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Xiaojing Chen,1– 3,&ast; Qilin Yang,4,&ast; Li Gao,1– 3 Weinan Chen,1 Xiaoyu Gao,1– 3 Yameng Li,1– 3 Liying Ao,5 Dejun Sun1– 3 1Department of Respiratory and Critical Care Medicine, Inner Mongolia People’s Hospital, Hohhot, 010017, People’s Republic of China; 2NHC Key Laboratory of Diagnosis & Treatment of COPD, Inner Mongolia People’s Hospital, Hohhot, 010017, People’s Republic of China; 3Inner Mongolia Key Laboratory of Respiratory Diseases, Inner Mongolia People’s Hospital, Hohhot, 010017, People’s Republic of China; 4Department of Critical Care, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Otolaryngology, Inner Mongolia People’s Hospital, Hohhot, 010017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dejun Sun, Department of Respiratory and Critical Care Medicine, Inner Mongolia People’s Hospital, No. 26 Zhaowuda Road, Saihan District, Hohhot, 010017, People’s Republic of China, Email nmg_sdj@163.comBackground: Serum anion gap (AG) has been proven to be associated with prognosis in critically ill patients. However, few studies have investigated the association between AG and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD).Objective: We hypothesized that the initial AG level would predict the mortality risk in critically ill patients with COPD.Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC) IV database. We extracted demographics, vital signs, laboratory tests, comorbidity, and scoring systems from the first 24 hours after patient ICU admission. Multivariable logistic regression analysis models were used to explore the association between serum AG levels and mortality. Interaction and stratified analyses were conducted including age, gender and comorbidity.Results: A total of 5531 critically ill patients with COPD were enrolled, composed of 53.6% male and 46.4% female with a median age of 73 years. The all-cause mortality of these patients during ICU hospitalization was 13.7%. The risk of all-cause mortality increased as the AG level increased in the univariate logistic regression analysis (OR=1.13, 95% CI: 1.11– 1.15, p< 0.01). After adjusting for all the covariates in multivariate logistic regression analysis, the odds ratio was 1.06 (95% CI: 1.04– 1.09, p< 0.01). Compared with the lowest AG group Q1 (≤ 11mmol/L), the adjusted OR value for AG and mortality in Q2 (12– 13mmol/L) was 0.89 (95% CI: 0.63– 1.25, p=0.502), Q3 (14– 15mmol/L) was 0.95 (95% CI: 0.68– 1.34, p=0.788), and Q4 (≥ 16mmol/L) was 1.49 (95% CI: 1.10– 2.02, p=0.009) respectively. In addition, the results of the subgroup and stratified analyses were robust.Conclusion: AG is positively related to all-cause mortality in critically ill patients with COPD.Keywords: AG, COPD, mortality, MIMIC IV

Ying Zhao,1,&ast; Liqing Yao,1,&ast; Lijuan Ao,2 Jibing Ou,1 Ying He,1 Yunyun Shang1 1The Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China; 2School of Rehabilitation, Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijuan AoSchool of Rehabilitation, Kunming Medical University, Kunming, 650500, People’s Republic of ChinaTel +86 13508710081Fax +8687165338994Email lijuandrao@163.comObjective: In this study, umbilical cord mesenchymal stem cell (UC-MSC) transplantation was used to treat patients with spinal cord injury (SCI). The microstructural changes of the spinal cord before and after transplantation were observed by diffusion tensor imaging (DTI).Methods: From January 2014 to May 2015, seven patients who met the inclusion criteria were enrolled in this study. In the experimental group, both UC-MSC transplantation and comprehensive rehabilitation treatment were applied, while the control group received only comprehensive rehabilitation treatment. American Spinal Injury Association (ASIA) sensory and motor scores and the degree of SCI, spasticity, and urine/defecation functions were measured and evaluated together with DTI before the treatment and again at two and six months after the first treatment.Results: From the DTI, the changes in the fractional anisotropy (FA) value and the apparent diffusion coefficient (ADC) value were as follows: in the experimental group, there were significant differences in the FA and ADC values before and after treatment (P < 0.05) with a decreased ADC value and an increased FA value. The differences in the ADC and FA values of the normal layer and the lesion layer before and after treatment were compared. The differences in ADC and FA at the lesion layer before and after transplantation were greater than those of the normal layer, and the differences were statistically significant (P < 0.05). In the experimental group, one patient with incomplete SCI and one patient with a short course of complete SCI improved in terms of light touch, acupuncture sensation, and motor score. One patient with incomplete SCI achieved improvement in spasticity and urine/defecation functions.Conclusion: The combination of UC-MSC transplantation and comprehensive rehabilitation therapy could help to promote the structural repair of the spinal nerve in patients with SCI.Keywords: spinal cord injury, stem cell, DTI, ADC, FA

Background: Balance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke., Methods: A prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30-80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up., Discussion: This trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke., Trial Registration: Chinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024., (© 2024. The Author(s).)

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer., (© 2024. The Author(s).)

Introduction: Ovarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells., Objectives: To elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer., Methods: Study the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo., Results: RNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue., Conclusion: This study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest, (Copyright © 2024. Published by Elsevier Inc.)

Simultaneous detection of the dynamic distribution of long-chain fatty acid ethyl esters (LCFAEEs) during Baijiu distillation is crucial for optimizing its flavor and health attributes. In this study, we synthesized a simple, cost-effective Fe 3 O 4 @NH 2 adsorbent to simultaneously extract eight LCFAEEs from Baijiu. Through density functional theory and adsorption experiments, we elucidated 1,6-hexanediamine as a surface modifier, with the -NH 2 groups providing adsorption sites for the LCFAEEs via hydrogen-bonding interactions and van der Waals forces. Additionally, we established the magnetic solid-phase extraction-GC-MS extraction technique combined with stable isotope dilution analysis to analyze LCFAEEs. This method revealed the dynamic distribution patterns of LCFAEEs during strong aroma-type Baijiu (SAB) distillation. We observed that the concentrations of the eight LCFAEEs gradually decreased with prolonged distillation and were significantly correlated with ethanol concentration. To ensure optimal flavor and clarity in SAB, it is recommended to select the heart-stage base Baijiu with an alcohol content of 58%-63%.

