difficulty of manipulation, the unmanned sailboats have a weaker maneuverability than the propeller-driven vessels in the complex and variable marine environment. Typically, the turning motion is evaluated to characterize the maneuverability of a vessel, which has rarely been investigated in the existing research on unmanned sailboats. Therefore, this study builds a motion simulation platform for unmanned sailboats based on the 3 m class Petrel Sail to investigate the turning characteristics. The index of the approximate turning circle is introduced based on the turning motion trajectory, which is used to obtain the effect of rudder angle, wind angle, wind speed, and current speed on the turning performance of the sailboat in ideal hydrostatic conditions and under flow disturbance, respectively. Finally, a harbor pool test is conducted with an unmanned sailboat to verify the analysis results, and the errors in maximum transverse distance and maximum advance distance are in the reasonable range, proving the correctness of the theoretical results. The current study also provides theoretical guidance for subsequent research on sailboat manipulation and maneuverability.

Background Sepsis can disrupt immune regulation and lead to acute respiratory distress syndrome (ARDS) frequently. Remazolam, a fast-acting hypnotic drug with superior qualities compared to other drugs, was investigated for its potential protective effects against sepsis-induced ARDS. Methods Forty Sprague-Dawley rats were randomly divided into four groups, including the sepsis + saline group, sham operation + saline group, sham operation + remazolam group and the sepsis + remazolam group. Lung tissues of rats were extracted for HE staining to assess lung damage, and the wet weight to dry weight (W/D) ratio was calculated. The levels of proinflammatory factors, anti-inflammatory factors, CD4+ and CD8+ T cells in peripheral blood, MDA, MPO, and ATP in the lung tissue were measured by using ELISA. Western blotting was performed to determine the protein expression of HMGB1 in lung tissues. Results In comparison to the sham operation + saline and sham operation + remazolam groups, the sepsis + saline group exhibited significantly higher values for W/D ratio, lung damage score, IL-1β, IL-6, TNF-α, PCT, CRP, MDP and MPO, while exhibiting lower levels of CD4+ and CD8+ T lymphocytes, PaO2, PCO2, and ATP. The rats in the sepsis + saline group displayed ruptured alveolar walls and evident interstitial lung edema. However, the rats in the sepsis + remazolam group showed improved alveolar structure. Furthermore, the HMGB1 protein expression in the sepsis + remazolam group was lower than the sepsis + saline group. Conclusion Remazolam can alleviate the inflammatory response in infected rats, thereby alleviating lung injury and improving immune function, which may be attributed to the reduction in HMGB1 protein expression.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial and venous thrombosis, habitual fetal miscarriages, often accompanied by mild to moderate thrombocytopenia, and persistent moderate-to-high titer positivity for antiphospholipid antibodies (aPLs). However, patients with antiphospholipid antibodies may also present with several nonthrombotic clinical manifestations, such as thrombocytopenia, cardiac valve disease, nephropathy, skin ulcers, or cognitive dysfunction, which are collectively referred to as nonstandard manifestations of APS. Of these, for APS with predominantly cutaneous ulcers, previous reports have focused on APS with combined cutaneous vasculitis, and its medical treatment, rather than cutaneous ulcers with predominantly fatty inflammatory lesions, and the associated surgical treatment. Here, we admitted a relatively rare case of primary APS with extensive skin ulceration of the right lower extremity, without cutaneous vasculitis, in the presence of extensive and severe inflammatory lipoatrophy, carrying anti-β2-glycoprotein I and lupus anticoagulant, which is reported as follows, with a view to raising awareness of this disease.

Subcortical band heterotopia (SHB) is a rare severe brain developmental malformation caused by deficient neuronal migration during the development of cerebral cortex. Here, a human induced pluripotent stem cell (iPSCs) line was established from a 4-year-1-month-old girl with SHB carrying a heterozygous mutation (c.568A > G, p.K190E) in DCX. The generated iPSC line showed the ability to differentiate into three lineages in vitro and was confirmed by pluripotency markers and the original gene mutation.

