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Ting-Ting Ni, Yuan-Yuan Yao, Xiao-Xia Zhou, Tao Lv, Jing-Cheng Zou, Ge Luo, Jin-Ting Yang, Da-Wei Sun, Qi Gao, Ting-Ting Wang, Rui-Yu Wang, Xin-Chen Tao, Min Yan Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 330100, People’s Republic of ChinaCorrespondence: Min Yan, Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 330100, People’s Republic of China, Email zryanmin@zju.edu.cnPurpose: Postinduction hypotension (PIH), occurring between anaesthesia induction and surgical incision, is particularly concerning in older adults undergoing transcatheter aortic valve replacement (TAVR) due to their multiple comorbidities and age-related cardiovascular changes. This study aimed to assess the relationship between PIH and postoperative adverse events in TAVR patients.Patients and Methods: A total of 777 patients underwent TAVR at The Second Affiliated Hospital of Zhejiang University School of Medicine from January 1, 2020 to February 28, 2023. Four thresholds of MAP were defined, including two absolute thresholds (< 65, < 60 mmHg) and two relative thresholds (20% and 30% lower than baseline). The relationships between PIH and the composite outcome, which included all-cause in-hospital mortality, stroke, acute kidney injury (AKI), and myocardial infarction (MI), were examined using unadjusted analysis, 1:1 propensity score matching(PSM), and inverse probability of treatment weighting (IPTW).Results: A total of 643 older adults were included in the study ultimately. The composite outcome incidence was significantly greater in patients with PIH than in those without PIH (relative risk [RR]: 2.47, 95% CI: 1.66– 3.73 for MAP < 60 mmHg; RR: 1.66, 95% CI: 1.14– 2.46 for a > 30% decrease from baseline). PIH was significantly associated with stroke (RR: 5.22, 95% CI: 1.98– 17.75) and AKI (RR: 2.82, 95% CI: 1.73– 4.79) with a MAP < 60 mmHg.Conclusion: PIH significantly increases the risk of composite outcomes, especially stroke and AKI, in TAVR patients.Keywords: postinduction hypotension, adverse postoperative outcomes, transcatheter aortic valve replacement, older adults

Shuang-Jiang Zhou,1,&ast; Rui Yang,2,&ast; Lei-Lei Wang,1 Meng Qi,1 Xiao-Fei Yuan,2 Ting-Ting Wang,3 Tian-He Song,4 Yun-Yue Zhuang,4 Hong-Juan Li,1 Yun-Long Tan,1 Xue Wang,2 Jing-Xu Chen1 1Sleep Medicine Center, Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, People’s Republic of China; 2Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3School of Mental Health, Bengbu Medical College, Bengbu, People’s Republic of China; 4Department of Psychology, Chengde Medical University, Chengde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Wang, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China, Tel +86-10-58303034, Email xuew37@ccmu.edu.cn Jing-Xu Chen, Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, 100096, People’s Republic of China, Tel +86-10-83024278, Email chenjx1110@163.comObjective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA).Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness.Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h.Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary.Keywords: wearable multi-sensor system, polysomnography, sleep stages, obstructive sleep apnea

Tian-He Song,1,2,&ast; Ting-Ting Wang,2,3,&ast; Yun-Yue Zhuang,1,2 Hua Zhang,4 Jun-Hui Feng,5 Tang-Ren Luo,6 Shuang-Jiang Zhou,2 Jing-Xu Chen2 1Department of Psychology, Chengde Medical University, Chengde, Hebei, People’s Republic of China; 2Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, People’s Republic of China; 3School of Mental Health, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 4Dongying People’s Hospital, Dongying, Shandong, People’s Republic of China; 5Jining Psychiatric Hospital, Jining, Shandong, People’s Republic of China; 6The Third Hospital of Longyan, Longyan, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang-Jiang Zhou; Jing-Xu Chen, Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, 10096, People’s Republic of China, Tel +86 13466401377 ; +86 13681394260, Email zhoushuangjiang@126.com; chenjx1110@163.comPurpose: Nightmare is common and is also independently implicated in suicide risk among the adolescent population. Adolescents with major depressive disorder (MDD) are at an increased risk of suicide. Therefore, comorbid nightmares may amplify suicide risk among this clinical population. This study aimed to explore the effects of nightmares on suicide risk among adolescents with MDD.Patients and Methods: Subjects were 499 outpatients aged 12– 18 in four large psychiatric hospitals clinic of China, from January 1 to October 31, 2021. Simultaneously, we matched 499 healthy controls according to gender and age. All participants underwent affective state (depressive and anxiety symptoms) and sleep variable (nightmare frequency/distress, insomnia symptoms, and daytime sleepiness) evaluation as well as MDD diagnoses and determination of suicide risk by a fully structured diagnostic clinical interview.Results: Adolescents with MDD reported a higher incidence of frequent nightmares (at least one night per week) and level of nightmare distress than healthy controls (22.0% vs 6.1%; 28.85 ± 11.92 vs 17.30 ± 5.61). Over half of the patients with suicide risk (51.6%) experienced frequent nightmares compared with approximately one-third of those at a risk for suicide (30.7%). Patients with suicide risk scored scientifically higher on sleep variables, depressive and anxiety symptoms than those without the risk. Further logistic regression analysis indicated that female gender, junior grade, recurrent depressive episode, severe nightmare distress and severe depressive symptoms were independently and significantly associated with suicide risk.Conclusion: Our study provided evidence that adolescents with MDD experienced a higher prevalence of frequent nightmares and suffered more nightmare distress. Nightmare distress is an independent risk factor for suicide risk.Keywords: major depressive disorder, sleep problems, nightmare, suicide risk, adolescent

