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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

Xiaojun Chen,1,&ast; Shushu Zuo,1,&ast; Chunhua Zhang,1 Bing Sun,1 Mengyue Zhang,1 Dandan Jiang,2 Yanyan Chen2 1School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Chen; Dandan Jiang, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan West Road, Lucheng District, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +86 13858855689 ; +86 13506649289, Email cyy@eye.ac.cn; jiangdandan@eye.ac.cnObjective: This study aims to explore the effects of eye exercises on the accommodative ability of Chinese school-aged children.Methods: This study used a convenience cluster sampling and selected 149 students from grades 2– 5 in a Wenzhou primary school to participate in the intervention in June 2022. This study involved a one-month intervention teaching eye exercises using a composite feedback model. Assessments were made at 3 and 9 months post-intervention. Data collection occurred thrice, including a baseline and two follow-ups, measuring monocular and binocular accommodative facility, monocular and binocular accommodative amplitude, CISS scale, spherical equivalent refraction, and uncorrected visual acuity. Analysis used chi-square tests and generalized estimating equations to evaluate the exercises’ effectiveness, with a significance threshold of P < 0.05.Results: 134 students completed the follow-up, including 61 females (45.52%). After teaching intervention, students showed significant improvements in the accuracy of manipulation, rhythm, acupoint location, strength effectiveness and rhythm of acupressure eye exercises (all P < 0.05), with increases of 10.37%, 13.03%, 16.96%, and 25.17%, respectively. Follow-up assessments revealed both monocular and binocular accommodative amplitude at T3 were significantly higher than at T1 and T2. Moreover, the binocular accommodative amplitude in the high-quality eye exercise group remained significantly higher than that in the low-quality group even(B=1.39,1.46, P < 0.01). Eye exercises could improve monocular and binocular accommodative amplitude in the short term(P < 0.05). High-quality eye exercises could alleviate visual fatigue (B=− 2.00--3.49, both P < 0.05). However, eye exercises did not demonstrate any advantages in affecting spherical equivalent refraction or uncorrected visual acuity (P > 0.05).Conclusion: Eye exercises can alleviate myopia-related symptoms in Chinese children aged 7 to 11 years. However, this study did not find that eye exercises effectively reduce the degree of myopia in children.Trial Registration: The original trial (Registration site: https://www.chictr.org.cn/ Registration number: ChiCTR2300070903) was retrospectively registered on 26/04/2023.Keywords: Eye exercises, myopia, accommodative facility, accommodative amplitude, visual fatigue

Yiwen Sun,1 Wenzhe Zhou,2 Shushu Zuo,1 Chen Chen,1 Qiqi Zhang,1 Yanyan Chen3 1School of Ophthalmology and Optometry, Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Glaucoma Clinical Center, the Eye Hospital of Wenzhou Medical University, National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, People’s Republic of China; 3Nursing Department, the Eye Hospital of Wenzhou Medical University, National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yanyan Chen, The Eye Hospital of Wenzhou Medical University, National Clinical Research Center for Ocular Diseases, No. 270, West College Road, Wenzhou City, Zhejiang Province, People’s Republic of China, Tel +86 13858855689, Email cyy@eye.ac.cnPurpose: To explore the level of participation in shared decision-making by patients with glaucoma and identify influencing factors, to subsequently provide references to promote shared decision-making in ophthalmology, and achieve patient-centered care.Patients and Methods: A questionnaire was completed by 148 patients with glaucoma who had been admitted to a specialized ophthalmic hospital in China, between October 2021 and January 2022. The participants’ responses to the nine-item Shared Decision-Making Questionnaire (SDM-Q-9) and a general information survey were analyzed to determine their level of participation in shared decision-making and influencing factors. Multiple linear regression was used to identify factors that influence shared decision-making at the time of clinical practice.Results: The mean score of SDM-Q-9 was 71.73± 21.27 (n=140). Multiple linear regression analysis showed that patients with negative attitudes towards participation in decision-making (P=0.023) and those who had rural insurance (P=0.017) had significantly lower SDM-Q-9 scores than those with positive attitudes and those with medical insurance. Patients who were more satisfied with their medical service had higher SDM-Q-9 scores (P< 0.05).Conclusion: Patients with glaucoma presented a high level of shared decision-making. Patients’ attitudes towards participating in decision-making, the payment method of medical expenses, and the level of satisfaction with medical services are factors that influence their level of participation in shared decision-making.Keywords: glaucoma, shared decision-making, patient participation, influencing factor