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, #615075), a rare autosomal dominant genetic disorder caused by heterozygous mutation in the CTNNB1 gene, is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Here, we established an iPSC line (SDQLCHi055-A) from a patient with NEDSDV carrying a heterozygote mutation (c.854 T > A, p.L285*) in the CTNNB1 gene. The iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

Canavan disease (CD, OMIM# 271900) is an autosomal recessive neurodegenerative disorder caused by homozygous or compound heterozygous mutations in ASPA gene, which result in catalytic deficiency of the aspartoacylase enzyme and the accumulation of N-acetylaspartic acid (NAA). Clinical presentation varies according to the age of disease onset. Here, we generated a human induced pluripotent stem cell line (hiPSCs) SDQLCHi064-A from a 5-month old boy with CD carrying two novel frame shift mutations c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) of the ASPA gene, in order for us to better understanding the disease.

Introduction: Zearalenone-14-glucoside (Z14G) is a modified mycotoxin that widely contaminates food across the world. Our preliminary experiment showed that Z14G degrades to zearalenone (ZEN) in the intestine exerting toxicity. Notably, oral administration of Z14G in rats induces intestinal nodular lymphatic hyperplasia. Objectives: To investigate the mechanism of Z14G intestinal toxicity and how it differs from ZEN toxicity. We conducted a precise toxicology study on the intestine of rats exposed to Z14G and ZEN using multi-omics technology. Methods: Rats were exposed to ZEN (5 mg/kg), Z14G-L (5 mg/kg), Z14G-H (10 mg/kg), and pseudo germ free (PGF)-Z14G-H (10 mg/kg) for 14 days. Histopathological studies were performed on intestines from each group and compared. Metagenomic, metabolomic, and proteomic analyses were performed on rat feces, serum, and intestines, respectively. Results: Histopathological studies showed that Z14G exposure resulted in dysplasia of gut-associated lymphoid tissue (GALT) compared to ZEN exposure. The elimination of gut microbes in the PGF-Z14G-H group alleviated or eliminated Z14G-induced intestinal toxicity and GALT dysplasia. Metagenomic analysis revealed that Z14G exposure significantly promoted the proliferation of Bifidobacterium and Bacteroides compared to ZEN. Metabolomic analysis showed that Z14G exposure significantly reduced bile acid, while proteomic analysis found that Z14G exposure significantly reduced the expression of C-type lectins compared to ZEN. Conclusions: Our experimental results and previous research suggest that Z14G is hydrolyzed to ZEN by Bifidobacterium and Bacteroides promoting their co-trophic proliferation. This leads to inactivation of lectins by hyperproliferative Bacteroides when ZEN caused intestinal involvement, resulting in abnormal lymphocyte homing and ultimately GALT dysplasia. It is noteworthy that Z14G is a promising model drug to establish rat models of intestinal nodular lymphatic hyperplasia (INLH), which is of great significance for studying the pathogenesis, drug screening and clinical application of INLH.

Abstract Objectives To build a combined model based on the ultrasound radiomic and morphological features, and evaluate its diagnostic performance for preoperative prediction of central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC). Method A total of 295 eligible patients, who underwent preoperative ultrasound scan and were pathologically diagnosed with unifocal PTC were included at our hospital from October 2019 to July 2022. According to ultrasound scanners, patients were divided into the training set (115 with CLNM; 97 without CLNM) and validation set (45 with CLNM; 38 without CLNM). Ultrasound radiomic, morphological, and combined models were constructed using multivariate logistic regression. The diagnostic performance was assessed by the area under the curve (AUC) of the receiver operating characteristic curve, accuracy, sensitivity, and specificity. Results A combined model was built based on the morphology, boundary, length diameter, and radiomic score. The AUC was 0.960 (95% CI, 0.924–0.982) and 0.966 (95% CI, 0.901–0.993) in the training and validation set, respectively. Calibration curves showed good consistency between prediction and observation, and DCA demonstrated the clinical benefit of the combined model. Conclusion Based on ultrasound radiomic and morphological features, the combined model showed a good performance in predicting CLNM of patients with PTC preoperatively.