Rui Yang,&ast; Xiao-Xia Xu,&ast; Hu Liu, Wei Dai, Zheng-Qin Zhang, Ting-Ting Wang, Shi-Shou Chen, Er-Wei Gu, Xue-Sheng Liu, Bin Mei Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue-Sheng Liu; Bin Mei, Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 551-62922344, Fax +86 551 62923704, Email liuxuesheng@ahmu.edu.cn; binmei@ahmu.edu.cnObjective: Postoperative sleep disturbance after surgery is not conducive to the recovery of patients. The purpose of this study was to determine the influence of the timing of surgery (morning vs afternoon) on the postoperative sleep quality of elderly patients and to analyze the relationship between the timing of surgery and the change in the melatonin level.Methods: Sixty patients who received hip surgery were randomly assigned to the Morning Group (Group M) or the Afternoon Group (Group A). The sleep quality was assessed by the Richards–Campbell Sleep Questionnaire. Before and after surgery, the nocturnal urine was collected over a 12-h period, and the 6-sulfatoxymelatonin concentration was measured. Also, the incidence of postoperative delirium (POD) was observed.Results: On the first and second nights after surgery, the sleep quality scores of the patients in Group A were greater than those in Group M, and there was no difference in the sleep quality scores between the two groups on the third night after surgery (P=0.000, P=0.002, P> 0.05, respectively). In addition, the urine 6-sulphatoxymelatonin concentration was found to be greater in Group A than in Group M on the first night of surgery (P=0.00). Both the postoperative sleep quality scores and urine 6-sulphatoxymelatonin concentration were significantly less than those before surgery (P=0.00, P=0.00).Conclusion: The postoperative sleep quality scores and melatonin levels of elderly patients who received hip surgery under general anesthesia were significantly less than those of the patients before surgery. Furthermore, the short-term sleep quality of the patients who received surgery in the afternoon was better than that of the patients who received surgery in the morning. This difference may be related to the short-term change of the melatonin level after surgery.Keywords: sleep quality, melatonin, timing of surgery

Lei Jin,1,2,* Xue-Mei Ma,1,2,* Ting-Ting Wang,1,2 Yao Yang,1,2 Nan Zhang,2,3 Na Zeng,2,4 Zhi-Gang Bai,1,2 Jie Yin,1,2 Jun Zhang,1,2 Guo-Qian Ding,1,2 Zhong-Tao Zhang1,2 1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2National Clinical Research Center for Digestive Diseases, Beijing, People’s Republic of China; 3Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Qian Ding; Zhong-Tao Zhang Email dingguoqian@gmail.com; zhangzhongtao@ccmu.edu.cnPurpose: The present study aimed to investigate the impact of psoralen on miR-196a-5p expression and function, and to reveal the mechanism underlying miR-196a-5p-mediated inhibition and the reversal of cisplatin (DDP) resistance.Methods: Serum samples were collected from 50 patients with gastric cancer (GC), and the association between miR-196a-5p expression and the response to chemotherapy was assessed. A DDP-resistant GC cell line was also established to determine the effects of miR-196a-5p and psoralen on DDP resistance. MGC803 cells were transfected with miR-196a-5p mimic and inhibitor vectors for the overexpression and downregulation of miR-196a-5p, respectively.Results: Clinical data analysis showed that the lower expression levels of miR-196a-5p were significantly associated with chemoresistance in patients with GC. Upregulation of miR-196a-5p significantly enhanced the anti-proliferative effect, apoptosis and sensitivity to DDP by regulating the protein expression levels of HOXB7, HER2, Bcl-2 and G1/S-specific cyclin-D1 (CCND1). Furthermore, psoralen reversed miR-196a-5p-induced DDP resistance and reduced the expression levels of HOXB7, HER2, Bcl-2 and CCND1.Conclusion: miR-196a-5p may be a novel biomarker of chemotherapeutic success in patients with GC and may also influence the sensitivity of GC cells to DDP. Moreover, psoralen can increase chemotherapeutic sensitivity by upregulating miR-196a-5p and then downregulating HOXB7-HER2 signaling axis.Keywords: miR-196a-5p, psoralen, chemoresistance, cisplatin, gastric cancer, HOXB7

Huimin Tao,1,* Yafeng Li,1,* Tingting Wang,2 Changhui Zhou3 1Department of Gastroenterology, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, People’s Republic of China; 2Department of Health Care, Weifang People’s Hospital, Weifang, Shandong Province, People’s Republic of China; 3Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, People’s Republic of China *These authors contributed equally to this work Objective: The aim of the study was to evaluate the efficacy and safety of umbilical cord blood stem cells (USCs) transplantation combined with routine supportive therapy (RST) for liver cirrhosis (LC).Materials and methods: Clinical trials involved in this research were searched from Web of Science, PubMed, EMBASE, Cochrane Library, Wanfang and CNKI database. Treatment effects, quality of life (QoL), adverse events and other outcome measures were extracted and evaluated.Results: A total of 10 trials including 616 LC patients were involved in this study. Based on our analysis, the liver function of LC patients was significantly improved after USCs transplantation and RST combined therapy, indicated by decreased total bilirubin, alanine aminotransferase, aspartate aminotransferase levels and prothrombin time and increased serum albumin level and prothrombin activity. Compared to those treated by RST alone, patients treated by combined therapy showed more satisfied treatment effects, improved QoL reflected by improved appetite (odds ratio [OR]=5.43, 95% CI=2.84 to 10.38, P

Li Zhang,1,2 Tengteng Wang,1,2 Qiang Li,1,2 Jing Huang,3 Hao Xu,1,2 Jinlong Li,1,2 Yongjun Wang,1,2 Qianqian Liang1,21Department of Orthopaedics, Longhua Hospital, 2Institute of Spine, Shanghai University of Traditional Chinese Medicine, 3Biochemistry and Molecular Biology, School of Life Science, East China Normal University, Shanghai, People’s Republic of China Abstract: Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is –35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. Keywords: triptolide, toxicity, poly-γ-glutamic acid, drug carrier system

Zhang L, Wang TT, Li Q, et al. Int J Nanomedicine. 2016;11:2663–2673.Following a review of their data post-publication, the authors found errors in the kidney and PPT group image used for Figure 7 on page 2671 and the spleen control and PP group images and liver PP and PPT group images used for Figure 8 on page 2671. For accuracy and experimental integrity these images have been corrected, with no impact to the conclusions of the study. The authors apologize for these errors. Read the original article

The purpose of this study is to evaluate the use of endovascular stent grafts in the treatment of para-anastomotic aneurysms (PAAs) as an alternative to high-risk open surgical repair. We identified all patients with previous open aortic aneurysm repair who underwent infrarenal endovascular aneurysm repair (EVAR) at our institution from June 1998 to April 2007. Patient demographics, previous surgery, and operative complications were recorded. One hundred forty-eight patients underwent EVAR during the study period and 11 patients had previous aortic surgery. Of these 11 redo patients, the mean age was 62 years at initial surgery and 71 years at EVAR. All patients were male. Initial open repair was for rupture in five (45%) patients. The average time between initial and subsequent reintervention was 9 years. All patients were ASA Grade III or IV. Fifty-five percent of the PAAs involved the iliac arteries, 36% the abdominal aorta, and 9% were aortoiliac. Ten patients had endovascular stent-grafts inserted electively, and one patient presented with a contained leak. Aorto-uni-iliac stent-grafts were deployed in seven patients, and bifurcated stent-grafts in four patients. A 100% successful deployment rate was achieved. Perioperative mortality was not seen and one patient needed surgical reintervention to correct an endoleak. Endovascular repair of PAAs is safe and feasible. It is a suitable alternative and has probably now become the treatment of choice in the management of PAAs. [ABSTRACT FROM AUTHOR]

