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Chenhao Suo,1,* Yiru Gao,2,* Sheng Yang,2 Wanli Zhang,2 Chao Li,3 Lanjing Ma,2 Yingchun Xu,4,5 Jianjun Lei,1 Chen Ding,2 Hailong Li,6 He Zhang,1 Tianshu Sun4,7 1Laboratory Animal Department, Northern Theater General Hospital, Shenyang, Liaoning, 110000, People’s Republic of China; 2College of Life and Health Science, Northeastern University, Shenyang, Liaoning, 110000, People’s Republic of China; 3Department of Emergency Medicine, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, 100730, People’s Republic of China; 5Medical Research Centre, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China; 6Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; 7Clinical Biobank, Medical Research Center, National Science and Technology Key Infrastructure on Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianshu Sun; He Zhang, Email sun_tianshu@163.com; alwayszhh@163.comIntroduction: The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking.Objective: In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence.Methods: Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions.Results: In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25.Discussion: These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.Keywords: endocytosis, Sla1, cell wall integrity, drug susceptibility, fungal pathogenicity

Ziheng Chen,1 Jinxin Ma,1 Jiahui Lei,1 Yi Li,1 Ruijuan Zhao,1 Limin Zhao2 1Department of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Limin Zhao, Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, 7 Weiwu Road, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Email zhaolimin2002@126.comPurpose: This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25– 75% (FEF25-75%) and FAO.Patients and Methods: We analyzed data from 312 han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score 10 years (2.01 [1.06– 3.86], P=0.035) and occupational exposure for > 20 years (2.67 [1.24– 5.91], P=0.013) were associated with asthmatic FAO. In cross-sectional analyses, compared with the normal FEF25-75%/ asthmatics without FAO (NON-FAO) group, the low FEF25-75%/ asthmatics with FAO (FAO) group had lower FEV1 z-scores and FEV1/FVC z-scores, more pack-years and years of biomass and occupational exposure, higher Asthma Control Questionnaire-5 and Chronic Obstructive Pulmonary Disease Assessment Test scores, and more frequent exacerbations. The low FEF25-75%/NON-FAO group showed the same trend, but to a lesser extent.Conclusion: Chronic airway inflammation is not the only driver of asthmatic FAO, and management and treatment targeting environmental risk factors (smoking and biomass and occupational exposures) may slow FAO progression in asthmatics. The FEF25-75% determined by the z-score is a reliable marker of small airway abnormalities, and patients with low FEF25-75% are at greater risk for FAO, requiring more frequent follow-up.Keywords: asthma, fixed airflow obstruction, environmental exposures, forced expiratory flow at 25-75%

Baokun Liu,1,2,&ast; Lujun Shen,3,4,&ast; Wen Liu,5 Zhiyong Zhang,1,2 Jieqiong Lei,1,2 Zhengguo Li,1,2 Qinquan Tan,6 Hengfei Huang,7 Xingdong Wang,1,2 Weijun Fan3,4 1Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center Gansu Hospital, Lanzhou, 730050, People’s Republic of China; 2Department of Minimally Invasive Interventional Therapy, Gansu Provincial Cancer Hospital, Lanzhou, 730050, People’s Republic of China; 3Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 5Department of Radiotherapy, Lanzhou University Second Hospital, Lanzhou, 730030,People’s Republic of China; 6Department of Oncology, Dongguan People’s Hospital, Dongguan, 523000, People’s Republic of China; 7Department of General Surgery, Chongzuo People’s Hospital, Chongzuo, 523000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingdong Wang; Weijun Fan, Email wxd101027@163.com; fanwj@sysucc.org.cnPurpose: The majority of new diagnoses of hepatocellular carcinoma (HCC) still pertain to unresectable cases. Currently, the combination therapy of tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors has become the mainstream treatment. According to multiple clinical guidelines, it is strongly advised to consider local therapy as the primary treatment choice for uHCC. This research was conducted to examine the safety and effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with TKIs and PD-1 inhibitors for the treatment of uHCC.Methods: Between 2015 and 2020, 208 HCC patients received HAIC alone or HAIC in combination with TKIs and PD-1 inhibitors. The overall survival(OS), and progression-free survival(PFS) and the best treatment response were compared between the two treatment groups. Propensity score matching (PSM)was used to minimize confounding bias.Results: Among the enrolled patients, 116 patients (55.8%) received combination therapy, while 92 patients (44.2%) received HAIC alone. The baseline characteristics were similar between the two groups. After PSM, 82 pairs of well-matched liver cancer patients were selected; the overall response rate in the combination group trended better than that in the HAIC alone group. The hazard ratios (HRs) for OS and PFS of the combination approach compared to the HAIC-alone approach were 0.47 (95% CI, 0.322– 0.687; p< 0.001) and 0.58 (95% CI, 0.397– 0.848; p=0.005), respectively.Conclusion: For uHCC patients, combination therapy can provide better OS and PFS compared to HAIC alone.Keywords: hepatocellular carcinoma, TKIs, PD-1, HAIC, combination therapy

