Design and Synthesis of Novel Factor XIa Inhibitors with Bicyclic Isoquinoline and Naphthalene Fragments (preprint)

FXIa has emerged as a promising therapeutic target for treating thrombotic diseases. With the aim to replace the aniline motif of asundexian with novel P2’ fragments, bicyclic isoquinoline and naphthalene rings were designed. The target compounds with isoquinoline ring were synthesized via 13 steps of chemical reactions. Substituents within the rings were investigated to elucidate the structural determinants governing selective or dual inhibition of FXIa and Plasma Kallikrein (PKa). In vitro testing showed that some of designed compounds exhibited comparable potency against both FXIa and PKa, while others achieved up to 94-fold selectivity. Analysis of structure-activity relationships (SARs) uncovered the pivotal role of the carboxylic acid moiety in retaining inhibition of FXIa and PKa, and the steric hindrance and hydrogen-bond receptor functional groups were identified as key factors influencing the selectivity of FXIa inhibition over PKa. The docking study additionally unveiled different binding modes that play a significant role in the observed activity and selectivity. Furthermore, the selected compounds significantly extended the plasma coagulation time in a dose-dependent manner. Altogether, the bicyclic compounds may be promising lead compounds for the development of highly effective FXIa inhibitors.

Efficacy and safety of acupuncture for post-COVID-19 depression: a protocol for systematic review and meta-analysis.

INTRODUCTION: Post-COVID-19 depression (PCD) is a possible sequela of COVID-19. Some doctors have used acupuncture to treat PCD, but no systematic review or meta-analysis has yet evaluated its efficacy and safety for the treatment of PCD. The aim of this systematic review is to assess the efficacy and safety of acupuncture therapy for PCD. METHODS AND ANALYSIS: Two reviewers will independently search the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (PubMed), Excerpt Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and Wan-Fang Database from inception to 24 January 2023. Study selection, data extraction and assessment of study quality will be independently performed by two reviewers. If a meta-analysis is appropriate, Review Manager V.5.3 will be used for data synthesis; otherwise, a descriptive analysis will be conducted. Data will be synthesised using a fixed-effects or random-effects model, according to the results of a heterogeneity test. The results will be presented as risk ratios with 95% CIs for dichotomous data, and weighted mean differences or standardised mean differences with 95% CIs for continuous data. ETHICS AND DISSEMINATION: The entire process used for this systematic review does not use private information, so ethical approval is not required. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal and/or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022379312.

[Clinical features of children with coronavirus disease 2019 caused by Delta variant infection in different age groups]. / 不同年龄段儿童Deltaå˜å¼‚æ ªæ„ŸæŸ“æ‰€è‡´æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with coronavirus disease 2019 (COVID-19) caused by Delta variant infection in different ages groups. METHODS: A total of 45 children with COVID-19 caused by Delta variant infection who were hospitalized in the designated hospital in Henan Province, China, from November 17 to December 17, 2021, were included. They were divided into three groups: <6 years group (n=16), 6-13 years group (n=16), and >13 years group (n=13). The three groups were compared in clinical features and laboratory examination data. RESULTS: COVID-19 in all age groups was mainly mild. Main manifestations included cough and expectoration in the three groups, and fever was only observed in the 6-13 years group. The <6 years group had significantly higher serum levels of aspartate aminotransferase, lactate dehydrogenase, and creatine kinase isoenzymes than the other two groups (P<0.05). The 6-13 years group had the highest proportion of children with elevated serum creatinine levels (50%). Among the three groups, only 4 children in the >13 years group had an increase in serum C-reactive protein levels. The 6-13 years group had the lowest counts of CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, and natural killer cells in the peripheral blood among the three groups. The >13 years group had a significantly higher positive rate of SARS-CoV-2 IgG on admission than the other two groups (P<0.05). There was no significant difference in the imaging findings on chest CT among the three groups (P>0.05). CONCLUSIONS: The clinical features of COVID-19 caused by Delta variant infection in children of different age groups may be different: children aged <6 years tend to develop myocardial injury, and those aged 6-13 years have fever except cough and expectoration and tend to develop renal and immune dysfunction.