Nitrogen (N) utilisation efficiency (NUE, milk N yield [g/d]/N intake [g/d]) is an important performance indicator in dairy farming. Determining the NUE-associated blood metabolite profile will contribute to the optimisation of nutritional strategies to further improve NUE among dairy cows. Here, 20 primiparous lactating cows with days in milk ranging from 95 to 115 days were selected from a total of 1 221 cows. Each cow's N intake and milk N yield were measured for 7 days. Subsequently, blood samples were collected before morning feeding. Based on analysis and calculations, cows were retrospectively classified into two groups based on their NUE values, namely, a low NUE group (LNUE, NUE = 24.8 ± 1.6%, n = 10, mean ± SD) and a high NUE group (HNUE, NUE = 35.2 ± 1.7%, n = 10, mean ± SD). Plasma samples were selected from six cows in each group for metabolomics and amino acid profiling. Among the 41 differential metabolites (DMs) identified in the metabolomic analysis, sucrose, MG(0:0/22:1(13Z)/0:0), 2-amino-6-hydroxyhexanoic acid, and L-glutamine exhibited significant correlations with NUE, milk yield, and BW (P < 0.05). Moreover, the five differential amino acids and amino acid metabolites (DAAs) identified in the amino acid profiling and 5 of the 6 differential amino acids and amino acid conjugates identified by plasma metabolomics were found to be less abundant in the HNUE group (P < 0.05). Specifically, there was a 39.4% decrease in L-arginine content and a 29.2% decrease in L-glutamine content (P < 0.05). Pathway analysis indicated that the DMs and DAAs were mainly involved in arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, and tryptophan metabolism (pathway impact > 0.1). These results provided new insights into the new blood metabolite profile associated with NUE in dairy cows. These new insights can provide foundational information for the formulation of new strategies to further enhance NUE in dairy cows., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC), a hypervascular tumor, is the most frequent primary malignant tumor of the liver. Angiogenesis inhibitors, such as endogenous angiogenesis inhibitors, are essential for HCC therapy and have generated significant interest owing to their safety, efficacy, and multitargeting attributes. Canstatin is an angiogenesis inhibitor derived from the basement membrane and exerts anti-tumor effects. However, the inhibitory effects and underlying mechanisms of action of canstatin on HCC remain unclear. Therefore, in this study, HepG2 and Huh7 cells were used to investigate the inhibitory effects of recombinant canstatin on HCC cells. Subsequently, the biosafety and inhibitory effects of recombinant canstatin on tumor growth were investigated in a xenograft animal model of liver cancer. Canstatin inhibited the growth of liver cancer cells by regulating their proliferation, apoptosis, and migration. Additionally, it suppressed the occurrence and progression of HCC by modulating the HIF-1α/VEGF signaling pathway. In mice, canstatin exerted no discernible harmful side effects and suppressed the growth of HCC subcutaneous xenograft tumors. Overall, our findings shed light on the molecular pathways underlying canstatin-induced HCC cell death that may help develop novel HCC treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Splenic flexure mobilization (SFM) is a major challenge in laparoscopic left hemicolectomy. This study aims to assess the safety and effectiveness of the pancreas-guided SFM technique during laparoscopic left hemicolectomy., Methods: From January 2018 to December 2023, 352 patients with left-sided colon cancer underwent laparoscopic left hemicolectomy. Based on the SFM method used, the patients were divided into the pancreas-guided group (167 cases) or the "Three Approaches Roundabout"/classic group (185 cases). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups., Results: The two groups had no significant differences in baseline indicators (P > 0.05). All surgeries were successful without needing to convert to laparotomy, and there were no combined organ resections involving the spleen or pancreas in either group. The mean duration of surgery was significantly lower in the pancreas-guided group than in the classic group (P < 0.01). The median volume of intraoperative blood loss in the pancreas-guided group was lower than that in the classic group (P < 0.01). Through video playback, it was found that the retro-pancreatic space had been entered during operation in 8 cases (4.3%) in the classic group, while there were no such occurrences in the pancreas-guided group. This difference was statistically significant (P < 0.05). The difference in the number of lymph nodes cleared, postoperative hospital stays, and incidence of complications were not statistically significant (all P > 0.05) between the groups., Conclusion: The pancreas-guided SFM technique is a safe and feasible option for laparoscopic left hemicolectomy. Our study's findings suggest that this approach facilitates accurate access to the correct anatomic plane, potentially improving surgical efficiency., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL -1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe 3 O 4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL -1 , tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers., (© 2024 Wiley‐VCH GmbH.)

To address the urgent need for efficient removal of lead-containing wastewater and reduce the risk of toxicity associated with heavy-metal wastewater contamination, materials with high removal rates and easy separation must be developed. Herein, a novel organic-inorganic hybrid material based on phosphorylated magnetic chitosan (MSCP) was synthesized and applied for the selective removal of lead (II) from wastewater. From the characterization and the experimental results can be obtained that the magnetic saturation strength of MSCP reaches 14.65 emu/g, which can be separated quickly and regenerated readily, and maintains high adsorption performance even after 5 cycles, indicating that the adsorbent possesses good magnetic separation performance and durability. Also, MSCP showed high selective adsorption performance for lead in the multiple metal ions coexistence solutions at pH 6.0 and room temperature, with an adsorption coefficient S Pb-MSCP of 78.85%, which was much higher than that of MSC (the S Pb-MSC was 11.59%). Additionally, in the single lead system, the sorption characteristics of Pb(II) on MSCP and MCP had obvious pH-responsiveness, and their adsorption capacity increased with the increase of solution pH, reaching the maximal values of 80.19 and 72.68 mg/g, respectively. It is noteworthy that the acid resistance of MSCP with an inert layer coated on the core is significantly improved, with almost no iron leaching from MSCP over the entire acidity range, while MCP has 7.63 mg/g of iron leaching at pH 1.0. Significantly, MSCP exhibited a maximum adsorption capacity of 102.04 mg/g, which matches the Langmuir model at pH 6.0 and 298.15 K, and points to the pseudo-second-order kinetics of the chemisorption process of Pb(II) on MSCP. These findings highlight the great potential of MSCP for Pb(II) removal from aqueous solution, making it a promising solution for Pb(II) contamination in wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Infectious diseases persistently pose global threats, and it is imperative to accelerate the professionalization of public health workforce. This study aimed to develop and validate the infectious disease control competency scale (IDCCS) for public health professionals to fill a theoretical gap and elevate practical capabilities by informing public health professionals' development goals., Methods: The initial item pool was generated through a literature review, and categorized into three dimensions (knowledge, practical skills, and leadership) based on the competency iceberg model and public health leadership framework. A two-round Delphi process was conducted to determine indicators within the scale. A pilot survey was utilized for item analysis and exploratory factor analysis (EFA). A formal survey was employed for confirmatory factor analysis (CFA). The weight value of each indicator was calculated using the analytic hierarchy process., Results: An initial scale with three primary items, 14 secondary items, and 81 tertiary items was generated. Twenty experts participated in the two rounds of the Delphi process. Authority coefficients exceeded 0.9 in both rounds. Kendall's W was 0.29 and 0.19, respectively (both P < 0.001). Item analysis presented a Cronbach's Alpha of 0.98, with corrected item-total correlation coefficients ranging from 0.33 to 0.78. EFA demonstrated that cumulative variance explanations for the four primary dimensions (knowledge, practical skills, leadership, and personal quality) were 77.463%, 73.976%, 81.174%, and 68.654%, respectively. CFA indicated that all composite reliability values and average variance extracted surpassed 0.8 and 0.5, respectively. The standardized factor loadings of the items ranged from 0.630 to 0.977. Among the seven model fit indices, each of the four dimensions satisfied at least five criteria. A final three-level scale comprising four primary items, 14 secondary items, and 64 tertiary items was constructed. The weight values for the four primary items were 0.4064, 0.2878, 0.2082, and 0.0981, respectively., Conclusions: The IDCCS was established to evaluate the competencies of knowledge, practical skills, leadership, and personal quality for public health professionals in infectious disease control. This scale demonstrates good reliability and validity, and can be used for performance evaluation, recruitment processes, curriculum development, and individual self-assessment., (© 2024. The Author(s).)

