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Dan-Dan Li,1,&ast; Xue Yang,1,&ast; Yang Yang,2,&ast; Li-Hua Zhao,1 Tian-Tian Zhang,3 Yi-Nan Wang,1 Jian-Bin Su,1 Li-Hua Wang,4 Hai-Yan Shi3 1Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 2Department of General Practice, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 4Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Hua Wang, Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email wlh512512@163.com Hai-Yan Shi, Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email 1198827119@qq.comBackground: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied.Methods: A total of 615 patients with T2D were selected by convenient sampling. The patients were investigated with the International Physical Activity Questionnaire (IPAQ-S). Moreover, biochemical indices were collected, and the progression of the body composition of the subjects was determined via dual-energy X-ray absorptiometry (DXA). The variables included lumbar bone mineral density (LSBMD), femoral neck bone mineral density (FNBMD), hip bone mineral density (HBMD), whole-body bone mineral density (TBMD), limb skeletal muscle mass index (ASMI), whole-body fat percentage (B-FAT) and trunk fat percentage (T-FAT). Moreover, the levels of physical activity (high level of physical activity [H-PA], medium level of physical activity [M-PA] and low level of physical activity [L-PA]) were divided into three groups to analyze the changes in patient body composition with changes in physical activity level.Results: One-way analysis of variance showed that β-CTX, TP1NP, HbA1c, B-FAT and T-FAT increased significantly (p< 0.05), while 25(OH)D, LSBMD, FNBMD, HBMD, TBMD and ASMI decreased significantly (p< 0.001) with the decrease of physical activity. However, there was no significant difference in serum lipids between lnHOMA-ir and lnHOMA-β (p> 0.05). Multiple linear regression model was established to gradually adjust for clinical confounding factors. It was found that physical activity level was independently positively correlated with LSBMD, FNBMD, HBMD, TBMD, and ASMI, and was independently negatively correlated with B-FAT and T-FAT in patients with type 2 diabetes.Conclusion: A lack of physical activity is an independent risk factor for decreased bone mineral density, decreased skeletal muscle content and increased fat content in patients with T2D.Keywords: type 2 diabetes, physical activity, body composition, correlation

Qing-Bing Zhou,1 Yao Chen,1 Yan Zhang,1 Dan-Dan Li,1 Hong-Qin Wang,1 Zi-Jun Jia,1 Yu Jin,2 Feng-Qin Xu,1 Ying Zhang1 1Institute of Geriatric Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 2The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, People’s Republic of ChinaCorrespondence: Feng-Qin Xu; Ying ZhangInstitute of Geriatric Medicine, Xiyuan Hospital, Xiyuan Playground No. 1, Haidian District, Beijing, 100091, People’s Republic of ChinaTel/Fax +86 10-62835003Email dr.xufengqin@outlook.comYing Zhang Email doctoronline@126.comPurpose: To investigate if a traditional Chinese medicine formulation, called “Yiqihuoxue” (YQHX), could improve diabetic atherosclerosis (DA) and explore potential mechanisms based on DNA methylation.Methods: Apolipoprotein E-knockout mice were administered streptozotocin (50 mg/d, i.p.) for 5 days and fed a high-fat diet for 16 weeks. Mice were divided randomly into DA model, rosiglitazone, as well as low-, medium-, and high-dose YQHX groups. Ten healthy C57BL/6J mice were the control group. Serum levels of fasting insulin, blood glucose, homeostasis model-insulin resistance index (HOMA-IR), serum lipids, and inflammatory factors were analyzed after the final treatment. Aorta tissues were collected for staining (hematoxylin and eosin, and Oil red O). Genomic DNA was extracted for methyl-capture sequencing (MC-seq). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze differentially methylated genes. Pyrosequencing was used to verify MC-seq data.Results: Low-dose and high-dose YQHX could reduce the HOMA-IR (P < 0.05). Low-dose YQHX reduced expression of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), TNF-α, andI L-6 in serum compared with that in the model group (P < 0.05). Medium-dose YQHX decoction inhibited the expression level of TNF-α (P < 0.05). High-dose YQHX decreased the expression level of IL-6 (P < 0.05). Staining also showed the anti-atherosclerosis effects of YQHX (P < 0.05). MC-seq revealed many abnormally hypermethylated and hypomethylated genes in DA mice compared with those in the control group. KEGG database analysis showed that the hypermethylated genes induced by YQHX treatment were related to pathways in cancer, Hippo signaling, and mitogen activated protein kinase. The network analysis suggested that the hypermethylated genes epidermal growth factor receptor(Egfr) and phosphoinositide-3-kinase regulatory subunit 1(Pik3r1) induced by YQHX treatment had important roles in DA. Pyrosequencing revealed that YQHX treatment increased methylation of AKT1, Nr1h3 and Fabp4 significantly (P < 0.05).Conclusion: YQHX decoction had positive treatment effects against DA, because it could regulate aberrant hypomethylation of DNA.Keywords: diabetic atherosclerosis, YQHX decoction, DNA methylation, hypermethylation