Evaluation on the Specificity and Sensitivity of a COVID-19 and A+B Influenza Antigen Combo Test for Detection and Application in Rapid Chromatographic Immunoassays

[...]fecal-oral transmission, where rotavirus is present in the feces of a patient is excreted and often contaminates water, food, clothing, toys, utensils, and other high touch objects. When a healthy person comes into contact with these items, the virus can enter the body through the hand or mouth and cause lesions in the digestive tract [4, 7]. Since 2019, the spread of COVID-19 has posed a public health threat throughout the world, endangering people's lives. According to research, N95 masks are more protective against COVID-19 than normal masks. Limiting aggregation is also an important means to limit the spread of the viruses. [...]control measures to limit the number of people gathering and intervening in public places are effective [7].

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Significance of SARS-CoV-2 and Influenza A+B Antigen Combo Rapid Test for Distinguishing Influenza from COVID-19

According to the Centers for Disease Control (CDC), typical flu symptoms include fever, cough, sore throat, muscle aches, headache, runny or stuffy nose, fatigue, and sometimes even vomiting and diarrhea [1]. Healthcare providers should follow the Centers for Disease Control and Prevention (CDC) recommendations for infection control and the appropriate use of personal protective equipment [5]. Because some of the symptoms of influenza and COVID-19 are similar, it may be difficult to distinguish between the two respiratory diseases based on symptoms alone. [...]it is necessary to test for both viruses in anyone with symptoms of COVID-19 or influenza. [...]after the test is completed, place all the components into the plastic bag and tightly seal and dispose of according

Time-Resolved Persistent Luminescence Encoding for Multiplexed Severe Acute Respiratory Syndrome Coronavirus 2 Detection.

Capable of precise simultaneous multitarget identifications within a minimized sample, optical multiplexing is vital for accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) while remaining spectral crowding and background interfering. In merits of an autofluorescence-free background and high-capability throughput, a persistent luminescence (PersL) lifetime/color binary encoding strategy was herein proposed for SARS-CoV-2 diagnosis. Based on luminescence resonance energy transfer processes, the intense lifetimes and representative emissions of PersL nanoplatforms were rationally manipulated to create a temporal coding dimension within a wide seconds-to-minutes range through three individual channels. Particularly, at least four populations of barcoding in a certain channel were successfully decoded by a purpose-built time-resolved PersL technology. As a proof-of-concept, functionalized PersL nanoplatforms were further well developed for the simultaneous quantification of five-plex SARS-CoV-2 biomarkers with limits of detection in the subnanomolar range. Remarkably, PersL nanoplatforms enabled a highly differentiable discrimination of multitargets at various concentrations of ultralow background and high-fidelity resolutions, thereby advancing a powerful tool for optical multiplexing in biomedical applications.

Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics

Purpose 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis and maturation of spike protein is essential for SARS-CoV-2 infection in vivo. The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the infection of the SARS-CoV-2 and its variants. However, it is not clear about the mechanism of N-0385 treatment COVID-19. Therefore, this study used computer simulations to investigate the mechanism of N-0385 treatment COVID-19 by impeding SARS-CoV-2 infection. Methods The GeneCards database was used to search disease gene targets, core targets were analyzed by PPI, GO and KEGG. Molecular docking and molecular dynamics were used to validate and analyze the binding stability of small molecule N-0385 to target proteins. The supercomputer platform was used to simulate and analyze the number of hydrogen bonds, binding free energy, stability of protein targets at the residue level, radius of gyration and solvent accessible surface area. Results There were 4,600 COVID-19 gene targets from GeneCards database. PPI, GO and KEGG analysis indicated that signaling pathways of immune response and inflammation played crucial roles in COVID-19. Molecular docking showed that N-0385 could block SARS-CoV-2 infection and treat COVID-19 by acting on ACE2, TMPRSS2 and NLRP3. Molecular dynamics was used to demonstrate that the small molecule N-0385 could form very stable bindings with TMPRSS2 and TLR7. Conclusion The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and damage caused by inflammatory responses.