The genetic landscape of cardiometabolic risk factors has been explored extensively. However, insight in the effects of genetic variation on these risk factors over the life course is sparse. Here, we performed genome-wide interaction studies (GWIS) on different cardiometabolic risk factors to identify age-specific genetic risks. This study included 270,276 unrelated European-ancestry participants from the UK Biobank (54.2% women, a median age of 58 [interquartile range (IQR): 50, 63] years). GWIS models with interaction terms between genetic variants and age were performed on apolipoprotein B (ApoB), low-density lipoprotein-cholesterol (LDL-C), log-transformed triglycerides (TG), body mass index (BMI) and systolic blood pressure (SBP). Replication was subsequently performed in the Copenhagen General Population Study (CGPS) and the Estonian Biobank (EstBB). Multiple lead variants were identified to have genome-wide significant interactions with age (P interaction  < 1e - 08). In detail, rs429358 (tagging APOE4) was identified for ApoB (P interaction  = 9.0e - 14) and TG (P interaction  = 5.4e - 16). Three additional lead variants were identified for ApoB: rs11591147 (R46L in PCSK9, P interaction  = 3.9e - 09), rs34601365 (near APOB, P interaction  = 8.4e - 09) and rs17248720 (near LDLR, P interaction  = 2.0e - 09). Effect sizes of the identified lead variants were generally closer to the null with increasing age. No variant-age interactions were identified for LDL-C, SBP and BMI. The significant interactions of rs429358 with age on ApoB and TG were replicated in both CGPS and EstBB. The majority of genetic effects on cardiometabolic risk factors remain relatively constant over age, with the noted exceptions of specific genetic effects on ApoB and TG., (© 2024. The Author(s).)

Background: Human Aortic valve interstitial cells (AVICs) from calcific aortic valve disease (CAVD)-affected valves exhibit elevated fibrocalcific activity although the underlying mechanism remains incompletely understood. This study aimed to identify endogenous factors that promote aortic valve fibrocalcification., Methods and Results: Proteomic analysis found increased cathepsin D levels in AVICs from CAVD-affected valves compared to AVICs from normal valves, and this finding was validated by immunoblotting. ELISA assay identified exacerbated release of cathepsin D by AVICs of diseased valves. Recombinant human cathepsin D upregulated the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), collagen I and collagen IV in human AVICs, resulting in the deposition of calcium and collagen. Blocking of the ERK1/2-Sox9 signaling pathway markedly reduced the pro-fibrocalcific effect of cathepsin D. Moreover, normal AVICs express and release greater levels of cathepsin D when exposed to soluble matrilin 2. Knockdown of cathepsin D attenuated the fibrocalcific response induced by soluble matrilin 2., Conclusion: AVICs of diseased aortic valves produce and release greater levels of cathepsin D that exerts a pro-fibrocalcific effect on AVICs through the ERK1/2-Sox9 pathway. Soluble matrilin 2 up-regulates cathepsin D to elevate AVIC fibrocalcific activity. Over-expression of cathepsin D in the aortic valve may enhance the pathobiological activities in AVICs., 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., (© 2024 Yao, The, Nedumaran, Zhai, Ao, Fullerton and Meng.)

Rheumatoid arthritis (RA) is a common autoimmune disease characterized primarily by persistent synovial inflammation and joint destruction. In recent years, ferroptosis, as a novel form of cell death, has garnered widespread attention due to its critical role in various diseases. This review explores the potential mechanisms of ferroptosis in RA and its relationship with the pathogenesis of RA, systematically analyzing the regulatory role of ferroptosis in synovial cells, chondrocytes, and immune cells. We emphasize the evaluation of ferroptosis-related pathways and their potential as therapeutic targets, including the development and application of inhibitors and activators. Although ferroptosis shows some promise in RA treatment, its dual role and safety issues in clinical application still require in-depth study. Future research should focus on elucidating the specific mechanisms of ferroptosis in RA pathology and developing more effective and safer therapeutic strategies to provide new treatment options for RA patients., 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 Zhao, Dong, Hua, Wu and Ao.)