Yijie Zhang,1,2,&ast; Jin Lei,3,&ast; Huaxing Ma,3 Shi Zuo2 1Department of General Surgery, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3School of Basic Medical Sciences, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shi Zuo, Email drzuoshi@gmc.edu.cnBackground: Lenvatinib is the first-line treatment option for patients with advanced hepatocellular carcinoma (HCC); however, the impact of lenvatinib resistance on patient prognosis is unknown.Methods: We recruited all patients with advanced HCC who received first-line lenvatinib treatment between February 2019 and February 2023 at two medical centers in China, according to the selection criteria. The patients were divided into primary and secondary resistance groups based on tumor progression within 3 months. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Logistic regression and Cox proportional hazards models were used to explore factors influencing drug resistance and prognosis. The study end points were drug resistance, PFS, and OS.Results: A total of 531 patients met the study criteria, with 169 (31.8%) and 362 (68.2%) patients in the primary and secondary groups, respectively. An alpha-fetoprotein (AFP) concentration > 400 ng/mL was an independent risk factor for primary drug resistance. Patients in the primary group had a significantly shorter median OS (11.0 vs 31.0 months, P< 0.001) than those in the secondary group. The 1-, 2- and 3-year cumulative survival rates in the primary group were 46.3%, 22.2%, and 10.1%, while those in the secondary group were 82.3%, 59.1% and 44.9%, respectively. Compared to tyrosine kinase inhibitor (TKI) monotherapy, longer median PFS (4.0 vs 7.0 months, P=0.008) and OS (11.0 vs 23.0 months, P=0.024) were achieved with the combination of a TKI plus a PD-1 inhibitor as a second-line therapy after lenvatinib resistance.Conclusion: There is a high rate of primary resistance to lenvatinib in patients with HCC and the prognosis for those with primary resistance is poor. TKI combined with PD-1 inhibitors should be preferentially recommended for lenvatinib-resistant patients.Keywords: hepatocellular carcinoma, resistance, lenvatinib, programmed cell death protein-1 inhibitor, tyrosine kinase inhibitor, second-line

