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Yan Guo,1,* Jing-Jing Pan,2,* Wen Zhu,1 Mu-Zi Wang,3 Tian-Yu Liu,4 Xiao-Xin Wang,5 Qian-Qian Wu,1 Yi-Xin Cheng,1 Yi-Sen Qian,1 Xiao-Guang Zhou,1 Yang Yang1 1Department of Neonatology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neonatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Neonatology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 4Department of Neonatology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China; 5Department of Pediatrics, Shandong Tumor Hospital, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Guang Zhou; Yang Yang, Department of Neonatology, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email gzzhouxg@163.com; yy860507@126.comObjective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD).Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤ 32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤ 32 weeks). The classical lung biological markers in serum were also measured simultaneously.Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738– 0.968; adjusted odds ratio:6.033, 95% CI:2.373– 13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058.Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤ 32 weeks.Keywords: bronchopulmonary dysplasia, circular RNAs, high-throughput sequencing, preterm infants

ChunYing Cui,1 Lie Wang,1 XiaoXi Wang2 1Department of Social Medicine, School of Public Health, China Medical University, Shenyang North New Area, Shenyang, Liaoning, 110122, People’s Republic of China; 2Medical Basic Experimental Teaching Center, China Medical University, Shenyang North New Area, Shenyang, Liaoning, 110122, People’s Republic of ChinaCorrespondence: XiaoXi Wang Email xiaoxiwang@cmu.edu.cnBackground: Anxiety and depression are the most common psychological causes of distress in infertile women. Our study aimed to evaluate the prevalence of depression and anxiety and investigate the effects of self-esteem on the association of infertility-related stress with depression and anxiety among infertile women.Methods: This study was conducted between December 2017 and May 2018. Questionnaires containing Fertility Problem Inventory (FPI), Rosenberg self-esteem scale (RSES) and Hospital Anxiety and Depression Scale (HADS) were distributed among 536 female infertility patients in Shenyang, China. Hierarchical linear regression analyses were used to examine the mediating and moderating role of self-esteem. Baron and Kenny’s technique, asymptotic, and resampling strategies were used to confirm the mediating role of self-esteem on the associations between infertility-related stress with depression and anxiety.Results: The prevalence of depression and anxiety was 27.9% and 42.2% among Chinese female infertility patients, respectively. Infertility-related stress was positively associated with depression and anxiety, whereas self-esteem was negatively associated with depression and anxiety. Additionally, the effects of infertility-related stress on depression and anxiety gradually decreased along with an increase in self-esteem. Meanwhile, self-esteem partially mediated the associations between infertility-related stress with depression and anxiety.Conclusion: A high prevalence of psychological distress was found among infertile women. Self-esteem mediated and moderated the effects of infertility-related stress on depression and anxiety. Additionally, infertility-related stress and self-esteem were associated with psychological distress, which explained why infertile women had a higher prevalence of depression and anxiety. Therefore, interventions that focus on self-esteem may be effective and should be used as a resource to combat mental health problems.Keywords: infertility-related stress, depression, anxiety, self-esteem, infertility

Fan Yang,1,2 Xu Xia Wang,1,3 Dan Ma,1,2 Qun Cui,1,2 De Hua Zheng,1,2 Xiao Can Liu,1,2 Jun Zhang1,2 1Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Jun ZhangDepartment of Orthodontics, School of Stomatology, Shandong University, 44 Wenhua West Road, Jinan 250012, People’s Republic of ChinaTel +86 139 5310 9816Fax +86-531-88565657Email zhangj@sdu.edu.cnPurpose: The aim of this study was to investigate the effects of triptolide on the tooth movement and root resorption in rats during orthodontic treatment.Material and methods: A total of 48 male Wistar rats were divided into three groups of 16 each. The right maxillary first molars of rats were drawn mesially by closed coil nickel–titanium spring with a force of 50 g. The two experimental groups received intraperitoneal injections of triptolide for 14 days at a dose of 15 μg/kg/day and 30 μg/kg/day, respectively. The control group received vehicle injections. After 14 days, the rats were humanely killed. The amount of tooth movement was measured. Eight rats from each group were randomly chosen for analysis of the percentage of root resorption area by scanning electron microscopy. For the remaining eight rats in each group, the H&E staining, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemistry analysis were performed.Results: The amount of tooth movement and the ratio of root resorption area were significantly decreased in the triptolide-treated rats. The number of TRAP-positive cells was significantly lower in triptolide-treated groups. Moreover, the expression of nuclear factor kappa B ligand (RANKL) was reduced. In contrast, the expression of osteoprotegerin was significantly up-regulated. In the tension side, the expressions of runt-related transcription factor 2 and osteocalcin were significantly enhanced by triptolide injection.Conclusion: Triptolide injection could arrest orthodontic tooth movement and reduce root resorption in rats via inhibition of osteoclastogenesis. In addition, triptolide may exert a positive effect on osteoblastogenesis.Keywords: triptolide, osteoclast, scanning electron microscope, tooth movement, bone formation