Bo Yin,*,1 Dan-Dong Li,*,2,3 Shang-Yu Xu,3 Huan Huang,4 Jian Lin,3 Han-Song Sheng,3 Jun-Hao Fang,3 Jin-Ning Song,2 Ming Zhang11Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workBackground: The use of thrombolysis with tissue-plasminogen activator (t-PA) in patients with acute ischemic stroke (AIS) is limited by increased levels of matrix metalloproteinase-9 (MMP-9) and by the increased risk of hemorrhagic transformation (HT). In this study, we investigated the effects of simvastatin pretreatment on t-PA-induced MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and HT aggravation in a rat AIS model.Methods: The rat AIS model was established by autologous blood emboli. Two weeks before surgery, rats were pretreated with simvastatin (60 mg/kg/d), and three hours after surgery, t-PA (10 mg/kg) was administered. MMP-9 and TIMP-1 levels in the infarcted zone and plasma were evaluated by Western blot analysis and ELISA; the level of HT was quantified by determining the hemoglobin content. RhoA activation was determined to clarify the potential effect.Results: The results suggested that pretreatment with simvastatin suppressed the increase in t-PA-induced MMP-9 levels and neutralized the elevated MMP-9/TIMP-1 ratio, but had no effect on TIMP-1 levels. Thrombolysis with t-PA after ischemia improved neurological outcome, but increased intracranial hemorrhage. Moreover, t-PA-induced HT aggravation was reduced by simvastatin pretreatment. In addition, we showed that t-PA-induced activation of RhoA was suppressed by simvastatin, and that t-PA-induced MMP-9/TIMP-1 imbalance and hemorrhage was reduced by Rho kinases (ROCK) inhibitor Y-27632.Conclusion: In this study, we showed that simvastatin pretreatment ameliorated t-PA-induced HT and MMP-9/TIMP-1 imbalance, and demonstrated that the RhoA/ROCK pathway was implicated.Keywords: simvastatin, acute ischemic stroke, t-PA, MMP-9/TIMP-1, RhoA/ROCK pathway, hemorrhagic transformation

Xiao-Ming Hou,1,2 Zulqarnain Baloch,3,4 Zhan-Hong Zheng,3,4 Wen-Hui Zhang,1,2 Ying Feng,5 Duan-Duan Li,3,4 Xin-An Wu,2,6 Shi-Hua Yang3,41Department of Oncology, The First Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China; 2Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China; 3College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 4Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 5Department of Pathology, The First Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China; 6Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of ChinaPurpose: The aim of the present study was to explore the role of CHPF in non-small-cell lung cancer (NSCLC) and to develop an shRNA vector-based therapy to repress the expression of CHPF gene in NSCLC cell lines.Methods: In this study, we used immunohistochemical staining to verify the expression of CHPF in NSCLC tissue. Then, we determined the expression of CHPF gene in different NSCLC cell lines with RT-PCR and Western blotting. Specific CHPF shRNA was used to knockdown the expression of CHPF. Celigo image cytometry, cell cycle analysis, and flow cytometry assay were performed.Results: The results showed that expression level of CHPF was higher in NSCLC tissues than normal lung tissues. Further, we established that CHPF expression knockdown in NSCLC cells could substantially restrain the cell proliferation, apoptosis, and cell cycle in vitro.Conclusion: On the basis of these results, we concluded that CHPF expression has an important role in the progression of human NSCLC cells. Therefore, its interference could possibly be used as a potential therapeutic target against NSCLC.Keywords: NSCLC, CHPF, progression, knockdown