Juanjuan Lei,1,2 Huijing Lai,1,3 Siting Zhong,4 Xiaoli Zhu,5 Dianyu Lu6 1School of Nursing, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Pneumology, Foshan Hospital of TCM, Foshan, People’s Republic of China; 4Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Nursing, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Anaesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Dianyu Lu, Department of Anaesthesiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Yuexiu District, Guangzhou, 510095, People’s Republic of China, Tel +86-020-66673666, Email ldy020505@163.com Xiaoli Zhu, Department of Nursing, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 78 Hengzhigang Road, Yuexiu District, Guangzhou, 510095, People’s Republic of China, Tel +86-15902037400, Email zhuxseven@163.comObjective: The primary objective of this cross-sectional study was to examine the prevalence of different types of intimate partner violence (IPV) among female nurses employed in public hospitals across China. Additionally, the study sought to investigate the relationship between nurses’ psychological resilience and their experiences of work thriving and work alienation in the aftermath of IPV.Methods: This cross-sectional study utilized an online self-report survey to collect data from a sample of 522 female nurses working in public healthcare facilities across several major cities in China. The survey instrument collected information on participants’ sociodemographic characteristics, experiences of intimate partner violence (IPV), psychological resilience, work thriving, and work alienation. The Kruskal–Wallis one-way ANOVA test was used to compare outcome variables across IPV exposure groups, and multiple linear regression modeling was subsequently performed to examine the associations between the dependent variables (work thriving and work alienation) and the independent variables, including IPV exposure and resilience.Results: The overall prevalence of IPV reported by the female nurse participants was 74.26%. Specifically, the rates of emotional IPV, physical IPV, and sexual IPV were 74.06%, 24.27%, and 7.53%, respectively. The results indicated that total IPV exposure, the three IPV subtypes, psychological resilience, work thriving, and work alienation were all significantly and positively interrelated. IPV scores demonstrated a negative association with psychological resilience and work thriving, but a positive association with work alienation. Importantly, psychological resilience was found to be positively correlated with work thriving and negatively correlated with work alienation.Conclusion: The findings suggest that psychological resilience plays a pivotal role, both directly and indirectly, in influencing the work-related outcomes of female nurses who have experienced IPV. Specifically, resilience was positively associated with thriving at work and directly negatively associated with work alienation, though a partial mediating effect of resilience was also observed.Keywords: resilience, Chinese female nurses, intimate partner violence, thriving at work, work alienation

Aijun Zheng,1 Fangfang Zheng,1 Kai Jin,1 Ming Chi,1 Jiajia Mu,1 Hongxia Wei,2 Jian Lei,2 Chao Xu3 1Department of Acupuncture and Moxibustion, Peking University Third Hospital Yanqing Hospital, Beijing, 102100, People’s Republic of China; 2Department of Traditional Chinese Medicine, Nancaiyuan Community Hospital, Beijing, 102100, People’s Republic of China; 3Department of Pharmacy, Peking University Third Hospital Yanqing Hospital, Beijing, 102100, People’s Republic of ChinaCorrespondence: Aijun Zheng, Email zaj1970@163.comObjective: Knee osteoarthritis (KOA) is a common chronic degenerative joint disease, and acupuncture is an alternative therapy for KOA. This study aims to detect the effectiveness of acupuncture at LI11 in improving pain and function for KOA patients.Methods: A total of 108 patients with KOA were randomly allocated to Control Group (local points), Treatment Group A (LI11), and Treatment Group B (local points and LI11) with a treatment phase of 4 weeks and a follow-up phase of 4 weeks. Primary outcome was response rate. Secondary outcomes included Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and recurrence rate. Study was registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2000034926).Results: The response rate in Treatment Group A, Treatment Group B, and Control Group was 71.43%, 85.29%, and 51.53%, respectively, at Week 4, and Treatment Group B was significantly higher than Control Group (difference[98.3% CI]: 33.86[0.135,0.543], P = 0.003). Although no significant difference was found, Treatment Group A had a better response rate compared with Control Group (difference[98.3% CI]: 20.00 [− 0.072, 0.472], P = 0.086). For VAS and WOMAC, there were significant differences within 3 groups at Week 4 compared with the baseline. There was a significant improvement in VAS scores and WOMAC function and pain subscales at Week 4 in Treatment Group B compared with Control Group and Treatment Group A.Conclusion: LI11 is an effective point for patients with KOA, and it could be a selection for young acupuncturists and acupuncturists who work in rural areas; however, large-sample studies are necessary to further verify results in the future.Keywords: knee osteoarthritis, manual acupuncture, Quchi, LI11, pilot randomized controlled trial

Fission and gamma decay probabilities of 237U and 239Np have been measured, for the first time simultaneously in dedicated experiments, via the surrogate reactions 238U(3He, 4He) and 238U(3He,d), respectively. While a good agreement between our data and neutron-induced data is found for fission probabilities, gamma decay probabilities are several times higher than the corresponding neutron-induced data for each studied nucleus. We study the role of the different spin distributions populated in the surrogate and neutron-induced reactions. The compound nucleus spin distribution populated in the surrogate reaction is extracted from the measured gamma-decay probabilities, and used as input parameter in the statistical model to predict fission probabilities to be compared to our data. A strong disagreement between our data and the prediction is obtained. Preliminary results from an additional dedicated experiment confirm the observed discrepancies, indicating the need of a better understanding of the formation and decay processes of the compound nucleus.