Aims: To estimate the prevalence and severity of periodontal disease (PD) in the Taiwanese population aged 35-44 years and to investigate the association between demographic factors and PD. Materials and Methods: Between 2003 and 2005, residents of Keelung of the appropriate age were invited to screening. The community periodontal index (CPI) and loss of attachment (LA) index were used to measure the periodontal status at subject (prevalence) and sextant levels (severity). Basic demographic information was also collected by a questionnaire. Results: Of 8462 enrollees, 94.8% had some signs of PD, of whom 29.7% had periodontal pockets >3 mm and 35% LA >3 mm. Calculus was the most common problem in terms of both prevalence (49.6%) and severity (affecting an average of 3.0 sextants per person). Risk factors for poor periodontal status (as measured by CPI) were older age (odds ratio, OR: 1.44), male gender (OR: 2.70), low education level (OR: 1.40), and being a manual worker (OR: 1.51). Similar findings were observed for LA. Conclusion: The prevalence of PD in 35-44-year-olds was found to be high in this large community-based study of screening for PD with CPI and LA. Poorer periodontal health was observed in males, the less educated, and manual workers. [ABSTRACT FROM AUTHOR]

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1‒KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-β-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1‒KLF5 axis., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The animal experiment was approved by the Laboratory Animal Ethics Committee of Kunming Medical University (kmmu20241035)., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Recent findings implicate somatic NRAS Q61R mutation in human endothelial cells in the pathogenesis of vascular anomalies. Our previous study demonstrated that RAB27B, a small GTPase of the RAB family, regulates NRAS palmitoylation in leukemia cells and is essential for NRAS-mutant leukemia development. However, the role of RAB27B in NRAS Q61R mutant endothelial cells are still unknown. Our present study revealed that knockdown of RAB27B, but not knockdown of RAB27A, inhibited the enhanced proliferation and migration of human umbilical vein endothelial cells (HUVEC) overexpressing NRAS Q61R by suppressing ERK activation. Notably, RAB27B protein and gene expression levels were significantly elevated in HUVEC overexpressing NRAS Q61R compared to those overexpressing NRAS WT or empty vector. Treatment with a MEK1/2 inhibitor, but not a PI3K/mTOR inhibitor, markedly decreased RAB27B gene expression in HUVEC overexpressing NRAS Q61R . Furthermore, we identified CCAAT enhancer binding protein beta as a downstream transcription factor of NRAS Q61R /ERK pathway that induced RAB27B gene expression. Taken together, our study unmasked a positive feedback loop between NRAS Q61R mutation and RAB27B expression in endothelial cells. Moreover, RAB27B is associated with the dysfunction of NRAS Q61R mutant endothelial cells, highlighting RAB27B as a potential therapeutic target for NRAS-mutant vascular anomalies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian-Gang Ren reports financial support was provided by National Natural Science Foundation of China. 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 © 2025 Elsevier Inc. All rights reserved.)

Background: Rheumatoid arthritis (RA) is an inflammatory disease of the joints mediated by immune cells. As an immune-related mode of cell death, pyroptosis has yet to be fully understood in RA. This research identified novel pyroptosis-related markers in RA and confirmed its functional significance in RA., Methods: Initially, crucial pyroptosis-related genes of RA were identified through GEO database, and biological pathways were determined through enrichment analysis. Then, PPI network, WGCNA and CIBERSORT analysis was utilized to screen hub genes and evaluate immune cell infiltration levels. Finally, validation experiments determined hub genes expression and regulatory roles in RA pathogenesis, and screened potential therapeutic drugs., Results: A total of 46 DEPRGs in RA were identified, which involved in NOD-like receptor and Toll-like receptor signaling pathway. Further screening revealed 3 crucial hub genes: CCL5, LY96, and TLR3 had significantly increased expression in RA synovial tissue and FLS, which might become diagnostic markers of RA. Analysis of immune infiltration revealed that hub genes exhibited associations with plasma cells, T lymphocytes, and macrophages. Further study on the crucial hub gene TLR3 revealed that knocking down TLR3 significantly inhibited the RA FLS hyperproliferation and pyroptosis, and dexamethasone and doxorubicin, as potential drugs, could treat RA by inhibiting TLR3., Conclusion: Our study indicates that high expression of TLR3 promotes FLS pyroptosis and RA progression, suggesting its potential as both a biomarker and a therapeutic target for RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

River ecosystems are facing significant degradation from human activities, which impact both biotic (e.g., fish and invertebrates) and abiotic components (e.g., water and habitat). A comprehensive comparison of energy flow patterns and system attributes among river food webs under different levels of human interference is highly important for developing management strategies to protect river ecosystems. Along the subtropical Pearl River, six spatial zones, including agricultural, industrial, island, urban, factory, and estuarine areas, were chosen to construct the Ecopath models. The output results revealed that the highest trophic level of the Pearl River was 3.8-4.2, which was occupied by softshell turtles and piscivorous/carnivorous fish. The most diverse functional groups were found in island and estuarine zones due to their heterogeneous habitats (e.g., high submerged vegetation coverage and the transition area between fresh and brackish water). In contrast, the food web structure in the industrial zone was destroyed due to water pollution (e.g., sewage discharge) and habitat degradation. The increase in exotic species and the decrease in native top predators were two factors that result in the low efficiency of energy transmission. A series of trophic (e.g., Lindeman transfer efficiency and mixed predator-prey impacts), structural (e.g., keystoneness, omnivory, and Finn's path length), and theoretical (e.g., connectance and ascendency) indices revealed that the health and maturity of the Pearl River sections can be ranked as island > estuarine > agricultural > urban > factory > industrial zones. The food chains led by softshell turtles ( Pelodiscus sinensis ), piscivores (e.g., Elopichthys bambusa ), molluscivores (e.g., Mylopharyngodon piceus ), and herbivores (e.g., Ctenopharyngodon idelus ) could be used to indicate the health and functioning of river ecosystems. Our results suggest that the ecological management of river ecosystems should focus more efforts on protecting original habitats (e.g., the island zone with fish feeding/spawning grounds), monitoring bioindicators with keystone trophic impacts in the food web, and evaluating the food chains that play important roles in upward energy transmission., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Neuronal accumulation and spread of pathological α-synuclein (α-syn) fibrils are key events in Parkinson's disease (PD) pathophysiology. However, the neuronal mechanisms underlying the uptake of α-syn fibrils remain unclear. In this work, we identified FAM171A2 as a PD risk gene that affects α-syn aggregation. Overexpressing FAM171A2 promotes α-syn fibril endocytosis and exacerbates the spread and neurotoxicity of α-syn pathology. Neuronal-specific knockdown of FAM171A2 expression shows protective effects. Mechanistically, the FAM171A2 extracellular domain 1 interacts with the α-syn C terminus through electrostatic forces, with >1000 times more selective for fibrils. Furthermore, we identified bemcentinib as an effective blocker of FAM171A2-α-syn fibril interaction with an in vitro binding assay, in cellular models, and in mice. Our findings identified FAM171A2 as a potential receptor for the neuronal uptake of α-syn fibrils and, thus, as a therapeutic target against PD.

