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The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention., Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.

Lithium-sulfur (Li–S) batteries have high expectations for large-scale applications in energy devices because of their high theoretical capacity and low cost. However, due to the insulation and shu...

The progress of flexible/wearable electronic devices with multi-functionality has stimulated the rapid development of the matching power supply devices. Flexible supercapacitors with high electrochemical performance and mechanical flexibility are considered as attractive technologies to power flexible electronics and have been studied intensively. Carbon nanomaterials, such as carbon nanotube, graphene, and their composites, possess unprecedented physical/chemical properties and exhibit great potential for use in flexible supercapacitors. In this review, the recent progress of state-of-the-art flexible supercapacitors using advanced carbon nanomaterials is expounded comprehensively and systematically, the topic covered the micro/nano-structure control, macroscopic morphologies design, property optimization and application of carbon nanomaterials. Based on the current advances, the challenges and prospects of carbon nanomaterials applied in flexible supercapacitors are outlined and highlighted. As last, the matching between the characters of carbon nanomaterials, construction of flexible supercapacitors and fabrication technologies are put forward.

Yumei Ge,1,&ast; Xiaoyu Gou,1,&ast; Xiaoyan Dong,1,2 Yumeng Peng,1,3 Fangfang Yang4 1Department of Laboratory Medicine Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2The Second Medical College, Zhejiang Chinese Medical University, Hangzhou, 310014, People’s Republic of China; 3Department of Clinical Laboratory Diagnostics, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 4Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, 621000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangfang Yang, Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan mental health center), Mianyang, Sichuan, 621000, People’s Republic of China, Email yhge2159@163.comPurpose: At present, there is no gold standard or unified standard for the diagnosis of neurosyphilis, and the rate of misdiagnosis is high. The diagnosis of neurosyphilis is still challenging. This study compared the clinical indicators between neurosyphilis and latent syphilis infection in the central nervous system. The purpose of this study was to provide evidence for the differential diagnosis and prognosis of patients with neurosyphilis and latent syphilis infection of the central nervous system.Methods: The clinical data of 59 patients with neurosyphilis and 30 patients with latent syphilis infection in the nervous system from 2008 to 2021 were analyzed. The cerebrospinal fluid and serum biochemical markers were evaluated for all patients.Results: CSF-nucleated cells, CSF-TRUST, CSF-totalprotein and CSF-IgG (P< 0.001) were significantly different between neurosyphilis and latent syphilis infection in the central nervous system. CSF-TRUST titer was positively correlated with D-D concentration (r = 0.274, P < 0.05), sodion (r =0.251, P < 0.05), respectively. Glucose concentration is the most unreliable in the diagnosis of neurosyphilis (AUC=0.445, P=0.395), and TRUST combined with nucleated cells and total protein is the most accurate in the diagnosis of neurosyphilis (AUC=0.989, P< 0.001).Conclusion: The combination of TRUST, nucleated cell count and totalprotein detection in CSF can distinguish the patients with neurosyphilis and latent syphilis infection in the central nervous system, which has a significant diagnostic value.Keywords: neurosyphilis, latent syphilis infection, diagnosis, detection index

PurposeThe purpose of the paper is to investigate how cross-cultural elements such as cultural difference and stereotype are integrated into collaborative modes and actions and to explore their corresponding effectiveness.Design/methodology/approachThe sample of the quantitative content analysis is drawn from the posts with the topic of China on Quora. A collaborative case, where two users have a question-and-answer interaction, is taken as the unit of analysis. The effectiveness of collaboration is operationalized as the extent to which a collaboratively produced answer is visited and favorably reviewed, using the feedback index (the number of upvotes*1,000/views). One of the sampled collaborative cases is further analyzed qualitatively to see how cultural differences, stereotypes and other factors are incorporated into users' interaction.FindingsThis content analysis reveals nine modes of collaborative production of knowledge on Quora: initial questioning, pointed answering, raising doubts, responding to others, agreeing with others, correcting mistakes, enriching content, further questioning and extending issues. Diversity of the cross-cultural acts of collaborative production, particularly two of often-used collaborative actions, correcting stereotypes and supplementing cultural differences, helps to enhance overall collaborative effectiveness.Practical implicationsThis paper offers new perspectives and ideas for strategies to change socially problematic stereotypes, e.g. to correct stereotypes where necessary and use more convincing resources such as reliable images as collaborative actions to bridge cultural differences. It also calls on social Q&A website developers to create more international users-friendly design by providing various channels for users with diverse cultural backgrounds to interact with each other.Originality/valueThis study is one of the first to investigate online collaborative knowledge production within a broader cross-cultural context. Specifically, cultural factors and cross-cultural collaborative actions have been innovatively integrated into this research, enriching the dimensions that can be used for collaboration classification. It is helpful for users from different countries to actively adopting different strategies to overcome cultural differences, preconceptions and other negative factors that are not conducive to communication and knowledge acquisition.