Wen-Xiu Yuan,1 Xu-Xia Wang,2 De-Hua Zheng,1 Dan Ma,1 Qun Cui,1 Fan Yang,1 Jun Zhang1 1Department of Orthodontics, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong Province, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Jun ZhangDepartment of Orthodontics, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration, No. 44-1 Wenhua Road West, Jinan, Shandong Province, People’s Republic of ChinaTel +86 139 5310 9816Email zhangj@sdu.edu.cnObjectives: This study was performed to evaluate the effects of muscone on the proliferation, migration and differentiation of human gingival mesenchymal stem cells (GMSCs) and to explore the relevant mechanisms.Materials and methods: We performed studies to determine the effects and mechanisms of muscone on GMSC proliferation, migration and differentiation. We conducted CCK-8, colony formation, transwell chamber, scratch wound, alkaline phosphatase (ALP) staining and activity, and alizarin red and oil red O staining assays, as well as real-time quantitative polymerase chain reaction (qRT-PCR), to ascertain the effects of muscone on GMSC proliferation, migration and differentiation in vitro. The mechanism by which muscone influences the osteogenic and adipogenic differentiation of GMSCs was elucidated by qRT-PCR and Western blotting.Results: We found that muscone significantly promoted GMSC proliferation, chemotaxis, wound healing and fat droplet formation and inhibited ALP activity and mineral deposition. Notably, we observed that the Wnt/β-catenin pathway was closely related to the ability of muscone to inhibit the osteogenic differentiation and promote the adipogenic differentiation of GMSCs. The effect of muscone on the multidirectional differentiation capacity of GMSCs was significantly reversed by the agonist lithium chloride through the Wnt/β-catenin signaling pathway.Conclusion: Muscone effectively increased the proliferation and migration, promoted the adipogenic differentiation and inhibited the osteogenic differentiation of GMSCs by inhibiting the Wnt/β-catenin signaling pathway. These results may provide a theoretical basis for the application of GMSCs and muscone in tissue engineering and regenerative medicine.Keywords: muscone, gingival mesenchymal stem cells, GMSCs, differentiation, Wnt/β-catenin signaling pathway, proliferation, chemotaxis

De-Hua Zheng,1 Xu-Xia Wang,2 Dan Ma,1 Li-Na Zhang,3 Qing-Fang Qiao,1 Jun Zhang41Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School of Dentistry, Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Department of Orthodontics, Liaocheng People’s Hospital, Liaocheng, Shandong Province, People’s Republic of China; 4Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, People’s Republic of ChinaObjectives: The aim of this study is to examine the roles of erythropoietin (EPO) in regulating proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes.Materials and methods: PDLSCs were isolated and characterized. The PDLSCs were transfected with β-catenin shRNA. qRT-PCR and Western blot analysis were used to examine the osteogenic effects of EPO on the expression of osteogenic-related genes and protein (Runx2, OCN and Osterix) in PDLSCs. Alizarin Red-S staining was used to detect mineralized nodule formation. In addition, the relationship between the Wnt/β-catenin pathway and the effect of EPO on the osteogenesis of PDLSCs was investigated.Results: The results suggested that EPO exerts positive osteogenic effects on PDLSCs. The results showed that EPO decreased the growth of PDLSCs slightly and increased alkaline phosphatase activity and calcium deposition in a dose-dependent manner. The expression of Runx2, Osterix and OCN was increased after EPO administration. EPO increases β-catenin and Cyclin D1 in PDLSCs. After transfected with β-catenin shRNA, the osteogenic effect of EPO on PDLSCs was attenuated.Conclusion: EPO promotes osteogenic differentiation of PDLSCs. The underlying mechanism may be activating Wnt/β-catenin signaling pathway.Keywords: erythropoietin, periodontal ligament stem cell, osteogenesis, Wnt/β-catenin

