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Luyang Pi,1 Yu Wang,1 Lirong Zou,1 Xinxin Mo,2 Leilei Guo3 1College of Humanities and Law, Guangdong University of Petrochemical Technology, Maoming, People’s Republic of China; 2School of Education Science, Guangdong Preschool Normal College in Maoming, Maoming, People’s Republic of China; 3School of Marxism, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Leilei Guo, Email guollei3@mail.sysu.edu.cnPurpose: To explore the potential classification of Problematic Mobile Social Media Usage (PMSMU) in Chinese college students, analyze whether there is group heterogeneity in PMSMU, and discuss the differences in the latent profile of PMSMU in fear of missing out, online positive feedback, and boredom proneness.Methods: A total of 2591 Chinese college students were investigated using the Problematic Mobile Social Media Usage Questionnaire, Fear of Missing Out (FOMO) Scale, Online Positive Feedback Scale and Short-form Boredom Proneness Scale, and heterogeneity was tested by latent profile analysis.Results: The PMSMU of college students can be divided into three latent profiles: no-problem use group (26.44%), mild problem use group (56.66%), and severe problem use group (16.91%). Male students, as compared to female students, showed a significantly lower likelihood of being classified as mild problematic users (OR=0.50, p< 0.001) and severe problematic users (OR=0.29, p< 0.001). Additionally, students with higher levels of FOMO, a stronger craving for online positive feedback, and increased boredom proneness are more likely to belong to the severe problematic use group (OR=2.91, p< 0.001; OR=1.42, p< 0.01; OR=8.72, p< 0.001).Conclusion: The results of this study highlight the factors influencing the heterogeneity of individual PMSMU. Specifically, female college students and those with a higher fear of missing out, greater susceptibility to boredom, and a stronger craving for positive online feedback are more likely to exhibit severe PMSMU. These findings provide valuable empirical evidence for developing preventive strategies to address PMSMU among college students.Keywords: problematic mobile social media usage, latent profile analysis, fear of missing out, online positive feedback, boredom proneness

Zhaojin Lu,1,&ast; Zepeng Zheng,1,&ast; Yufen Xu,1,&ast; Chenlu Wang,1 Yueling Lin,1 Kun Lin,1 LanYan Fu,1 Huazhong Zhou,1 Lei Pi,1 Di Che,1 Xiaoqiong Gu1,2 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076562, Email chedi@gwcmc.org Xiaoqiong Gu, Department of Clinical Biological Resource Bank, Department of Clinical Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076561, Email guxiaoqiong@gwcmc.orgBackground: Kawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.Methods: A total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.Results: Both of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06– 3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10– 2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62– 4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37– 3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22– 2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24– 2.27, p = 0.0008).Conclusion: Our findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.Keywords: Kawasaki disease, ZNF112/rs8113807, ZNF180/rs2571051, IVIG resistance, inflammatory gene, polymorphism

Graft dysfunction following cardiac transplantation is treated aggressively regardless of etiology; however, graft dysfunction requiring durable LVAD implantation has rarely been described. We present a case of cardiac transplantation complicated by late graft dysfunction requiring durable LVAD implantation. A 52 year-old woman presented to hospital in cardiogenic shock (CS) with refractory ventricular arrhythmias (VAs). LVEF was 20% with global hypokinesis. Coronary angiogram revealed mild coronary artery disease, and endomyocardial biopsy (EMB) diagnosed giant cell myocarditis. Due to worsening CS and VAs despite escalating inotropic support and IABP insertion, she underwent temporary LVAD implantation as a bridge to decision, then cardiac transplantation 2 months later due to lack of recovery of cardiac function. Her post-transplant course was complicated by progressive graft dysfunction with LVEF deteriorating from >70% two weeks post-transplant, to 15-20% 8 months post-transplant (Table 1). CT thorax revealed no coronary artery calcification to implicate severe cardiac allograft vasculopathy. EMBs demonstrated ISHLT Grade 2R rejection treated with methylprednisolone and thymoglobulin. Donor-specific antibodies (DSAs) increased to 9,837 MFI 7 months post-transplant despite EMB showing antibody-mediated rejection (AMR) Grade 0. She was diagnosed with presumed AMR causing late graft dysfunction, and treated with thymoglobulin, plasmapheresis/IVIg, then bortezomib, with reduction in DSAs but no improvement in cardiac function. Her invasive hemodynamics remained consistent with CS. Immediate re-transplantation was considered immunologically high risk, thus she underwent durable LVAD implantation 14 months post-transplant, as a bridge to potential re-transplantation. This case report highlights the importance of aggressive intervention for cardiac allograft rejection, and presents an uncommon course of treatment for severe late graft dysfunction. [ABSTRACT FROM AUTHOR]

