bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism
Authors: Zhang Xuebin , Duan Yu , Zhang Xiao , Jiang Mengyuan , Man Wanrong , Zhang Yan , Wu Dexi , Zhang Jiye , Song Xinglong , Li Congye , Lin Jie , Sun Dongdong 
Published: May 2023

Abstract
Background
Microvascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive.

Methods
Experimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (AdipsinLSL/LSL-Cre) and their respective control (AdipsinLSL/LSL). In addition, cultured CMECs were subjected to high glucose/palmitic acid (HG + PA) treatment to simulate diabetes for a mechanistic approach.

Results
The results showed that Adipsin overexpression significantly reduced cardiac microvascular permeability, preserved coronary microvascular integrity, and increased coronary microvascular density. Adipsin overexpression also attenuated cardiac dysfunction in diabetic mice. E/A ratio, an indicator of cardiac diastolic function, was improved by Adipsin. Adipsin overexpression retarded left ventricular adverse remodeling, enhanced LVEF, and improved cardiac systolic function. Adipsin-enriched exosomes were taken up by CMECs, inhibited CMECs apoptosis, and increased CMECs proliferation under HG + PA treatment. Adipsin-enriched exosomes also accelerated wound healing, rescued cell migration defects, and promoted tube formation in response to HG + PA challenge. Furthermore, Adipsin-enriched exosomes maintained adherens junctions at endothelial cell borders and reversed endothelial hyperpermeability disrupted by HG + PA insult. Mechanistically, Adipsin blocked HG + PA-induced Src phosphorylation (Tyr416), VE-cadherin phosphorylation (Tyr685 and Tyr731), and VE-cadherin internalization, thus maintaining CMECs adherens junctions integrity. LC-MS/MS analysis and co-immunoprecipitation analysis (Co-IP) unveiled Csk as a direct downstream regulator of Adipsin. Csk knockdown increased Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685 and Tyr731), while abolishing Adipsin-induced inhibition of VE-cadherin internalization. Furthermore, Csk knockdown counteracted Adipsin-induced protective effects on endothelial hyperpermeability in vitro and endothelial barrier integrity of coronary microvessels in vivo.

Conclusions
Together, these findings favor the vital role of Adipsin in the regulation of CMECs adherens junctions integrity, revealing its promises as a treatment target against diabetic coronary microvascular dysfunction.

Graphical Abstract
Graphical abstract depicting the mechanisms of action behind Adipsin-induced regulation of diabetic coronary microvascular dysfunction.
Biomechanics of open-globe injury: a review
Authors: Wang Songtao , Li Fuqiang , Jin Siyan , Zhang Yu , Yang Ning , Zhao Jinsong 
Published: May 2023

AbstractOpen-globe injury is a common cause of blindness clinically caused by blunt trauma, sharp injury, or shock waves, characterised by rupture of the cornea or sclera and exposure of eye contents to the environment. It causes catastrophic damage to the globe, resulting in severe visual impairment and psychological trauma to the patient. Depending on the structure of the globe, the biomechanics causing ocular rupture can vary, and trauma to different parts of the globe can cause varying degrees of eye injury. The weak parts or parts of the eyeball in contact with foreign bodies rupture when biomechanics, such as external force, unit area impact energy, corneoscleral stress, and intraocular pressure exceed a certain value. Studying the biomechanics of open-globe injury and its influencing factors can provide a reference for eye-contact operations and the design of eye-protection devices. This review summarises the biomechanics of open-globe injury and the relevant factors.
Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment
Authors: Lu Lu , Quan Lingli , Li Jian , Yuan Junbin , Nie Xinmin , Huang Xueyuan , Dong Hang , Su Yanrong , Huang Yufen , Kou Qingjie , Liu Leping , Liu Haiting , Zhou Xionghui , Gui Rong , Gu Lan 
Published: May 2023

Abstract
Background
Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management.

Results
Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time.