Xiao-Xiao Wang,1,* Fu-Gui Ye,2,* Jie Zhang,1,* Jun-Jing Li,1 Qing-Xia Chen,1 Pei-Yang Lin,1 Chuan-Gui Song1 1Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Neoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response. Patients and methods: We recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients. Results: No significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity. Conclusion: Our results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity. Keywords: miR-4530, serum, neoadjuvant chemotherapy, chemotherapeutic resistance, RUNX2

Xixia Liu,1,2 Yuhan Liao,1 Xiuxiu Wang,1 Donghua Zou,1 Chun Luo,1 Chongdong Jian,1 Yuan Wu1 1Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 2Department of Rehabilitation, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China Abstract: MicroRNA (miRNA) is believed to play a crucial role in the cause and treatment of epilepsy by controlling gene expression. However, it is still unclear how miRNA profiles change after multiple prolonged seizures and aggravation of brain injury in chronic epilepsy (CE). To investigate the role of miRNA in epilepsy, we utilized the CE rat models with pentylenetetrazol (PTZ) and miRNA profiles in the hippocampus. miRNA profiles were characterized using miRNA microarray analysis and were compared with the rats in the sham group, which received 0.9% physiological saline treatment at the same dose. Four up-regulated miRNAs (miR-139–3p, -770–5p, -127–5p, -331–3p) and 5 down-regulated miRNAs (miR-802–5p, -380–5p, -183–5p, -547–5p, -344a/-344a–5p) were found in the CE rats (fold change >1.5, P

Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO) synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress

Shuya Zhao,1,* Xuxia Wang,2,* Na Li,3 Yun Chen,1 Yuran Su,1 Jun Zhang1 1Department of Orthodontics, 2Department of Oral and Maxillofacial Surgery, Faculty of Stomatology, Shandong University; 3Department of Orthodontics, Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The aim of this experimental study was to investigate the effects of strontium ranelate on bone regeneration in the mid-palatal suture in response to rapid maxillary expansion (RME).Methods: Thirty-six male 6-week-old Wistar rats were randomly divided into three groups, ie, an expansion only (EO) group, an expansion plus strontium ranelate (SE) group, and a control group. An orthodontic appliance was set between the right and left upper molars of rats with an initial expansive force of 0.98 N. Rats in the SE group were administered strontium ranelate (600 mg/kg body weight) and then euthanized in batches on days 4, 7, and 10. Morphological changes in the mid-palatal suture were investigated using micro-computed tomography and hematoxylin and eosin staining after RME. Bone morphogenetic protein-2 expression in the suture was also examined to evaluate bone formation in the mid-palatal suture. Image-Pro Plus software was then used to determine the mean optical density of the immunohistochemical images. Analysis of variance was used for statistical evaluation at the P0.05) between the SE and EO groups. The bone volume of the suture decreased after RME, but was higher in the SE group than in the EO group on days 7 and 10. Further, expression of bone morphogenetic protein-2 in the SE group was higher than in the other two groups (P

Li Zhao,1,* Peng Yang,2,* Pengmei Li,1 Xiaoxing Wang,1 Wangjun Qin,1 Xianglin Zhang1 1Department of Pharmacy, 2Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Digoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4–1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8–2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC. Methods: The study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively.Results: The correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P