[This retracts the article on p. 1354 in vol. 14, PMID: 39319232.]., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this retraction note., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Polyploidization is a common occurrence in the evolutionary history of flowering plants, significantly contributing to their adaptability and diversity. However, the molecular mechanisms behind these adaptive advantages are not well understood. Through comprehensive phenotyping of diploid and tetraploid clones from Citrus and Poncirus genera, we discovered that genome doubling significantly enhances salt stress resilience. Epigenetic and transcriptomic analyses revealed that increased ethylene production in the roots of tetraploid plants was associated with hypomethylation and enhanced chromatin accessibility of the ACO1 gene. This increased ethylene production activates the transcription of reactive oxygen species scavenging genes and stress-related hormone biosynthesis genes. Consequently, tetraploid plants exhibited superior root functionality under salt stress, maintaining improved cytosolic K + /Na + homeostasis. To genetically validate the link between salt stress resilience and ACO1 expression, we generated overexpression and knockout lines, confirming the central role of ACO1 expression regulation following genome doubling in salt stress resilience. Our work elucidates the molecular mechanisms underlying the role of genome doubling in stress resilience. We also highlight the importance of chromatin dynamics in fine-tuning ethylene gene expression and activating salt stress resilience pathways, offering valuable insights into plant adaptation and crop genome evolution., (© 2025 The Author(s). New Phytologist © 2025 New Phytologist Foundation.)

Objective: To determine the prevalence and associates of hyperuricemia (HUA) among the middle- and older-aged population of the island and mountainous areas in Taizhou City of Zhejiang Province. Methods: A cross-sectional study was conducted on individuals aged 45 and above in the island and mountainous area of Taizhou City. The study included questionnaires, physical examinations, and laboratory tests. Data were primarily collected on sociodemographic characteristics, chronic disease history, lifestyle factors, waist circumference, blood pressure, and serum uric acid levels. The association between hyperuricemia and these factors was analyzed by logistic regression. Results: A total of 971 individuals were included in the study, comprising 468 from island and 503 from mountainous area. The prevalence of hyperuricemia was 17.9%, with a significantly higher prevalence in the island area (25.6%) compared to the mountainous area (10.7%). Stratified by gender and age, differences in the prevalence of hyperuricemia between island and mountainous areas were observed in males aged 55 to 64, females aged 45 to 54, 55 to 64, 75 and above (all P <0.05). Multiple logistic regression analysis showed that high intake of sea food (>3 times/week) was positively associated with hyperuricemia ( OR =2.10, 95% CI :1.33-3.34). Furthermore, separate regionally stratified logistic regression analyses showed that in the island area, male gender ( OR =3.15, 95% CI :1.78-5.66), central obesity ( OR =2.38, 95% CI :1.46-3.93), and hypertriglyceridemia ( OR =2.00, 95% CI :1.22-3.30) were positively correlated with hyperuricemia (all P <0.05). In the mountainous area, the age group of 65 and above ( OR =3.50, 95% CI :1.09-12.50), male ( OR =6.79, 95% CI :2.87-17.81), those employed in enterprises and institutions ( OR =6.57, 95% CI :1.92-23.73) and hypertension ( OR =3.68, 95% CI :1.66-8.87) were positively correlated with hyperuricemia (all P <0.05). Conclusions: The prevalence of hyperuricemia among the middle- and older-aged population in the island of Taizhou City is significantly higher than that in the mountainous areas. Targeted comprehensive behavioral interventions such as routine screening of chronic diseases, low-fat diet, alcohol control, reduced seafood intake, enhanced exercise, weight management, and blood pressure control are warranted.