Xiangyang Deng,1 Dongdong Lin,1 Lisheng Yu,1 Xingxing Xu,2 Nu Zhang,1 Hui Zhou,1 Hansong Sheng,1 Bo Yin,1 Fengchun Lin,1 Shangyu Xu,1 Dandong Li,1 Junhao Fang,1 Xiangqi Lu,1 Jian Lin1 1Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China; 2Department of Physiology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China Purpose: The main objectives of this study were to clarify the efficacy of postoperative radiotherapy (PORT) for pediatric intracranial grade II ependymomas (EPNs) and to explore whether various characteristics are associated with different outcomes in patients with and without PORT.Patients and methods: Data from patients younger than 18 years diagnosed with grade II intracranial EPNs and treated by surgery, with or without PORT, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2013 data set). Propensity score-matched analysis was conducted to balance clinical variables. Patient characteristics were stratified and analyzed.Results: In total, data from 632 patients with grade II EPNs treated by cancer-directed surgery with or without PORT were obtained from the SEER database. Multivariable Cox analysis in the matched cohort suggested that undergoing PORT (overall survival [OS], P=0.020; cancer-specific survival [CSS], P=0.031), undergoing gross total resection (GTR; subtotal resection [STR] vs GTR; OS, P

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1β, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke., Competing Interests: Declarations. Ethics Approval and Consent to Participate: The project “PRDX1 peptide attenuates ischemic brain injury through inhibition of TLR4/NF-κB signaling pathway” was examined and verified by the Laboratory Animal Ethics Committee of Xuzhou Medical University in accordance with the Guide to Laboratory Animal Ethics Examination of Xuzhou Medical University (202211S030). The related animal experiments were permitted. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Capsular contracture (CC) is one of the most common complications of breast implant usage in breast augmentation or reconstruction. The CC approach can cause breast hardening, pain, and varying degrees of deformity, affecting the quality of life of patients. Considerably, it has become one of the most common reasons for frequent surgeries. Nonetheless, the etiology and pathogenesis of CC remain unclear. Moreover, there exist still a lot of uncertainties regarding prevention and treatment measures. In this article, we present discussions on the research status of the etiology, pathogenesis, prevention, and treatment measures of CC. In summary, this study provides a reference for further research on CC and clinical use.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable., (© 2024. The Author(s).)