The large Stokes shifts usually result in open circuit voltage (VOC) reduction, which will affect the photovoltaic performance of the material. Recently, three-dimensional organosulfide-halide perovskites (CYS)PbCl2 and (CYS)PbBr2 [CYS: +NH3(CH2)2S−] have received much attention in the photovoltaic field due to their higher stability and similar photoelectric properties (desirable direct bandgap, band dispersion, and light absorption) than MAPbX3 (X = Cl, Br, and I). Unfortunately, both materials exhibit large Stokes shifts emission. Thus, to be clear about their application prospects in the photovoltaic field, the origin of the large Stoke shift needs to be investigated. Moreover, the bandgaps of (CYS)PbBr2 (2.17 eV) and (CYS)PbCl2 (2.32 eV) are higher than the ideal bandgap value of (0.9–1.6 eV) for photovoltaic materials. Based on density functional theory, this paper explores the cause of large Stokes shifts and further improves the photovoltaic performance of the materials by halogen substitution. The calculation results show that the large Stokes shifts come from defect emission rather than intrinsic self-trapping emission and the I atom substitution can reduce the bandgap [(CYS)PbI2; gap = 1.85 eV] and enhance the optical absorption and carrier migration ability without destroying the direct bandgap. Our research will promote the experimental synthesis of more excellent perovskite photovoltaic materials. [ABSTRACT FROM AUTHOR]

We explored the role of negative performance beliefs and self-focused attention considered central to psychological models of social anxiety but not studied in autism. Firstly, we compared self- and observer ratings of performance on a social task for 71 young autistic people, 41 high and 30 low in social anxiety, finding a significant main effect of social anxiety but not rater. Subsequently, 76 autistic young people, 46 high and 30 low social anxiety completed measures of interoceptive sensibility and focus of attention following a social task. Only heightened interoceptive sensibility fully mediated the relationship between self-ratings of social performance and social anxiety. These findings suggest awareness of bodily sensations are critical to anxiety in social situations with implications for treatment.

Xingrui Li,1,&ast; Yue Wang,1,&ast; Denghao Huang,1 Zhonghao Jiang,1 Zhiyu He,1 Maoxuan Luo,2 Jie Lei,1,2 Yao Xiao1– 3 1Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Chengbei Outpatient, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Xiao; Jie Lei, Email orthoxiaoyao@outlook.com; 1067233579@qq.comAbstract: The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as “mesenchymal stem cells”, “nanotechnology”, “biomaterials”, “dentistry” and “tissue regeneration”. From 2013 to 2023, we selected approximately 150 articles that align with our philosophy.Keywords: nano-material, stem cell, tissue reconstruction, cell differentiation

Chen Yang,1 Jiaxing Lei,1 Ximeng Kang,1 Peipei Zhang,1 Shaohua Zheng,2 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@mail.xjtu.edu.cn; zjy2011@mail.xjtu.edu.cnIntroduction: The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.Methods: The novel hybrid hydrogel was prepared, and its physicochemical properties were examined. Its effect towards melanoma prevention and treatment was evaluated via a melanoma-bearing mice model.Results: The CM-ICG-hybrid hydrogel was successfully prepared with excellent injectability, self-healing, drug loading, rheological, in vitro and in vivo photothermal stability, and retention properties. It also exhibited good cellular and in vivo safety profiles. In the primary melanoma mice model, it quickly ablated the in-situ melanoma, effectively inhibited the tumor growth, increased the survival rate of melanoma-bearing mice, and increased the level of IFN-γ and TNF-α. In the distal secondary melanoma model, it efficiently prevented the reoccurrence of melanoma and activated the memory T cells. In both models, a synergistic effect of photothermal therapy and immune therapy was found. The hydrogel effectively recruited CD3+ CD4+ T cells and CD3+ CD8+ T cells, inhibited the proliferation of melanoma cells, and induced the apoptosis of melanoma cells.Conclusion: The hybrid hydrogel was successfully prepared, and it showed excellent efficacy towards melanoma prevention and treatment due to its efficient tumor ablation and immune activation capability.Graphical Abstract: Keywords: chitin, β-glucan, hybrid hydrogel, melanoma cell membrane, photo thermotherapy, immunotherapy