Nickel-titanium (NiTi) is the most ordinarily used shape memory alloy (SMAs), which has important implications in aerospace, medical devices and so on. However, NiTi parts were limited in their application scope and ability due to the difficulty of processing. Until the appearance of laser powder bed fusion (LPBF) technology, it overcame NiTi alloy preparation's multiple challenges and became the preferred method to fabricate NiTi alloy. Nevertheless, the NiTi parts fabricated by LPBF that have a great shortage still exist in corrosion resistance. Therefore, in this paper, a series of micro-nano structures with different characteristics were constructed in LPBF-NiTi by orthogonal experiment for the first time, which wants to explore the degree of influence of various parameters on the wettability of samples. After variance analysis, the nanolaser processing parameters which are most suitable for constructing lotus leaf structures on NiTi alloy surfaces are obtained. The surface morphology and composition were studied by SEM, XRD, EDS, and XPS, respectively. Finally, the corrosion resistance of samples was tested by electrochemical analysis. The results show that the laser power during processing has the greatest influence on the surface morphology of LPBF-NiTi alloy. And the wettability is affected by surface morphology and –CF/-CF2 adsorption. Furthermore, we compared the corrosion resistance of the superhydrophobic samples which was obtained based on the variance analysis with that of the substrate in 3.5 wt% NaCl solution. The result shows that the corrosion resistance and corrosion stability of superhydrophobic samples are brilliantly increased compared with the substrate.

Integrating the developed-market resources after acquisitions is a crucial tool for Chinese multinational enterprises (CMNEs) to accelerate industrial high-quality development. However, existing theories have scarce thorough explanations of the dynamic mechanism of CMNEs’ post-merger integrating resources. Our research aims at disclosing CMNEs’ post-merger integration (PMI) long-term dynamics under resource relatedness changes. We applied a multiple-case study with four typical CMNEs’ German-market PMI cases and proposed a theoretical framework based on a coding analysis of 38 interviews. Our findings highlight that: CMNEs change initial gentle integrations (partnering/preservation) to balance dependence when pre-merger resources complementary decreases with similarity increasing, or to extreme dependence when pre-merger resources similarity continually increases to extremely high. Pre-merger resource relatedness basics and later changes and CMNEs’ dynamic capability (threat and development potentials’ perception capabilities and utilization capability) are crucial factors in promoting CMNEs’ PMI changes. Our originality lies in that we consider the interactions resource relatedness changes and CMNEs’ PMI dynamics, strongly replenishing the deficiency of current PMI dynamic studies that lack considerations of resource relatedness changing; also, we simultaneously consider the two facets of dependence asymmetry and joint dependence such that broadened the application of resource dependence theory (RDT) in PMI studies. Our study offers managerial insights into CMNEs’ development leapfrog through acquisitions in developed markets that CMNEs should focus on the vital role of inter-firm resource relatedness changing. Initial gentle integration can be deepened when original resource backgrounds become more similar but should be cautious of the effect of power imbalance and selfish actions.

ObjectChronic pain and negative emotions are often linked, and both can impact the reward circuit. The use of electroacupuncture (EA) has been found to regulate and improve these conditions. This study explores the potential mechanism of chronic pain relief by adding acupoints with emotional regulation effect to the basis of routine EA analgesia, to optimize the acupoint compatibility scheme of EA in the treatment of analgesia.MethodFor this study, 42 male Wistar rats were used. Recombinant adeno-associated viruses were used to label and regulate the activity of dopamine (DA) neurons. The rat model was established by complete Freund’s adjuvant (CFA). Lower limb electroacupuncture (LEA) was applied to the ST36 and BL60 acupoints. In addition, LEA + scalp EA (SEA) was given using the GV20 and GV24+ acupoints besides ST36 and BL60. To evaluate the pain threshold, we measured 50% paw withdrawal thresholds and thermal paw withdrawal latencies. Negative emotions were evaluated through the open field test, marble-burying test, sucrose preference test, and forced swimming test. Moreover, the conditional place preference test was conducted to measure the reward behavior in response to pain relief. Immunofluorescence staining, Western blotting, and qPCR were used to detect the activity of the VTADA-NAc reward circuit.ResultThe injection of CFA significantly lowered the pain threshold. As the pain persisted, the anxiety and depression-like behaviors escalated while the response to reward reduced. Meanwhile, the VTADA-NAc pathway was suppressed with pain chronification. However, activating DA neurons in VTA attenuated the effects induced by CFA. LEA could relieve chronic pain, negative emotions, and reward disorders, while also activating the VTADA-NAc pathway. In addition, LEA + SEA exhibited a more pronounced effect compared with LEA alone. Nevertheless, chemogenetic inhibition of DA neurons decreased the efficacy of LEA + SEA in the treatment of chronic pain and associated comorbidities.ConclusionAdding SEA to conventional LEA effectively alleviates negative emotions and chronic pain, potentially due to the activation of the VTADA-NAc reward neural circuit. Thus, LEA + SEA is a more effective treatment for hyperalgesia and associated negative emotions compared with LEA alone.