Conclusions
Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.
Carbon dots induce pathological damage to the intestine via causing intestinal flora dysbiosis and intestinal inflammation
Authors: Jia Mengmeng , Yi Bingcheng , Chen Xian , Xu Yongzhi , Xu Xinkai , Wu Zhaoxu , Ji Jing , Tang Jinglong , Yu Dianke , Zheng Yuxin , Zhou Qihui , Zhao Yanjie 
Published: May 2023

Abstract
Background
Carbon dots (CDs), as excellent antibacterial nanomaterials, have gained great attention in treating infection-induced diseases such as periodontitis and stomatitis. Given the eventual exposure of CDs to the intestine, elucidating the effect of CDs on intestinal health is required for the safety evaluation of CDs.

Results
Herein, CDs extracted from ε-poly-l-lysine (PL) were chosen to explore the modulation effect of CDs on probiotic behavior in vitro and intestinal remodeling in vivo. Results verify that PL-CDs negatively regulate Lactobacillus rhamnosus (L. rhamnosus) growth via increasing reactive oxygen species (ROS) production and reducing the antioxidant activity, which subsequently destroys membrane permeability and integrity. PL-CDs are also inclined to inhibit cell viability and accelerate cell apoptosis. In vivo, the gavage of PL-CDs is verified to induce inflammatory infiltration and barrier damage in mice. Moreover, PL-CDs are found to increase the Firmicutes to Bacteroidota (F/B) ratio and the relative abundance of Lachnospiraceae while decreasing that of Muribaculaceae.

Conclusion
Overall, these evidences indicate that PL-CDs may inevitably result in intestinal flora dysbiosis via inhibiting probiotic growth and simultaneously activating intestinal inflammation, thus causing pathological damage to the intestine, which provides an effective and insightful reference for the potential risk of CDs from the perspective of intestinal remodeling.
Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation
Authors: Mu Wenqing , Xu Guang , Wang Zhilei , Li Qiang , Sun Siqiao , Qin Qin , Li Zhiyong , Shi Wei , Dai Wenzhang , Zhan Xiaoyan , Wang Jiabo , Bai Zhaofang , Xiao Xiaohe 
Published: May 2023

Abstract
Background
Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood.

Methods
We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and Nlrp3 knockout (Nlrp3−/−) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in Nlrp3−/− mice.

Results
We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by Nlrp3 deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events.

Conclusion
Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury.
METTL3 and STAT3 form a positive feedback loop to promote cell metastasis in hepatocellular carcinoma
Authors: Liu Bowen , Cao Jinling , Wu Biting , Hao Kaixuan , Wang Xiangyun , Chen Xin , Shen Zhifa 
Published: May 2023

Abstract
Background
It is well-established that most Hepatocellular carcinoma (HCC) patients die of metastasis, yet the potential mechanisms orchestrating metastasis remain poorly understood. Current evidence suggests that the dysregulation of METTL3-mediated m6A methylation modification is closely associated with cancer progression. STAT3 is an oncogenic transcription factor that reportedly plays a central role in the occurrence and development of HCC. However, the relationship between METTL3 and STAT3 in HCC metastasis remains unclear.

Methods
The relationship between METTL3 expression and the survival of HCC patients was assessed by online tools GEPIA and Kaplan–Meier Plotter. Western blotting, Tissue microarray (TMA), and immunohistochemistry (IHC) staining were used to evaluate the expression levels of METTL3 and STAT3 in HCC cell lines and metastatic and non-metastatic tissues. Methylated RNA immunoprecipitation (MeRIP), MeRIP sequencing (MeRIP-seq), qRT-PCR, RNA immunoprecipitation (RIP), Western blotting and luciferase reporter gene assay were utilized to clarify the mechanism of METTL3 regulating STAT3 expression. Immunofluorescence staining, Western blotting, qRT-PCR, Co-immunoprecipitation (Co-IP), IHC staining, TMA and Chromatin immunoprecipitation (ChIP) assay were performed to explore the mechanism of STAT3 modulating METTL3 localization. Cell viability, wound healing and transwell assay, and orthotopic xenograft model were used to evaluate the role of METTL3-STAT3 feedback loop in the promotion of HCC metastasis in vitro and in vivo.