In this work, the performance of the carbon doped compositionally complex alloy (CCA) MoNbTaW was studied under ambient and high pressure and high temperature conditions. TaC and NbC carbides were formed when a large concentration of carbon was introduced while synthesizing the MoNbTaW alloy. Both FCC carbides and BCC CCA phases were detected in the sample compound at room temperature, in which the BCC phase was believed to have only refractory elements MoNbTaW while FCC carbide came from TaC and NbC. Carbides in the carbon doped MoNbTaW alloy were very stable since no phase transition was obtained even under 3.1 GPa and 870◦C by employing the resistor-heating diamond anvil cell (DAC) synchrotron X-ray diffraction technique. Via in situ examination, this study confirms the stability of carbides and MoNbTaW in the carbon doped CCA even under high pressure and high temperature.

Peiru Si,1 Jiaxing Lei,1 Chen Yang,1 Peipei Zhang,1 Xiaojiao Li,2 Shaohua Zheng,3 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Biobank, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@xjtu.edu.cn; zjy2011@xjtu.edu.cnIntroduction: Hepatic ischemia-reperfusion injury (HIRI) is the main reason for liver dysfunction or failure after liver resection and liver transplantation. As excess accumulation of reactive oxygen species (ROS) is the leading factor, ceria nanoparticle, a cyclic reversible antioxidant, is an excellent candidate for HIRI.Methods: Manganese doped mesoporous hollow ceria nanoparticles (MnOx-CeO2 NPs) were prepared, and the physicochemical characteristics, such as particle size, morphology, microstructure, etc. were elucidated. The in vivo safety and liver targeting effect were examined after i.v. injection. The anti-HIRI was determined by a mouse HIRI model.Results: MnOx-CeO2 NPs with 0.40% Mn doped exhibited the strongest ROS-scavenging capability, which may due to the increased specific surface area and surface oxygen concentration. The nanoparticles accumulated in the liver after i.v. injection and exhibited good biocompatibility. In the HIRI mice model, MnOx-CeO2 NPs significantly reduced the serum ALT and AST level, decreased the MDA level and increased the SOD level in the liver, prevent pathological damages in the liver.Conclusion: MnOx-CeO2 NPs were successfully prepared and it could significantly inhibit the HIRI after i.v. injection.Graphical Abstract: Keywords: hepatic ischemia reperfusion injury, Mn-doped mesoporous hollow cerium oxide nanoparticles, oxidative stress

Jin Lei,1,&ast; Sibo Yang,1,&ast; Bowen Chen,2,&ast; Linzhi Zhang,3 Tao Yan,3 Gangqi Yang,1 Yue Chen,1 Yinyin Li,3 Yinying Lu,1,3,4 Shi Zuo1,5 1School of Clinical Medicine, Guizhou Medical University, Guiyang, People’s Republic of China; 2 302 Clinical Medical School, Peking University, Beijing, People’s Republic of China; 3Comprehensive Liver Cancer Center, the 5th Medical Center of the PLA General Hospital, Beijing, People’s Republic of China; 4Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua, Beijing, People’s Republic of China; 5Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinying Lu; Shi Zuo, Tel +86 13301256799 ; +86 13908516978, Email luyinying1973@163.com; drzuoshi@gmc.edu.cnBackground: Tyrosine kinase inhibitors (TKI) combined with programmed cell death-1 (PD-1) inhibitor is a potential treatment modality for patients with HCV-related unresectable hepatocellular carcinoma (uHCC).Methods: The participants of the present work included the patients having HCV-related uHCC who were treated with TKI monotherapy (TKI group) or TKI combined with PD-1 inhibitors therapy (combination group) in our center between June 2018 and June 2021. In addition, the patients were classified into RNA-positive and RNA-negative groups based on whether or not the baseline HCV RNA was detectable. The overall survival (OS) was used as the primary efficacy endpoint, while progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were used as secondary endpoints. The adverse events were recorded and evaluated.Results: Among the 67 patients contained this work, 43 patients were classified into the TKI group, while 24 patients formed the combination group. In relative to the TKI group, the combination group presented notably better median OS (21 months vs 13 months, p = 0.043) and median PFS (8 months vs 5 months, p = 0.005). No evident differences were observed between the two groups in terms of the DCR (58.1% vs 79.2%, p = 0.080), ORR (13.9% vs 25.0%, p = 0.425) and the incidence of grade 3– 4 adverse events (34.8% vs 33.3%, p = 1.000). In addition, there existed no obvious difference between the RNA-positive group and RNA-negative group in terms of median OS (14 months vs 19 months, p = 0.578) and median PFS (4 months vs 6 months, p = 0.238).Conclusion: The patients having HCV-related uHCC after being treated with the TKI and PD-1 inhibitor combination therapy exhibited a better prognosis and manageable toxicity compared to the patients who underwent TKI monotherapy.Keywords: hepatitis C virus, hepatitis C virus reactivation, hepatocellular carcinoma, tyrosine kinase inhibitor, programmed death-1 inhibitor