Accumulation of senescent cells (SnCs) plays a causative role in many age-related diseases and has also been implicated in the pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Senolytics that can selectively kill SnCs have the potential to be developed as therapeutics for these diseases. Here we report the finding that 753b, a dual BCL-xL/BCL-2 proteolysis-targeting chimera (PROTAC), acts as a potent and liver-tropic senolytic. We found that treatment with 753b selectively reduced SnCs in the liver in aged mice and STAM mice in part due to its sequestration in the liver. Moreover, 753b treatment could effectively reduce the progression of MASLD and the development of hepatocellular carcinoma (HCC) in STAM mice even after the mice developed substantial metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis. These findings suggest that BCL-xL/BCL-2 PROTACs have the potential to be developed as therapeutics for MASLD to reduce MASH-driven HCC., Competing Interests: Competing interests: Y.Y., Y.H., P.Z., W.H., G.Z., L.P. and D.Z. are inventors on patents for the use of BCL-xL PROTACs as anti-tumor agents and senolytics. R.H., G.Z. and D.Z. are cofounders of and have equity in Dialectic Therapeutics, which develops BCL-xL/2 PROTACs to treat cancer. The other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions., Methods: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs)., Results: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,228,000 to 3,876,000) and 173.6% (from 4,123,000 to 11,279,000) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most GBD regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks., Conclusions: DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030., (Copyright © 2025 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Scalp seborrheic dermatitis (SD) is a chronic, recurrent inflammatory skin condition associated with scalp sebum secretion and dysbiosis., Aims: The aim of this study is to evaluate the efficacy and safety of a topical salicylic acid/piroctone olamine/zinc salt of L-pyrrolidone carboxylate (Zinc PCA) scalp pre-application gel in combination with a salicylic acid/piroctone olamine/antimicrobial peptide cleansing lotion for the treatment of moderate to severe scalp SD., Patients/methods: In this prospective cohort study, 20 patients with moderate to severe scalp SD were treated with a combination of the scalp pre-application gel and cleansing lotion for 4 weeks (one tube of the pre-application gel per week and the cleansing lotion used every 1-3 days depending on the frequency of hair washing). This was followed by maintenance treatment with the cleansing lotion for 12 weeks. Efficacy was assessed through clinical and trichoscopic examinations, measuring the severity of dandruff, itching, erythema, and greasiness using a 4-point scale., Results: This cohort study included a total of 20 patients with moderate to severe scalp SD. By the 4th week, the average dandruff score had significantly decreased from a baseline of 2.45 to 1.10 (p < 0.01). The average itchiness score reduced from 2.35 to 1.10 (p < 0.01), the erythema score dropped from 1.55 to 1.10 (p < 0.05), and the greasiness score decreased from 2.60 to 1.40 (p < 0.01). After 16 weeks, 12 patients with severe SD improved to mild SD, and six patients with moderate SD also improved to mild. During the treatment, two patients experienced a recurrence of dandruff, which subsequently resolved. The overall clinical improvement was 80%., Conclusions: Our study results indicate that the combination treatment of the scalp pre-application gel and cleansing lotion is highly effective and safe for treating SD. The subsequent use of the cleansing lotion effectively maintains the benefits of the combined treatment. Trichoscopic examination provides accurate and reliable quantifiable data, aiding in the monitoring of treatment progress., (© 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Van der Waals (vdW) crystals with strong spin-orbit coupling (SOC) provide great opportunities for exploring unconventional 2D superconductors, wherein new pairing states emerge due to the interplay of SOC with crystalline symmetries, electronic correlations, quenched disorders and external modulation forces, etc. Here, a distinct mirror-symmetry protected Ising pairing state with unprecedented Γ- and M-valley symmetries in natural vdW heterostructures (vdWH) of interweaving tetragonal SnSe and trigonal 1H-TaSe 2 monolayers is reported, in which the unidirectional lattice interlocking effectively suppresses the K-valley Ising pairing mechanism by incommensurate charge-density-wave (CDW) transitions. In the 2D limit of an TaSe 2 /SnSe bilayer with intact basal mirror symmetry (M z ), the mirror-symmetric vdWH Ising superconductors show anomalous in-plane magnetic field B ‖ -controlled enhancements in the critical temperature T c , which is completely absent for multilayer vdWHs with broken M z induced by orthorhombic stacking between nearest-neighbour TaSe 2 monolayers. The experimental observations consistently reveal a mirror symmetry-protected type-III Ising state in the inversion asymmetric lattice of 1H-TaSe 2 , which is predicted to be a mixture of spin-singlet and spin-triplet states., (© 2024 Wiley‐VCH GmbH.)

Objective: COVID-19 has evolved into a seasonal coronavirus disease, characterized by prolonged infection duration and repeated infections, significantly increasing the risk of patients developing long COVID. Our research focused on the immune responses in asymptomatic and mild cases, particularly the critical factors influencing serum immunoglobulin G (IgG) levels and their predictive value., Methods: We conducted a retrospective analysis on data from 1939 asymptomatic or mildly symptomatic COVID-19 patients hospitalized between September 2022 and June 2023. Spearman methods were used to test the correlation between serum IgG and age, immunoglobulin M (IgM), procalcitonin (PCT), interleukin-6 (IL-6), nucleic acid conversion time, and BMI. Univariate and multivariate logistic regression analyses identified independent key factors influencing serum IgG levels, which were integrated and visualized in a nomogram. Finally, receiver operating characteristic (ROC) curves were plotted to predict the model's diagnostic performance by calculating the AUC., Results: Mild patients showed higher levels of IgG, IgM, and longer nucleic acid conversion times than asymptomatic patients, and a lower proportion of them had received ≥ 3 COVID-19 vaccine doses. Serum IgG was positively correlated with serum IgM and negatively correlated with age, PCT, IL-6, and BMI. Notably, it showed a moderate negative correlation with nucleic acid conversion time (r = -0.578, P < 0.001). Logistic regression results showed that younger age, lower IL-6 levels, ≥ 3 doses of vaccine, and no comorbidities were independent predictors of serum IgG levels ≥ 21.08 g/L. We used age, IL-6 levels, vaccine doses, and comorbidities to create a nomogram for predicting serum IgG levels, with the area under the ROC curve reaching 0.772., Conclusion: Age, IL-6 levels, vaccination status, and comorbidities were independent predictors of serum IgG levels in asymptomatic or mild COVID-19 patients, facilitating risk stratification and clinical decision-making. Notably, receiving ≥3 doses of the COVID-19 vaccine was the most beneficial factor for elevated serum IgG levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yi, Liu, Cao, Pi, Zhou and Mu.)