AUTS2 syndrome is a neurodevelopmental disorder caused by pathogenic variants and deletions of the AUTS2 gene, resulting in intellectual disability, microcephaly, and other phenotypes. Here, we generated a human induced pluripotent stem cell (iPSC) line from a 21-month-old boy with AUTS2 syndrome caused by a heterozygous mutation (c.1486C > T, p.Q496X) in the AUTS2 gene. The iPSCs had normal morphology and karyotype, expressed pluripotency markers, showed differentiation potential in vitro, and carried the AUTS2 gene mutation.

Mulberry leaf has potential in lipid-lowering. Here, we compared the chemical composition and lipid-lowering effects of different mulberry leaf-derived teas, and investigated their underlying gut microbiome-related mechanisms. The main components of mulberry leaf-derived tea were flavonoids, phenolic acids and alkaloids, with green tea (0.60% polyphenols, 3.35% polysaccharides, 0.20% DNJ) containing higher levels than black tea (0.40% polyphenols, 2.95% polysaccharides, 0.15% DNJ). Accordingly, the lipid-lowering efficacy of green tea was superior to that of black tea in high-fat (HFD)-induced hyperlipidemic mice. Black tea increased 2 genera and 130 metabolites, decreased 6 genera and 90 metabolites, while green tea increased 5 genera and 127 metabolites, decreased 15 genera and 64 metabolites. Correlation analysis showed that the alterations of gut microbiota and metabolic profiles caused by mulberry leaf tea were tightly associated with its lipid-lowering effect. Altogether, this study provided a promising functional food targeting gut microbiota for the management of lipid metabolism.

ABSTRACTCompelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, Blautia producta exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of Bl. Producta. In vivo experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on Bl. producta and its metabolite.

Introduction: Acute myocardial infarction (AMI) accounts for the majority of deaths caused by coronary artery disease (CAD). Early warning of AMI, especially for patients with stable coronary artery disease (sCAD), is urgently needed. Our previous study showed that alterations in the gut microbiota were correlated with CAD severity. Objectives: Herein, we tried to discover accurate and convenient biomarkers for AMI by combination of gut microbiota and fecal/blood/urinary metabolomics. Methods: We recruited 190 volunteers including 93 sCAD patients, 49 AMI patients, and 48 subjects with normal coronary artery (NCA), and measured their blood biochemical parameters, 16S rRNA-based gut microbiota and NMR-based fecal/blood/urinary metabolites. We further selected 20 subjects from each group and analyzed their gut microbiota by whole-metagenome shotgun sequencing. Results: Multi-omic analyses revealed that AMI patients exhibited specific changes in gut microbiota and serum/urinary/fecal metabolites as compared to subjects with sCAD or NCA. Fourteen bacterial genera and 30 metabolites (11 in feces, 10 in blood, 9 in urine) were closely related to AMI phenotypes and could accurately distinguish AMI patients from sCAD patients. Some species belonging to Alistipes, Streptococcus, Ruminococcus, Lactobacillus and Faecalibacterium were effective to distinguish AMI from sCAD and their predictive ability was confirmed in an independent cohort of CAD patients. We further selected nine indicators including 4 bacterial genera, 3 fecal and 2 urinary metabolites as a noninvasive biomarker set which can distinguish AMI from sCAD with an AUC of 0.932. Conclusion: Combination of gut microbiota and fecal/urinary metabolites provided a set of potential useful and noninvasive predictive biomarker for AMI from sCAD.