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

Jing Wang,1 Shuting Zuo,1 Yan Zhang,1 Shanzhi Li,2 Ying Shi,1 Tonghua Du,1 Jicheng Han,2 Ningyi Jin,2– 4 Yiquan Li,2 Xiao Li2,3 1Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China; 2Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 3Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People’s Republic of China; 4Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, People’s Republic of ChinaCorrespondence: Yiquan Li; Xiao Li, Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Liuying West Road, 666, Jingyue Economic & Technological Development Zone, Changchun, People’s Republic of China, Tel +86-431-86985923, Fax +86-431-87985861, Email 905381255@qq.com; 1077614276@qq.comPurpose: Oncolytic virus therapy has gradually become an integral approach in cancer treatment. We explored the therapeutic effects of the combination of a dual cancer-selective anti-tumor recombinant adenovirus (Ad-Apoptin-hTERTp-E1a) and cyclophosphamide on breast cancer cells.Methods: The inhibition of MCF-7 and MDA-MB-231 breast cancer cells by Ad-Apoptin-hTERTp-E1a (Ad-VT), cyclophosphamide, and Ad-VT + Cyclophosphamide was investigated using the CCK-8 assay. The combination index (CI) was calculated using CalcuSyn software to determine the best combination based on the inhibition rates of the different treatment combinations. The CCK-8 assay and crystal violet staining were used to detect the cytotoxicity of the combined Ad-VT and cyclophosphamide in breast cancer cells and breast epithelial cells. Subsequently, Hoechst staining, annexin V flow cytometry, and JC-1 staining were used to analyze the inhibitory pathway of Ad-VT plus cyclophosphamide on breast cancer cells. Cell migration and invasion of breast cancer cells were assessed using the cell-scratch and Transwell assays. The anti-tumor effects of different treatment groups in a tumor-bearing nude mouse model also were analyzed.Results: The treatment combination of Ad-VT (40 MOI) and cyclophosphamide (400 μM) significantly inhibited MCF-7 and MDA-MB-231 cells and reduced the toxicity of cyclophosphamide in normal cells. Ad-VT primarily induced breast cancer cell apoptosis through the endogenous apoptotic pathway. Apoptosis was significantly increased after treatment with Ad-VT plus cyclophosphamide. The combination significantly inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells. The in vivo experiments demonstrated that exposure to Ad-VT plus cyclophosphamide significantly inhibited tumor growth and extended the survival time of the nude mice.Conclusion: Ad-VT plus cyclophosphamide reduced toxicity and exhibited increased efficacy in treating breast cancer cells.Keywords: cyclophosphamide, recombinant adenovirus, breast cancer, synergy, toxicity

Shuting Zuo, Yan Zhang, Zhenyu Wang, Jing Wang Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jing Wang, Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Tel/Fax +86 431-81136122, Email wangjing001@jlu.edu.cnBackground: Sonodynamic therapy (SDT) has rapidly advanced as a promising alternative to conventional photodynamic therapy owing to its preferable therapeutic depth. However, single-modal SDT exhibits limited efficacy due to the long-term hypoxia in tumors.Method and Results: To address these issues, we proposed a synergistic SDT strategy that integrates mitochondrial targeting with nitric oxide (NO) gas therapy by using multifunctional nanoplatforms. The nanoplatform, which was named as T-mTNPs@L-Arg, was composed of mesoporous titanium dioxide loaded with the NO donor precursor L-arginine (L-Arg) and modified with triphenyl phosphonium (TPP), a mitochondria-targeting ligand. Therefore, T-mTNPs@L-Arg could efficiently concentrate into mitochondria and release NO gas as well as generate reactive oxygen species (ROS) with ultrasound stimulus. Importantly, the released NO gas exerted multiple synergies with SDT, including inducing NO poisoning, generating more lethal reactive nitrogen species (RNS) by reaction with ROS, and alleviating hypoxia through NO-mediated mitochondrial respiration inhibition. On account of the synergistic effects, T-mTNPs@L-Arg showed an outstanding SDT efficacy and a reduced side effect.Conclusion: This work designed a nanoplatform to integrate mitochondria targeting, SDT and NO gas therapy, providing a new strategy for highly efficient breast cancer therapy.Keywords: mitochondria-targeting, nitric oxide, sonodynamic therapy, titanium dioxide, synergistic