Ying Men*, Xiao-Xing Wang*, Ruo-Jing Li, Yan Zhang, Wei Tian, Hong-Juan Yao, Rui-Jun Ju, Xue Ying, Jia Zhou, Nan Li, Liang Zhang, Yang Yu, Wan-Liang LuState Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China*These authors contributed equally to this manuscriptBackground: Multidrug resistance (MDR) of cancers can be circumvented by inducing programmed cell death, which is known as apoptosis. Mitochondria play a crucial role in apoptosis. Mitochondria-specific therapy would provide an efficient strategy for treating resistant cancers.Design and methods: A strategy was proposed here to overcome MDR by designing cancer mitochondria-specific drug-loaded liposomes, namely, antiresistant epirubicin mitosomes, aimed at treating resistant leukemia by targeting mitochondria. Evaluations were performed on human chronic leukemia K562, MDR K562/ADR cells, and female BALB/c nude mice xenografted with MDR K562/ADR cells. The liposomes were characterized through assays of cytotoxicity, mitochondrial targeting, caspase-9 and caspase-3, antitumor activities, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis.Results: The average size of antiresistant epirubicin mitosomes was in the range of 105–115 nm. Antiresistant epirubicin mitosomes were effective in inhibiting proliferation of MDR K562/ADR cells in vitro and selectively accumulated into the mitochondria. Caspase-9 and caspase-3 activity was increased after applying antiresistant epirubicin mitosomes. In xenografted resistant MDR K562/ADR tumor in nude mice, antiresistant tumor effect of antiresistant epirubicin mitosomes was evidently observed. Apoptotic inducing effects by antiresistant epirubicin mitosomes were noticeably evidenced via mitochondrial pathway.Conclusions: Antiresistant epirubicin mitosomes had significant inhibitory effect against resistant leukemia in vitro and in vivo, hence providing a promising strategy for improving therapeutic efficacy in resistant human leukemia.Keywords: mitosomes, mitochondria signaling pathway, nude mice

PURPOSE: The purpose of this study was to investigate the effects of biomimetically and electrochemically deposited hydroxyapatite on the fixation of an implant with bone tissue. MATERIALS AND METHODS: Implants were separated into 3 groups: roughened group, biomimetically deposited calcium-phosphorus (BDCaP) group, and electrochemically deposited hydroxyapatite (EDHA) group. We randomly inserted 90 implants into the femurs of 45 rabbits. After 2, 4, and 8 weeks, the femurs were retrieved and prepared for removal torque tests (RTQs) and field-emission scanning electron microscopy observation. RESULTS: During the test period, the EDHA group showed significantly greater RTQ values than did the roughened group and BDCaP group. The BDCaP group failed to increase the RTQ values compared with the roughened group. Field-emission scanning electron microscopy observation showed that the amount of attached bone tissue on the EDHA-coated implant surface was more than that on the roughened and BDCaP-coated implant surfaces during the test period. CONCLUSION: The electrochemical hydroxyapatite coating contributes to the fixation between bone and implant compared with the roughened surface, whereas the biomimetic calcium-phosphorus coating has little effect on the fixation. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that stroke may be associated with an increased prevalence of restless legs syndrome (RLS) as a comorbidity or a risk factor. We aimed to explore the association between acute ischemic stroke (AIS) and RLS, and the possible pathogenesis of acute ischemic stroke related restless legs syndrome (AIS-RLS), for guiding its diagnosis and treatment., Methods: In this single-center, prospective study, we identified consecutive AIS patients and segregated into AIS-RLS group and non-AIS-RLS group based on the diagnostic criteria of RLS. The differences in baseline data, clinical features, examination results, stroke etiology, stroke location, and clinical prognosis (functional disability, cognitive and mood disorders) of the two groups were analyzed. Logistic regression analysis was used to evaluate the risk factors for RLS., Results: A total of 201 AIS patients were included in our study, and 21 (10.45 %) demonstrated RLS. Compared with non-AIS-RLS group, AIS-RLS group patients had higher systolic blood pressure (SBP) at admission (P < 0.05), higher mean 24-h SBP (P < 0.01), higher mean 24-h diastolic blood pressure (DBP) (P < 0.01), higher mean daytime SBP (P < 0.01), higher mean daytime DBP (P < 0.01), higher mean nocturnal SBP (P < 0.01), higher mean nocturnal DBP (P < 0.05), smaller variation coefficient of 24-h SBP (P < 0.05). The distribution of AIS-RLS and non-AIS-RLS was not different for each subtype according to the cortical and subcortical classification of lesion sites. The NIHSS score, GAD-7 score and PHQ-9 score were higher at 7 days (P < 0.05), and the modified Rankin scale (mRS) was higher at 3 months follow-up (P < 0.05) in the AIS-RLS group. In the logistic regression, the higher SBP at admission had a statistically significant effect on AIS-RLS(OR = 1.030,P = 0.016)even after adjusting for age and gender(OR = 1.030,P = 0.014)., Conclusion: Stroke anatomy did not differ between AIS-RLS and non-AIS-RLS groups. AIS-RLS group patients tend to experience higher blood pressure. Moreover, AIS-RLS patients had worse clinical prognosis (functional disability and mood disorders) compared with non-AIS-RLS patients., 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 © 2025 Elsevier B.V. All rights reserved.)