[Clinical features of children with coronavirus disease 2019 Delta variant infection after vaccination with inactivated SARS-CoV-2 vaccine]. / æŽ¥ç§æ–°åž‹å† çŠ¶ç— æ¯’ç­æ´»ç–«è‹—åŽæ„ŸæŸ“Deltaå˜å¼‚æ ªçš„æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£å„¿ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with coronavirus disease 2019 (COVID-19) Delta variant infection vaccinated or not vaccinated with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. METHODS: A total of 11 children with COVID-19 Delta variant infection who were vaccinated with inactivated SARS-CoV-2 vaccine and were hospitalized in the designated hospital in Henan Province, China, from November 3 to December 17, 2021 were enrolled as the vaccinated group. Thirty-one children with COVID-19 Delta variant infection who were not vaccinated and were hospitalized during the same period were enrolled as the unvaccinated group. A retrospective analysis was performed on their epidemiological data, clinical features, and laboratory examination results. RESULTS: There was no significant difference in gender composition and disease classification between the two groups (P>0.05), and there was also no significant difference in the incidence rates of the clinical symptoms such as cough, expectoration, and fever between the two groups (P>0.05). No significant difference was found between the two groups in leukocyte count, lymphocyte percentage, alanine aminotransferase, and serum creatinine (P>0.05). Compared with the unvaccinated group, the vaccinated group had significantly lower levels of aspartate aminotransferase, lactate dehydrogenase, and creatine kinase-MB (P<0.05). There was no significant difference between the two groups in the proportion of children with elevated C-reactive protein or procalcitonin and the levels of peripheral blood cytokines (P>0.05). The vaccinated group had significantly lower counts of B lymphocytes and total T lymphocytes (CD3+) than the unvaccinated group (P<0.05). Compared with the unvaccinated group, the vaccinated group had a significantly higher positive rate of IgG on admission and at week 2 of the course of disease (P<0.05), as well as a significantly higher Ct value of nucleic acid at weeks 1 and 2 of the course of disease (P<0.05). CONCLUSIONS: Vaccination with inactivated SARS-CoV-2 vaccine may reduce myocardial injury caused by SARS-CoV-2 Delta variant. For children with SARS-CoV-2 Delta variant infection after the vaccination, more attention should be paid to their immune function.

Safety and Immunogenicity of Inactivated and Recombinant Protein SARS-CoV-2 Vaccines in Patients With Thyroid Cancer.

Background: This study aimed at assessing the safety and immunogenicity of SARS-CoV-2 vaccines in patients with thyroid cancer. Methods: This observational study included thyroid cancer patients between April 1, 2021, and November 31, 2021, in the Second Affiliated Hospital of Chongqing Medical University. All participants received at least one dose of the SARS-CoV-2 vaccine. SARS-CoV-2 IgG was tested, and the interval time between the last dose and humoral response test ranged from <1 to 8 months. The complications after SARS-CoV-2 vaccines were recorded. Results: A total of 115 participants at least received one dose of SARS-CoV-2 vaccines with a 67.0% IgG-positive rate. Among them, 98 cases had completed vaccination, and the positivity of SARS-CoV-2 IgG antibodies was 96% (24/25) with three doses of ZF2001. SARS-CoV-2 IgG antibodies' positivity was 63.0% (46/73) of two doses of CoronaVac or BBIBP-CorV vaccine. Additionally, after 4 months of the last-dose vaccination, the IgG-positive rate (31.6%, 6/19) significantly decreased in thyroid cancer patients. The IgG-positive rate (81.0%, 64/79) was satisfactory within 3 months of the last-dose vaccination. Ten (10.2%) patients had side effects after SARS-CoV-2 vaccination. Among them, two (2.0%) patients had a fever, five (5.1%) patients had injection site pain, one (1.0%) patient felt dizzy, and one patient felt dizzy and had injection site pain at the same time. Conclusion: SARS-CoV-2 vaccines (CoronaVac, BBIBP-CorV, and ZF2001) are safe in thyroid cancer patients. The regression time of SARS-CoV-2 IgG is significantly shorter in thyroid cancer patients than in healthy adults. Therefore, a booster vaccination dose may be earlier than the systematic strategy for thyroid cancer patients.