Xingming Xie,1,2 Chaochun Chen,1,2 Shu Feng,1,3 Shi Zuo,2 Xueke Zhao,3 Haiyang Li1,2 1School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Haiyang LiDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou, People’s Republic of ChinaTel/Fax +86 851-6855119Email lihaiyang@gmc.edu.cnPurpose: Acyl-CoA thioesterase 7(ACOT7) plays an important role in the metabolism of fatty acids. Hepatocellular carcinoma (HCC) has an abnormal lipid profile, and the role of ACOT7 in hepatocellular carcinoma has not been detailedly elucidated. Therefore, we conducted the study to explore the role of ACOT7 in HCC.Materials and Methods: The ACOT7 and Krüppel-like factor 13 (KLF13) mRNA expression levels were obtained from The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis identified the underlying upstream regulator of ACOT7. Quantitative real-time PCR was used to detect the expression of mRNA, and immunohistochemical staining and Western blotting were used to detect the expression of protein. Cell Counting Kit-8 and EdU assays were employed to assess the proliferation of HCC cells. Wound-healing and Transwell migration assays were utilized to test the migration ability of HCC cells. Dual-luciferase reporter assay and ChIP assay were used to explore the potential mechanism. Gas chromatography-mass spectrometer was used to analyze the content of free fatty acids. Xenograft tumour growth was used to evaluate the effect of ACOT7 in vivo.Results: According to The Cancer Genome Atlas (TCGA) database, ACOT7 mRNA was found to be upregulated and predicted the poor prognosis. Overexpression of ACOT7 enhanced the proliferation, migration and invasion abilities of HCC cells in vitro, as well as the HCC cells proliferation in vivo. Moreover, ACOT7 overexpression increased the yield of the monounsaturated fatty acid Oleic acid (C18:1), which strengthened the proliferation and migration abilities of HCC cells. Mechanistically, KLF13 transcriptionally promoted ACOT7 expression. Further, KLF13 was also overexpressed in HCC tissues and facilitated HCC progression.Conclusion: Acyl-CoA thioesterase 7 is transcriptionally activated by Krüppel-like factor 13 and promotes the progression of hepatocellular carcinoma.Keywords: acyl-CoA thioesterase 7, Krüppel-like factor 13, hepatocellular carcinoma, unsaturated fatty acid, prognosis

Bin Zheng,1,* Yakun Yang,1,* Jinghan Li,1 Jing Li,1 Saijie Zuo,1 Xi Chu,2 Shan Xu,3 Donglai Ma,1 Li Chu1,4 1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Hebei Province Hospital of Chinese Medicine, Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donglai Ma; Li ChuSchool of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of ChinaTel/Fax +86 311 89926719Email mdl_hebei@aliyun.com; chuli0614@126.comPurpose: Magnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through anti-inflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism.Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection.Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased.Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.Keywords: magnesium isoglycyrrhizinate, arsenic trioxide, cardiotoxicity, Nrf2, TLR4/NF-κB