Patients with locally advanced oral squamous cell carcinoma (OSCC) have poor outcomes with standard care. Neoadjuvant therapy is shown to be effective for these patients. In the randomized, two-arm, phase 2, non-comparative trial, we investigate the efficacy and safety of the neoadjuvant programmed cell death 1 (PD-1) inhibitor camrelizumab with or without docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy in patients with resectable locally advanced OSCC. Patients with stage III-IVA OSCC receive neoadjuvant therapy with three cycles of camrelizumab (arm Cam) with or without two cycles of TPF chemotherapy (arm Cam+TPF), followed by surgery and adjuvant therapy. Major pathological response (MPR) is achieved in both arm Cam (5/34, 14.7%) and arm Cam+TPF (26/34, 76.4%). With a median follow-up of 32 months, the 2-year event-free survival (EFS) rate of arm Cam and Cam+TPF is 52.9% and 91.2%, respectively. This work demonstrates feasibility and safety for immunochemotherapy in the neoadjuvant setting for OSCC. This study was registered at ClinicalTrials.gov (NCT04649476)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: This study was aimed at comparing the efficacy of different modes of transvaginal temperature-controlled radiofrequency (TTCRF) in improving female stress urinary incontinence (SUI)., Methods: A randomized trial with a nested prospective cohort included 89 women with SUI, who were randomized into a unipolar group (n = 35) and a comprehensive group (n = 54). The comprehensive mode group was treated with unipolar and bipolar combination therapy. The 1-h pad test (1-h PWT) was used as the primary metric by which to gauge improvement of SUI. The effective rate was defined as (cure + improvement cases/total cases) × 100%. Daily leakage episodes and urinary incontinence questionnaires were also documented to compliment this metric in assessing treatment efficacy. Patient satisfaction was assessed and adverse reactions were monitored., Results: No significant difference in the effective rate between the unipolar and comprehensive groups was observed at 1, 3, 6, and 12 months after the end of treatment (62.9% vs 66.7%, 68.6% vs 68.5%, 80.0% vs 71.7%, 74.3% vs 62.5% respectively). Objective improvement of SUI symptoms and subjective satisfaction for all SUI patients were achieved after TTCRF treatment. Ten-course treatment of TTCRF achieved significantly greater treatment effects than five-course treatment as measured by 1-h PWT, daily leakage episodes, International Consultation on Incontinent Questionnaire-Short Form, and Pelvic Organ Prolapsed-Urinary Incontinence Sexual Questionnaire-12. No significant side effects occurred in any patients during treatment., Conclusions: We consider TTCRF treatment to be a viable outpatient option for SUI, with unipolar and comprehensive modes both showing similar efficacy for SUI., Competing Interests: Declarations. IRB Approval: This study protocol was approved by the ethical committee of Fujian Maternity and Child Health Hospital (2020YJ149), and written informed consent was obtained from all patients before the study was initiated. Conflicts of Interest: None., (© 2025. The International Urogynecological Association.)

Lithium-oxygen (Li-O 2 ) batteries with high energy density have given rise to tremendous advances in developing highly efficient energy storage devices. However, the barrier of Li dendrite growth and the liquid electrolyte volatilization under semi-open architectures still restrict their future applications. Poly(vinylidene fluoride) (PVDF)-based polymer electrolytes are considered to be an effective solution to these issues, but the presence of highly reactive residual solvents severely disrupts the long-term cycling stability of the battery. Herein, a tailoring strategy to confine and redistribute the solvent molecules by introducing porous metal-organic framework (MOF) is proposed. The Lewis acid sites and functional groups on MOFs offer more binding sites for residual solvents, leading to more involved anions in Li + solvation. Benefiting from the tailored coordination environment of polymer electrolytes, the Li dendrite growth and liquid electrolyte volatilization are effectively suppressed in the composite polymer electrolyte (MOF@PVDF). As a result, the MOF@PVDF enables the Li//Li symmetrical cells ultra-stable cycling over 800 h at  0.2 mA cm -2 . Meanwhile, the MOF@PVDF-based Li-O 2 battery has realized a long life above 1100 h at 200 mA g -1 . This work opens a direction in developing stable polymer electrolytes for high energy density Li-O 2 batteries by tailoring the solvation structures of polymer electrolytes., (© 2025 Wiley‐VCH GmbH.)