Abstract Background As an important component of accelerated rehabilitation surgery, goal-directed fluid therapy (GDT) is one of the optimized fluid therapy strategies and is closely related to perioperative complications and mortality. This article aimed to study the effect of combining plasma colloid osmotic pressure (COP) with stroke volume variation (SVV) as a target for intraoperative GDT for postoperative pulmonary complications in older patients undergoing major abdominal surgery. Methods In this study, older patients (n = 100) undergoing radical resection of gastroenteric tumors were randomized to three groups: Group C (n1 = 31) received a conventional infusion regimen, Group S1 (n2 = 34) received GDT based on SVV, and Group S2 (n3 = 35) received GDT based on SVV and COP. The results were recorded, including the lung injury score (LIS); PaO2/FiO2 ratio; lactic acid value at the times of beginning (T0) and 1 h (T1), 2 h (T2), and 3 h (T3) after liquid infusion in the operation room; the total liquid infusion volume; infusion volumes of crystalline and colloidal liquids; urine production rate; pulmonary complications 7 days after surgery; and the severity grading of postoperative pulmonary complications. Results The patients in the S2 group had fewer postoperative pulmonary complications than those in the C group (P

BackgroundA significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC.MethodsIMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys.ResultsIn vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt’s lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile.ConclusionIMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.

Abstract Selective laser melting of nickel‐titanium alloy (SLM‐NiTi) can precisely control the size of the sample molding structure and has attracted extensive attention due to its special superelasticity and shape memory effect. However, the biological inertness and poor corrosion resistance of SLM‐NiTi alloy limit their wide application as biomedical implant materials. In this study, polycaprolactone (PCL) coating was prepared on SLM‐NiTi alloy by dipping and pulling method, and the effects of alkali heat pretreatment on the morphology, adhesion, corrosion resistance, long‐term stability and biomineralisation of the PCL coatings were investigated. The results showed that PCL coating can substantially improve the performance of SLM‐NiTi alloy, and the PCL coating after alkali heat pretreatment has higher adhesion (increased from 1,747 to 2,498 mN) and lower corrosion current density (reduced by about an order of magnitude compared to PCL coating alone). In addition, the necessary stability, biomineralisation and biocompatibility ability of coatings were also further improved. Therefore, the alkali heat pretreated PCL‐coated SLM‐NiTi alloy has good application prospects in implants due to its superior properties.

Objective: Lynch syndrome (LS) pre-screening methods remain under-investigated in colorectal cancers (CRCs) in Asia. Here, we aimed to systematically investigate LS pre-screening and comprehensively characterize LS CRCs. Methods: Microsatellite instability (MSI) and germline variants of DNA mismatch repair (MMR) genes were examined in 406 deficient MMR (dMMR) and 250 proficient MMR CRCs. The genetic differences between LS and sporadic CRCs were studied with whole exome sequencing analysis. Results: The incidence of dMMR in Chinese patients with CRCs was 13.8%. Consistency analysis between MMR immunohistochemistry (IHC) and MSI testing showed the kappa value was 0.758. With next-generation sequencing (NGS), germline variants were detected in 154 CRCs. Finally, 88 patients with CRC were identified as having LS by Sanger sequencing. Among them, we discovered 21 previously unreported pathogenic germline variants of MMR genes. Chinese patients with LS, compared with sporadic CRCs, tended to be early-onset, right-sided, early-stage and mucinous. Overall, the performance of MMR IHC and MSI testing for LS pre-screening was comparable: the area under the ROC curve for dMMR, MSI-H, and MSI-H/L was 0.725, 0.750, and 0.745, respectively. dMMR_MSI-H LS and sporadic CRCs showed substantial differences in somatic genetic characteristics, including different variant frequencies of APC, CREBBP, and KRAS, as well as different enriched pathways of VEGF, Notch, TGFβR, mTOR, ErbB, and Rac protein signal transduction. Conclusions: MMR IHC and MSI testing were effective methods for LS pre-screening. The revealed clinical and somatic genetic characteristics in LS CRCs may have the potential to improve the performance of LS pre-screening in combination with dMMR/MSI.

