bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
Authors: Xiao Zhuanglong , Xu Jing , Tan Jun , Zhang Shengyan , Wang Nian , Wang Ruiyun , Yang Pengcheng , Bai Tao , Song Jun , Shi Zhaohong , Lyu Wenliang , Zhang Lei , Hou Xiaohua 
Published: November 2022

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD).Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats.Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.
Proteomics analysis reveals novel insights into the mechanism of hepatotoxicity induced by Tripterygium wilfordii multiglycoside in mice
Authors: Miao Yingying , Zhang Qin , Yuan Zihang , Wang Jie , Xu Yunxia , Chai Yuanyuan , Du Min , Yu Qinwei , Zhang Luyong , Jiang Zhenzhou 
Published: November 2022

Tripterygium wilfordiimultiglycoside (GTW), extracted and purified from the peeled roots ofT. wilfordiiHook.f. (TwHF), is a well-known traditional Chinese medicine and applied to various autoimmune diseases clinically. However, it has been reported to cause severe liver injury. At present, the mechanism underlying GTW-induced hepatotoxicity remain poorly defined. Here, we evaluated the effects of GTW on mouse liver and elucidated the associated mechanismsvialabel-free proteomics combined with bioinformatics analysis. Male C57BL/6J mice were randomly divided into normal group, a low-dose GTW (70 mg/kg) group and a high-dose GTW (140 mg/kg) group. After 1-week administration, GTW dose-dependently induced hepatotoxicity. Further analysis showed that GTW could act on the intestinal immune network for IgA production pathway, which plays an important role in maintaining intestinal homeostasis and influences the crosstalk between gut and liver. Western blots confirmed that GTW could decrease pIgR protein expression in the liver and ileum, and, as a result, the secretion of IgA into gut lumen was reduced. Further validation showed that intestinal barrier integrity was impaired in GTW-treated mice, promoting bacteria transferring to the liver and triggering proinflammatory response. Our study demonstrated that gut-liver axis may play a vital part in the progression of GTW-induced hepatotoxicity, which provides guidance for basic research and clinical application of GTW.
Exploring the potential mechanism of Fritiliariae Irrhosae Bulbus on ischemic stroke based on network pharmacology and experimental validation
Authors: Zijie Wang , Anan Jiang , Hongmei Xiao , Xiaofan Yuan , Shaoru Zhang , Xinyue Qin 
Published: November 2022

Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments.Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue.Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis—multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2.Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.
Suppressing circ_0008494 inhibits HSCs activation by regulating the miR-185-3p/Col1a1 axis
Authors: Li Binbin , Zhou Jiaming , Luo Yuanyuan , Tao Kegong , Zhang Lifen , Zhao Ying , Lin Yong , Zeng Xin , Yu Hongyu 
Published: November 2022

Background: Hepatic fibrosis (HF) is characterized by activation of hepatic stellate cells (HSCs) and extensive deposition of extracellular matrix components, especially collagens. However, effective antifibrotic therapies are still lacking. Recently, circular RNAs (circRNAs) have been identified as novel regulators of HF.Methods: circRNAs profile was screened by RNA sequencing and the location of circ_0008494 was confirmed by fluorescence in situ hybridization assay in human HF tissues. Bioinformatics analysis was used for result prediction and dual-luciferase reporter, together with AGO-RIP and biotin-coupled miRNA capture assays, were used to determine miR-185-3p/collagen type I alpha 1 chain (Col1a1) as the target of circ_0008494. A stable circ_0008494-interfering human HSCs cell line was constructed and used to determine the regulatory mechanism of circ_0008494/miR-185-3p/Col1a1 axis.Results: circ_0008494 was abundantly and significantly over-expressed in human HF tissues and located at the cytoplasm of HSCs. Together, dual-luciferase reporter, AGO-RIP and biotin-coupled miRNA capture assays confirmed that circ_0008494 acted as a sponge of miR-185-3p. Cell functional experiments and rescue assays demonstrated suppressing circ_0008494 could inhibit activation, proliferation, migration of HSCs and promote their apoptosis through miR-185-3p. In particular, the HF indicator, Col1a1, was validated as the direct target of miR-185-3p and the suppression of circ_0008494 inhibited the expression of Col1a1 by releasing miR-185-3p.Conclusion: Knocking down circ_0008494 inhibited HSCs activation through the miR-185-3p/Col1a1 axis. circ_0008494 could be a promising treatment target for HF.
Knockdown of Ift88 in fibroblasts causes extracellular matrix remodeling and decreases conduction velocity in cardiomyocyte monolayers
Authors: Ernault Auriane C. , Kawasaki Makiri , Fabrizi Benedetta , Montañés-Agudo Pablo , Amersfoorth Shirley C. M. , Al-Shama Rushd F. M. , Coronel Ruben , De Groot Joris R. 
Published: November 2022