Parotid gland tuberculosis constantly results in unnecessary medical examinations and surgery because of its similarities in the presentation to neoplasms of the parotid gland. Although parotid gland involvement is extremely rare even in tuberculosis-endemic countries, accurate diagnosis of this clinical entity is of great significance because tuberculous parotitis can be successfully treated medically without surgical therapy. Fine needle aspiration cytology (FNAC) and molecular identification of the parotid swellings are efficient in making a rapid diagnosis. Herein, we report an early misdiagnosis of malignancy from a renal transplantation patient on long-term immunologic inhibitor therapy, who ultimately proved to have tuberculosis of the parotid gland by FNAC and molecular identification. The aim of this study is to describe and analyze the etiologic characteristics, epidemiology, clinical presentations, diagnostic methods, histopathologic findings, and pathogenic mechanisms of these rare infections.

Background Recently, the rise of syphilitic seroresistance brings great confusion to the clinical diagnosis and treatment of syphilis, and no clear diagnostic marker has been found to distinguish syphilitic seroresistance from other progression of syphilis. This study evaluated the serum chemokines levels of CCL2, CXCL8, CXCL9, and CXCL10 and its correlation with blood routine, coagulation, and biochemical indexes in seroresistant syphilitic patients. Method Serum levels of chemokines were quantitatively determined by Flow Cytometric Bead Array (CBA). The results expressed in pg/ml. Clinical parameters were detected and analyzed according to the clinical laboratory standards. A correlation analysis was subsequently performed. Results The seroresistant syphilitic patients increased significantly serum chemokines levels of CXCL8 (***p, In this study, the concentration of cytokines in blood samples of patients with Treponema pallidum infection in Zhejiang Provincial People's Hospital was detected by flow cytometry. Our data showed that seroresistant syphilitic patients presented significantly increased levels of the serum chemokines CXCL8, CXCL9, and CXCL10 when compared to non‐infected individuals.

Background Nocardia is an opportunistic pathogen, which occurs in patients with autoimmune diseases and immune dysfunction, and can cause bacteremia and other life‐threatening complications. The clinical manifestations of Nocardia pneumonia are similar to tuberculous and other clinical common bacterial pneumonia, but its antibacterial treatments are different and detection methods are unique, which may lead patients to suffer for many years due to clinical misdiagnosis and missed diagnosis. Methods Imaging and laboratory examinations were performed for preliminary diagnosis, and next‐generation sequencing was used to identify the exact species type of Nocardia in the bronchoalveolar lavage fluid (BALF) of the patient. Results Imaging and laboratory parameters preliminarily implied that the patient was infected with Nocardia with Sjogren's syndrome (SS), and NGS showed that the strain was N. terpenica. Conclusions Accurate etiological diagnosis and corresponding antibiotics are key to improve the prognosis of pulmonary nocardiosis in this case. Nocardia pneumonia is rare in clinical practice; it is of great medical significance to improve the understanding of pulmonary nocardiosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic conditions increased GP73 production and secretion. Secreted GP73 then trafficked to the liver and kidney to stimulate gluconeogenesis through the cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of the PKA kinase hub exerted by GP73. Notably, plasma GP73 levels were elevated and positively correlated with blood glucose in patients with COVID19 and diabetes. Neutralization of circulating GP73 in serum of individuals infected with SARS-CoV-2 or with diabetes reduced excessive gluconeogenesis in cultured hepatocytes, and lowered blood glucose levels in animal models of diabetes. Ablation of GP73 from whole animals has a profound glucose-lowering effect secondary to reduced gluconeogenesis. Thus, GP73 is a key glucogenic hormone contributing to SARS-CoV-2-induced glucose abnormality.

SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic condition increased the cellular secretion of GP73. Secreted GP73 trafficked to the liver and kidney to stimulate gluconeogenesis through cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of PKA kinase hub exerted by GP73. Notably, COVID-19 patients showed pathologically elevated plasma GP73, and neutralization of the secreted GP73 inhibited enhanced PKA signaling and glucose production associated with SARS-CoV-2 infection. GP73 blockade also reduced gluconeogenesis and lowered hyperglycemia in type 2 (T2D) diabetic mice. Therefore, our findings provide novel insight into the roles of GP73 as a key glucogenic hormone and mechanistic clues underlying the development of SARS-CoV-induced glucose abnormalities.

In recent years, the incidence of tumors has been increasing, and the overall cure rate by traditional treatment methods does not exceed 20%. One of the most effective and promising strategies for comprehensive treatment of tumors is immunotherapy, such as treatment with the PD-1/PD-L1 antibody. Here, we showed that ring finger protein 125 (RNF125), an E3 ligase in the RING domain family, could interact with PD-L1 to reduce the stability of PD-L1 protein. In addition, RNF125 downregulated the expression of PD-L1 by promoting its ubiquitination at K48, whereas a mutation in the RING domain of RNF125 disrupted this function. A significant positive correlation between RNF125 and genes involved with tumor immunity was determined in cancer samples, as determined using data from The Cancer Genome Atlas (TCGA). Furthermore, we elucidated the effects of RNF125 on the occurrence and development of tumors in mice. Analyses of wild-type and RNF125 knockout mice transplanted with MC-38 cells revealed enhanced MC-38 tumor growth in KO mice. These data indicated that RNF125 could participate in tumor immunity by promoting the K48-linked ubiquitination of PD-L1 to affect the occurrence and development of tumors, providing a potential target for enhancing therapeutic efficacy for human cancer treatment.

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.

Introduction Mycoplasma pneumoniae is a common cause of respiratory infections in humans. The aim of this study was to investigate the infection of Mycoplasma pneumoniae (MP) in patients with acute respiratory tract infections in Zhejiang Province from 2008 to 2017, and to provide evidence for the early diagnosis and prevention of MP pneumonia. Methods MP‐DNA was detected in nasopharyngeal swabs of patients with acute respiratory tract infection by real‐time fluorescent PCR (TaqMan probe). Statistical analysis and epidemiological investigation were carried out on the test results. Results There were 10 296 patients with acute respiratory tract infection in Zhejiang Provincial People's Hospital from 2008 to 2017, including 4387 females and 5909 males. A total of 1251 MP‐DNA–positive patients were detected, with a total positive rate of 12.2% (1251/10296). Among 1251 patients with MP infection, 571 were female positive, with an average positive rate of 13.0% (571/4387), and 680 were male positive, with a positive rate of 11.5% (680/5909). From 2008 to 2017, the positive rates were 22.8% (33 cases), 20.9% (211 cases), 20.9% (350 cases), 5.5% (70 cases), 11.7% (136 cases), 15.2% (190 cases), 7.8% (94 cases), 5.9% (62 cases), 7.8% (56 cases), and 6.0% (49 cases), respectively. Of 1251 MP‐DNA–positive patients, 1243 (99.4%) were younger than 18 years old. Conclusions Mycoplasma pneumoniae infection mainly occurs from late summer to autumn and in the age below 18 years, suggesting that early diagnosis and prevention of MP infection in adolescents should be emphasized., Figure 1. Annual, quarter, and monthly cases and positivity of MP from 2008 to 2017