Third-party punishment (TPP) is the punishment that an individual executes on a violator as a third party or observer to maintain social norms. Many studies have provided insights into the neural mechanisms of third-party punishment in group environments. Still, only some studies have focused on the neural mechanisms of third-party punishment in different group sizes. This study used EEG analysis to explore the effects of group size on third-party punishment and its neural activity characteristics from the context of gain and loss. The results show that the punishment rate and amount of the third party in the small group size and loss context were significantly higher than that in the large group size and gain context. EEG results showed that third-party punishment in small groups induced greater P2 than in large groups. In the loss context, the third-party punishment in the large group size induced more negative LNP and activated more theta band activation than in the small group. The results showed that the motivation of the third party to seek a positive reputation in the small size exceeds the balance of its economic interests and tends to punish the violator for maintaining fair norms. The loss context plays a promoting role in this process. However, in the large size, the third-party consideration of its interests was stronger than the willingness to maintain social norms. This study provided neuroscientific evidence for third-party punishment to maintain fair norms in a group environment and further explanations from neuroscience for understanding Indirect Reciprocity Theory., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Family resilience is crucial for individual's psychological health. Previous studies explored the protective factors of anxiety at the individual level, with less attention paid to the impact of family interaction from a dyadic perspective. This study utilized the Actor-Partner Interdependence Mediation Model to investigate the relationship between family resilience, emotional flexibility, and anxiety symptoms. A sample of 2144 Chinese parent-adolescent dyads (36% upper grades of primary school, 64% secondary school, 49.39% girls; 70.38% mothers) was recruited. Perceived family resilience was inversely related to anxiety symptoms, directly or indirectly, through the mediation of emotional flexibility at the individual level. At the dyadic level, adolescents' perceived family resilience was significantly associated with parents' anxiety symptoms through their own or parents' emotional flexibility. Parents' perceived family resilience was inversely link to adolescents' anxiety symptoms through parents' emotional flexibility. Parents emotional flexibility also mediated the association between adolescents' perceived family resilience and their anxiety symptoms. These findings contribute to understanding the intricate dynamics of family resilience and psychological outcomes in parent-child relationships under adversity, emphasizing the need for child-centered interventions to improve family members' mental health., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bone metastasis (BM) is a mortality-related event of late-stage cancer, with non-small cell lung cancer (NSCLC) being a common origin for BM. However, the detailed molecular profiling of the metastatic bone ecosystem is not fully understood, hindering the development of effective therapies for advanced patients. In this study, we examined the cellular heterogeneity between primary tumours and BM from tissues and peripheral blood by single-cell transcriptomic analysis, which was verified using multiplex immunofluorescence staining and public datasets. Our results demonstrate a senescent microenvironment in BM tissues of NSCLC. BM has a significantly higher infiltration of malignant cells with senescent characteristics relative to primary tumours, accompanied by aggravated metastatic properties. The endothelial-mesenchymal transition involved with SOX18 activation is related to the cellular senescence of vascular endothelial cells from BM. CD4Tstr cells, with pronounced stress and senescence states, are preferentially infiltrated in BM, indicating stress-related dysfunction contributing to the immunocompromised environment during tumour metastasis to bone. Moreover, we identify the SPP1 pathway-induced cellular crosstalk among T cells, vascular ECs and malignant cells in BM, which activates SOX18 and deteriorates patient survival. Our findings highlight the roles of cellular senescence in modulating the microenvironment of BM and implicate anti-senescence therapy for advanced NSCLC patients., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Social norms and altruistic punitive behaviours are both based on the integration of information from multiple contexts. Individual behavioural performance can be altered by loss and gain contexts, which produce different mental states and subjective perceptions. In this study, we used event-related potential and time-frequency techniques to examine performance on a third-party punishment task and to explore the neural mechanisms underlying context-dependent differences in punishment decisions. The results indicated that individuals were more likely to reject unfairness in the context of loss (vs. gain) and to increase punishment as unfairness increased. In contrast, fairness appeared to cause an early increase in cognitive control signal enhancement, as indicated by the P2 amplitude and theta oscillations, and a later increase in emotional and motivational salience during decision-making in gain vs. loss contexts, as indicated by the medial frontal negativity and beta oscillations. In summary, individuals were more willing to sanction violations of social norms in the loss context than in the gain context and rejecting unfair losses induced more equity-related cognitive conflict than accepting unfair gains, highlighting the importance of context (i.e., gain vs. loss) in equity-related social decision-making processes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Low-temperature and low-salt fermented Chinese kohlrabi (LSCK) represents a novel approach to producing low-salt kohlrabi without the need for desalination during processing, as compared to traditional techniques. However, the profile of its non-volatile metabolites remains unclear. In order to investigate the non-volatile metabolites and their changes in LSCK during fermentation, the LSCKs fermented for 0 day (0D), 45 days (45D) and 90 days (90D) were analyzed using LC-MS/MS non-targeted metabolomics coupled with multivariate statistical analysis. The results showed that 60, 74, and 68 differential metabolites were identified in the three groups A1 (0D and 45D), A2 (0D and 90D), and A3 (45D and 90D) (VIP >1, p < 0.05, Log2FC >1), respectively. The differential metabolites were mainly amino acids, peptides, and analogues, fatty acyls, organic acids and derivatives, and carbohydrates and carbohydrate conjugates. Seventeen common differential metabolites were identified in A1, A2, and A3 groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the alanine, aspartate and glutamate metabolism, butanoate metabolism, α-linolenic acid metabolism, arginine biosynthesis, and phenylalanine metabolism were significantly correlated with the differential metabolites. The present study elucidates for the first time the changes in non-volatile differential metabolites and their associated metabolic pathways in the novel Chinese low-salt kohlrabi, providing a theoretical basis for improving the industrial fermentation process of this innovative product., 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 Jia, Wang, Chen, Liu, Deng, Ao, Yang, Nie and Zhao.)

Purpose: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy., Materials and Methods: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18 F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected., Results: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin., Conclusions: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18 F-PSMA PET/CT.

The funding details have been incorporated upon author's request in the funding section of this article titled "B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema ," 2024, 27(1), 168-185 [1]. Details of the error and a correction are provided here. Original: This work was supported by grants from the Chongqing Natural Science Gene General Project (No. YWRYPYG). Corrected: This work was supported by General Project of Chongqing Natural Science Foundation cstc2020jcyj-msxmX0227. We regret the error and apologize to the readers. The original article can be found online at www.eurekaselect.com/article/131669., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods., Methods: The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications., Results: Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO., Conclusions: The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy., (© 2024. The Author(s).)