Background: Monitoring nitrate and nitrite levels in water is vital for protecting human health, aquatic ecosystems, and regulatory compliance. However, traditional detection methods often involve environmentally harmful chemicals. This study introduces a sustainable alternative by leveraging metabolically engineered E. coli to biosynthesize para-aminobenzoic acid (PABA) via the shikimate pathway, replacing conventional sulfonamides in the Griess reaction. This approach significantly reduces environmental impact while maintaining high analytical performance., Results: This study introduces a sustainable approach for simultaneously detecting nitrate and nitrite in water using a combination of E. coli strains DH5α and BL21. Metabolically engineered E. coli BL21 produces PABA via the shikimate pathway, replacing synthetic chemicals in the modified Griess reaction. The modified Griess reaction, utilizing PABA, achieved a high sensitivity detection limit of 0.57 μM with excellent selectivity for nitrite over other ions. Recognizing the importance of portability for on-site, real-time water quality assessment, we developed a paper-based detection system utilizing lyophilized cell supernatant. To enhance portability, we developed a paper-based method for detecting nitrite using lyophilized cell supernatant. This approach confirmed successful nitrite detection through a clear colorimetric response, enabling immediate and quantitative analysis of nitrate and nitrite. Validation with real-world water samples yielded a recovery rate of 90-100 %, comparable to the Griess Reagent, confirming the effectiveness and reliability of the proposed sensors for environmental monitoring. By integrating the capabilities of two E. coli strains, this dual-detection system uniquely allows simultaneous quantification of nitrate and nitrite in a single sample, significantly advancing the field of water quality monitoring., Significance and Novelty: This study demonstrates a sustainable, high-sensitivity solution for water quality monitoring by combining microbial metabolic engineering with a portable, paper-based detection platform. The approach meets EPA standards, minimizes environmental impact, and provides a practical tool for field-testing, underscoring the potential of engineered microbes for eco-friendly and effective environmental monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: To compare the advantages of long slim metal stents (LSMS) versus conventional metal stents in bilateral endoscopic side-by-side (SBS) deployment for malignant hilar biliary obstruction (MHBO)., Methods: 140 consecutive MHBO patients treated by endoscopic bilateral SBS deployment at a high-volume tertiary referral center were analyzed retrospectively, including 50 patients in LSMS group and the other 90 patients in conventional SBS group as control. Propensity score matching (PSM) at a 1:2 ratio was used to reduce selection bias. Primary outcomes were stent patency., Results: After PSM, no significant difference was obseved in stent patency (267 vs. 268 days, P=0.969) or overall survival (OS) (225 vs. 211 days, P=0.883) between the two groups. The technical success rate was 100% in both groups, and the clinical success rate was 91.1% in LSMS group and 92.9% in control group (P=0.735). Early and late adverse events were similar (24.4% vs. 34.3%, P=0.423; 42.2% vs. 38.6%, P=0.697), while the procedure time and bilateral metal stenting time in LSMS group were significantly shorter (41.0 min vs. 57.5 min, P=0.000; 19.0 min vs. 28.5 min, P=0.000). The success rate of endoscopic bilateral revisionary stent insertion in LSMS group was also higher (100% vs. 33.3%, P=0.000)., Conclusions: Bilateral LSMS placement is a viable option for MHBO patients with advantages of less operative difficulty and easier future re-intervention over conventional SBS stenting., (Copyright © 2025 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) have attracted considerable attention because of their toxicity, persistence and bioaccumulation potential. With the construction of the Hainan Free Trade Port and the rapid development of economy, environmental pollution on Hainan Island is becoming increasingly prominent. PFASs have been detected in the seawater and sediments of mangrove ecosystems on Hainan Island. As the receiving water of wastewater treatment plants (WWTPs) and industrial wastewater, rivers are inevitably contaminated by PFASs. However, few studies have focused on PFAS pollution in three large rivers (the Nandu, Changhua, and Wanquan rivers) on Hainan Island. In the present study, the pollution status, potential sources, and ecological risks of PFASs in these three major rivers were explored. Perfluorobutanonic acid (PFBA) (48.7%) was found to be the major PFASs in the surface waters, and perfluoroundecanoic acid (PFUnDA) (19.7%) was the major PFASs in the sediments of the three major rivers. The concentrations of ∑PFASs in the upper-midstream region were low due to minimal human influence and increased in the middle-lower reaches with increasing industrial activity and urbanization, whereas decreased at downstream sites near estuaries where river water was diluted with seawater. WWTP effluent, industrial wastewater discharge, the application and discharge of aqueous fire-fighting foam, storm runoff and landfill leachate were the major sources of PFASs in the three major rivers. In surface water, perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA) and perfluorooctadecanoic acid (PFODA) posed low-moderate risks at 5.71-85.6% of the sampling sites. PFASs in the sediment posed no ecological risk. This study provides key data regarding the pollution status and potential sources of PFASs in large rivers on subtropical islands., 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.)

Purpose: To investigate the efficacy of penehyclidine (PHC) for preventing postoperative nausea and vomiting (PONV) after laparoscopic sleeve gastrectomy (LSG) under general anesthesia., Materials and Methods: In this prospective study, 219 patients who were scheduled to undergo LSG were randomly assigned to three cohorts: the control cohort (received normal saline), the infusion cohort (administered 0.25 mg of PHC intravenously followed by an additional 0.25 mg through an intravenous analgesia pump for 48 h after LSG), and the bolus cohort (received a single intravenous dose of 0.5 mg of PHC). The study outcomes included the incidence of PONV within the first 48 h postoperatively, the severity and intensity of PONV, side effects and postoperative recovery outcomes. Univariate and multivariate logistic analyses were performed to identify independent risk factors associated with PONV., Results: Compared with the control cohort, both the infusion and bolus cohorts presented considerably lower incidences of PONV (61.64% vs. 12.33% vs. 38.36%, P < 0.05), as well as significantly decreased PONV severities (P < 0.05) and intensities (P < 0.05). There were no significant differences in side effects and postoperative recovery outcomes among the three cohorts, with the exception of dry mouthand the administration of rescue antiemetic therapy (P < 0.05). Additionally, the Apfel risk score and PHC intervention were identified as independent risk factors associated with PONV incidence following LSG (P < 0.05)., Results: PHC effectively prevented PONV occurrence and reduced its severity in LSG patients without decreasing postoperative recovery outcomes, particularly in the infusion cohort., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to declare in this work. Ethical Approval and informed consent: His study received approval from the Institutional Ethics Committee, and informed consent was not required from the included participants (2022-YLJSA084), in compliance with the Helsinki., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NH 4 Cl), indicating entry via the endocytosis route. Although TMPRSS2 expression on target cell surface was required for HCoV-HKU1 spike-mediated entry and cell-cell fusion, we found that only the serine protease domain of TMPRSS2 and not the serine protease activity of TMPRSS2 was required for viral entry via endocytic route. However, the serine protease activity of TMPRSS2 and a furin processing site (RKRR) at the S1/S2 junction were essential for efficient HCoV-HKU1 spike-mediated cell-cell fusion. Additionally, we show that dibasic and monobasic arginine residues at the S1/S2 junctions of spike proteins of HCoV-NL63 and -229E are essential for virus entry, but multi-basic furin processing site at the S1/S2 junction was dispensable for HCoV-HKU1 viral entry. Our findings highlight features of the entry mechanisms of seasonal HCoVs that may support the development of novel treatment strategies. IMPORTANCE Details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain to be fully explored. To investigate spike-mediated virus entry of HCoV-NL63, -229E, and -HKU1 CoVs, we employed 293T cells that stably express angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2) to study entry mechanisms of pseudoviruses bearing spike proteins of HCoV-NL63, -229E, and -HKU1, respectively. We found that HCoV-NL63, -229E, and -HKU1 pseudoviruses entered cells via the endocytic route independently of cellular serine protease activity and therefore likely depended on endosomal cathepsin activity. Furthermore, we showed that arginine amino acids in S1/S2 junctions of HCoV-NL63 and -229E spikes were essential for entry but not essential for HCoV-HKU1 entry. Our results provide new insights into the S1/S2 junctional residues, cellular receptors, and protease requirements for seasonal HCoV pseudovirus entry into cells that may support the development of novel inhibitors.