Objective: Investigating the changes of phenotype and moleculars associated with aging with the increase of passage times of human dental pulp stem cells (hDPSC), to explore the role of WW-containing transcriptional regulator 1 (WWTR1) in the aging mechanism. Methods: hDPSCs were cultured by tissue block method, and were divided into 4 groups according to the age, algebra, cell knockdown and overexpression of WWTR1 in hDPSCs. Group I: hDPSCs from human teeth were further divided into youth group (15-25 years old) and group middle-aged group (40-50 years old)] according to different ages. Group Ⅱ: according to different passage, hDPSCs were divided into young cells group (hDPSCs were transmitted to P3 generation), and old cells group (hDPSCs were transmitted to P10 generation). Group Ⅲ: hDPSCs were knocked down of WWTR1, which were further divided into knockdown group (sh-WWTR1) and knockdown carrier group (sh-NC). Group Ⅳ: hDPSCs were overexpressed of WWTR1, which were further divided into overexpression group (OE-WWTR1) and overexpression carrier group (OE-NC). Real-time quantitative fluorescent PCR (RT-qPCR) was used to detect the changes of WWTR1 expression in groups Ⅰ and Ⅱ, and cell counting kit-8 (CCK-8) was used for groups Ⅱ, Ⅲ, and Ⅳ. Cell proliferation capacity was detected by CCK-8 assay. The ability of osteogenic differentiation was detected by alizarin red staining. Cell senescence positive rate was detected by age-related β-galactosidase staining. The expression levels of age-related genes p53 and p21 were detected by RT-qPCR. Results: The proportion of senescent cells increased gradually with continuous culture. The proliferation and osteogenic differentiation of hDPSCs in the old group were significantly lower than those in the young group ( P <0.001). The expression levels of senescence related genes p53 (2.09±0.24) and p21 (4.91±0.54) in old cell group were higher than those in young cell group respectively [p53: (1.08±0.09) and p21: (1.09±0.08)] ( P <0.01, P <0.001). The WWTR1 expression levels of hDPSCs in middle-aged group and old cells group were both decreased compared with those in young group and young cells group ( P <0.01). The proportion of senescent cells in knockdown group (44.50±2.42) was higher than that in knockdown carrier group (22.27±0.56) ( P <0.001). After knocking down WWTR1 in hDPSCs, the expression levels of age-related genes p53 and p21 were up-regulated ( P <0.001), and the abilities of proliferation and osteogenic differentiation in the knockdown group were lower than those in the knockdown carrier group ( P <0.001). The proportion of senescent cells in overexpression empty carrier group (20.4±0.79) was higher than that in overexpression group (10.07±0.61) ( P <0.001). After WWTR1 overexpression ins hDPSCs, the expression levels of age-related genes p53 and p21 were down-regulated, and the proliferation and osteogenic differentiation ability in overexpression group were higher than those in OE-NC group ( P <0.001). Conclusions: WWTR1 can inhibit the expression levels of age-related genes p53 and p21, thus delaying the aging process as well as promoting the proliferation and osteogenic differentiation of hDPSCs.

Objectives: To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics., Methods: A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital, Capital Medical University, from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition., Results: A total of 118 children with CD were included, among whom there were 68 boys (57.6%) and 50 girls (42.4%), with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7%, 87/118), diarrhea (37.3%, 44/118), and hematochezia (32.2%, 38/118), and 63.6% (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6% (75/118), and the children with moderate or severe malnutrition accounted for 67% (50/75). There were 50 children (42.4%) with emaciation, 8 (6.8%) with growth retardation, and 9 (7.6%) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3%), anemia in 74 children (62.7%), and a reduction in 25 hydroxyvitamin D in 15 children (60%, 15/25). The children with malnutrition had significantly higher disease activity, proportion of children with intestinal stenosis, and erythrocyte sedimentation rate and a significant reduction in serum albumin ( P <0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD ( OR =4.416, P <0.05)., Conclusions: There is a high incidence rate of malnutrition in children with CD at diagnosis, which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

4-Alkylation of pyridines has been achieved by a photocatalyzed three-component reaction of an olefin, an aryloxyacetic acid, and cyanopyridine using Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 as a photocatalyst. In this way, a new type of 4-alkylpyridines bearing aryl and aryloxy substituents on the phenyl was accessed with potential pharmaceutical value. In addition to mild reaction conditions, the method has several other advantages, including a multicomponent one-pot protocol, good functional group tolerance, and easy amplification of the reaction scale. The reaction mechanism has been clarified by control experiments and computation of the reaction energy profile.

Background: Recurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL., Methods: Immune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored., Results: In the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-γ were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-L-tryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis., Conclusion: The study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL., 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 Ye, Ma, Guo, Guo, Li, Zhou, Hu, Hong, Xie and Wang.)