Background: Phospholipid transfer protein (PLTP) transfers surface phospholipids between lipoproteins and as such plays a role in lipoprotein metabolism, but with unclear effects on coronary artery disease (CAD) risk. We aimed to investigate the associations of genetically-influenced PLTP activity with 1-H nuclear magnetic resonance ( 1 H-NMR) metabolomic measures and with CAD. Furthermore, using factorial Mendelian randomization (MR), we examined the potential additional effect of genetically-influenced PLTP activity on CAD risk on top of genetically-influenced low-density lipoprotein-cholesterol (LDL-C) lowering., Methods: Using data from UK Biobank, genetic scores for PLTP activity and LDL-C were calculated and dichotomised based on the median, generating four groups with combinations of high/low PLTP activity and high/low LDL-C levels for the factorial MR. Linear and logistic regressions were performed on 168 metabolomic measures (N = 58,514) and CAD (N = 318,734, N-cases=37,552), respectively, with results expressed as β coefficients (in standard deviation units) or odds ratios (ORs) and 95% confidence interval (CI)., Results: Irrespective of the genetically-influenced LDL-C, genetically-influenced low PLTP activity was associated with a higher high-density lipoprotein (HDL) particle concentration (β [95% CI]: 0.03 [0.01, 0.05]), smaller HDL size (-0.14 [-0.15, -0.12]) and higher triglyceride (TG) concentration (0.04 [0.02, 0.05]), but not with CAD (OR 0.99 [0.97, 1.02]). In factorial MR analyses, genetically-influenced low PLTP activity and genetically-influenced low LDL-C had independent associations with metabolomic measures, and genetically-influenced low PLTP activity did not show an additional effect on CAD risk., Conclusions: Low PLTP activity associates with higher HDL particle concentration, smaller HDL particle size and higher TG concentration, but no association with CAD risk was observed., Competing Interests: Declarations of Competing Interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The purpose of this study was to present the classification of navicular bones and the anatomical basis for the diagnosis and treatment of navicular fractures of the foot., Method: 351 computed tomographic (CT) images of the navicular bone were analyzed and classified. The navicular bone's anatomical morphology was measured by three independent researchers in each type. Analysis and recording of the measurement results followed., Result: Navicular bones were assorted into three types: I shape(37.04%), II shape(54.41%), and III shape(8.55%). The left and right sides did not differ in any appreciable ways, except ab, bc, and ∠abc (P < 0.05); And all data were statistically different between men and women except for ∠abc (p > 0.05)., Conclusion: The classification of the navicular bone in this study may be helpful in making the treatment decision for navicular fracture., Level of Clinical Evidence: 4., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-β-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No reports was provided by None. Nobody reports a relationship with No that includes:. No has patent No pending to No. We have no conflicts of interest to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" of several pro-inflammatory factors to express immunosuppressive molecular profiles, which determines the therapeutic efficacy of MSCs in immune-mediated inflammatory diseases. Of those, interferon-γ (IFN-γ) is a key inducer for the expression of immunosuppressive molecular profiles; however, the mechanism underlying this effect is unknown., Objectives: To elucidate the regulation mechanism and biological functions of N 6 -methyladenosine (m 6 A) modification in the immunosuppressive functions by the IFN-γ-licensing MSCs., Methods: Epitranscriptomic microarray analysis and MeRIP-qPCR assay were performed to identify the regulatory effect of WTAP in the IFN-γ-licensing MSCs. RIP-qPCR, western blot, qRT-PCR and RNA stability assays were used to determine the regulation of WTAP/m 6 A/YTHDF1 signaling axis in the expression of immunosuppressive molecules. Further, functional capacity of T cells was tested using flow cytometry, and both DSS-induced colitis mice and CIA mice were constructed to clarify the effect of WTAP and YTHDF1 in MSC-mediated immunosuppression., Results: We identified that IFN-γ increased the m 6 A methylation levels of immunosuppressive molecules, while WTAP deficiency abolished the IFN-γ-induced promotion of m 6 A modification. IFN-γ activated ERK signaling, which induced WTAP phosphorylation. Additionally, the stabilization of WTAP post-transcriptionally increased the mRNA expression of immunosuppressive molecules (IDO1, PD-L1, ICAM1, and VCAM1) in an m 6 A-YTHDF1-dependent manner; this effect further impacted the immunosuppressive capacity of IFN-γ licensing MSCs on activated T cells. Notably, WTAP/YTHDF1 overexpression enhanced the therapeutic efficacy of IFN-γ licensing MSCs and restructures the ecology of inflammation in both colitis and arthritis models., Conclusion: Our results showed that m 6 A modification of IDO1, PD-L1, ICAM1, and VCAM1 mRNA mediated by WTAP-YTHDF1 is involved in the regulation of IFN-γ licensing MSCs immunosuppressive abilities, and shed a light to enhance the clinical therapeutic potential of IFN-γ-licensing MSCs., 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. Production and hosting by Elsevier B.V.)

The aim of the present study was to explore the effects of dexmedetomidine (DEX) combined with ketorolac on postoperative patient-controlled analgesia (PCA), the balance of Th1/Th2 and the level of vascular endothelial growth factor (VEGF) in patients with cervical cancer following laparoscopic radical surgery. A total of 70 women with cervical cancer undergoing laparoscopic radical hysterectomy were enrolled in the study to randomly receive postoperative dexmedetomidine combined with ketorolac analgesia (DK group) and postoperative sufentanil analgesia (SUF group). The primary outcomes were the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and VEGF, and the IFN-γ/IL-4 ratio 30 min before induction (T 0 ), and 24 and 48 h after surgery. Secondary outcomes included numerical rating scale scores at 0 h (T 0 ), 4 h (T 1 ), 12 h (T 2 ), 24 h (T 3 ) and 48 h (T 4 ) postoperatively, cumulative times of rescue analgesia, as well as the incidence of postoperative side effects within 48 h from surgery. Patients in the DK group reported similar analgesic effects as patients in the SUF group at T 2 , T 3 and T 4 , and the incidence of postoperative nausea and vomiting was significantly lower in the DK group. In the DK group, the serum concentration of IFN-γ and IFN-γ/IL-4 ratio at 24 and 48 h after surgery were higher compared with those in the SUF group. Conversely, the serum concentrations of IL-4 at 24 h after surgery and VEGF at 24 and 48 h after surgery were significantly lower. The results indicated that the combination of DEX and ketorolac for PCA significantly improved postoperative pain and decreased the serum level of VEGF, which are associated with tumor angiogenesis. In addition, it maintained the homeostasis of postoperative immune dysfunction of patients with cervical cancer by shifting the balance between type 1 T helper cells and type 2 T helper cell (Th1/Th2 balance) to Th1 (registration no. ChiCTR1900027979; December 7, 2019)., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Ao et al.)

Chronic kidney disease (CKD) is linked to greater prevalence and rapid progression of calcific aortic valve disease (CAVD) characterized by valvular leaflet fibrosis and calcification. Fibroblast growth factor 23 (FGF23) level is elevated, and anti-aging protein Klotho is reduced in CKD patients. However, the roles of FGF23 and Klotho in the mechanism of aortic valve fibrosis and calcification remain unclear. We hypothesized that FGF23 mediates CKD-induced CAVD by enhancing aortic valve interstitial cell (AVIC) fibrosis and calcification, while soluble Klotho inhibits FGF23 effect. Methods and Results: In an old mouse model of CKD, kidney damages were accompanied by aortic valve thickening and calcification. FGF23 levels in plasma and aortic valve were increased, while Klotho levels were decreased. Recombinant FGF23 elevated the inflammatory, fibrogenic, and osteogenic activities in AVICs. Neutralizing antibody or shRNA targeting FGF23 suppressed the pathobiological activities in AVICs from valves affected by CAVD. FGF23 exerts its effects on AVICs via FGF receptor (FGFR)/Yes-associated protein (YAP) signaling, and inhibition of FGFR/YAP reduced FGF23's potency in AVICs. Recombinant Klotho downregulated the pathobiological activities in AVICs exposed to FGF23. Incubation of FGF23 with Klotho formed complexes and decreased FGF23's potency. Further, treatment of CKD mice with recombinant Klotho attenuated aortic valve lesions. Conclusion: This study demonstrates that CKD induces FGF23 accumulation, Klotho insufficiency and aortic valve lesions in old mice. FGF23 upregulates the inflammatory, fibrogenic and osteogenic activities in AVICs via the FGFR/YAP signaling pathway. Soluble Klotho suppresses FGF23 effect through molecular interaction and is capable of mitigating CKD-induced CAVD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Disturbances in habitual sleep have been associated with multiple age-associated diseases. However, the biological mechanisms underpinning these associations remain largely unclear. We assessed the possible involvement of the circulating immune system by determining the associations between sleep traits and white blood cell counts using multivariable-adjusted linear regression and Mendelian randomization., Methods: Cross-sectional multivariable-adjusted linear regression analyses were done using participants within the normal range of total white blood cell counts (>4.5 × 10 9 and <11.0 × 10 9 /μL) from UK Biobank. For the sleep traits, we examined (short and long) sleep duration, chronotype, insomnia symptoms and daytime dozing. Two-sample Mendelian randomization analyses were done using instruments for sleep traits derived from European-ancestry participants from UK Biobank (over 410,000 participants) and using SNP-outcome data derived from European-ancestry participants from the Blood Cell Consortium (N = 563,946) to which no data from UK Biobank contributed., Results: Using data from 357,656 participants (mean [standard deviation] age: 56.5 [8.1] years, and 44.4% men), we did not find evidence that disturbances in any of the studied sleep traits were associated with differences in blood cell counts (total, lymphocytes, neutrophiles, eosinophiles and basophiles). Also, we did not find associations between disturbances in any of the studied sleep traits and white blood cell counts using Mendelian Randomization., Conclusion: Based on the results from two different methodologies, disturbances in habitual sleep are unlikely to cause changes in blood cell counts and thereby differences in blood cell counts are unlikely to be underlying the observed sleep-disease associations., (© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