Piezocatalysis is considered to be a favorable catalytic technology by utilizing external mechanical stimulation to promote the specific redox reactions. The application of piezocatalysis in batteries is promising but faces formidable challenges. Herein, the operation principles of piezocatalysis were successfully demonstrated by constructing solid-state Li-Se and Li-S battery models with interfacial stress accumulation. Lead zirconate titanate with an ultra-high piezoelectric coefficient was applied as the piezoelectric catalyst. The uniformity of the dipole orientation in materials was essential for achieving piezocatalysis in batteries. The accumulated high-stress converts to piezopotential for catalyzing most reaction processes in batteries, while the rapid stress change prevents the internal charge reorganization, ensuring continuous efficient catalysis. The internal stress change alters the internal polarisation strength, driving excess screening charge to participate in the electrochemical reaction. Under piezocatalysis, solid-state Li-Se batteries exhibited a initial discharge capacity of 670.9 mAh g -1 (99.4 % of the theoretical value) at 0.1 C, and Li-S batteries showed a capacity of 1463 mAh g -1 at 0.2 C, which was still maintained up to 1084 mAh g -1 at an elevated rate of 0.5 C. This piezocatalysis strategy provides a strong theoretical basis and design specification for enhancing Li-Se and Li-S battery reaction kinetics., (© 2024 Wiley-VCH GmbH.)

Introduction: Retinitis pigmentosa (RP) is a type of inherited retinal degeneration (IRD) that typically leads to vision loss in individuals of working age. Currently, over 100 genes and loci, as well as over 1000 individual variants, have been identified in relation to RP. The aim of this study was to investigate the genetic distribution and characteristics of Chinese patients with RP, as well as to describe and analyze the genetic features of the high-frequency variant from the RPGR gene., Methods: A total of 69 Chinese patients diagnosed with RP from 36 families were included in this study. Blood samples were collected, and DNA was extracted for genetic analysis. A custom panel targeting 822 genes associated with RP was designed for next-generation sequencing (NGS) analysis. The sequenced data were processed and analyzed using bioinformatics tools to identify genetic variants. Variant classification followed the guidelines provided by the American College of Medical Genetics and Genomics (ACMG), taking into consideration functional effects, population frequencies, and previous literature reports. Variant validation was performed using Sanger sequencing to confirm the presence of identified variants. The inheritance pattern of RP-associated variants was determined by analyzing the segregation pattern within families. Pedigrees were constructed based on the clinical and genetic information of the participants. Statistical analysis was conducted to summarize the clinical characteristics of the RP patients using descriptive statistics. Ethical considerations were strictly followed throughout the study, with approval obtained from the ethics committee and informed consent obtained from all participants., Results: Following this, the identified variants were classified and subjected to statistical analysis. A total of 15 candidate genes associated with RP were identified, along with 39 variants, consisting of 36 reported variants and 3 novel variants. The majority of these variants were classified as pathogenic. The most common changes observed in this study were substitutions, followed by missense variants. Genetic analysis indicated that all variants occurred in the exon region. In the RPGR gene, half the variants are located in the ORF15. Gene, with half of variants located in ORF15. The most frequent variant within this group was RPGR NM&#95;001034853.1: c.2236&#95;2237del, which was identified in a large five-generation pedigree. The three novel variants reported in this study include NM&#95;015629.3: c.1168&#95;1169insGATTCAGCCTGGCC of PRPF31, NM&#95;001034853.1: c.3026&#95;3027insAGAGGGAGAGGAAGAAGG and NM&#95;000328.2: c.611T>G of RPGR., Conclusions: The findings of this study offer valuable insights into the genetic variants responsible for RP in affected individuals, which can be utilized for genetic counseling and diagnosis. This underscores the significance of genetic testing in the management and treatment of RP., (© 2025 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The behavior of resistant starch (RS) in meat matrix depends largely on its type. Hence, the comparative impacts of high amylose corn starch (RS2), retrograded starch (RS3), acetylated starch (RS4) and high amylose-lauric acid complex (RS5) on water-fat binding capacities, texture, color and microstructure of low-fat meat emulsions were investigated. Four types of RS improved water retention, emulsion stability, textural properties and brightness of low-fat meat emulsions, displaying even better potential than inulin (positive control). Compared with inulin, RS2 ∼ RS5 induced the transition from free water to immobilized water, increased storage modulus G' (by 21.90 %, 38.13 %, 55.73 % and 45.92 %, respectively), hydrophobic interactions (by 36.03 %, 60.84 %, 44.40 % and 48.04 %, respectively), disulfide bonds and β-sheet, which promoted the formation of tight protein gel networks. Notably, physical or chemical modified RS (RS3, RS4, RS5) displayed preferable and more similar water-fat binding properties, making them more promising for personalized application in low-fat functional meat products., 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 Ltd. All rights reserved.)