The accurate quantification of multicomponents using LC-MS is pivotal for ensuring the quality control of herbal medicine, as well as the investigation of their analysis of biological tissue distribution. However, two significant challenges persist: the scarcity of authentic standards and the selection of appropriate internal standards. In this study, we present a highly sensitive isotope-coded equivalent reporter ion assay (iERIA) that combines equivalently quantitative ion and isotope-coded derivatization strategies. This method offers triple functionality: enabling the semidetermination of multiple components using a single standard, introducing stable isotope-labeled internal standards, and enhancing MS detection signals. Using four isocoumarins as a model, namely, 5-carboxylmellein, 5-hydroxymethylmellein, 5-methylmellein, and 5-hydroxymellein, we successfully quantified these compounds across various matrices, including herbal extracts, plasma, urine, and liver tissue. Reporter ions at m / z 170 and 234 generated by the dansulfonyl derivatives of isocoumarins, were subsequently detected for calculating the concentrations of samples based on the equivalent ion method. It is very beneficial for trace detection in biological samples free of any concentration steps, with an increased LOD of 50 times after dansyl chloride derivatization. Additionally, the introduction of stable isotope-labeled internal standards using d 6 -dansyl chloride mitigated matrix effects and instrument drift, ensuring the accuracy and precision of the semiquantification. This practical UPLC-MS/MS strategy significantly expands the applicability of multicomponent determination, with promising implications in diverse domains such as herbal medicine active ingredient analysis, food function and safety assessment, and metabolomics research.

We previously reported that mutations outside the spike protein play a role in the attenuation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 variant in human ACE2 transgenic mice (K18-hACE2). Here, we assessed the pathogenicity of SARS-CoV-2 (WA1/2020) containing mutations from the Omicron BA.1 variant in K18-hACE2 mice. At an infection dose of 10 4 plaque-forming units (PFU), WA1 virus carrying Omicron BA.1 Nsp14(I42V), E(T9I), M(D3G/Q19E/A63T), but not Nsp6(Δ105-107, I189V), substitutions showed significant reduction in lethality. Interestingly, reduction of viral load is more pronounced in the brains than in the lungs. Subsequent analyses suggest that BA.1 E(T9I) and M(D3G/Q19E/A63T) substitutions result in less efficient packaging of virus-like particles. Given that Nsp14(I42V), E(T9I), M(Q19E/A63T) are well preserved in subsequent omicron subvariants, including currently circulating variants, our findings highlight the importance of understanding how non-spike mutations affect the pathogenicity of SARS-CoV-2 variants., Importance: Inoculation of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) with SARS-CoV-2 often leads to a fatal brain infection. Omicron BA.1 variant, however, was found to be non-lethal in this model. Here, we systematically assessed the effect of individual mutations of Omicron BA.1 on the pathogenicity of the virus in hACE2 transgenic mice and found that combination of 5 mutations of Nsp14, E, and M of BA.1 variant significantly lowered brain viral load and reduced lethality. These results provide new insights into how SARS-CoV-2 Omicron BA.1 is attenuated., Competing Interests: The authors declare no conflict of interest.

Objective: To develop and validate a predictive model for hyperlipidemia risk among middle-aged and older adult individuals in China, this study aims to offer an effective screening tool for identifying those at risk., Methods: In this study, we included 6,629 middle-aged and older adult individuals, aged 45 and above, who met the inclusion criteria from the 2015 China Health and Retirement Longitudinal Study (CHARLS) as our research subjects. Utilizing the LASSO regression and multivariate Logistic regression method, we analyzed the independent risk factors associated with hyperlipidemia among these subjects. Subsequently, we established a risk prediction model for hyperlipidemia in the middle-aged and older adult population using statistical software Stata 17.0., Results: The prevalence rate of hyperlipidemia among the 6,629 middle-aged and older adult participants was 26.32% (1,745 out of 6,629). The LASSO regression and multivariate Logistic regression analysis all revealed that Body Mass Index (BMI), fasting blood glucose, serum uric acid, C-reactive protein, and white blood cell count were independent risk factors for hyperlipidemia in this demographic (with Odds Ratios (OR) greater than 1 and p -values less than 0.05). From these findings, a nomogram prediction model was constructed to estimate the risk of hyperlipidemia for middle-aged and older adult individuals. The Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for the nomograms was 0.717 (95% Confidence Interval (CI): 0.703-0.731), indicating good discrimination. The Decision Curve Analysis (DCA) demonstrated that when the probability of hyperlipidemia in the middle-aged and older adult population falls between 0.11 and 0.61, the application of the nomogram yields the highest net benefit, suggesting that the nomogram model possesses good clinical applicability. The Spiegelhalter's z-statistic test confirmed that the predicted probabilities from the nomogram model are in good agreement with the observed frequencies of hyperlipidemia ( p = 0.560). The Brier score for the nomogram model was 17.1%, which is below the threshold of 25%, indicating good calibration. To internally validate the nomogram model, we performed bootstrap resampling 500 times. The C-statistic for the nomogram model from this internal validation was 0.716, and the Brier score was 11.4%, suggesting that the model not only has good predictive efficiency but also good stability., Conclusion: The nomogram model, which incorporates the identified risk factors for hyperlipidemia in middle-aged and older adult individuals, has demonstrated good predictive efficiency and clinical applicability. It can serve as a valuable tool to assist healthcare professionals in screening for high-risk groups and implementing targeted preventive interventions. By doing so, it has the potential to significantly reduce the incidence of hyperlipidemia among this demographic., 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 © 2025 Zhang, Hou, Zhao, Wang, Jiang, Zhou and Cao.)