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

In this study, we specifically addressed the connection between the SARS-CoV-2 virus with host cholesterol metabolism. Plasma lipid profile was measured in 861 COVID-19 patients classified as mild (n=215), moderate (n=364), severe (n=217) or critical (n=65) and 1108 age- and sex-matched healthy individuals. We showed that the levels of both TG and HDL-C were significantly lower in patients with severe disease than in patients with moderate or mild disease. After successful treatment, cholesterol metabolism was reestablished in patients with SARS-CoV-2 infection. The serum concentrations of TC and HDL-C can be used as indicators of disease severity and prognosis in COVID-19 patients.

s: Hazard identification is the basis and premise of underlying risk management in underground coal mines. Although a large amount of research has been conducted on hazard identification methods applied to underground coal mines, additional improvements are possible. The traditional hazard identification methods apply to a specific incident or event or are based on experience and therefore lack a systematic and comprehensive identification framework. In this paper, the Root-State Hazard Identification (RSHI) method is proposed to solve the above issues and identify the hazards in underground coal mine risk management. Firstly, the paper categorizes the underground coal mine hazards into root hazards and state hazards and then differentiates their internal relationships. Secondly, the paper explores the relationships among the hazards, risks and accidents in detail. Thirdly, the framework of the RSHI method is proposed based on the hazard classification and relationships among the hazards, risks and accidents. Finally, the proposed RSHI method is applied to identify hazards associated with the risk management of six mines that belong to the Yima Coal Industry Group in China. The results indicate that the RSHI method is capable of comprehensively identifying root hazards and state hazards associated with the underground coal mine risk management. Moreover, its application procedure is simple and convenient and reduces the need for the joint identification and coordination of various types of workers.

Summary: Recent reports have shown the critical role of the mitochondrial antiviral signaling (MAVS) protein in virus-induced apoptosis, but the involvement of MAVS in tumorigenesis is still poorly understood. Herein, we report that MAVS is a key regulator of p53 activation and is critical for protecting against tumorigenesis. We find that MAVS promotes p53-dependent cell death in response to DNA damage. MAVS interacts with p53 and mediates p53 mitochondrial recruitment under genotoxic stress. Mechanistically, MAVS inhibits p53 ubiquitination by blocking the formation of the p53-murine double-minute 2 (MDM2) complex, leading to the stabilization of p53. Notably, compared with their wild-type littermates, MAVS knockout mice display decreased resistance to azoxymethane (AOM) or AOM/dextran sulfate sodium salt (DSS)-induced colon cancer. MAVS expression is significantly downregulated in human colon cancer tissues. These results unveil roles for MAVS in DNA damage response and tumor suppression. : Zhang et al. show that MAVS interacts with p53 and regulates p53-dependent apoptosis, indicating roles for MAVS in tumor suppression and the DNA damage response. Keywords: MAVS, p53, ubiquitination, tumor suppression

Viral infection triggers the formation of mitochondrial antiviral signaling protein (MAVS) aggregates, which potently promote immune signaling. Autophagy plays an important role in controlling MAVS‐mediated antiviral signaling; however, the exact molecular mechanism underlying the targeted autophagic degradation of MAVS remains unclear. Here, we investigated the mechanism by which RNF34 regulates immunity and mitophagy by targeting MAVS. RNF34 binds to MAVS in the mitochondrial compartment after viral infection and negatively regulates RIG‐I‐like receptor (RLR)‐mediated antiviral immunity. Moreover, RNF34 catalyzes the K27‐/K29‐linked ubiquitination of MAVS at Lys 297, 311, 348, and 362 Arg, which serves as a recognition signal for NDP52‐dependent autophagic degradation. Specifically, RNF34 initiates the K63‐ to K27‐linked ubiquitination transition on MAVS primarily at Lys 311, which facilitates the autophagic degradation of MAVS upon RIG‐I stimulation. Notably, RNF34 is required for the clearance of damaged mitochondria upon viral infection. Thus, we elucidated the mechanism by which RNF34‐mediated autophagic degradation of MAVS regulates the innate immune response, mitochondrial homeostasis, and infection.