Cognitive dysfunction is increasingly recognized as a complication and comorbidity of diabetes, supported by evidence of abnormal brain structure and function. Although few mechanistic metabolic studies have shown clear pathophysiological links between diabetes and cognitive dysfunction, there are several plausible ways in which this connection may occur. Since, brain functions require a constant supply of glucose as an energy source, the brain may be more susceptible to abnormalities in glucose metabolism. Glucose metabolic abnormalities under diabetic conditions may play an important role in cognitive dysfunction by affecting glucose transport and reducing glucose metabolism. These changes, along with oxidative stress, inflammation, mitochondrial dysfunction, and other factors, can affect synaptic transmission, neural plasticity, and ultimately lead to impaired neuronal and cognitive function. Insulin signal triggers intracellular signal transduction that regulates glucose transport and metabolism. Insulin resistance, one hallmark of diabetes, has also been linked with impaired cerebral glucose metabolism in the brain. In this review, we conclude that glucose metabolic abnormalities play a critical role in the pathophysiological alterations underlying diabetic cognitive dysfunction (DCD), which is associated with multiple pathogenic factors such as oxidative stress, mitochondrial dysfunction, inflammation, and others. Brain insulin resistance is highly emphasized and characterized as an important pathogenic mechanism in the DCD.

DM domain genes are a group of transcription factors that are integral to sexual development and its evolution in metazoans. Their functions and regulatory mechanisms are not well understood in Malacostraca (crabs and crayfish) while these sex regulators have been widely identified in the past decade. In this study, the Dmrt family was investigated in the decapod crab, Eriocheir sinensis. We find that most members of the EsDmrt family begin to enrich around the juvenile 1 stage. In reproductive organs, EsDsx1, EsDsx2, EsiDMY and EsiDmrt1a highly express in the male-specific androgenic gland (AG), while EsDmrt-like, EsDsx-like, EsDmrt11E, and EsiDmrt1b show relatively high expression in testis. Also, we find the highly aberrant expression of EsiDMY and EsiDmrt1a in the chimeric AG, strongly indicating their function in AG development. Moreover, RNA interference of EsDsx1, EsiDMY, and EsiDmrt1a results in a significant decrease in transcription of the Insulin-like androgenic hormone (IAG), respectively. Our findings suggest that Dmrt genes in E. sinensis primarily function in male sexual differentiation, especially in AG development. Besides, this study identifies two unique groups of Dmrt genes in Malacostraca: Dsx and iDmrt1. In Malacostraca Dsx, we uncover a cryptic mutation in the eight zinc motif-specific residues, which were firmly believed to be invariant across the Dmrt family. This mutation sets the Malacostraca Dsx apart from all the other Dmrt genes and implies a different way of transcriptional regulation. Genes from the iDmrt1 group show phylogenetical limitation to the malacostracan species and underwent positive selection, suggesting their highly specialized gene function to this class. Based on these findings, we propose that Dsx and iDmrt1 in Malacostraca have developed unique transcriptional regulation mechanisms to facilitate AG development. We hope that this study would contribute to our understandings of sexual development in Malacostraca and provide new insights into the evolutionary history of the Dmrt family.

The dynamic changes over time in the relationships between impulsivity, interpersonal problems, and depression warrant further exploration. This study delves into the roles of impulsivity and interpersonal issues in the progression of adolescent depression over a year, using a sample of 271 Chinese adolescents (51.7% male, Mage = 12.60 ± 0.69). At three time points, impulsivity levels were assessed with the Chinese version of the Barratt Impulsiveness Scale-11, interpersonal problems with the Adolescent Self-Rating Life Events Check List, and depression with the Center for Epidemiologic Studies Depression Scale. Results revealed that both impulsivity and interpersonal problems serve as risk factors for depression, but the primary risk factor shifted over time. In early middle school stages, impulsivity was the predominant risk factor, while in later stages, interpersonal problems became the primary risk factor. These findings carry significant implications for directing prevention efforts and interventions for adolescent depression.