Results
METTL3 and STAT3 are both abundantly expressed in high-metastatic HCC cells and tissues. Moreover, a positive correlation was found between the expression of STAT3 and METTL3 in HCC tissues. Mechanistically, METTL3 could induce the m6A modification of STAT3 mRNA, and then promote the translation of m6A-contained STAT3 mRNA by interacting with the translation initiation machinery. In contrast, STAT3 promoted nuclear localization of METTL3 via transcriptionally upregulating WTAP, a vital member of the methyltransferase complex, and facilitated the methyltransferase function of METTL3. METTL3 and STAT3 form a positive feedback loop to accelerate HCC metastasis in vitro and in vivo.

Conclusions
Our findings reveal a novel mechanism of HCC metastasis and uncover the METTL3-STAT3 feedback signaling as a potential target for the anti-metastatic treatment of HCC.
Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases
Authors: Sun Mingchu , Jiang Wenhua , Mu Nan , Zhang Zihui , Yu Lu , Ma Heng 
Published: May 2023

AbstractCardiovascular disease (CVD) is the leading cause of noncommunicable disease-related death worldwide, and effective therapeutic strategies against CVD are urgently needed. Mitochondria dysfunction involves in the onset and development of CVD. Nowadays, mitochondrial transplantation, an alternative treatment aimed at increasing mitochondrial number and improving mitochondrial function, has been emerged with great therapeutic potential. Substantial evidence indicates that mitochondrial transplantation improves cardiac function and outcomes in patients with CVD. Therefore, mitochondrial transplantation has profound implications in the prevention and treatment of CVD. Here, we review the mitochondrial abnormalities that occur in CVD and summarize the therapeutic strategies of mitochondrial transplantation for CVD.
The potential role of scavenging flies as mechanical vectors of Lagovirus europaeus/GI.2
Authors: Lopes Ana M. , Almeida Tereza , Diz Sílvia , Côrte-Real João V. , Osório Hugo C. , Ramilo David W. , Rebelo Maria Teresa , da Fonseca Isabel Pereira , Esteves Pedro J. , Alves Paulo C. , Santos Nuno , Abrantes Joana 
Published: May 2023

AbstractThe European rabbit (Oryctolagus cuniculus) populations of the Iberian Peninsula have been severely affected by the emergence of the rabbit haemorrhagic disease virus (RHDV) Lagovirus europaeus/GI.2 (RHDV2/b). Bushflies and blowflies (Muscidae and Calliphoridae families, respectively) are important RHDV vectors in Oceania, but their epidemiological role is unknown in the native range of the European rabbit. In this study, scavenging flies were collected between June 2018 and February 2019 in baited traps at one site in southern Portugal, alongside a longitudinal capture-mark-recapture study of a wild European rabbit population, aiming to provide evidence of mechanical transmission of GI.2 by flies. Fly abundance, particularly from Calliphoridae and Muscidae families, peaked in October 2018 and in February 2019. By employing molecular tools, we were able to detect the presence of GI.2 in flies belonging to the families Calliphoridae, Muscidae, Fanniidae and Drosophilidae. The positive samples were detected during an RHD outbreak and absent in samples collected when no evidence of viral circulation in the local rabbit population was found. We were able to sequence a short viral genomic fragment, confirming its identity as RHDV GI.2. The results suggest that scavenging flies may act as mechanical vectors of GI.2 in the native range of the southwestern Iberian subspecies O. cuniculus algirus. Future studies should better assess their potential in the epidemiology of RHD and as a tool for monitoring viral circulation in the field.
The relationship between coping strategies with sexual satisfaction and sexual intimacy in women with multiple sclerosis
Authors: Imanpour Barough Samaneh , Riazi Hedyeh , Keshavarz Zohreh , Nasiri Maliheh , Montazeri Ali 
Published: May 2023

Abstract
Background
Multiple sclerosis profoundly affects the sexual aspects of patients’ life, especially in women. Various coping strategies are used by women with multiple sclerosis to overcome, tolerate, or minimize these sexual effects. The present study aimed to assess the relationship between sexual satisfaction, sexual intimacy, and coping strategies in women with multiple sclerosis.