Background: Atrial fibrosis plays an important role in the development and persistence of atrial fibrillation by promoting reentry. Primary cilia have been identified as a regulator of fibroblasts (FB) activation and extracellular matrix (ECM) deposition. We hypothesized that selective reduction of primary cilia causes increased fibrosis and facilitates reentry.Aim: The aim of this study was to disrupt the formation of primary cilia in FB and examine its consequences on ECM and conduction in a co-culture system of cardiomyocytes (CM) and FB.Materials: Using short interfering RNA (siRNA), we removed primary cilia in neonatal rat ventricular FB by reducing the expression of Ift88 gene required for ciliary assembly. We co-cultured neonatal rat ventricular cardiomyocytes (CM) with FB previously transfected with Ift88 siRNA (siIft88) or negative control siRNA (siNC) for 48 h. We examined the consequences of ciliated fibroblasts reduction on conduction and tissue remodeling by performing electrical mapping, microelectrode, and gene expression measurements.Results: Transfection of FB with siIft88 resulted in a significant 60% and 30% reduction of relative Ift88 expression in FB and CM-FB co-cultures, respectively, compared to siNC. Knockdown of Ift88 significantly increased the expression of ECM genes Fn1, Col1a1 and Ctgf by 38%, 30% and 18%, respectively, in comparison to transfection with siNC. Conduction velocity (CV) was significantly decreased in the siIft88 group in comparison to siNC [11.12 ± 4.27 cm/s (n = 10) vs. 17.00 ± 6.20 (n = 10) respectively, p &lt; 0.05]. The fraction of sites with interelectrode activation block was larger in the siIft88 group than in the siNC group (6.59 × 10−2 ± 8.01 × 10−2 vs. 1.18 × 10−2 ± 3.72 × 10−2 respectively, p &lt; 0.05). We documented spontaneous reentrant arrhythmias in two cultures in the siIft88 group and in none of the siNC group. Action potentials were not significantly different between siNC and siIft88 groups.Conclusion: Disruption of cilia formation by siIft88 causes ECM remodeling and conduction abnormalities. Prevention of cilia loss could be a target for prevention of arrhythmias.
Comparison of zinc bioavailability in zinc-glycine and zinc-methionine chelates for broilers fed with a corn-soybean meal diet
Authors: Chen Xiaohui , He Chao , Zhang Keying , Wang Jianping , Ding Xuemei , Zeng Qiufeng , Peng Huanwei , Bai Jie , Lv Li , Xuan Yue , Bai Shiping 
Published: November 2022

The objective of this study was to compare the bioavailability of zinc (Zn) from zinc-glycine (Zn-Gly) and zinc-methionine (Zn-Met) as compared with zinc sulfate (ZnSO4) used as a standard in broilers. A total of 1,200 one-day-old male broilers (Cobb 500) were randomly allotted to one of 10 treatments with eight replicate cages of 15 birds each. The broilers were fed a corn-soybean meal basal diet (containing 26.46 mg Zn/kg; control) or the basal diet added with 40, 80, and 120 mg Zn/kg as Zn-Gly, Zn-Met, or ZnSO4 for 14 days. The relative bioavailability value (RBV) was calculated based on multiple linear regression slope ratios of Zn concentrations in tibia and pancreas, pancreas metallothionein (MT) concentration, and pancreas MT mRNA abundance on added Zn intake. When comparing the control with all Zn-supplemented treatments, Zn addition did not significantly affect average feed intake and bodyweight gain during days 1–14 (p &gt; 0.10). However, Zn concentrations in the tibia, pancreas, and liver and pancreas MT concentration and MT mRNA abundance increased in all Zn-supplemented treatments compared with the control (p &lt; 0.05), and these indices increased linearly (p &lt; 0.001) with increasing added Zn levels on days 7 and 14. The RBV of Zn as Zn-Met was similar to that as Zn-Gly or ZnSO4 (p &gt; 0.40) on days 7 and 14, based on tibia and pancreas Zn. In contrast, on days 7 and 14, the RBVs of Zn were in the following order: Zn-Met &gt; Zn-Gly &gt; ZnSO4 (p &lt; 0.05), based on pancreas MT concentration. The bioavailable Zn from Zn-Met was 1.20 or 1.25 times that from Zn-Gly on day 7 or 14, respectively, evaluated by pancreas MT content. The RBV of Zn as Zn-Met was similar to that as Zn-Gly or ZnSO4 on day 7, whereas it was higher than that as Zn-Gly or ZnSO4 on day 14, based on pancreas MT mRNA abundance. In conclusion, Zn-Met had higher bioavailable Zn than Zn-Gly for the starter broilers fed with the corn-soybean meal diet, using pancreas MT concentration as the response criterion.
Sustainable Cannabis Nutrition: Elevated root-zone phosphorus significantly increases leachate P and does not improve yield or quality
Authors: Westmoreland F. Mitchell , Bugbee Bruce 
Published: November 2022