Owing to the negative impact of the extensive utilization of batteries on the environment, sustainability of the cells needs to be included in the systemic research of batteries. Herein, a dissolvable ionic crosslinked polymer (DICP) is exploited as a binder for lithium–sulfur batteries by crosslinking the polyacrylic acid and polyethyleneimine through carboxy-amino ionic interaction. This interaction is pH-controlled, and therefore, the crosslinked binder network can be readily dissociated under basic conditions, providing a facile strategy enabling valuable components recycled through a convenient washing method. The sulfur cathode prepared using the recycled carbon–sulfur composite can deliver comparable capacity as that of fresh electrode. In addition, evidence from cell performance and characterizations, such as in situ X-ray absorption spectroscopy, in situ UV–visible spectroscopy, X-ray photoelectron spectroscopy, and density functional theory calculation, confirms that DICP is a more effective binder than its commercial counterpart on suppressing polysulfide dissolution in the electrolyte. Exploiting reversible crosslinked polymer binder for recyclable Li–S batteries with ameliorated electrochemical performance, this study illuminates sustainable development for large-scale energy storage systems.

The differential strain behavior of Ta x W 1-x B solid solutions has been studied as a function of composition using high-pressure radial X-ray diffraction in a diamond-anvil cell under non-hydrostatic pressure (up to ∼65 GPa) to understand the hardening mechanisms in this family of materials. The hardness of tungsten monoboride (WB) can be increased by adding tantalum and reaches a maximum at a doping level of 50 at. % with a value of 42.8 ± 2.6 GPa under an applied load of 0.49 N. Plateaus were observed in the differential strain data for both the (020) and (002) directions, suggesting that this is the primary slip system in this material. These plateaus were modified by the addition of Ta, indicating that strengthening of the (002) and (020) planes by solid solution hardening was primarily responsible for the hardness enhancements in Ta x W 1-x B solid solutions. In contrast, the differential strain supported by the (200) plane linearly increases with pressure up to the highest pressures reached in this work (>60 GPa) and shows almost no change with metal composition. Because of the very different compression behavior in the (200) and (020) planes, change in the b/a ratio with pressure provides a unique way to visualize the onset of plastic behavior. This onset varies from ∼15 GPa for samples with 5% Ta to more than 30 GPa for the sample with 50% Ta. In addition, the ambient bulk modulus of each solid-solution sample was determined using the second-order Birch-Murnaghan equation-of-state and found to be ∼340 GPa for all phases.

The fibrocartilage stem cells (FCSCs) on the surface of the condyle play an essential role in cartilage homeostasis and regeneration. However, few well-defined stem cell markers have been identified for the analysis of FCSCs' cell fate and regulation mechanism. In this study, we first mapped the transcriptional landscape of the condylar cartilage and identified a Gli1+ subset. Label-retaining cells and our lineage-tracing study showed that Gli1 labeled a group of FCSCs. Conditional knockout β-catenin inhibited Gli1+ cells differentiating into hypertrophic chondrocytes. In discectomy-induced temporomandibular joint osteoarthritis (TMJOA), Gli1+ cells were further activated, and their differentiation into hypertrophic chondrocytes was accelerated, which induced stem cell pool depletion. The deletion of β-catenin in Gli1+ cells preserved the FCSC pool and alleviated TMJOA cartilage degeneration. Collectively, we uncovered that a Gli1+ FCSC subpopulation and Wnt/β-catenin signaling orchestrate the Gli1+ cell fate in condyle postnatal development and TMJOA. [ABSTRACT FROM AUTHOR]