The industrial bacterium Bacillus licheniformis has long been used as a microbial factory for the production of enzymes due to its ability to secrete copious amounts of native extracellular proteins and its generally regarded as safe (GRAS) status. However, most attempts to use B. licheniformis to produce heterologous and cytoplasmic enzymes primarily via the general secretory (Sec) pathway have had limited success. The twin-arginine transport (Tat) pathway offers a promising alternative for the extracellular export of Sec-incompatible proteins because it transports full, correctly folded proteins. However, compared to the Sec pathway, the yields of the Tat pathway have historically been too low for commercial use. To improve the export efficiency of the Tat pathway, we identified the optimal Tat-dependent signal peptides and increased the abundance of the Tat translocases, the signal peptidase (SPase), and the intracellular chaperones. These strategic modifications significantly improved the Tat-dependent secretion of the cytoplasmic enzyme arginase into the culture medium using B. licheniformis. The extracellular enzymatic activity of arginase showed a 5.2-fold increase after these modifications. Moreover, compared to the start strain B. licheniformis 0F3, the production of extracellular GFP was improved by 3.8 times using the strategic modified strain B. licheniformis 0F13, and the extracellular enzymatic activity of SOX had a 1.3-fold increase using the strain B. licheniformis 0F14. This Tat-based production chassis has the potential for enhanced production of Sec-incompatible enzymes, therefore expanding the capability of B. licheniformis as an efficient cellular factory for the production of high-value proteins. KEY POINTS: • Systematic genetic modification of Tat-pathway in B. licheniformis. • Significant enhancement of the secretion capacity of Tat pathway for delivery the cytoplasmic enzyme arginase. • A new platform for efficient extracellular production of Sec-incompatible enzymes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: LncRNAs play diverse roles and participate in various biological processes within the human body. It has been frequently reported that they are involved in the occurrence and development of recurrent spontaneous miscarriage. PRNCR1 , a crucial player in several types of cancers, may also have implications for recurrent spontaneous miscarriage risk. However, the correlation between PRNCR1 rs13252298 A > G polymorphism and this risk remains unclear. In summary, we conducted the following experiments to investigate the association between the PRNCR1 polymorphic site rs13252298 and susceptibility to recurrent spontaneous miscarriage., Method: Our research included 695 healthy controls and 413 patients with recurrent spontaneous miscarriage from southern China. Genotyping was performed using the TaqMan method., Result: Our findings revealed that there is a relationship between PRNCR1 rs13252298 A > G polymorphism and lower susceptibility to recurrent spontaneous miscarriage (AG and AA: adjusted OR = 0.794, 95% CI = 0.527-1.196, p  = 0.2696; GG and AA: adjusted OR = 0.705, 95% CI = 0.542-0.917, p  = 0.0092; dominant model: adjusted OR = 0.722, 95% CI = 0.563-0.926, p  = 0.0104; recessive model: adjusted OR = 0.949, 95% CI = 0.644-1.398, p  = 0.7912)., Conclusion: The results of our study demonstrate that the PRNCR1 rs13252298 A > G allele may contribute to a decreased risk of recurrent spontaneous miscarriage. The rs13252298 polymorphism could potentially serve as a biomarker for detecting recurrent spontaneous miscarriage risk and aiding prevention efforts., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

By introducing first-order quantum phases as topological invariants, recent symmetry analysis-based theories have reinvigorated magnetic quantum oscillations as a versatile quantum probe for unfolding the Fermi surface topology along with the geometry information, i.e., topo-Fermiology. Here, we demonstrate the comprehensive topo-Fermiology of high-mobility Rashba two-dimensional electron gases with ultragate tunability of spin-orbit coupling parameter in few-layer black arsenic. The remarkable consistencies with the key theoretical predictions of period doubling in quantum oscillations, gate-tunable aperiodic beating patterns, and the symmetry-enforced Landau level crossing phenomena controlled by the competition between Rashba coupling and the Zeeman interaction, which ultimately manifests as all odd-filling factor integer quantum Hall effect with superb sensitivity to quantum phases, establish topo-Fermiology as an indispensable methodology for studying topological quantum matters.

Generally, the dissipationless Hall effect in solids requires time-reversal symmetry breaking (TRSB), where TRSB induced by external magnetic field results in the ordinary Hall effect, while TRSB caused by spontaneous magnetization gives rise to the anomalous Hall effect (AHE) which scales with the net magnetization. The AHE is therefore not expected in antiferromagnets with vanishing small magnetization. However, large AHE was recently observed in certain antiferromagnets with noncollinear spin structure and nonvanishing Berry curvature. Here, we report another origin of AHE in a layered antiferromagnet EuAl&#95;{2}Si&#95;{2}, namely, the domain wall (DW) skew scattering with Weyl points near the Fermi level, in experiments for the first time. Interestingly, the DWs form a unique periodic stripe structure with controllable periodicity by external magnetic field, which decreases nearly monotonically from 975 nm at 0 T to 232 nm at 4 T. Electrons incident on DW with topological bound states experience strong asymmetric scattering, leading to a giant AHE, with the DW Hall conductivity (DWHC) at 2 K and 1.2 T reaching a record value of ∼1.51×10^{4}  Scm^{-1} among bulk systems and being 2 orders of magnitude larger than the intrinsic anomalous Hall conductivity. The observation not only sets a new paradigm for exploration of large anomalous Hall effect, but also provides potential applications in spintronic devices.

In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) for various variables influencing ASC-specific mortality was computed. A Fine-Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics such as the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A corresponding risk classification system was constructed based on nomogram-derived scores. Factors such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols.