Objective: This study sought to investigate the cellular and molecular alterations during the injury and recovery periods of ALI and develop effective treatments for ALI., Methods: Pulmonary histology at 1, 3, 6, and 9 days after lipopolysaccharide administration mice were assessed. An unbiased single-cell RNA sequencing was performed in alveoli tissues from injury (day 3) and recovery (day 6) mice after lipopolysaccharide administration. The roles of Fpr2 and Dpp4 in ALI were assessed., Results: The most severe lung injury occurred on day 3, followed by recovery entirely on day 9 after lipopolysaccharide administration. The numbers of Il1a + neutrophils, monocytes/macrophages, and Cd4 + and Cd8 + T cells significantly increased at day 3 after LPS administration; subsequently, the number of Il1a + neutrophils greatly decreased, the numbers of monocytes/macrophages and Cd4 + and Cd8 + T cells continuously increased, and the number of resident alveolar macrophages significantly increased at day 6. The interactions between monocytes/macrophages and pneumocytes during the injury period were enhanced by the Cxcl10/Dpp4 pair, and inhibiting Dpp4 improved ALI significantly, while inhibiting Fpr2 did not., Conclusions: Our results offer valuable insights into the cellular and molecular mechanisms underlying its progression and identify Dpp4 as an effective therapeutic target for ALI., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Recurrent spontaneous abortion (RSA) is a multifactorial disease, the exact causes of which are still unknown. Environmental, maternal, and genetic factors have been shown to contribute to this condition. The aim of this study was to investigate the presence of mutations in the ANXA4 gene in patients with RSA., Methods: Genomic DNA was extracted from 325 patients with RSA and 941 control women with a normal reproductive history for whole-exome sequencing (WES). The detected variants were annotated and filtered, and the pathogenicity of the variants was predicted through the SIFT online tool, functional enrichment analyses, Sanger sequencing validation, prediction of changes in protein structure, and evolutionary conservation analysis. Furthermore, plasmid construction, Western blotting, RT-qPCR, and cell migration, invasion and adhesion assays were used to detect the effects of ANXA4 mutations on protein function., Results: An ANXA4 mutation (p.G8D) in 1 of the 325 samples from patients with RSA (RSA-219) was identified through WES. This mutation was not detected in 941 controls or included in public databases. Evolutionary conservation analysis revealed that the amino acid residue affected by the mutation (p.G8D) was highly conserved among 13 vertebrate species, and the SIFT program and structural modeling analysis predicted that this mutation was harmful. Furthermore, functional assays revealed that this mutation could inhibit cell migration, invasion and adhesion., Conclusion: Our study suggests that an unreported novel ANXA4 mutation (p.G8D) plays an important role in the pathogenesis of RSA and may contribute to the genetic diagnosis of RSA., 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 Ye, Liu, Xia, Chen, Zou, Wu, Li, Xia, Huang, Cui and Zou.)

Background: A direct aspiration first pass technique (ADAPT) has emerged as a fast, safe, and efficacious method for treating acute large vessel occlusion. However, successful clot aspiration is not guaranteed in every ADAPT procedure. We have observed that when the catheter effectively ingested the clot, the catheter tip displayed a distinct fluttering motion, referred to herein as tip flutter. Thus this study aimed to assess whether this catheter tip flutter can be used as a sign of successful clot aspiration., Methods: This retrospective study included 231 consecutive patients admitted to our institution due to acute ischemic stroke and treated with ADAPT between October 2018 and November 2023. We obtained baseline and procedural data from all patients. Additionally, we assessed the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the tip flutter in predicting clot aspiration., Results: The incidence of embolus translocation was significantly higher in the tip flutter positive group than in the tip flutter negative group (P < 0.001). Also, hyperdense artery presentation was more prevalent in the positive group (P<0.001), whereas the clot burden score was higher in the negative group (P=0.002). Clot aspiration in the first pass occurred in 83 (96.5%) and 37 (25.5%) patients in the positive and negative groups, respectively (P<0.001). Multivariable logistic regression analysis showed the tip flutter sign (OR 1.09, 95% CI 0.16 to 1.29; P<0.001) was an independent predictor of successful clot aspiration. Sensitivity, specificity, PPV, NPV, and accuracy of the tip flutter for predicting clot aspiration were 69.2%, 97.3%, 96.5 %, 74.5%, and 82.7%, respectively., Conclusions: In this study, we found that tip flutter was a reliable indicator of successful clot aspiration during ADAPT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms., Methods and Results: Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies., Conclusions: Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes., (© 2024. The Author(s).)