Methods
This cross-sectional study was performed on a sample of 122 married women who were members of Iran’s MS society in Tehran, Iran. The study was conducted from December 2018 to September 2019. Data were collected using the Index of Sexual Satisfaction (ISS), the Sexual Intimacy Questionnaire (SIQ), and the Folkman and Lazarus Coping Strategies Questionnaire. Frequency, percentage, mean and standard deviation were used to explore the observations. Independent t-test and logistic regression were applied to analyze the data using the SPSS-23.

Results
The majority (n = 71, 58.2%) used an emotion-focused coping strategy with the highest score for the escape-avoidance subscale [mean (SD): 13.29 (5.40)]. However, 41.8% of the patients (n = 51) used a problem-focused coping strategy with the highest score for the positive reappraisal strategy subscale [mean (SD): 10.50 (4.96)]. The sexual satisfaction in women with problem-focused coping strategies was significantly higher than women who used emotion-focused coping strategies (95.6 vs. 84.71, P-value = 0.001). There was a negative association between sexual intimacy and higher emotion-focused coping strategy (OR = 0.919, 95% CI 0.872–0.968, P = 0.001).

Conclusions
Problem-focused coping strategy in women with multiple sclerosis increases sexual satisfaction, while the emotion-focused coping strategy has a significant negative relationship with sexual intimacy.
l-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway
Authors: Liao Taiyang , Mei Wei , Zhang Li , Ding Liang , Yang Nan , Wang Peimin , Zhang Li 
Published: May 2023

Abstract
Background
Knee osteoarthritis (KOA) is a disability-associated condition that is rapidly growing with the increase in obesity rates worldwide. There is a pressing need for precise management and timely intervention in the development of KOA. l-carnitine has been frequently recommended as a supplement to increase physical activity in obese individuals due to its role in fatty acid metabolism, immune disorders, and in maintaining the mitochondrial acetyl-CoA/CoA ratio. In this study, we aimed to investigate the anti-inflammatory effects of l-carnitine on KOA and delineate a potential molecular mechanism.

Methods
Lipopolysaccharide-stimulated primary rat fibroblast-like synoviocytes (FLS) were treated with an AMP-activated protein kinase (AMPK) inhibitor or siRNA and carnitine palmitoyltransferase 1 (CPT1) siRNA to examine the synovial protective effects of l-carnitine. An anterior cruciate ligament transection model of rats was treated with an AMPK agonist (metformin) and CPT1 inhibitor (etomoxir) to define the therapeutic effects of l-carnitine.

Results
l-carnitine displayed a protective effect against synovitis of KOA in vitro and in vivo experiments. Specifically, l-carnitine treatment can reduce synovitis by inhibiting AMPK-ACC-CPT1 pathway activation and showed an increase in fatty acid β-oxidation, a lower lipid accumulation, and a noticeable improvement in mitochondrial function.

Conclusions
Our data suggested that l-carnitine can mitigate synovitis in FLS and synovial tissue, and the underlying mechanism may be related to improving mitochondrial function and reducing lipid accumulation via the AMPK-ACC-CPT1 signaling pathway. Therefore, l-carnitine may be a potential treatment strategy for KOA.
The 100 most cited papers on total anomalous pulmonary venous connection: a bibliometric analysis
Authors: Wen Chen , Liu Wei , Fang Chenhao , Shentu Jin , Ma Ruixiang , Zhang Han , Zhang Hao , Zhu Zhongqun , Chen Huiwen 
Published: May 2023

Abstract
Background
The number of citations a paper receives reflects its impact on the scientific community. We aimed to identify and explore the characteristics of the most cited papers on total anomalous pulmonary venous connection (TAPVC).