Background: Endovascular thrombectomy (EVT) alone was not demonstrated to be noninferior to intravenous alteplase bridging EVT in acute large vessel occlusion stroke. Using the cerebral ischemia/reperfusion (I/R) injury model, intravenous tenecteplase (TNK) was administrated after ischemia, followed by reperfusion at various time points., Objectives: To investigate whether intravenous TNK bridging EVT vs EVT alone could improve I/R injury, and this effect may be associated with the time from TNK to reperfusion., Methods: Rats received intravenous TNK (1.4 mg/kg) or vehicle (sterile water) 1.0 hours after middle cerebral artery occlusion, followed by reperfusion after 0.5 or 1.0 hours following TNK. Neurological deficit scores, infarct volume, and brain edema were measured 24 hours after middle cerebral artery occlusion. Microthrombi were determined by immunofluorescence staining for CD31 + /fibrinogen + and CD31 + /thrombocyte + . Inflammatory cell infiltration in the ischemic brain region was determined by flow cytometry., Results: Compared with vehicle, TNK significantly reduced neurological deficit scores, brain infarction, neuroinflammation, and blood-brain barrier disruption, and significantly reduced intravascular fibrin and platelet deposition and brain inflammatory cell infiltration in the penumbra of I/R rats. Furthermore, a better beneficial trend was found in TNK bridging reperfusion at 0.5 hours after TNK compared with TNK bridging reperfusion at 1.0 hours after TNK., Conclusion: Our results demonstrate that intravenous TNK bridging reperfusion produced neuroprotective action through dissolving microvascular thrombus and alleviating inflammatory cell infiltration to improve microcirculation, with the result of maintaining blood-brain barrier integrity and inhibiting neuroinflammation, and the neuroprotective benefit may be associated with the time from TNK to reperfusion., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2025 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to develop and validate a prediction model for fall risk factors in hospitalized older adults with osteoporosis., Methods: A total of 615 older adults with osteoporosis hospitalized at a tertiary (grade 3A) hospital in Nantong City, Jiangsu Province, China, between September 2022 and August 2023 were selected for the study using convenience sampling. Fall risk factors were identified using univariate and logistic regression analyses, and a predictive risk model was constructed and visualized through a nomogram. Model performance was evaluated using the area under the receiver operator characteristic curve (AUC), Hosmer-Lemeshow goodness-of-fit test, and clinical decision curve analysis, assessing the discrimination ability, calibration, and clinical utility of the model., Results: Based on logistic regression analysis, we identified several significant fall risk factors for older adults with osteoporosis: gender of the study participant, bone mineral density, serum calcium levels, history of falls, fear of falling, use of walking aids, and impaired balance. The AUC was 0.798 (95% CI: 0.763-0.830), with a sensitivity of 80.6%, a specificity of 67.9%, a maximum Youden index of 0.485, and a critical threshold of 121.97 points. The Hosmer-Lemeshow test yielded a χ 2 value of 8.147 and p  = 0.419, indicating good model calibration. Internal validation showed a C-index of 0.799 (95% CI: 0.768-0.801), indicating the model's high discrimination ability. Calibration curves showed good agreement between predicted and observed values, confirming good calibration. The clinical decision curve analysis further supported the model's clinical utility., Conclusion: The prediction model constructed and verified in this study was to predict fall risk for hospitalized older adults with osteoporosis, providing a valuable tool for clinicians to implement targeted interventions for patients with high fall risks., 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 © 2025 Sun, Gu, Xu, Jiang, Wang, Li and Cui.)

While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains., Competing Interests: Declaration of interests T.T.W. is a scientific advisor for Nuvig Therapeutics. M.S.D. is a consultant or on the Scientific Advisory Board for Inbios, Vir Biotechnology, Topspin Therapeutics, Akagera Medicines, Merck, GlaxoSmithKline, and Moderna. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Emergent BioSolutions, Moderna, Topspin Therapeutics, and Vir Biotechnology., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Type 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear., Aim of the Study: This study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both in vitro and in vivo experiments., Materials and Methods: In this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients., Results: Serum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1., Conclusion: PCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study aimed to develop and validate a predictive model for major depression risk in adult patients with coronary heart disease (CHD), offering evidence for targeted prevention and intervention., Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, 1098 adults with CHD were included. A weighted logistic regression model was applied to construct and validate a nomogram-based prediction tool for major depression in this population., Results: The weighted prevalence of major depression among these patients was 13.95%. Multivariate weighted logistic regression revealed that waist circumference, smoking status, arthritis, sleep disorders, and restricted work capacity were independent risk factors for major depression (odds ratio (OR) >1, p < 0.05). The areas under the receiver operating characteristic (ROC) curve in the nomogram model for both the development and validation cohorts were 0.816 (95% confidence interval (CI): 0.776-0.857) and 0.765 (95% CI: 0.699-0.832), respectively, indicating the model possessed strong discriminative ability. Brier scores in the development and validation cohorts were 0.107 and 0.127, respectively, both well below the 0.25 threshold, demonstrating good calibration. Decision curve analysis (DCA) showed that when the threshold probability for major depression ranged from 0.04 to 0.54 in the development group and from 0.08 to 0.52 in the validation group, the nomogram provided the highest clinical net benefit compared to "Treat All" and "Treat None" strategies, confirming its strong clinical utility., Conclusions: With a weighted prevalence of 13.95%, this nomogram model shows excellent predictive performance and clinical relevance for predicting major depression risk in patients with CHD. Thus, the model can be applied to aid healthcare professionals in identifying high-risk individuals and implementing targeted preventive strategies, potentially lowering the incidence of major depression in this patient population., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2025 The Author(s). Published by IMR Press.)

Objective: To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia. Methods: Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc . Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results: A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR =2.65, 95% CI : 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P <0.05). Conclusions: Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.