This study presents a framework for classifying a wooden mannequin's poses using a single-photon avalanche diode (SPAD) array in dynamic and heterogeneous fog conditions. The target and fog generator are situated within an enclosed fog chamber. Training datasets are continuously collected by configuring the temporal and spatial resolutions on the sensor's firmware, utilizing a low-cost SPAD array sensor priced below $ 5, consisting of an embedded SPAD array and diffused VCSEL laser. An extreme learning machine (ELM) is trained for rapid pose classification, as a benchmark against CNN. We quantitatively justify the selection of nodes in the hidden layer to balance the computing speed and accuracy. Results demonstrate that ELM can accurately classify mannequin poses when obscured by dynamic heavy fog to 35 cm away from the sensor, enabling real-time applications in consumer electronics. The proposed ELM achieves 90.65% and 89.58% accuracy in training and testing, respectively. Additionally, we demonstrate the robustness of both ELM and CNN as the fog density increases. Our study also discusses the sensor's current optical limitations and lays the groundwork for future advancements in sensor technology.

Autoantibody-mediated glomerulonephritis (AGN) arises from dysregulated renal inflammation, with urgent need for improved treatments. IL-17 is implicated in AGN and drives pathology in a kidney-intrinsic manner via renal tubular epithelial cells (RTECs). Nonetheless, downstream signaling mechanisms provoking kidney pathology are poorly understood. A noncanonical RNA binding protein (RBP), Arid5a, was upregulated in human and mouse AGN. Arid5a-/- mice were refractory to AGN, with attenuated myeloid infiltration and impaired expression of IL-17-dependent cytokines and transcription factors (C/EBPβ, C/EBPδ). Transcriptome-wide RIP-Seq revealed that Arid5a inducibly interacts with conventional IL-17 target mRNAs, including CEBPB and CEBPD. Unexpectedly, many Arid5a RNA targets corresponded to translational regulation and RNA processing pathways, including rRNAs. Indeed, global protein synthesis was repressed in Arid5a-deficient cells, and C/EBPs were controlled at the level of protein rather than RNA accumulation. IL-17 prompted Arid5a nuclear export and association with 18S rRNA, a 40S ribosome constituent. Accordingly, IL-17-dependent renal autoimmunity is driven by Arid5a at the level of ribosome interactions and translation., (© 2024 Li et al.)

Diffuse correlation spectroscopy (DCS) is a powerful tool for assessing microvascular hemodynamic in deep tissues. Recent advances in sensors, lasers, and deep learning have further boosted the development of new DCS methods. However, newcomers might feel overwhelmed, not only by the already-complex DCS theoretical framework but also by the broad range of component options and system architectures. To facilitate new entry to this exciting field, we present a comprehensive review of DCS hardware architectures (continuous-wave, frequency-domain, and time-domain) and summarize corresponding theoretical models. Further, we discuss new applications of highly integrated silicon single-photon avalanche diode (SPAD) sensors in DCS, compare SPADs with existing sensors, and review other components (lasers, sensors, and correlators), as well as data analysis tools, including deep learning. Potential applications in medical diagnosis are discussed and an outlook for the future directions is provided, to offer effective guidance to embark on DCS research., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The impact of climate warming on soil microbes has been well documented, with studies revealing its effects on diversity, community structure and network dynamics. However, the consistency of soil microbial community assembly, particularly in response to diverse plant root exudates under varying temperature conditions, remains an unresolved issue. To address this issue, we employed a growth chamber to integrate temperature and root exudates in a controlled experiment to examine the response of soil bacteria, fungi, and protists. Our findings revealed that temperature independently regulated microbial diversity, with distinct patterns observed among bacteria, fungi, and protists. Both root exudates and temperature significantly influenced microbial community composition, yet interpretations of these factors varied among prokaryotes and eukaryotes. In addition to phototrophic bacteria and protists, as well as protistan consumers, root exudates determined to varying degrees the enrichment of other microbial functional guilds at specific temperatures. The effects of temperature and root exudates on microbial co-occurrence patterns were interdependent; root exudates primarily simplified the network at low and high temperatures, while responses to temperature varied between single and mixed exudate treatments. Moreover, temperature altered the composition of keystone species within the microbial network, while root exudates led to a decrease in their number. These results emphasize the substantial impact of plant root exudates on soil microbial community responses to temperature, underscoring the necessity for future climate change research to incorporate additional environmental variables., 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 GmbH. All rights reserved.)