Methods
Web of Science Core Collection Expanded Science Citation Index (1900 to present) was searched and papers on TAPVC were reviewed. Articles were ranked by the number of citations and the 100 most cited papers were analyzed.

Results
The 100 most cited papers were published between 1952 and 2018 with a mean number of citations of 52 (range 26 to 148). The 1990s was the most productive decade. All articles except one were written in English. The 100 most cited articles were published in 24 journals, led by Journal of Thoracic and Cardiovascular Surgery (21 articles), followed by Annals of Thoracic Surgery (20 articles), and Circulation (16 articles). The United States of America contributed most of the 100 most cited papers (60 articles). Hospital for Sick Children, Toronto led the list of citation classics with six papers. Christopher A. Caldarone, John W. Kirklin, and P. E. F. Daubeney were the most productive authors with 3 articles each. More than half of the papers were cohort studies (51 articles). Surgery, radiology and etiology were the main topics. Thirty-one articles were funded by public foundations, and none received support from commercial companies.

Conclusions
The bibliometric analysis gives a historical perspective on scientific progress in the field of TAPVC and lays the foundation for future research.
Betacellulin regulates gap junction intercellular communication by inducing the phosphorylation of connexin 43 in human granulosa-lutein cells
Authors: Li Yuxi , Chang Hsun-Ming , Sung Yu-Wen , Zhu Hua , Leung Peter C. K. , Sun Ying-Pu 
Published: May 2023

Abstract
Background
The gap junction protein, connexin 43 (Cx43) is highly expressed in human granulosa-lutein (hGL) cells. The phosphorylation of certain amino acid residues in the Cx43 protein has been shown to be related to a decline in gap junction intercellular communication (GJIC), which subsequently affects oocyte meiotic resumption. As a member of the epidermal growth factor (EGF) family, betacellulin (BTC) mediates luteinizing hormone (LH)-induced oocyte maturation and cumulus cell expansion in mammalian follicles. Whether BTC can regulate Cx43 phosphorylation, which further reduces Cx43-coupled GJIC activity in hGL cells remains to be determined.

Methods
Immortalized human granulosa cells (SVOG cells) and primary human granulosa-lutein cells obtained from women undergoing in vitro fertilization in an academic research center were used as the study models. The expression levels of Cx43 and phosphorylated Cx43 were examined following cell incubation with BTC at different time points. Several kinase inhibitors (sotrastaurin, AG1478, and U0126) and small interfering RNAs targeting EGF receptor (EGFR) and receptor tyrosine-protein kinase 4 (ErbB4) were used to verify the specificity of the effects and to investigate the molecular mechanisms. Real-time-quantitative PCR and western blot analysis were used to detect the specific mRNA and protein levels, respectively. GJIC between SVOG cells were evaluated using a scrape loading and dye transfer assay. Results were analyzed by one-way analysis of variance.

Results
The results showed that BTC induced the rapid phosphorylation of Cx43 at serine368 without altering the expression of Cx43 in primary and immortalized hGL cells. Additionally, using a dual inhibition approach (kinase inhibitors and siRNA-based expression knockdown), we demonstrated that this effect was mainly mediated by the EGFR but not the ErbB4 receptor. Furthermore, using a protein kinase C (PKC) kinase assay and a scrape-loading and dye transfer assay, we revealed that PKC signaling is the downstream signaling pathway that mediates the increase in Cx43 phosphorylation and subsequent decrease in GJIC activity in response to BTC treatment in hGL cells.

Conclusions
BTC promptly induced the phosphorylation of connexin 43 at Ser368, leading to decreased GJIC activity in hGL cells. The BTC-induced cellular activities were most likely driven by the EGFR-mediated PKC-dependent signaling pathway. Our findings shed light on the detailed molecular mechanisms by which BTC regulates the process of oocyte meiotic resumption.