Different track failures are proven to have different influences on train-track interactions, but their influence on pantograph-catenary interactions has not been investigated thus far. In this work, the influences of typical track failures on pantograph-catenary interaction dynamics are first investigated. A reduced train-track-pantograph-catenary interaction model is developed to study these effects. In this model, the long catenary is reduced to a small moving area around the moving pantograph, and this area is considered and modelled as the reduced catenary model based on the arbitrary Lagrangian–Eulerian method. The reduced catenary model and moving pantograph are formulated as the reduced pantograph-catenary interaction model, and it is further unidirectionally connected with the existing reduced train-track interaction model to formulate the reduced train-track-pantograph-catenary interaction model. The present reduced pantograph-catenary model is first validated by the EN50318-2018 standard, and the influences of track irregularity, track buckling, fastening failure, and track settlement on pantograph-catenary interaction dynamics are studied. The investigation results first show that the track settlement with a long wavelength has a significant influence on the pantograph-catenary interaction dynamics and can even cause contact loss with a good train-track interaction behaviour. Thus, it should be further mentioned in the maintenance of the track structure. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to enhance the quintessential "five temporomandibular disorder (TMD) symptoms" (5Ts) screener by incorporating frequency options and distinguishing between TMJ and muscle pain. The diagnostic accuracy along with cut‐off points for the effective identification of TMDs was also established. Methods: Participants, aged ≥18 years, were recruited from a university‐based hospital. After completing surveys encompassing demographic data and the enhanced 5Ts (with frequency options [5Ts‐F] and differentiation of TMJ/muscle pain [6Ts‐F]), protocolized interviews and clinical examinations were performed following DC/TMD. The diagnostic accuracy and best cut‐off points were determined with the area under the receiver operating characteristic curves (AUCs). Results: 324 participants were recruited (mean age 30.0 ± 11.4 years). Among these, 86.4% had TMDs. 5Ts exhibited high diagnostic accuracy for detecting all TMDs (AUC = 0.92) with sensitivity/specificity values of 83.9%/88.6%. Both 5Ts‐F and 6Ts‐F had slightly better accuracy (AUCs = 0.95/0.96), comparable sensitivity, and superior specificity (97.7%) compared to 5Ts. The best cut‐off points were 1.5 for 5Ts and 2.5 for 5Ts‐F/6Ts‐F. Conclusions: Although all three TMD screeners presented high diagnostic accuracy, 5Ts‐F/6Ts‐F had notably improved specificity. 5Ts scores of >1.5 and 5Ts‐F/6Ts‐F scores of >2.5 are to be applied for screening the presence of TMDs. [ABSTRACT FROM AUTHOR]

The sulfur induced embrittlement of polycrystalline nickel (Ni) metal has been a long-standing mystery. It is suggested that sulfur impurity makes ductile Ni metal brittle in many industry applications due to various mechanisms, such as impurity segregation and disorder-induced melting etc. Here we report an observation that the most ductile measurement occurs at a critical sulfur doping concentration, 14 at.% at pressure from 14 GPa up to 29 GPa through texture evolution analysis. The synchrotron-based high pressure texturing measurements using radial diamond anvil cell (rDAC) X-ray diffraction (XRD) techniques reveal that the activities of slip systems in the polycrystalline nickel metal are affected by sulfur impurities and external pressures, giving rise to the changes in the plastic deformation of the nickel metal. Dislocation dynamics (DD) simulation on dislocation density and velocity further confirms the pressure induced ductilization changes in S doped Ni metal. This observation and simulation suggests that the ductilization of the doped polycrystalline nickel metal can be optimized by engineering the sulfur concentration under pressure, shedding a light on tuning the mechanical properties of this material for better high pressure applications.