Stem cells in plant meristems are kept undifferentiated by signals from surrounding cells and provide the basis for continuous organ formation. In the stem cell organizer of the Arabidopsis thaliana root, the quiescent centre (QC), the WOX5 transcription factor, functions as a central hub in regulating columella stem cell (CSC) homoeostasis. However, the processes mediating WOX5 function are only poorly understood. Here we identify the transcription factor HAN as a central mediator of WOX5-regulated stem cell maintenance. HAN is required for mitotic quiescence of QC and CSC maintenance and is sufficient to induce ectopic stem cells. WOX5 and HAN repress transcription of the differentiation factor gene CDF4 in a coherent feed-forward loop (cFFL), one output of which is the expression of the auxin biosynthesis gene TAA1 and maintenance of auxin response maxima in the organizer. These findings and mathematical modelling provide a mechanistic framework for WOX5 function in the root stem cell niche., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In multicellular organisms, communication between cells is vital for their fate determination. In plants, the quiescent center (QC) signals to adjacent stem cells to maintain them undifferentiated. However, how surrounding stem cells instruct the QC remains poorly understood. Here, we show that in the Arabidopsis root, microRNA160 (miR160) moves from stele stem cells (SSCs) to the QC, where it degrades the mRNAs of two auxin response factors, ARF10 and ARF17. This degradation relieves BRAVO from direct transcriptional repression, maintaining QC quiescence. We further identify that blocking miR160 movement due to DNA damage-induced SSC death and restricted symplastic transport reduces BRAVO and WOX5 expression, leading to QC division to replenish damaged stem cells during root regeneration. Together, our results demonstrate that a transcriptional axis initiated by mobile miR160 regulates the QC and stem cell behavior, advancing our understanding of the communication between stem cells and their surrounding cellular environment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Extracellular matrix protein 1 (ECM1) can inhibit TGFβ activation, but its antifibrotic action remains largely unknown. This study aims to investigate ECM1 function and its physical interaction with the profibrotic connective tissue growth factor (CTGF) in fibrosis and ductular reaction (DR)., Methods: Ecm1 knockouts or animals that ectopically expressed this gene were subjected to induction of liver fibrosis and DR by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or α-naphthyl-isothiocyanate (ANIT). ECM1 and CTGF were also examined in the livers of patients with alcohol-associated liver disease (ALD) or ethanol-exposed animals that were fed the western diet for 4 months in the WDA model with liver pathology resembing ALD in patients., Results: ECM1 bound to CTGF in yeast two-hybrid systems, cultured liver cells, and cholestatic livers damaged by DDC or α-naphthyl-isothiocyanate. This interaction blocked integrin αvβ6-mediated TGFβ activation, thereby reducing fibrotic responses in vitro. ECM1 downregulation was associated with biliary CTGF induction during human ALD progression. In experimental models, Ecm1 loss enhanced susceptibility to DDC-induced cholestasis with upregulation of Ctgf, αvβ6, alpha-smooth muscle actin, procollagen type I, serum transaminase, and total bilirubin levels in germline knockouts, whereas forced expression of this gene significantly attenuated DR and biliary fibrosis after the feeding of DDC or α-naphthyl-isothiocyanate containing diets. Moreover, ectopic Ecm1 inhibited not only alcohol-associated fibrosis but also TGFβ-mediated deregulation of hepatocyte nuclear factor 4α, preventing the production of the fetal p2 promoter-driven isoforms in the WDA model., Conclusions: We uncover a novel antifibrotic action by ECM1 that binds CTGF and inhibits integrin αvβ6-mediated TGFβ activation. Targeting its loss has therapeutic potential for the treatment of DR and liver fibrosis in chronic conditions, such as cholangiopathy and ALD., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

The Yes1-associated transcriptional regulator-mastermind-like transcriptional co-activator 2 (YAP1-MAML2 [YM]) fusion protein arises from an intrachromosomal inversion and is implicated in various cancers. However, the oncogenic role of the endogenous YM fusion protein remained undefined. In this study, we employed YM-positive ES-2 ovarian cancer cells as a model to explore the roles of the YM fusion in cancer initiation and maintenance. The YM fusion protein localizes to nuclear speckles and contains bifunctional domains: the YAP1 N-terminal domain interacts with transcriptional enhanced associate domain (TEAD) transcription factors, while the MAML2 C-terminal domain activates YAP1/TEAD-driven transcription. YM exhibited transforming activity, as shown by its ability to induce focus formation in immortalized epithelial cells. YM depletion reduced cancer cell proliferation and survival both in vitro and in xenograft tumor models. This effect was correlated with a downregulation of YAP1/TEAD-driven genes essential for cellular proliferation and survival, as revealed by transcriptomic analysis. Importantly, YM-positive cancer cells were sensitive to YAP1/TEAD-targeted pharmacologic inhibition. Collectively, these findings establish the YM fusion as a critical driver of oncogenesis and a promising therapeutic target for cancers harboring the YM fusion., Competing Interests: 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., (© 2024 The Authors.)

Background: China's rapidly aging population necessitates effective strategies for ensuring older adults' quality of life (QOL). While individual factors (IF) and family factors (FF) are known to influence QOL, existing research often examines these factors in isolation or focuses on specific subpopulations, overlooking potential interactions and mediating pathways., Objective: This study aims to examine both direct and indirect pathways connecting IF and FF to older adults' QOL, focusing on the mediating roles of health risks (HR) and health care service demand (HSD)., Methods: This study uses structural equation modeling (SEM) to analyze cross-sectional data from 8600 older participants in the 2015 China Health and Retirement Longitudinal Study (CHARLS), a nationally representative study using a multistage probability proportional to size sampling method., Results: Among the 8600 participants, the majority (5586/8502, 65.7%) were aged 60-70 years, with a near-equal distribution of males and females at around 50%. The average PCS score was 76.77, while the MCS score averaged 59.70. Both IF (β=0.165, P<.001) and FF (β=0.189, P<.001) had a direct positive effect on QOL. Furthermore, the indirect effects of IF (β=0.186, P<.001) and FF (β=0.211, P<.001) through HR and HSD were also significant. In the direct model, IF and FF had a greater impact on MCS (β=0.841) than on PCS (β=0.639). However, after including the 2 mediating factors, HR and HSD, the influence of IF and FF on MCS (β=0.739) became consistent with that on PCS (β=0.728). Subgroup analyses revealed that the direct effect of IF on QOL was significant in the 60-70 age group (β=0.151, P<.001) but not in those over 70 years old (β=0.122, P=.074). Comorbidity status significantly influenced the pathway from HR to HSD, with older adults having 2 or more chronic diseases (β=0.363) showing a greater impact compared to those with fewer than 2 chronic diseases (β=0.358)., Conclusions: Both IF (education, per capita disposable income, and endowment insurance) and FF (satisfaction with a spouse and children) directly impact the QOL in older people. Meanwhile, IF and FF have equal influence on QOL through the mediating role of HR and HSD. Recognizing the interplay among these factors is crucial for targeted interventions to enhance the well-being of older adults in China., (©Yuting Wu, Cong Gong, Lifang Pi, Meixin Zheng, Weifang Liu, Yamei Wang. Originally published in JMIR Aging (https://aging.jmir.org), 28.10.2024.)