Phosphorus (P) is an essential but often over-applied nutrient in agricultural systems. Because of its detrimental environmental effects, P fertilization is well studied in crop production. Controlled environment agriculture allows for precise control of root-zone P and has the potential to improve sustainability over field agriculture. Medical Cannabis is uniquely cultivated for the unfertilized female inflorescence and mineral nutrition can affect the yield and chemical composition of these flowers. P typically accumulates in seeds, but its partitioning in unfertilized Cannabis flowers is not well studied. Here we report the effect of increasing P (25, 50, and 75 mg P per L) in continuous liquid fertilizer on flower yield, cannabinoid concentration, leachate P, nutrient partitioning, and phosphorus use efficiency (PUE) of a high-CBD Cannabis variety. There was no significant effect of P concentration on flower yield or cannabinoid concentration, but there were significant differences in leachate P, nutrient partitioning, and PUE. Leachate P increased 12-fold in response to the 3-fold increase in P input. The P concentration in the unfertilized flowers increased to more than 1%, but this did not increase yield or quality. The fraction of P in the flowers increased from 25 to 65% and PUE increased from 31 to 80% as the as the P input decreased from 75 to 25 mg per L. Avoiding excessive P fertilization can decrease the environmental impact of Cannabis cultivation.
A man-made divide: Investigating the effect of urban–rural household registration and subjective social status on mental health mediated by loneliness among a large sample of university students in China
Authors: Yu Hui , Xu Shicun , Li Hui , Wang Xiaofeng , Sun Qian , Wang Yuanyuan 
Published: November 2022

IntroductionThe urban–rural household registration system in China has been documented with profound social consequences in almost all areas of people’s life. This study aims to investigate the underlying mechanism of the rural and urban discrepancies on mental health conditions among a large sample of college students in China.MethodsA survey was distributed among college students in China. A total of 96,218 college students from 63 colleges completed the survey, answering questions on their urban–rural household registration, disposable household income, subjective social status, feelings of loneliness, and anxiety and depression symptoms. Confirmatory Factor Analysis (CFA) and Structural Equation Modelling (SEM) analyses were conducted, testing the effect of urban–rural registration on one’s mental health, mediated by subjective social status, and loneliness.ResultsStructural Equation Modelling (SEM) results revealed that the urban–rural household registration showed a direct effect on anxiety (B = −0.03, 95% CI [−0.038, −0.022], β = −0.03, p &lt; 0.001) and depression (B = −0.03, 95% CI [−0.035, −0.023], β = −0.03, p &lt; 0.001), indicating that rural household registration had a negative association with anxiety and depression symptoms, albeit the standardised estimate being very small. The indirect path from the urban–rural registration mediated through subjective social status and loneliness to anxiety and depression was both significant, with B = 0.01, 95% CI [0.010, 0.010], β = 0.01, p &lt; 0.001, and B = 0.01, 95% CI [0.0090, 0.0090], β = 0.01, p &lt; 0.001, respectively. The results of the indirect paths demonstrated that students of the rural household registration reported higher anxiety and depression symptoms through a lower subjective social status and higher level of loneliness.ConclusionThis study indicated that decreasing the disparity of social status and tackling loneliness is the key to improve the overall mental health of college students. The urban–rural household registration system may have a very small direct effect on the college students’ mental health; but students of urban registration enjoyed higher subjective social status, which had a clear protective effect against anxiety and depression symptoms.
Relationship between psychological capital and depression in Chinese physicians: The mediating role of organizational commitment and coping style
Authors: Sun Li , Zhang Yuan , He Jingyun , Qiao Kexin , Wang Ce , Zhao Shuai , Zhao Jinxin , Qiu Xiaohui , Yang Xiuxian , Zhou Jiawei , Bu Tianyi , Hu Xiaomeng , Qiao Zhengxue , Cao Depin , Yang Yanjie 
Published: November 2022