Evaluation of a Self-testing Rapid Diagnostic Test Device for Detecting SARS-CoV-2 in Oral Fluid

Objective: The aim of this evaluation report was to explore the reliability and performance of the All Test COVID-19 Antigen Rapid Test for Self-Testing (Oral Fluid) on clinical specimens collected for SARS-CoV-2 diagnosis and compared to a laboratory run RT-qPCR (real-time reverse transcription polymerase chain reaction) test. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019, which emerged as a novel human pathogen at the end of 2019. Since its emergence nearly two years ago, the virus has caused more than 257 million confirmed cases and has led to more than 5 million deaths globally as of November 22, 2021 [2]. [...]specimens need to be transported to and examined at sites that have RT-qPCR capability, which delays the test result and increases the anxiety of the suspected COVID-19 patients. Antigen tests are also important in the overall response against COIVD-19 as they can generally be produced at a lower cost than PCR tests and help public health officials better identify infection rates closer to real time.

Phylodynamic analysis and spike protein mutations in porcine deltacoronavirus with a new variant introduction in Taiwan.

Porcine deltacoronavirus (PDCoV) is a highly transmissible intestinal pathogen that causes mild to severe clinical symptoms, such as anorexia, vomiting, and watery diarrhea in pigs. By comparing the genetic sequences of the spike glycoprotein between historical and current Taiwanese PDCoV strains, we identified a novel PDCoV variant that displaced the PDCoV responsible for the 2015 epidemic. This PDCoV variant belongs to a young population within the US lineage, and infected pigs carry high concentrations of the virus. It also has several critical point mutations and an amino acid insertion at position 52 that may enhance the affinity between the B-cell epitopes located in the N-terminal domain with its complementarity regions, consequently facilitating binding or penetration between the fusion peptide and cellular membrane. Furthermore, viral protein structure prediction demonstrated that these amino acid changes may change the ability of the virus to bind to the receptor, which may consequently alter virus infectivity. Our results hence suggest the emergence of new PDCoV strains in Taiwan with the potential for greater transmission and pathogenesis.

Powerful CRISPR-Based Biosensing Techniques and Their Integration With Microfluidic Platforms

In the fight against the worldwide pandemic coronavirus disease 2019 (COVID-19), simple, rapid, and sensitive tools for nucleic acid detection are in urgent need. PCR has been a classic method for nucleic acid detection with high sensitivity and specificity. However, this method still has essential limitations due to the dependence on thermal cycling, which requires costly equipment, professional technicians, and long turnover times. Currently, clustered regularly interspaced short palindromic repeats (CRISPR)-based biosensors have been developed as powerful tools for nucleic acid detection. Moreover, the CRISPR method can be performed at physiological temperature, meaning that it is easy to assemble into point-of-care devices. Microfluidic chips hold promises to integrate sample processing and analysis on a chip, reducing the consumption of sample and reagent and increasing the detection throughput. This review provides an overview of recent advances in the development of CRISPR-based biosensing techniques and their perfect combination with microfluidic platforms. New opportunities and challenges for the improvement of specificity and efficiency signal amplification are outlined. Furthermore, their various applications in healthcare, animal husbandry, agriculture, and forestry are discussed.

Association of body composition parameters measured on CT with risk of hospitalization in patients with Covid-19.

PURPOSE: To assess prognostic value of body composition parameters measured at CT to predict risk of hospitalization in patients with COVID-19 infection. METHODS: 177 patients with SARS-CoV-2 infection and with abdominopelvic CT were included in this retrospective IRB approved two-institution study. Patients were stratified based on disease severity as outpatients (no hospital admission) and patients who were hospitalized (inpatients). Two readers blinded to the clinical outcome segmented axial CT images at the L3 vertebral body level for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), muscle adipose tissue (MAT), muscle mass (MM). VAT to total adipose tissue ratio (VAT/TAT), MAT/MM ratio, and muscle index (MI) at L3 were computed. These measures, along with detailed clinical risk factors, were compared in patients stratified by severity. Various logistic regression clinical and clinical + imaging models were compared to discriminate inpatients from outpatients. RESULTS: There were 76 outpatients (43%) and 101 inpatients. Male gender (p = 0.013), age (p = 0.0003), hypertension (p = 0.0003), diabetes (p = 0.0001), history of cardiac disease (p = 0.007), VAT/TAT (p < 0.0001), and MAT/MM (p < 0.0001), but not BMI, were associated with hospitalization. A clinical model (age, gender, BMI) had AUC of 0.70. Addition of VAT/TAT to the clinical model improved the AUC to 0.73. Optimal model that included gender, BMI, race (Black), MI, VAT/TAT, as well as interaction between gender and VAT/TAT and gender and MAT/MM demonstrated the highest AUC of 0.83. CONCLUSION: MAT/MM and VAT/TAT provides important prognostic information in predicting patients with COVID-19 who are likely to require hospitalization.