Purpose: Breast cancer is the most commonly diagnosed cancer in women, and triple-negative breast cancer (TNBC) accounts for approximately 15%-20% of all breast cancers. TNBC is highly invasive and malignant. Due to the lack of relevant receptor markers, the prognosis of TNBC is poor and the five-year survival rate is low. Paclitaxel is the first-line drug for the treatment of TNBC, which can inhibit cell mitosis. However, many patients develop drug resistance during treatment, leading to chemotherapy failure. Therefore, finding new therapeutic combinations to overcome TNBC drug resistance can provide new strategies for improving the survival rate of TNBC patients., Methods: Cell viability assay, RT-qPCR, Colony formation assay, Western blot, and Xenogeneic transplantation methods were used to investigate roles and mechanisms of IRE1α/XBP1s pathway in the paclitaxel-resistant TNBC cells, and combined paclitaxel and IRE1α inhibitor in the treatment of TNBC was examined in vitro and in vivo., Results: We found activation of UPR in paclitaxel-resistant cells, confirming that IRE1α/XBP1 promotes paclitaxel resistance in TNBC. In addition, we demonstrated that the combination of paclitaxel and IRE1α inhibitors can synergistically inhibit the proliferation of TNBC tumors both in vitro and in vivo,suggesting that IRE1α inhibitors combined with paclitaxel may be a new treatment option for TNBC., Conclusions: In this study, we demonstrated the important role of IRE1α signaling in mediating paclitaxel resistance and identified that combination therapies targeting IRE1α signaling could overcome paclitaxel resistance and enhance chemotherapy efficacy., (© 2024. Springer Nature Switzerland AG.)

During Arabidopsis embryogenesis, the transition of the embryo's symmetry from radial to bilateral between the globular and heart stage is a crucial event, involving the formation of cotyledon primordia and concurrently the establishment of a shoot apical meristem (SAM). However, a coherent framework of how this transition is achieved remains to be elucidated. In this study, we investigated the function of DELAYED GREENING 1 (DG1) in Arabidopsis embryogenesis using a newly identified dg1-3 mutant. The absence of chloroplast-localized DG1 in the mutants led to embryos being arrested at the globular or heart stage, accompanied by an expansion of WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM) expression. This finding pinpoints the essential role of DG1 in regulating the transition to bilateral symmetry. Furthermore, we showed that this regulation of DG1 may not depend on its role in plastid RNA editing. Nevertheless, we demonstrated that the DG1 function in establishing bilateral symmetry is genetically mediated by GENOMES UNCOUPLED 1 (GUN1), which represses the transition process in dg1-3 embryos. Collectively, our results reveal that DG1 functionally antagonizes GUN1 to promote the transition of the Arabidopsis embryo's symmetry from radial to bilateral and highlight the role of plastid signals in regulating pattern formation during plant embryogenesis., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Cordyceps sinensis, a traditionally prized medicinal fungus, contains polysaccharides as one of its main bioactive constituents, known for their significant immunomodulatory properties. In this study, we systematically investigated the composition and structure of Cordyceps sinensis polysaccharide, followed by an evaluation of its therapeutic effect on depression using a chronic restraint stress-induced depression model. The polysaccharide CSWP-2, extracted via hot water, precipitated with ethanol, and purified using DEAE-cellulose column chromatography from Cordyceps sinensis, is primarily composed of glucose, mannose, and galactose, with α-1,4-D-glucan as its major structural component. Behavioral tests, immunological profiling, metabolomics, and gut microbiota analyses indicated a notable ameliorative effect of CSWP-2 on depressive-like symptoms in mice. Furthermore, the action of CSWP-2 may be attributed to the modulation of the gut microbiome's abundance and its metabolic impacts, thereby transmitting signals to the host immune system and exerting immunomodulatory activity, ultimately contributing to its antidepressant effects., 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.)

Background: Type 2 diabetes mellitus (T2DM) is a public health crisis that requires adequate knowledge, attitudes, and practices (KAP) by health care providers to prevent or delay the progression of the disease. This study aimed to assess the KAP regarding T2DM among primary care providers (PCPs) in Central China., Methods: This multicenter cross-sectional study was conducted among 971 PCPs using self-employed KAP questionnaires. Questionnaires were designed to evaluate KAP regarding T2DM among PCPs, and was measured with SPSS software. Descriptive statistics, the Pearson correlation coefficients and multiple regression models used to analyze the data.70%, 80% and 70% of total values were considered as the cut-off point for defining good knowledge, positive attitude and correct practice., Results: A total of 971 PCPs with a mean age of 44.0 ± 10.2 years were evaluated. 620 (63.9%) PCPs worked at village clinic and 605 (62.3%) PCPs have been working more than 20 years. Only 26.3% of the respondents participated in Continued Medical Education (CME) programs regarding diabetes in the past year due to Covid-19 pandemic. Overall, despite positive attitudes toward diabetes, there were substantial gaps in knowledge and practices. The PCPs scored 7.25 out of 14 points on the knowledge subscales, 7.13 out of 8 on the attitude subscales, and 4.85 out of 11 on the practice subscales. Gender, age, practice setting, professional titles, duration of practice and CME attendance were significant predictors of knowledge; Age, practice setting and duration of practice were significant predictors of attitudes; and family history of diabetes affected PCP practices., Conclusions: Despite positive attitudes toward diabetes, there were substantial gaps in knowledge and practices. These findings call for action from relevant health authorities and policy makers to improve PCPs' KAP regarding diabetes in Central China., (© 2024. The Author(s).)

Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound C-3 from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription. Optimization led to the identification of a potent and covalent inhibitor CV-4-26 that exhibited great antitumor activity in HCC and HB cell lines in vitro, xenografted human HCC, and murine HB in vivo. These outcomes signify the potential of a highly promising therapeutic candidate for addressing a subset of HCC and HB cancers. In the cases of current treatment challenges due to high upregulation of YAP-TEAD activity, these findings offer a targeted alternative for more effective interventions against liver cancer.

Yes-associated protein (YAP) is a key oncogene in the Hippo tumor suppression pathway, historically challenging to target due to its intrinsically disordered nature. Leveraging recent advances in high-throughput screening that identified several YAP binders, we employed proteolysis-targeting chimera technology to develop a series of YAP degraders. Utilizing NSC682769, a known YAP binder, linked with VHL ligand 2 or pomalidomide via diverse linkers, we synthesized degraders including YZ-6 . This degrader not only recruits the E3 ligase VHL for the rapid and sustained degradation of YAP but also effectively inhibits its nuclear localization, curtailing YAP/TEAD-mediated transcription in cancer cell lines such as NCI-H226 and Huh7. This dual action significantly diminishes YAP's oncogenic activity, contributing to the potent antiproliferative effects observed both in vitro and in a Huh7 xenograft mouse model. These results underscore the potential of PROTAC-mediated YAP degradation as a strategy for treating YAP-driven cancers.

Industrial computed tomography (CT) is widely used in the measurement field owing to its advantages such as non-contact and high precision. To obtain accurate size parameters, fitting parameters can be obtained rapidly by processing volume data in the form of point clouds. However, due to factors such as artifacts in the CT reconstruction process, many abnormal interference points exist in the point clouds obtained after segmentation. The classic least squares algorithm is easily affected by these points, resulting in significant deviation of the solution of linear equations from the normal value and poor robustness, while the random sample consensus (RANSAC) approach has insufficient fitting accuracy within a limited timeframe and the number of iterations. To address these shortcomings, we propose a spherical point cloud fitting algorithm based on projection filtering and K-Means clustering (PK-RANSAC), which strategically integrates and enhances these two methods to achieve excellent accuracy and robustness. The proposed method first uses RANSAC for rough parameter estimation, then corrects the deviation of the spherical center coordinates through two-dimensional projection, and finally obtains the spherical center point set by sampling and performing K-Means clustering. The largest cluster is weighted to obtain accurate fitting parameters. We conducted a comparative experiment using a three-dimensional ball-plate standard. The sphere center fitting deviation of PK-RANSAC was 1.91 μm, which is significantly better than RANSAC's value of 25.41 μm. The experimental results demonstrate that PK-RANSAC has higher accuracy and stronger robustness for fitting geometric parameters.

Transcription factors (TFs) tightly control plant development by regulating gene expression. The phase separation of TFs plays a vital role in gene regulation. Many plant TFs have the potential to form phase-separated protein condensates; however, little is known about which TFs are regulated by phase separation and how it affects their roles in plant development. Here, we report that the rice (Oryza sativa) single Myb TF TELOMERE REPEAT-BINDING FACTOR 2 (TRBF2) is highly expressed in fast-growing tissues at the seedling stage. TRBF2 is a transcriptional repressor that binds to the transcriptional start site of thousands of genes. Mutation of TRBF2 leads to pleiotropic developmental defects and misexpression of many genes. TRBF2 displays characteristics consistent with phase separation in vivo and forms phase-separated condensates in vitro. The H1/H5 domain of TRBF2 plays a crucial role in phase separation, chromatin targeting, and gene repression. Replacing the H1/H5 domain by a phase-separated intrinsically disordered region from Arabidopsis (Arabidopsis thaliana) AtSERRATE partially recovers the function of TRBF2 in gene repression in vitro and in transgenic plants. We also found that TRBF2 is required for trimethylation of histone H3 Lys27 (H3K27me3) deposition at specific genes and genome wide. Our findings reveal that phase separation of TRBF2 facilitates gene repression in rice development., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In tissue culture, a high concentration of auxin in the callus induction medium (CIM) stimulates cell division and subsequent callus formation, which acquires root primordium-like characteristics necessary for cell pluripotency. In Arabidopsis, WUSCHEL-RELATED HOMEOBOX5 (WOX5) and its closest homolog WOX7, which are abundant in the middle cell layer of mature callus, play a crucial role in maintaining pluripotency by promoting auxin accumulation and enhancing cytokinin sensitivity. However, the mechanism by which WOX5/7 regulate callus formation remains unclear. In this study, we found that mutations in WOX5/7 resulted in a significant down-regulation of genes involved in the G2M and S phases during callus induction. Loss-of-function mutants of WOX5/7 exhibited reduced callus formation, which was correlated with decreased expression of CYCB1;1 compared to the wild-type. Furthermore, we provided evidence that WOX5 physically interacts with PHYTOCHROME A SIGNAL TRANSDUCTION1 (PAT1), which spatio-temporally co-expresses with WOX5 in early-induced callus, and up-regulates a subset of cycle-regulating genes targeted by PAT1. Collectively, our findings suggest a critical role for the WOX5-PAT1 protein complex in regulating cell cycle progression, thereby promoting the continuous growth capacity of pluripotent callus., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Retinoblastoma (RB) is a pediatric malignancy, typically diagnosed at birth or during early childhood. The pathogenesis of RB is marked by the amplification of the Basic Helix-Loop-Helix (BHLH) Transcription Factor MYCN, which serves as a transcriptional regulator capable of binding to Dickkopf 3 (DKK3). However, the precise role of DKK3 in the malignant progression of RB cells caused by MYCN remains elusive. In the present study, the expression of MYCN was either overexpressed or interfered in RB cells. Subsequently, the expression level of DKK3 was assessed through quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was evaluated using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine staining, while cell cycle progression and apoptosis were analyzed by flow cytometry and western blot analysis, respectively. Additionally, the expression of proteins involved in the Wnt/β-catenin/Fra-1/p53 signaling pathway was evaluated via western blot analysis. To gain further insights, Wnt agonists and the P53 inhibitor PFT-α were introduced into exploration. The current investigation revealed a negative correlation between the expression levels of MYCN and DKK3 in RB cells. Additionally, DKK3 overexpression inhibited cell proliferation, promoted cell apoptosis, and arrested cell cycle in RB cells with high expression of MYCN. Moreover, enhanced DKK3 expression inhibited proliferation, promoted cell cycle arrest and apoptosis of RB cells by modulating the wnt/βcatenin/Fra-1/p53 signaling pathway. Furthermore, in vivo experiments revealed that overexpression of DKK3 inhibits the growth of RB tumors. Collectively, our findings elucidate that MYCN stimulates the Wnt/β-catenin/Fra-1 pathway by suppressing DKK3 expression, ultimately suppressing p53 activity and contributing to malignant progression of RB., (© 2024 Wiley Periodicals LLC.)