Growing evidence suggests a link between couple relationships and sleep, yet findings are inconsistent. We conducted a systematic review and meta-analysis, searching four databases up to March 2023, and included 62 studies with 43,860 participants. Results indicated a moderate correlation between better couple relationship quality and better overall sleep quality (r = 0.34, 95%CI = 0.09-0.59), as well as longer sleep duration (r = 0.39, 95%CI = 0.04-0.65). Regarding specific couple relationship domains, greater partner responsiveness was linked to improved overall sleep quality (r = 0.19, 95%CI = 0.13-0.25), while partner support showed no significant association (r = 0.03, 95%CI = -0.02-0.09). Increased partner conflict was associated with poorer overall sleep quality (r = 0.17, 95%CI = 0.06-0.27). In the studies that could not be meta-analyzed, greater partner conflict significantly correlated with longer actigraphy-based sleep latency and more wake episodes, but not necessarily with shorter actigraphy-based sleep duration. Increased self-disclosure was related to better overall sleep quality, whereas higher perceived rejection was linked to worse overall sleep quality. Higher closeness was not consistently associated with better overall sleep quality. Our results suggest a significant link between better couple relationships and improved sleep. Improving couple relationships may enhance sleep. However, further long-term cohort studies outside the USA are needed to evaluate these associations, particularly regarding specific couple relationship domains and specific sleep indicators., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons and the consequent decline in motor and cognitive functions. The primary therapeutic agent levodopa necessitates precise dosing due to its narrow therapeutic window and complex pharmacokinetics. This study presents the development of a novel CuCoFe-LDHzyme-based sweat sensor for real-time monitoring of levodopa concentration in PD patients. Employing differential pulse voltammetry (DPV) technique, the sensor demonstrates high sensitivity and selectivity, achieving a detection limit of 28.1 nM. The sensor's design allows for non-invasive, continuous monitoring, significantly enhancing patient convenience compared to traditional blood sampling methods. Through pH correction, precise quantification of levodopa in sweat is accomplished, and a strong correlation (Pearson coefficient = 0.833) with blood levodopa levels is established. The pharmacokinetic profile of levodopa is reconstructed in real-time, offering a promising tool for optimizing PD treatment regimens. This study highlights the potential of CuCoFe-LDHzyme sensors to advance personalized treatment strategies, aiming to improve the quality of life for PD patients by providing clinicians with real-time data for medication adjustments., 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.)

Rechargeable batteries paired with lithium (Li) metal anodes are considered to be promising high-energy storage systems. However, the use of highly reactive Li metal and the formation of Li dendrites during battery operation would cause safety concerns, especially with the employment of highly flammable liquid electrolytes. Herein, a general strategy by engineering coordination-driven crosslinking networks is proposed to achieve high-performance solid polymer electrolytes. Through the coordination of metal-organic polyhedra (MOPs) with cellulose-based copolymers, the Li + -conducted hypercrosslinked MOP (CHMOP-Li) polymer network is capable of enabling the rapid transport of Li + . In addition to the high Li + conductivity (1.02×10 -3  S cm -1 at 25 °C), CHMOP-Li electrolyte also exhibits a high Li + transference number (0.75) and a wide electrochemical stability window. Benefiting from the thermally stable and mechanically strong CHMOP-Li electrolyte film, the short-circuiting of the symmetric batteries is prevented even after 3200 h of cycling and a high specific energy of 300 Wh kg -1 is achieved for the Li-metal battery. The solid-state Li-O 2 batteries fabricated with CHMOP-Li electrolyte also show good cycling performance (500 cycles) and high discharge capacity (15740 mAh g -1 ). The proposed coordination-driven crosslinking strategies offer an alternative route to design high-performance next-generation sustainable battery chemistries., (© 2024 Wiley-VCH GmbH.)