Shi Zuo,1,* Wei Zou,2,3,* Rong-Min Wu,4 Jing Yang,5 Jian-Nan Fan,2 Xue-Ke Zhao,5 Hai-Yang Li1 1Department of Hepatobiliary Surgery, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Sports Medicine, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Orthopedics, The Fourth People’s Hospital of Guiyang, Guizhou, People’s Republic of China; 4Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, People’s Republic of China; 5Department of Infectious Disease, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-Yang LiDepartment of Hepatobiliary Surgery, The Hospital Affiliated to Guizhou Medical University, No.28, Guiyi Street, Guiyang, Guizhou 550004, People’s Republic of ChinaEmail haiyangli666@sohu.comJian-Nan FanDepartment of Sports Medicine, The Hospital Affiliated to Guizhou Medical University, No.28, Guiyi Street, Guiyang, Guizhou 550004, People’s Republic of ChinaEmail publetscientific@126.comObjective: Osteoarthritis (OA) is characterized by progressive matrix destruction of articular cartilage. This study aimed to investigate the potential antioxidative and chondroprotective effects and underlying mechanism of Icariin (ICA) in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.Methods: Human chondrocyte cell line HC-A was treated with different doses of ICA, and then MTT assay and PI staining were used to estimate ICA-induced chondrocyte apoptosis. Intracellular ROS and superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured after treatment by IL-1β with or without ICA. The mRNA and protein expression levels of redox transcription factor Nrf2 and the downstream effector SOD-1, SOD-2, NQO-1 and HO-1 were assayed to explore the detailed mechanism by which ICA alleviates ECM degradation. Finally, to expound the role of Nrf2 in ICA-mediated chondroprotection, we specifically depleted Nrf2 in human chondrocytes and then pretreated them with ICA followed by IL-1β.Results: ICA had no cytotoxic effects on human chondrocytes and 10−9 M was selected as the optimum concentration. ROS induced by IL-1β could drastically activate matrix-degrading proteases and ICA could significantly rescue the matrix degradation and excess ROS generation caused by IL-1β. We observed that ICA activated the Nrf2/ARE pathway, consequently upregulating the generation of GPX and SOD. Ablation of Nrf2 abrogated the chondroprotective and antioxidative effects of ICA in IL-1β-treated chondrocytes.Conclusion: ICA alleviates IL-1β-induced matrix degradation and eliminates ROS by activating the Nrf2/ARE pathway.Keywords: icariin, Nrf2 signaling, ROS, human chondrocyte, ECM degradation

We consider the optimal stopping and optimal control problems related to stochastic variational inequalities modeling elasto-plastic oscillators subject to random forcing. We formally derive the corresponding free boundary value problems and Hamilton-Jacobi-Bellman equations which belong to a class of nonlinear partial of differential equations with nonlocal Dirichlet boundary conditions. Then, we focus on solving numerically these equations by employing a combination of Howard’s algorithm and the numerical approach [A backward Kolmogorov equation approach to compute means, moments and correlations of non-smooth stochastic dynamical systems; Mertz, Stadler, Wylie; 2017] for this type of boundary conditions. Numerical experiments are given.

Mao Mu,1,* Shi Zuo,2,* Rong-Min Wu,3 Kai-Sheng Deng,1 Shuang Lu,1 Juan-Juan Zhu,1 Gao-Liang Zou,1 Jing Yang,1 Ming-Liang Cheng,1 Xue-Ke Zhao1 1Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 3Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, China *These authors contributed equally to this work Purpose: Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo.Materials and methods: Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA.Results: TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment.Conclusion: Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis. Keywords: ferulic acid, TGF-β1, CCl4, hepatic fibrosis, Smad signaling pathway

Mu M, Zuo S, Wu RM, et al. Drug Des Devel Ther. 2018;12:4107–4115. An error has been found in a couple of the image labels for Figure 3F. On page 4112, the original Figure 3F image appears as: Read the original article:

Abstract The pore structure of coal plays a key role in the effectiveness of gas extraction. Conventional hydraulic fracturing techniques have limited success in modifying the pore structure using clean fracturing fluid (CFF), and the stimulating effects of ultrasonic can enhance the effectiveness of CFF in modifying coal pore structures. To research the effects of ultrasonic stimulation on the pore structure of medium to high-rank coal when using CFF, this study employed mercury intrusion porosimetry (MIP) and low-temperature nitrogen adsorption (LT-N2A) methods to analyze the changes in pore structures after cooperative modification. The results indicate that the pore volume and surface area of medium to high rank coal exhibit an increase and followed by a decrease with increasing R o,max values, while the average pore diameter and permeability demonstrate a decrease and followed by an increase with R o,max . Although there are some variations in the results of MIP and LT-N2A analysis for different pore size ranges, the overall findings suggest that ultrasonic stimulation in conjunction with CFF effectively alters the coal pore structure. The most significant improvement was observed in coking coal, where pore volume increased by 22%, pore area decreased by 11% and tortuosity decreased by 47%. The improvement of lean coal is the smallest, the pore volume increases by about 7%, and the surface area decreases by about 14%. It is found that the modification of coal pore volume is mainly concentrated in transition pores and macropores. These research outcomes provide valuable insights into the application of ultrasonic technology in coalbed gas extraction.