Printed porous titanium metaphyseal cones have become a mainstay for managing bone loss in revision total knee arthroplasty (rTKA). A short or long stem is routinely used when implanting a cone to augment fixation and offload stresses. This retrospective analysis compared the short-term survivorships and functional outcomes for use of a short or long stem with a metaphyseal cone.A total of 179 cases using metaphyseal cones and stems with median follow-up of 1.95 years (interquartile range, 1.00-2.14) were compared based on stem type. There were 55 cases with long stem(s) and 124 cases with short stem(s). Cases with both long and short stems were excluded. Demographics, Kaplan-Meier survivorships, and preoperative and 1-year postoperative patient-reported outcome measures (PROMs; 2011 Knee Society Score [KSS] objective knee score, function, and satisfaction scores; EuroQol five-dimension scale; and Short Form Survey Physical Component Summary and Mental Component Summary scores) were compared using t -tests with a significance level of α = 0.05. There were no significant differences in body mass index (mean ± standard deviation) or sex (men [%]) between the short and long stem cohorts (32.3 ± 5.3, 36.3% and 31.5 ± 5.5, 38.2%, respectively; p  > 0.05). Patients who had short stems were younger (65.9 ± 8.8 vs. 69.0 ± 9.4, p  = 0.0323).Revision-free survivorship for the femoral or tibial component was 100% for long stems and 98.2% for short stems at 1 and 2 years, respectively (log-rank p  = 0.6330). The two revisions in the short group were for infection, thus the survivorship for aseptic loosening was 100% at 2 years for both cohorts. There were no significant differences in preoperative or postoperative PROMs.This study demonstrated that highly porous printed metaphyseal cones provided rTKA with excellent early survivorship and similar PROMs whether a short or long stem was used. Additional studies will be needed to discern longer term differences., Competing Interests: None declared., (Thieme. All rights reserved.)

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Background: Resting energy expenditure (REE) refers to the energy consumption of the body in a resting state without skeletal muscle activity. This study aimed to examine the REE among children hospitalized with varying nutritional status., Methods: This was a retrospective study. We enrolled 109 pediatric cases that underwent indirect calorimetry (IC) and divided into four groups: mild malnutrition group (15 cases), moderate malnutrition group (30 cases), severe malnutrition group (32 cases), and obesity group (32 cases). We compared and analyzed the measured REE (mREE) using IC with the predicted REE (pREE) using five energy equations. The paired t-test was used to compare the results of two samples. Pearson analysis was used to assess the correlation between two values. The agreement analysis was performed using the Bland-Altman method., Results: There was no significant difference in mREE between the mild, moderate, and severe malnutrition groups, but each differed significantly from the obesity group. All populations exhibited significant correlation between the mREEs and all five energy equations, and the equation with the highest predictive accuracy was the Schofield equation, which achieved an accuracy of 47.7%. In subgroup analysis, there was no significant difference between mREE and pREE for each of the five equations in the mild, moderate malnutrition groups. Only the prediction result of the Liu equation was not significantly different from the mREE in the severe malnutrition group. The prediction accuracy of the Liu equation was relatively the highest (34.4%). However, in the obese group, there were significant differences in pREE and mREE between the Liu equation and Mifflin equation. Under different nutritional statuses, the results of the Bland-Altman analysis suggested that deviation values between REEs predicted by each equation and mREE were greater than ±10%., Conclusions: There were differences in REE among children with different nutritional status. The results obtained from the five predictive energy equations deviated from the IC results. When REE cannot be measured by IC, it is essential to choose an appropriate predictive energy equation based on the nutritional status of the individual., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-168/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Cerebrospinal fluid (CSF) laboratory tests are important for diagnosing central nervous system (CNS) diseases. Research on intrathecal immunoglobulin-related indexes has gradually attracted attention. The antibody index, which corrects for the effect of individual blood-brain barrier function on CSF antibody test results, is of great significance in the differential diagnosis, efficacy monitoring and prognostic assessment of CNS diseases. It is expected to become a new index for the diagnosis of CNS diseases. This article reviews the concept of antibody index and the research progress of differential diagnosis and treatment of various CNS diseases in order to provide references for the diagnosis, efficacy monitoring and disease progression assessment of CNS diseases.