In hepatocellular carcinoma (HCC), lenvatinib is a key first-line treatment that significantly improves survival in some patients with advanced stage. However, lenvatinib resistance presents a major clinical challenge. This study aims to identify key molecular factors driving lenvatinib resistance in HCC and propose intervention strategies to overcome this resistance, thereby enhancing therapeutic efficacy. A genome-wide CRISPR-Cas9 activation screen identified METTL8 as a crucial gene associated with lenvatinib resistance. Validation through in vitro and in vivo assays confirmed METTL8's role in mediating lenvatinib resistance. Higher METTL8 expression was observed in lenvatinib-resistant HCC cells compared to parental cells. Immunohistochemical staining of tissue sections from HCC patients revealed a negative correlation between high METTL8 expression and lenvatinib sensitivity. To inhibit the function of METTL8 that mediate lenvatinib resistance, we conducted a screening using a natural compound library, virtual drug screening identified Rabdosiin as a potential METTL8 inhibitor, subsequent experiments demonstrated that Rabdosiin could effectively overcome METTL8-mediated lenvatinib resistance. In conclusion, this research highlights METTL8 as a novel target for mitigating lenvatinib resistance, proposing that targeting METTL8 could restore lenvatinib sensitivity in HCC, and underscores its value as a biomarker for lenvatinib application in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease which afflicts about nearly 1% of global population. RA results in synovitis and cartilage/bone damage, even disability which aggravates the health burden. Many drugs are used to relieve RA, such as glucocorticoids (GCs), non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) in the clinical treatment. However, present clinical drugs have various disadvantages such as poor bioavailability and short biological half-life and drug resistance, or adverse effects. A recent study showed autophagy modulation may be a novel strategy in the treatment of RA. 3-Methylademine (3-MA), is the most widely used autophagy inhibitor, which blocks autophagy at the initiation and maturation stages. The aim of this study is to evaluate the effect of 3-MA in collagen-induced-arthritis (CIA) mice and further elucidate how 3-MA attenuated inflammation, and cartilage/bone damage in arthritis., Methods: An in-vivo mouse collagen-induced arthritis model was applied to compare differences in ankle destruction among control mice and CIA mice treated with or without 3-MA. Bone and cartilage destruction degree was evaluated by histology and micro-computed tomography (µCT). Further in-vivo assays utilized mouse serum samples to investigate inflammatory levels, oxidative levels, and bone resorption cytokines. At last, an immunofluorescence assay was applied to detect the autophagy level among the three groups., Results: The in-vivo mouse collagen-induced arthritis model showed that CIA mice revealed apparent hind paw and ankle swelling which was aggravated gradually along with time, while 3-MA treatment attenuated swelling gradually. µCT and histological results showed typical lesions in CIA group while 3-MA treatment alleviated arthritis-related destruction. Serum assay showed that 3-MA significantly reduced inflammatory cytokines levels, suppressed oxidative levels and bone resorption cytokines. Immunofluorescence assay revealed 3-MA significantly inhibited the abnormal autophagy level in CIA mouse ankle., Conclusions: 3-MA protects bone destruction in CIA-induced mice arthritis by anti-inflammatory effect and autophagy inhibition., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Ethical approval: Ethical approval for this study was obtained from *INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE OF YI SHENGYUAN GENE TECHNOLOGY (TIANJIN) (APPROVAL YSY-DWLL-2022132)*., (© 2025. The Author(s).)

Chiral metal organic cage compounds with excellent circularly polarized luminescent performance have broad application prospects in many fields. Herein, two lanthanide complexes with luminescent properties in the form of racemic hexagonal octahedral cages were synthesized using a tri (β-diketone) ligand. Eu 6 (C 21 H 6 F 15 O 6 ) 8 (H 2 O) 6 exhibited red light emission with high quantum yields of 61 %. Then, we successfully synthesized lanthanide compounds with circularly polarized luminescent activity by chiral induction of the racemic mixture with arginine. The luminescence asymmetry factor was 0.53, and the circularly polarized luminescent merit figure reached 0.323. High-performance circularly polarized luminescent of racemic cage like compound systems have achieved using cheap and readily available chiral amino acid molecules through chiral induction., (© 2025 Wiley-VCH GmbH.)