Fluorescence Immunoassay System Plays an Important Role in Timely Diagnosis of COVID-19 Infection

In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death. [...]there is giant demand for the COVID-19 tests. In samples without infected, since there is no target gene amplification, no increase in fluorescence signal can be detected. [...]nucleic acid detection is actually to determine whether there is novel coronavirus nucleic acid in the sample by detecting the accumulation of fluorescent signals. According to the principle of double-antibody sandwich method, using two antigen-specific antibodies to recognize and bind to different epitopes of a target antigen can greatly reduce the probability of cross-reaction, thereby effectively improving its specificity [1]. Positive detection of IgG in blood can be used as an indicator of infection and previous infection [8]. [...]an increase of IgM antibody indicates a recent acute infection, and an increase of IgG antibody indicates a previous infection.

Antigen Rapid Test is Expected to Accelerate the Detection Efficiency of the COVID-19 Epidemic

In samples without infected, since there is no target gene amplification, no increase in fluorescence signal can be detected. [...]nucleic acid detection is actually to determine whether there is novel coronavirus nucleic acid in the sample by detecting the accumulation of fluorescent signals. According to the principle of doubleantibody sandwich ELISA, using two antigen-specific antibodies to recognize and bind to different epitopes of a target antigen can greatly reduce the probability of cross-reaction, thereby effectively improving its specificity [2]. [...]to provide sufficient information for the research participants. [...]ensuring that participants are not subject to coercion to take part or not taking part [12], the survey is entirely dependent on the wishes of the participants.

The Significance of Oral Fluid Antigen Rapid Test in the Time of the COVID-19 Epidemic

Other infected patients have mild or severe symptoms and may be life-threatening. [...]there is giant demand for the COVID-19 rapid tests. In samples without infected, since there is no target gene amplification, no increase in fluorescence signal would be detected. [...]nucleic acid detection is actually to determine whether there is novel coronavirus nucleic acid in the sample by detecting the accumulation of fluorescent signals. According to the principle of doubleantibody sandwich ELISA, using two antigen-specific antibodies to recognize and bind to different epitopes of a target antigen can greatly reduce the probability of cross-reaction, thereby effectively improving its specificity [1]. Positive detection of IgG in blood can be used as an indicator of infection and previous infection [8]. [...]an increase of IgM antibody indicates a recent acute infection, and an increase of IgG antibody indicates a previous infection.

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion.

BACKGROUND: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. AIM: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. METHODS: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro. RESULTS: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly. CONCLUSION: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.

Identifying and Predicting the Credit Risk of Small and Medium-Sized Enterprises in Sustainable Supply Chain Finance: Evidence from China

COVID-19 has created a strong demand for supply chain finance (SCF) for small and medium-sized enterprises (SMEs). However, the rapid development of SCF leads to more complex credit risks. How to effectively discriminate and manage SMEs to reduce credit risk has become one of the most critical issues in SCF. In addition, sustainable SCF (SSCF) has received increasing attention, and credit risk management is important to achieve SSCF. Therefore, it is significant to identify the key factors influencing the credit risk of SMEs and construct a prediction model to promote SSCF. This study uses the lasso-logistic model to identify factors influencing the credit risk of SMEs and to predict the credit risk of SMEs. The empirical results show that (i) the key factors influencing SMEs’ credit risk include six variables—the matching degree of order data, ratio of contract enforcement, number of contract defaults, degree of business concentration, and number of administrative penalties;and (ii) the lasso-logistic model can identify the key factors influencing credit risk and have a better prediction performance. Moreover, transaction credit and reputation supervision significantly influence the credit risk of SMEs.