Tyramine signaling amplification (TSA) technology is generally applied in immunofluorescence, enzyme-linked immunoassays, in situ hybridization techniques, etc. Successful amplification of fluoresence signals cannot be achieved without excellent fluorescent dyes. BODIPY fluorophore is an ideal probe for cell fluorescence imaging, but pristine BODIPY cannot be direct used in the TSA system. In the paper, the new red-shifted tyramide-conjugated BODIPY (BDP-B/C/D) was synthesized via the Knoevenagel condensation reaction, which based on the tyramide-conjugated BODIPY (BDP-A). The synthesized dyes were combined with tyramine to obtain which could be used as a fluorescent substrate for enzymatic reaction of TSA. By using the selected substrate (BDP-C) in TSA, we found it to be more sensitive than the commercial dye 594 styramide for the detection of low-abundance antigen proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quantum entanglement uncovers the essential principles of quantum matter, yet determining its structure in realistic many-body systems poses significant challenges. Here, we employ a protocol, dubbed entanglement microscopy, to reveal the multipartite entanglement encoded in the full reduced density matrix of the microscopic subregion in spin and fermionic many-body systems. We exemplify our method by studying the phase diagram near quantum critical points (QCP) in 2 spatial dimensions: the transverse field Ising model and a Gross-Neveu-Yukawa transition of Dirac fermions. Our main results are: i) the Ising QCP exhibits short-range entanglement with a finite sudden death of the LN both in space and temperature; ii) the Gross-Neveu QCP has a power-law decaying fermionic LN consistent with conformal field theory (CFT) exponents; iii) going beyond bipartite entanglement, we find no detectable 3-party entanglement with our two witnesses in a large parameter window near the Ising QCP in 2d, in contrast to 1d. We further establish the singular scaling of general multipartite entanglement measures at criticality and present an explicit analysis in the tripartite case., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Intramural ectopic pregnancy (IMP) refers to the implantation and implantation of a gestational sac in the uterine muscle layer, which is a rare and potentially life-threatening disease. Early detection and diagnosis are significant, and treatment methods are often challenging., Presentation of Case: We report a case of IMP after embryo transfer in a 38-year-old woman. The patient developed persistent ectopic pregnancy after combined hysteroscopic and laparoscopic surgery. Intramuscular injection of methotrexate did not have a significant effect, and transabdominal ultrasound-guided in situ injection of methotrexate at the site of the lesion was performed with a significant impact., Discussion: This case emphasizes the complexity of the treatment of IMP. Surgery alone may not allow complete excision of the lesion, and residual chorionic tissue may invade the muscular vessels; this case emphasizes the importance of postoperative drug therapy., Conclusion: IMP invades the myometrium in a widely spreading manner, and methotrexate injection in situ at the site of the lesion after conservative surgery may become an efficacious treatment modality., Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Many oral and maxillofacial surgery patients are young, healthy adults who are opioid-naïve. Over-prescribing opioids increases the risk of subsequent misuse and diversion., Purpose: The purpose of this study was to measure and compare opioid prescriptions to opioid naïve and nonnaïve patients by oral and maxillofacial surgeons in Massachusetts from 2012 to 2022., Study Design, Setting, Sample: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2012 to 2022., Predictor/exposure/independent Variable: The predictor variable is opioid exposure coded as opioid naïve (yes/no). Opioid-naïve status was defined as not having filled an opioid prescription in the prior 12 months., Main Outcome Variable: The main outcome variable was the quantity of opioid prescribed by oral and maxillofacial surgeons measured using morphine milligram equivalent (MME) per prescription. The secondary outcome was days' supply prescribed., Covariates: Covariates of the study included patient age and sex., Analyses: Descriptive statistics and weighted linear regressions were used to analyze differences in MME per prescription and days's supply per prescription to opioid-naïve and nonnaive patients each year and throughout the study period. P < .05 was considered statistically significant., Results: The data included a total of 866,539 prescriptions to 679,616 opioid-naïve patients and 186,923 nonnaïve patients from 2012 to 2022. Compared to nonnaïve patients, the opioid-naïve cohort had a slightly higher proportion of females (P ≤ .01 except for 2020) and were significantly younger (35.9 vs 47.6 yrs, P ≤ .01 for all years). For every study year, there was no statistically significant difference in mean MME per prescription or days' supply per prescription between opioid-naïve and nonnaïve patients (P > .05 in all years for both variables). MME per prescription (β = -7.22, 95% CI: -7.65, -6.80; R 2  = 0.79) and days' supply per prescription (β = -0.11, 95% CI: -0.11, -0.10; R 2  = 0.78) decreased at a similar rate throughout the study period for both opioid-naïve and nonnaïve patients., Conclusions and Relevance: Oral and maxillofacial surgeons in Massachusetts predominantly prescribed opioids to opioid-naïve patients. The quantity and duration of initial prescriptions to opioid-naïve and nonnaïve patients were similar, yet both steadily decreasing, throughout the study period. These trends are encouraging in the context of recent responsible opioid prescribing policy interventions in Massachusetts., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. All rights reserved.)

The seasonal influenza vaccine contains strains of viruses from distinct subtypes that are grown independently and then combined. However, most individuals exhibit a more robust response to one of these strains and thus are vulnerable to infection by others. By studying a monozygotic twin cohort, we found that although prior exposure is a factor, host genetics are a stronger driver of subtype bias to influenza viral strains. We found that covalent coupling of heterologous hemagglutinin (HA) from different viral strains could largely eliminate subtype bias in an animal model and in a human tonsil organoid system. We proposed that coupling of heterologous antigens improves antibody responses across influenza strains by broadening T cell help, and we found that using this approach substantially improved the antibody response to avian influenza HA.

Insulin resistance, a key factor in the development of type 2 diabetes mellitus (T2DM), is defined as a defect in insulin-mediated control of glucose metabolism in tissues such as liver, fat and muscle. Insulin resistance is a driving force behind various metabolic diseases, such as T2DM, hyperlipidemia, hypertension, coronary heart disease and fatty liver. Therefore, improving insulin sensitivity can be considered as an effective strategy for the prevention and treatment of these complex metabolic diseases. Cell-based models are extensively employed for the study of pathological mechanisms and drug screening, particularly in relation to insulin resistance in T2DM. Currently, numerous methods are available for the establishment of in vitro insulin resistance models, a comprehensive review of these models is required and can serve as an excellent introduction or understanding for researchers undertaking studies in this filed. This review examines and discusses the primary methods for establishing and evaluating insulin resistance cell models. Furthermore, it highlights key issues and suggestions on cell selection, establishment, evaluation and drug screening of insulin resistance, thereby providing valuable references for the future research efforts., 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 Yang, Wang, Xie, Hu and Li.)

The development of bifunctional single-atom catalysts (SACs) for overall water splitting is crucial for clean energy production in the context of sustainable development. Using first-principles calculations, the catalytic capability of different transition metal (TM) atoms supported on biphenylene (Bip) monolayers (TM@Bip, TM = V-Cu, Ru-Ag, and Ir-Au) is comprehensively investigated. Bip can directly anchor TM atoms without engineered vacancies or nitrogen defects. Among the screened SACs, Pd@Bip is found to be an excellent bifunctional catalyst for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). The overpotentials for the HER and the OER were calculated to be 0.05 and 0.50 V, respectively, which are even superior to the commercialized catalysts like Pt and IrO 2 . Furthermore, adjusting the d-band center of TM atoms effectively modulates the catalytic activity, and the optimal OER performance of TM-Bip can be achieved with a d-band center of -2.32 eV, which can serve as a principle to design Bip-based SACs. Our findings may serve as a practical theoretical guide for the exploration of effective bifunctional SACs for overall water splitting.

Background: Pain in older adults is an increasing concern in low- and middle-income countries (LMICs), with literature suggesting an association with past traumatic events (TEs) in high-income settings. We aim to investigate this relationship in a population-representative sample of older adults with high burden of TEs in a rural South African community., Methods: The Health and Aging in Africa: A longitudinal Study of an INDEPTH Community in South Africa (HAALSI) study collected data pain intensity, using the Brief Pain Inventory, and TEs with a 16-item questionnaire, from 2411 participants aged 40-79 in 2014-15. We used logistic regression models to test the association between TE exposure and self-reported pain status., Results: TE experience was near-universal (99.1% experience of at least one), while 9.0% of participants reported current pain, of which 86.6% was moderate/severe. In multivariable regression, increased odds of moderate/severe pain was associated with more TEs of any kind (OR 1.08; 95%CI 1.02-1.15 per additional TE) and with past exposure to disasters, accidents and illnesses (men and women), violence in the community (women only) and social/family environment problems (men only)-but not with childhood or war-related TEs., Conclusions: TEs were associated with pain even within a rural resource-limited setting where trauma experiences were extremely common. However, associations varied by TE type and sex. Interventions to prevent pain in older adults need to be targeted to block specific mechanisms that vary within even at-risk populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)