The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P < 0.001). The cut-offs we calculated for hypoalbuminemia and severe hypoalbuminemia based on the IN were 25 and 15 g/L, which were 5 g/L lower than the cut-offs recommended by KIDGO, respectively. A pair of historical control samples (206 vs. 216) with ALB-B or ALB-I showed that the proportion of severe hypoalbuminemia was 14.60% greater in IN group (75.20% vs. 60.60%, P < 0.001). The misdiagnosis rate of severe hypoalbuminemia by IN was 33.77% when 20 g/L rather than 15 g/L was used as the cut-off. Furthermore, the proportion of patients receiving albumin injections increased by 10.20%, and the average consumption increased by 97.06% (P = 0.01) along with the use of IN. So, our results suggested that the difference between ALB-B and ALB-I led to misdiagnosis and prescription abuse in PNS children., (© 2024. The Author(s).)

In this article, we provided a comprehensive overview and in-depth analysis of global patterns and temporal trends in years lived with disability (YLDs) for musculoskeletal (MSK) disorders in individuals aged ≥70. Data on YLDs for MSK disorders in individuals aged ≥70 were obtained from the Global Burden of Disease 2019. The average annual percentage change (AAPC) was calculated to assess the temporal trends in the YLDs rate of MSK disorders. A Bayesian Age-Period-Cohort model was used to predict the YLDs rate up to the year 2040. In 2019, the global rate of YLDs for MSK disorders in individuals aged ≥70 were 4819.81 (95 % UI: 3402.91 - 6550.77) per 100,000 persons. The YLDs rate of MSK disorders in female was 1.36 times higher than that in male, and was highest in high SDI regions. From 1990 to 2019, the global YLDs rate showed a slightly downward trend (AAPC = -0.04 %, 95 % CI: -0.06 % to -0.03 %), while it significantly increased in high, low-middle, low SDI regions. Tobacco and high body mass index were the primary risk factors worldwide, while in low SDI regions, occupational risks emerged as the predominant factors. Up to 2040, the global YLDs rate of MSK disorders are expected to increase by 1.78 %, with 36.39 %, 20.66 %, 18.96 % and 5.32 % growth in other MSK disorders, rheumatoid arthritis, neck pain and osteoarthritis. MSK disorders are a significant and continuously growing public health concern among older adults. Tailored interventions should be developed for older adults, taking into account the variations across distributions, trends, and risk factors in terms of sex and SDI levels., Competing Interests: 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., (© 2024 The Authors.)