This study reported the fabrication of TiO2-decorated Fe2O3QDs/g-C3N4 ternary Z-scheme photocatalyst via low-temperature calcination followed by a nonaqueous route with tunable particle size and strong interfacial contact. The subsequent Fe2O3QDs/g-C3N4 and TiO2/Fe2O3QDs/g-C3N4 were investigated in terms of structure, morphology, optical properties, and surface chemical composition analysis via transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), energy dispersive x-ray spectroscopy (EDX), UV–visible spectroscopy, ESR and photoluminescence spectroscopy (PL). The crystalline parameters of the samples were investigated by X-ray diffraction (XRD) The Williamson-Hall method and geometrical phase analysis of HRTEM micrographs were employed to investigate lattice defects. Under visible light, the photocatalytic capabilities of as-fabricated TiO2/Fe2O3QDs/g-C3N4 were examined by degrading Rhodamine B (RhB), and an enhancement in photocatalytic efficacy was found. TiO2 works as a primary photosensitizer, providing extra photoinduced electrons influenced by oxygen vacancies, while Fe2O3 acts as a "bridge" for electron transport from the TiO2 moiety to the g-C3N4 thereby establishing an indirect charge transport pathway based on the Z-scheme. Radical scavenging tests were conducted to further explore the cause of increased activity and degradation mechanisms. Designing materials with oxygen vacancies and optimized structures can lead to improved solar energy conversion capabilities, particularly regarding contaminant removal. The proposed technique might be a viable option for the removal of rhodamine b compounds and for remedying freshwater reservoirs. TiO2 /Fe2O3QDs/g-C3N4Ternary Z-Scheme Photocatalysts! A facile strategy is exploited to modulate the crystallinity and surface properties of TiO2. TiO2 is incorporated into Fe2O3QDs/g-C3N4 through solvothermal treatment, which results in the formation of surface flaws and lattice-oxygen activated regions as well as the transformation of the Fe2O3QDs/g-C3N4 heterojunction into an indirect z-scheme system by rational modulation of the band alignment of two systems. The electron–hole pair is efficiently separated, conserving the electron reduction capability and the electron oxidation capability of the hole. The adapted structure and mesocrystalline nature resulted in a 7.3-fold improvement in the photocatalytic performance of TFCN over pure g-C3N4. [ABSTRACT FROM AUTHOR]

NiTi shape memory alloys are commonly subjected to mechanical stress and chemical corrosion challenges when used in orthodontic arch wires, cardiovascular stents, and fluid valve actuators. This exposure leads to hydrogen embrittlement to a certain degree, consequently affecting the reliability and safety of NiTi components.Focusing on the hydrogen effect in NiTi alloys, the location of hydrogen atoms, various states and diffusion behavior were reviewed in this paper. Methods to characterize hydrogen content, states, distributions and diffusivity were also summarized. The effects of hydrogen on the martensitic transformation and damping behavior of NiTi shape memory alloys were also introduced. Furthermore, hydrogen embrittlement behavior, influencing factors and mechanisms in NiTi alloys were discussed in this paper. Strategies to prevent or delay the hydrogen effect on NiTi shape memory alloys were also summarized. Finally, research directions, including diffusion behavior in each phase of NiTi alloys, visual characterization methods of hydrogen distribution, and hydrogen-martensitic transformation interaction were proposed in this paper, aiming to provide valuable insights and reference points for researchers studying NiTi shape memory alloys.