Objective: To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation., Methods: Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma (PRP), the key technical parameters (DMSO addition, incubation time, centrifugation conditions, etc.) of the preparation process were optimized, and the quality of the frozen platelets was evaluated by routine blood tests, apoptosis rate, platelet activation rate and surface protein expression level., Results: In the preparation protocol of novel frozen human platelets, the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing, and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800× g for 8 min. In addition, platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing. The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation., Conclusion: The preparation technique of novel frozen human platelets was established and the protocol was formulated. It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800× g for 8 min in the preparation of novel frozen human platelets.

In order to analyze the growth pattern of tree height of planted Pinus koraiensis and screen the provenances with fastest growth, we grouped the provenances using the differences in tree height, diameter at breast height (DBH) and volume of timber of 234 individuals of planted P. koraiensis from 26 provenances in Maoershan Experimental Forest Farm. We constructed the growth equation for tree height by combining the base models of Gompertz, Korf, Richards, Logistic, and Schumacher, and then selected the optimal one. We introduced the prove-nance grouping as a dummy variable into the base model, and evaluated the optimal tree height growth equation by a comprehensive evaluation of the model according to the coefficient of determination ( R 2 ), the root-mean-square error (RMSE), the Akaikei Information Criterion (AIC), and the model's predictive precision ( F P ). The results showed that the growth traits of the 26 provenances had significant difference among the groups, and that tree height and DBH showed significant differences among the provenances. According to the comprehensive consideration of different growth traits, the four groups of provenance growth were divided into group A (Wuying, Hebei, Linjiang, Dongfanghong, Huanan, Lushuihe, Fangzheng) >group B (Aihuisanzhan, Liangshui, Tieli, Qinghe) > group C (Wuyiling, Zhanhe, Liangzihe, Baihe, Chaihe, Caohekou, Bajiazi) >group D (Tongzigou, Dashitou, Wangqing, Helong, Yanshou, Dahailin, Xiaobeihu, Muling). The optimal base tree height growth model of the four groups was the Gompertz model, and the fitting accuracy of the model after the introduction of dummy variables ( R 2 =0.9353) was higher than that of the base model ( R 2 =0.9303), and the model prediction accuracy was also improved. The tree height growth curves of each provenance group conformed to the "S"-shaped rule of change. There were obvious differences among the groups, with the best performance of the provenances in group A. The growth of P. koraiensis from different provenances was different, and the tree height growth model with dummy variables of provenance groups could effectively improve the prediction accuracy of the model, reflect the differences in height growth of P. koraiensis of different provenances, which could provide the scientific basis for the selection and cultivation of P. koraiensis plantations.

In this paper, we collected the individual tree point cloud data in the plots of Larix olgensis plantations with different thinning intensities in Mengjiagang Forest Farm, applied the fractal analysis theory to extract box dimensions ( D b ) on MATLAB platform, and characterized the structural complexity of L. olgensis . We assessed the effect of different thinning intensities and tree attributes on the structural complexity of L. olgensis . The results showed significant differences in L. olgensis D b between control (CK: 1.68±0.07), low and medium intensity thinning (T 1 , T 2 , T 3 : 1.74±0.07), and high intensity thinning (T 4 : 1.81±0.06), which indicated that the thinning intensity increased tree structural complexity. For trunk attribute, the diameter at breast height and tree height was significantly positively correlated with D b , while the height-to-diameter ratio was significantly negatively correlated with D b . For canopy attribute, crown volume, surface area, projected area, and crown diameter was significantly positively correlated with D b . Hegyi competition index was significantly negatively correlated with D b in the control and low-moderate-intensity thinning treatments, but not significantly correlated with D b in the high-intensity thinning treatment. It indicated that thinning influenced L. olgensis structural complexity, with trunk attribute and canopy attribute as the main drivers of L. olgensis structural complexity.