BackgroundIt is well known that the medical profession is a high-risk practice, with intense work and complex situations. The physicians are prone to suffer from depression due to occupational stress under high workloads for long periods of time. Depression not only impairs physicians’ mental health, but also affects the quality of health services, so it is important to explore the factors and mechanisms affecting depression among physicians.MethodsIn this cross-sectional study, 1,139 physicians from Heilongjiang Province were surveyed by cluster sampling procedures. The questionnaires included Psychological Capital Questionnaire, Chinese Employee Organizational Commitment Questionnaire, Trait Coping Style Questionnaire and Self-rating Depression Scale. Pearson correlation analysis and Bootstrap were used for statistical analysis.ResultsThis study found that 41.6% of physicians suffering from depression. Among them, 17.0% of physicians showed moderate depression, and 2.6% of physicians exhibited severe depression. The serial-multiple mediation of organizational commitment and positive coping styles in the relationship between psychological capital and depression was significant.ConclusionThe results showed that the psychological capital was sequentially associated with increased organizational commitment, and then increased positive coping styles, which resulted in reduced depression among physicians.
Virtual-reality-based social cognition and interaction training for patients with schizophrenia: A preliminary efficacy study
Authors: Shen Zhi-Hua , Liu Meng-Hui , Wu Yue , Lin Qian-Qian , Wang Yong-Guang 
Published: November 2022

BackgroundSocial cognition and interaction training (SCIT) is a psychosocial intervention program for patients with psychosis, designed to improve their social functioning by improving social cognition. Although the feasibility and efficacy of SCIT have been verified, patients with schizophrenia tend to suffer from motivational deficits and low treatment adherence. It has been suggested that using virtual reality (VR) technology might be effective in addressing these issues. In this study, we aimed to develop a VR-based SCIT and compare its efficacy with that of traditional SCIT.Materials and methodsWe developed a novel VR-based social cognition and interaction training (VR-SCIT) that combines traditional SCIT (TR-SCIT) intervention with VR technology. Participants were randomly assigned in a 1:1:1 ratio to the VR-SCIT (n = 28), TR-SCIT (n = 30), or waiting-list groups (n = 29). All treatments were combined with treatment-as-usual. Assessments of social cognition (i.e., Chinese version of Face-Affective Identification Task, Chinese version of Social Cognition Screening Questionnaire) and social functioning (i.e., Chinese version of Personal and Social Performance Scale) were administered from baseline to post-intervention.ResultsPatients receiving VR-SCIT and TR-SCIT showed a significantly greater improvement on the assessments of emotion perception (Cohen’s d was 1.66, 0.55, and 0.10 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), hostile attributional bias (Cohen’s d was 0.48, 0.44, and 0.05 for VR-SCIT, TR-SCIT, and Waiting-list, respectively), metacognition (Cohen’s d was 1.66, 0.76, and 0.06 for VR-SCIT, TR-SCIT, and waiting-list, respectively), and social functioning (Cohen’s d was 1.09, 0.90, and 0.20 for VR-SCIT, TR-SCIT, and waiting-list, respectively) from baseline to post-intervention, compared to those in waiting-list group. Additionally, VR-SCIT showed an advantage over TR-SCIT in improving emotion perception and metacognition with higher treatment compliance.ConclusionThese preliminary findings indicate that VR-SCIT is a feasible and promising method for improving social cognition and social functioning in patients with schizophrenia.
Diagnosis of children with attention-deficit/hyperactivity disorder (ADHD) comorbid autistic traits (ATs) by applying quantitative magnetic resonance imaging techniques
Authors: Tang Shilong , Liu Xianfan , Nie Lisha , Chen Zhuo , Ran Qiying , He Ling 
Published: November 2022

ObjectiveTo explore the feasibility of applying quantitative magnetic resonance imaging techniques for the diagnosis of children with attention-deficit/hyperactivity disorder (ADHD) comorbid autistic traits (ATs).MethodsA prospective study was performed by selecting 56 children aged 4–5 years with ADHD-ATs as the study group and 53 sex- and age-matched children with ADHD without ATs as the control group. All children underwent magnetic resonance scans with enhanced T2*- weighted magnetic resonance angiography (ESWAN), 3D-PCASL, and 3D-T1 sequences. Iron content and cerebral blood flow parameters were obtained via subsequent software processing, and the parameter values in particular brain regions in both groups were compared and analyzed to determine the characteristics of these parameters in children with ADHD-ATs.ResultsIron content and cerebral blood flow in the frontal lobe, temporal lobe, hippocampus, and caudate nucleus of children with ADHD-ATs were lower than those of children with ADHD without ATs (p &lt; 0.05). Iron content and CBF values in the frontal lobe, temporal lobe and caudate nucleus could distinguish children with ADHD-ATs from those without ATs (AUC &gt; 0.5, p &lt; 0.05).ConclusionsQuantitative magnetic resonance techniques could distinguish children with ADHD-ATs.Trial registrationThis study protocol was registered at the Chinese clinical trial registry (ChiCTR2100046616).