The safety performance and structural stiffness of a rim, which is the main load-bearing structure of the loader during operation, influence the overall performance, stability, and braking capabilities of the machine. In the industry, researchers are currently pursuing lightweight and high-strength rims as a primary objective. A low weight not only enhances machinery fuel efficiency but also aligns with societal demands for sustainable development, energy conservation, and emission reduction. In this article, multiobjective optimization analysis on rims composed of three different materials is performed, and the relationships between various optimization parameters and target parameters are established using the results of response surface construction. Multiobjective genetic algorithms are utilized to derive various optimization plans, which are subsequently evaluated through static analysis, fatigue analysis, and weight loss analysis. The final optimization plan is determined based on the calculation results while considering production costs. Field tests are conducted on the optimized rims under various working conditions to verify the test results, evaluate the reliability of the finite element analysis results, and confirm the safety of the optimized rim., (© 2024. The Author(s).)

Objective: This research aimed to elucidate the relationship between testosterone levels and serum soluble klotho (S-klotho) concentrations in females aged 40-79 years using the National Health and Nutrition Examination Survey (NHANES) dataset., Design: Associations between testosterone and S-klotho were assessed through multivariable linear regression methodologies, spanning nonadjusted, minimally adjusted, and fully adjusted models., Settings: The investigation was conducted as a cross-sectional analysis utilizing the NHANES database., Participants: From 20,146 NHANES participants between 2013 and 2016, 2,444 females met the stipulated inclusion and exclusion criteria., Results: Free androgen index (FAI) showcased a negative correlation with S-klotho levels across all regression models (nonadjusted: β -7.08, 95% CI -13.39- -0.76; minimally adjusted: β -9.73, 95% CI -16.6- -2.84; fully adjusted: β -7.63, 95% CI -14.75-0.51). Conversely, total testosterone did not exhibit significant associations with S-klotho across the models. In the nonadjusted model, estradiol was positively associated with S-klotho concentrations (β 0.14, 95% CI 0.05-0.23), but this significance was not retained in subsequent regression models., Conclusion: Findings suggest that in U.S. females aged 40-79 years, FAI negatively correlates with S-klotho concentrations, while there is the lack of significant associations for total testosterone and estradiol., 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 Cao, Zhang, Hao, Du, Ao, Zhu and Huang.)

Transition metal trichalcogenides (TMTCs) offer remarkable opportunities for tuning electronic states through modifications in chemical composition, temperature, and pressure. Despite considerable interest in TMTCs, there remain significant knowledge gaps concerning the evolution of their electronic properties under compression. In this study, we employ experimental and theoretical approaches to comprehensively explore the high-pressure behavior of the electronic properties of TiS 3 , a quasi-one-dimensional (Q1D) semiconductor, across various temperature ranges. Through high-pressure electrical resistance and magnetic measurements at elevated pressures, we uncover a distinctive sequence of phase transitions within TiS 3 , encompassing a transformation from an insulating state at ambient pressure to the emergence of an incipient superconducting state above 70 GPa. Our findings provide compelling evidence that superconductivity at low temperatures of ∼2.9 K is a fundamental characteristic of TiS 3 , shedding new light on the intriguing high-pressure electronic properties of TiS 3 and underscoring the broader implications of our discoveries for TMTCs in general.

Introduction: Thalictrum fargesii is a medicinal plant belonging to the genus Thalictrum of the Ranunculaceae family and has been used in herbal medicine in the Himalayan regions of China and India. This species is taxonomically challenging because of its morphological similarities to other species within the genus. Thus, herbal drugs from this species are frequently adulterated, substituted, or mixed with other species, thereby endangering consumer safety., Methods: The present study aimed to sequence and assemble the entire chloroplast (cp) genome of T. fargesii using the Illumina HiSeq 2500 platform to better understand the genomic architecture, gene composition, and phylogenetic relationships within the Thalictrum., Results and Discussion: The cp genome was 155,929 bp long and contained large single-copy (85,395 bp) and small single-copy (17,576 bp) regions that were segregated by a pair of inverted repeat regions (26,479 bp) to form a quadripartite structure. The cp genome contains 133 genes, including 88 protein-coding genes (PCGs), 37 tRNA genes, and 8 rRNA genes. Additionally, this genome contains 64 codons that encode 20 amino acids, the most preferred of which are alanine and leucine. We identified 68 SSRs, 27 long repeats, and 242 high-confidence C-to-U RNA-editing sites in the cp genome. Moreover, we discovered seven divergent hotspot regions in the cp genome of T. fargesii , among which ndhD-psaC and rpl16-rps3 may be useful for developing molecular markers for identifying ethnodrug species and their contaminants. A comparative study with eight other species in the genus revealed that pafI and rps19 had highly variable sites in the cp genome of T. fargesii . Additionally, two special features, (i) the shortest length of the ycf1 gene at the IRA-SSC boundary and (ii) the distance between the rps19 fragment and trnH at the IRA-LSC junction, distinguish the cp genome of T. fargesii from those of other species within the genus. Furthermore, phylogenetic analysis revealed that T. fargesii was closely related to T. tenue and T. petaloidium ., Conclusion: Considering all these lines of evidence, our findings offer crucial molecular and evolutionary information that could play a significant role in further species identification, evolution, and phylogenetic studies on T. fargesii ., 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 Chen, Safiul Azam, Akter, Ao, Zou and Qian.)