Key Message: BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance in Arabidopsis roots. The formative divisions of cortex/endodermis initials (CEIs) and CEI daughter cells (CEIDs) in Arabidopsis roots are coordinately controlled by the longitudinal auxin gradient and the radial SHORT ROOT (SHR) abundance. However, the mechanism underlying this coordination remains poorly understood. In this study, we demonstrate that BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance. Mutations in BIG gene repressed cell cycle progression, delaying the formative divisions within the ground tissues and impairing the establishment of endodermal and cortical identities. In addition, we uncovered auxin's suppressive effect on BIG expression, triggering CYCLIND6;1 (CYCD6;1) activation in an SHR-dependent fashion. Moreover, the degradation of RETINOBLASTOMA-RELATED (RBR) is jointly regulated by BIG and CYCD6;1. The loss of BIG function led to RBR protein accumulation, detrimentally impacting the SHR/SCARECROW (SCR) protein complex and the CEI/CEID formative divisions. Collectively, these findings shed light on a fundamental mechanism wherein BIG intricately coordinates the interplay between SHR/SCR and auxin, steering ground tissue patterning within Arabidopsis root tissue., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polar metals have recently garnered increasing interest because of their promising functionalities. Here we report the experimental realization of an intrinsic coexisting ferromagnetism, polar distortion and metallicity in quasi-two-dimensional Ca 3 Co 3 O 8 . This material crystallizes with alternating stacking of oxygen tetrahedral CoO 4 monolayers and octahedral CoO 6 bilayers. The ferromagnetic metallic state is confined within the quasi-two-dimensional CoO 6 layers, and the broken inversion symmetry arises simultaneously from the Co displacements. The breaking of both spatial-inversion and time-reversal symmetries, along with their strong coupling, gives rise to an intrinsic magnetochiral anisotropy with exotic magnetic field-free non-reciprocal electrical resistivity. An extraordinarily robust topological Hall effect persists over a broad temperature-magnetic field phase space, arising from dipole-induced Rashba spin-orbit coupling. Our work not only provides a rich platform to explore the coupling between polarity and magnetism in a metallic system, with extensive potential applications, but also defines a novel design strategy to access exotic correlated electronic states., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study analysed the incidence of lower extremity amputation and its associated risk factors in patients with diabetic foot ulcers. This study systematically searched both Chinese and English databases, including CNKI, Wanfang, VIP, PubMed, EMBASE and Web of Science, to identify cohort studies related to lower extremity amputation and associated risk factors in patients with diabetic foot ulcers up to October 2023. The patients were stratified based on whether they underwent lower extremity amputation, and relevant data, including basic information, patient characteristics, complications, comorbidities and pertinent laboratory test data, were extracted from the included studies. The literature quality assessment in this study utilized the Newcastle-Ottawa Scale to screen for high-quality literature, resulting in the inclusion of 16 cohort studies, all of which were of at least moderate quality. Meta-analysis of outcome indicators was conducted using the Stata 14.0 software. The results indicate that the overall amputation rate of lower extremities in patients with diabetic foot ulcers is 31% (0.25, 0.38). Among the 16 variables evaluated, gender (male), smoking history, body mass index (BMI), hypertension, cardiovascular disease, kidney disease, white blood cell count, haemoglobin and albumin levels were found to be correlated with the occurrence of lower extremity amputation in patients with diabetic foot ulcers. However, no significant correlation was observed between age, diabetes type, duration of diabetes, stroke, glycosylated haemoglobin, creatinine and total cholesterol levels and lower extremity amputation in patients with diabetic foot ulcers. This meta-analysis indicates that the overall amputation rate in patients with diabetic foot ulcers is 31%. Factors such as gender (male), smoking history, high BMI, hypertension, cardiovascular disease, kidney disease, white blood cell count, haemoglobin and albumin levels are identified as significant risk factors for lower extremity amputation in diabetic foot ulcer patients. These findings suggest that attention should be focused on these risk factors in patients with diabetic foot ulcers to reduce the risk of lower extremity amputation. Therefore, preventive and intervention measures targeting these risk factors are of significant importance in clinical practice. (Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42024497538])., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: The objective of this study was to identify variables that predict adherence to follow-up visits among people who are positive for diabetes during screening and to investigate barriers to follow-up., Study Design: A retrospective cohort study linking individual-level registry data was performed., Methods: First, we compared the characteristics of attenders and non-attenders. Second, we investigated perceived barriers using a questionnaire in a random sample of people who failed to attend the follow-up visit., Results: A total of 27,806 (16.4%) patients attended the follow-up visits. Multiple logistic regression analysis revealed that individuals aged ≥75 years were more likely to attend follow-up than were those aged 35-45 years (odds ratio [OR]: 1.97 [95% confidence interval {CI}: 1.82-2.15]), male (OR: 1.15 [95% CI: 1.12-1.18]), obese (OR: 1.36 [95% CI: 1.29-1.43]), had positive family history of diabetes (OR: 1.37 [95% CI: 1.30-1.45]), hypertension (OR: 1.05 [95% CI: 1.01-1.09]), high glucose levels (OR: 1.10 [95% CI: 1.09-1.11]), and high diabetes risk scores (OR: 1.02 [95% CI: 1.02-1.03]) facilitated follow-up. However, overweight (OR: 0.95 [95% CI: 0.92-0.99]) and central obesity (OR: 0.86 [95% CI: 0.83-0.90]) predicted no follow-up. Among nonattenders, diabetes beliefs, time restrictions and distance from home to hospitals were the top three barriers hindering follow-up visits., Conclusions: Specific individual-level characteristics predicted adherence to follow-up visits, and some personal and sociocultural barriers hindered follow-up visits., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Hypoxic preconditioning has been recognized as a promotive factor for accelerating cutaneous wound healing. Our previous study uncovered that exosomal lncRNA H19, derived from adipose-derived stem cells (ADSCs), plays a crucial role in orchestrating cutaneous wound healing. Herein, we aimed to explore whether there is a connection between hypoxia and ADSC-derived exosomes (ADSCs-exos) in cutaneous wound healing. Exosomes extracted from ADSCs under normoxic and hypoxic conditions were identified using transmission electron microscope (TEM) and particle size analysis. The effects of ADSCs-exos on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8, EdU, wound healing, and tube formation assays. Expression patterns of H19, HIF-1α, and USP22 were measured. Co-immunoprecipitation, chromatin immunoprecipitation, ubiquitination, and luciferase reporter assays were conducted to confirm the USP22/HIF-1α/H19 axis, which was further validated in a mice model of skin wound. Exosomes extracted from hypoxia-treated ADSCs (termed as H-ADSCs-exos) significantly increased cell proliferation, migration, and angiogenesis in H 2 O 2 -exposed HUVECs, and promoted cutaneous wound healing in vivo. Moreover, H-ADSCs and H-ADSCs-exos, which exhibited higher levels of H19, were found to be transcriptionally activated by HIF-1α. Mechanically, H-ADSCs carrying USP22 accounted for deubiquitinating and stabilizing HIF-1α. Additionally, H-ADSCs-exos improved cell proliferation, migration, and angiogenesis in H 2 O 2 -triggered HUVECs by activating USP22/HIF-1α axis and promoting H19 expression, which may provide a new clue for the clinical treatment of cutaneous wound healing., (© 2024 Federation of American Societies for Experimental Biology.)