Background and Objective: Robot-assisted radical prostatectomy (RARP) is widely used because of the many advantages of a robotic approach. The da Vinci Si robot is one of the most commonly used surgical robot systems, but it may be associated with higher costs owing to the use of consumable surgical supplies. Our aim was to conduct a preliminary investigation of the capability of the MP1000 system for RARP., Methods: In this prospective, multicentre, single-blinded study, we randomly assigned 42 patients scheduled to undergo RARP between April and September 2021 to a da Vinci Si group (control) or an MP1000 group (intervention). Patients underwent RARP performed using the assigned robotic system and were followed up at 3-mo intervals. The primary outcome was the rate of conversion to open/laparoscopic surgery. Secondary outcomes were installation and operation times, intraoperative blood loss, postoperative surgical margin status, hospital stay, incontinence, complications, safety indicators, and surgeon ergonomics., Key Findings and Limitations: All procedures were successfully completed without conversion to open/laparascopic surgery or major complications. Secondary outcomes, including oncological and ergonomic indicators, did not differ significantly between the groups over the study period. One patient in the control group experienced dysuria (Clavien-Dindo grade 3). No patients had incontinence at 3 mo. A limitation of the study is the small sample size., Conclusions and Clinical Implications: RARP with the MP1000 system is feasible, safe, and effective in the management of localised prostate cancer., Patient Summary: We assessed the effectiveness and safety of the new MP1000 robot system for robot-assisted removal of the prostate in comparison to the da Vinci Si robot. We found no difference in effectiveness or safety among 42 patients with prostate cancer who were assigned randomly to one of the two systems. We conclude that the MP1000 is a suitable robot for this surgery., (© 2024 Published by Elsevier B.V. on behalf of European Association of Urology.)

Exposure to PM 2.5 , a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM 2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM 2.5 can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3'-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM 2.5 exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health., (© 2024. The Author(s).)

Introduction: Serum Klotho (S-Klotho) is a transmembrane protein holds pivotal roles in anti-aging. The Dietary Inflammation Index (DII), a meticulously dietary tool, quantifies the inflammatory potential of an individual's diet. The existing research strongly suggests that a low DII diet plays a significant role in delaying aging and reducing aging-related symptoms in males. Testosterone could potentially act as a mediating intermediary between DII and S-Klotho. However, this aspect remains unexplored. This study aims to investigate the potential causal link of testosterone between DII and S-Klotho in males., Methods: We utilized data from National Health and Nutrition Examination Survey (NHANES) which focused on male participants from 2013-2016. Mediation analyses were used to investigate the effects of testosterone (TT), free testosterone (FT), and free androgen index (FAI) on the DII-S-Klotho relationship, using three modes adjusting for covariates., Results: Mediation analysis unveiled a significant inverse correlation between DII and S-Klotho levels (model 1: c = -14.78, p = 0.046). The interaction between DII and S-Klotho was modulated by TT in model 1 (ab = -1.36; 95% CI: -5.59, -0.55; p = 0.008), but lost significance after adjustments (model 2: ab = -0.39; 95% CI: -4.15, 1.66; p = 0.378; model 3: ab = -0.59; 95% CI: -4.08, 2.15; p = 0.442). For FT, the mediating impact was not statistically significant (model 1: ab = 0.43; 95% CI: -0.51, 5.44; p = 0.188; model 2: ab = 0.72; 95% CI: -0.26, 5.91; p = 0.136; model 3: ab = 0.84; 95% CI: -0.02, 8.06; p = 0.056). Conversely, FAI consistently influenced the DII-S-Klotho relationship (model 1: ab = 2.39; 95% CI: 0.69, 9.42; p = 0.002), maintaining significance after adjustments (model 2: ab = 3.2; 95% CI: 0.98, 11.72; p = 0.004; model 3: ab = 3.15; 95% CI: 0.89, 14.51; p = 0.026)., Discussion: This study observed no mediating influence of TT or FT on the correlation between DII and S-Klotho after covariate control. Remarkably, FAI continued to significantly mediate the DII-S-Klotho connection even following covariate adjustment, although its significance in males warrants careful consideration., 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 Du, Zhao, Chou, Peng, Cao, Zeng, Ao and Wang.)

Background & Aims: Accumulating evidences suggest tumour microenvironment (TME) profoundly influence clinical outcome in hepatocellular carcinoma (HCC). Existing immune subtypes are susceptible to batch effects, and integrative analysis of bulk and single-cell transcriptome is helpful to recognize immune subtypes and TME in HCC., Methods: Based on the relative expression ordering (REO) of 1259 immune-related genes, an immuno-prognostic signature was developed and validated in 907 HCC samples from five bulk transcriptomic cohorts, including 72 in-house samples. The machine learning models based on subtype-specific gene pairs with stable REOs were constructed to jointly predict immuno-prognostic subtypes in single-cell RNA-seq data and validated in another single-cell data. Then, cancer characteristics, immune landscape, underlying mechanism and therapeutic benefits between subtypes were analysed., Results: An immune-related signature with 29 gene pairs stratified HCC samples individually into two risk subgroups (C1 and C2), which was an independent prognostic factor for overall survival. The machine learning models verified the immune subtypes from five bulk cohorts to two single-cell transcriptomic data. Integrative analysis revealed that C1 had poorer outcomes, higher CNV burden and malignant scores, higher sensitivity to sorafenib, and exhibited an immunosuppressive phenotype with more regulators, e.g., myeloid-derived suppressor cells (MDSCs), Mø&#95;SPP1, while C2 was characterized with better outcomes, higher metabolism, more benefit from immunotherapy, and displayed active immune with more effectors, e.g., tumour infiltrating lymphocyte and dendritic cell. Moreover, both two single-cell data revealed the crosstalk of SPP1-related L-R pairs between cancer and immune cells, especially SPP1-CD44, might lead to immunosuppression in C1., Conclusions: The REO-based immuno-prognostic subtypes were conducive to individualized prognosis prediction and treatment options for HCC. This study paved the way for understanding TME heterogeneity between immuno-prognostic subtypes of HCC., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The job performance of clinicians is a clear indicator of both hospital capacity and the level of hospital service. It plays a crucial role in maintaining the effectiveness and quality of medical care. Clinical pathways are a systematic method of quality improvement successfully recommended by broader healthcare systems. Since clinicians play a key role in implementing clinical pathways in public hospitals, this study aims to investigate the effect of the satisfaction of clinicians in public hospitals with clinical pathway implementation on their job performance., Methods: A cross-sectional study design was used. Questionnaires were administered online. A total of 794 clinicians completed the questionnaires in seven tertiary public hospitals in Sichuan Province, China, of which 723 were valid for analysis. Questionnaires contained questions on social demographic characteristics, satisfaction with clinical pathway implementation, work engagement, and job performance. Structural Equation Model (SEM) was used to test the hypotheses., Results: The satisfaction of clinicians in public hospitals with clinical pathway implementation was significantly positively correlated with work engagement (r = 0.570, P < 0.01) and job performance (r = 0.522, P < 0.01). A strong indirect effect of clinicians' satisfaction with clinical pathway implementation on job performance mediated by work engagement was observed, and the value of this effect was 0.383 (boot 95%CI [0.323, 0.448])., Conclusion: The satisfaction of clinicians in public hospitals with clinical pathway implementation not only directly influences their job performance, but also indirectly affects it through the mediating variable of work engagement. Therefore, managers of public hospitals need to pay close attention to clinicians' evaluation and perception of the clinical pathway implementation. This entails taking adequate measures, such as providing strong organizational support and creating a favorable environment for the clinical pathway implementation. Additionally, focusing on teamwork to increase clinicians' satisfaction can further enhance job performance. Furthermore, managers should give higher priority to increasing employees' work engagement to improve clinicians' job performance., (© 2024. The Author(s).)

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions., (© 2024. The Author(s).)

Background and Aims: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown., Methods: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated., Results: The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination., Conclusions: The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants., Competing Interests: HR has been an editor-in-chief of Journal of Clinical and Translational Hepatology since 2013, PH and DZ have been associate editors of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly worldwide. The exact etiology of AD, particularly its genetic mechanisms, remains incompletely understood. Traditional genome-wide association studies (GWAS), which primarily focus on single-nucleotide polymorphisms (SNPs) with main effects, provide limited explanations for the "missing heritability" of AD, while there is growing evidence supporting the important role of epistasis. In this study, we performed a genome-wide SNP-SNP interaction detection using a linear regression model and employed multiple GPUs for parallel computing, significantly enhancing the speed of whole-genome analysis. The cerebrospinal fluid (CSF) phosphorylated tau (P-tau)/amyloid-[Formula: see text] (A[Formula: see text]) ratio was used as a quantitative trait (QT) to enhance statistical power. Age, gender, and clinical diagnosis were included as covariates to control for potential non-genetic factors influencing AD. We identified 961 pairs of statistically significant SNP-SNP interactions, explaining a high-level variance of P-tau/A[Formula: see text] level, all of which exhibited marginal main effects. Additionally, we replicated 432 previously reported AD-related genes and found 11 gene-gene interaction pairs overlapping with the protein-protein interaction (PPI) network. Our findings may contribute to partially explain the "missing heritability" of AD. The identified subnetwork may be associated with synaptic dysfunction, Wnt signaling pathway, oligodendrocytes, inflammation, hippocampus, and neuronal cells., (© 2024. The Author(s).)

Perfluorooctane sulfonic acid (PFOS) as an archetypal representative of per- and polyfluoroalkyl substances (PFAS) is ubiquitously distributed in the environment and extensively detected in human bodies. Although accumulating evidence is suggestive of the deleterious effects of PFOS on male reproduction, the direct toxicity of PFOS towards spermatogenic cells and the relevant mechanisms remain poorly understood. The aims of the present study were to explore the direct effects and underlying molecular mechanisms of PFOS on spermatogenesis. Through integrating animal study, transcriptome profiling, in silico toxicological approaches, and in vitro validation study, we identified the molecular initiating event and key events contributing to PFOS-induced spermatogenic impairments. The mouse experiments revealed that spermatocytes were involved in PFOS-induced spermatogenic disorders and the activation of peroxisome proliferator-activated receptor delta (PPARδ) was linked to spermatocyte loss in PFOS-administrated mice. GC-2spd(ts) cells were treated with an increased gradient of PFOS, which was relevant to environmental and occupational exposure levels of PFOS in populations. Following 72-h treatment, cells was harvested for RNA sequencing. The transcriptome profiling and benchmark dose (BMD) modeling identified endoplasmic reticulum (ER) stress as the key event for PFOS-mediated spermatocyte apoptosis and determined the point-of-departure (PoD) for perturbations of ER stress signaling. Based on the calculated PoD value, further bioinformatics analyses combined with in vitro and in vivo validations showed that PFOS caused metabolic stress by activating PPARδ in mouse spermatocytes, which was responsible for Beclin 1-involved inositol 1,4,5-trisphosphate receptor (IP3R) sensitization. The disruption of IP3R-mediated ER calcium homeostasis triggered ER calcium depletion, leading to ER stress and apoptosis in mouse spermatocytes exposed to PFOS. This study systematically investigated the direct impacts of PFOS on spermatogenesis and unveiled the relevant molecular mechanism of PFOS-induced spermatogenic disorders, providing novel insights and potential preventive/therapeutic targets for PFAS-associated male reproductive toxicity., 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 © 2023 Elsevier Ltd. All rights reserved.)

A low-cost and simple boron-dipyrromethene (BODIPY)-labeled aptasensor (B-aptamer) was designed for rapid, sensitive and turn-on catechin detection. B-aptamer as signal indicator and recognition element initially stacked on the surface of multi-walled carbon nanotubes (MWCNTs) via π-π conjugation, resulting in efficient quenching of the fluorescence of the aptasensor. Upon addition of catechin, catechin was adsorbed to B-aptamer, thereby undergoing a conformational change to form B-aptamer/catechin complex, which prompted the release of the signaling probe from the surface of MWCNTs. Hence, the fluorescence intensity (FL) of the B-aptamer was increasing with the increase of catechin concentrations with the limit of detection (LOD) of 5 ng/mL. Furthermore, the method was used to analyze catechin in food samples with the recovery rate of 92.7-107.1 %. This method provided a proper analysis method for clinical analysis and pharmaceutical quality control., 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 © 2023. Published by Elsevier B.V.)

Competition is an essential component of social interaction and is influenced by interpersonal relationships. This study is based on social exchange theory and explores the relationship between brain synchronization and competition in the binary system of romantic relationships through electroencephalogram hyperscanning technology. The results found that females had a greater win rate in the romantic and friend groups. During the early stage (0-200 ms), when the competitive target appeared, the stranger group exhibited greater interbrain synchronicity in the Alpha frequency band. However, during the later stage (600-800 ms), the romantic group showed higher Alpha band interbrain synchrony when the competitive target appeared. Significant interbrain synchronizations were observed in the Theta frequency band of the stranger and friend groups at 400-600 ms and 800-1000 ms. Moreover, these interbrain synchronizations were significantly positively correlated with the winning rates of females in the competition. These findings suggest a close relationship between interpersonal coordination and interbrain synchronization. Furthermore, romantic relationships reduce participants' willingness to compete, affecting their attention regulation, emotional processing, and goal orientation, thus influencing competition. This study investigated the impact of romantic relationships on competition, providing a theoretical foundation for promoting the positive and healthy development of romantic relationships., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)