Case report: COVID-19-associated refractory thrombotic thrombocytopenic purpura complicated with Guillain-Barré syndrome.

Thrombotic thrombocytopenic purpura (TTP), a rare and lethal thrombotic microangiopathy, is an autoimmune disease that can be triggered by viral infections such as COVID-19. This condition is characterized by hemolytic microangiopathy, thrombocytopenia, and neurologic alterations, possibly accompanied by fever and renal damage. Moreover, more than 220 patients with Guillain-Barré syndrome (GBS) have been reported in association with the COVID-19 infection. In this report, we present a case of a patient who developed refractory TTP complicated by GBS following a SARS-CoV-2 infection. We aimed to highlight the importance of accurately diagnosing neurological complications associated with a COVID-19 infection and to demonstrate our strategies for treating a patient with COVID-19 infection-related refractory TTP complicated by GBS.

Effects of different levels of non-pharmaceutical interventions on hand, foot and mouth disease in Guangzhou, China.

BACKGROUND: Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) may have suppressed the transmission of other infectious diseases. This study aimed to evaluate the impact of different degrees of NPIs during the COVID-19 pandemic on hand, foot and mouth disease (HFMD) in Guangzhou, China. METHODS: Weekly reported HFMD cases and pathogens information during 2015-2021 in Guangzhou were collected from the China National Notifiable Disease Reporting System. The observed number of HFMD cases in 2020 and 2021 was compared to the average level in the same period during 2015-2019. Then, an interrupted time-series segmented regression analysis was applied to estimate the impact of NPIs on HFMD, such as social distancing, suspension of schools, community management and mask wearing. The effects across different subgroups stratified by gender, children groups and enterovirus subtype of HFMD were also examined. RESULTS: A total of 13,224 and 36,353 HFMD cases were reported in 2020 and 2021, which decreased by 80.80% and 15.06% respectively compared with the average number of cases in the same period during 2015-2019. A significant drop in the number of HFMD cases during time when strict NPIs were applied (relative change: 69.07% [95% confidence interval (CI): 68.84%-69.30%]). The HFMD incidence rebounded to historical levels in 2021 as the lockdown eased. The slightest reduction of HFMD cases was found among children at kindergartens or childcare centres among the three children groups (children at kindergartens or childcare centres: 55.50% [95% CI: 54.96%-56.03%]; children living at home: 72.64% [95% CI: 72.38%-72.89%]; others: 74.06% [95% CI: 73.19%-74.91%]). CONCLUSIONS: The strong NPIs during the COVID-19 epidemic may have a significant beneficial effect on mitigating HFMD. However, the incidence of HFMD rebounded as the NPIs became less stringent. Authorities should consider applying these NPIs during HFMD outbreaks and strengthening personal hygiene in routine prevention.

Correction: Incidence, clinical course and risk factor for recurrent PCR positivity in discharged COVID-19 patients in Guangzhou, China: A prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pntd.0008648.].

Viral proteins recognized by different TLRs.

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.

Sustainable Economic Development, Digital Payment, and Consumer Demand: Evidence from China.

In this era, the global COVID-19 pandemic has hit the economy hard. In the context of great challenges to sustainable economic development, it is of great practical significance to study how digital payment can promote consumer demand and sustainable economic development. From the perspective of sustainable economic development, this paper selects panel data of various provinces in China from 2011 to 2020 to test the correlation between digital payment and consumer demand by constructing econometric models and selecting relevant indicators, so as to reveal the impact of digital payment on consumer demand and sustainable economic development. Research shows that: (1) in the context of the COVID-19 pandemic, digital payments play a special and very important role in promoting household consumption and sustainable economic development; (2) the empirical results show that digital payment has a significant positive impact on consumer demand, which indicates that digital payment has an obvious promotion effect on consumer demand; (3) further research shows that the impact of digital payment on consumer demand has obvious heterogeneity. From the perspective of regional differences, digital payment has a significant positive impact on consumer demand in the eastern and western regions, while the impact is not obvious in the northeast and central regions, even though it also has a positive impact. From the perspective of urban-rural differences, digital payment has a significant impact on consumer demand in both urban and rural areas, and this impact is greater in rural areas than in urban areas. However, from the perspective of development stage, the stage characteristics of digital payment's impact on consumer demand in each region are not obvious, which may be caused by the short sample range. In addition, this paper also puts forward relevant suggestions for other countries to learn from.

Resilience and Prosocial Behavior Among Chinese University Students During COVID-19 Mitigation: Testing Mediation and Moderation Models of Social Support.

Purpose: Suffering during events such as the COVID-19 pandemic threatens university students' physical and psychological health. Given the literature indicating the protective role of resilience and social support, the current study explored the mediating and moderating roles of social support in the association between resilience and prosocial behavior among university students in mainland China during COVID-19 mitigation. Methods: We conducted an online survey using convenience sampling from 23rd February to 3rd March 2020 among Chinese university students who had encountered home-quarantine due to the COVID-19 pandemic. Self-report scales were used to measure levels of resilience (Connor-Davidson Resilience Scale), social support (the Social Support Scale), and prosocial behavior (Prosocial Tendencies Measure). A total of 313 university students participated in this online survey. Hayes PROCESS macro for SPSS was used to test the hypothesized mediating and moderating effects of social support in the relationship between resilience and prosocial behavior. Results: Pearson's correlations analysis showed that all outcomes of interest were positively associated. Importantly, social support (subjective support, objective support, and support utilization) mediated the indirect link of resilience with prosocial behavior. Furthermore, moderation analyses indicated that support utilization played a moderating role in this link. Support utilization may reduce the negative influence of COVID-19 on university students' prosocial behavior and serve as a protective factor between resilience and prosocial behavior in highly stressful contexts. Conclusion: Our findings enrich research on prosocial behavior by investigating the potential internal and external variables that influence such behavior during periods of suffering. Findings also provide evidence for the need to promote university students' prosocial behavior.

Application of genetic algorithm combined with improved SEIR model in predicting the epidemic trend of COVID-19, China.

Since the outbreak of the 2019 Coronavirus disease (COVID-19) at the end of 2019, it has caused great adverse effects on the whole world, and it has been hindering the global economy. It is ergent to establish an infectious disease model for the current COVID-19 epidemic to predict the trend of the epidemic. Based on the SEIR model, the improved SEIR models were established with considering the incubation period, the isolated population, and genetic algorithm (GA) parameter optimization method. The improved SEIR models can predict the trend of the epidemic situation better and obtain the more accurate epidemic-related parameters. Comparing some key parameters, it is capable to evaluate the impact of different epidemic prevention measures and the implementation of different epidemic prevention levels on the COVID-19, which has significant guidance for further epidemic prevention measures.

Contribution of CD4+ T cell-mediated inflammation to diarrhea in patients with COVID-19.

OBJECTIVES: This study aimed to explore the role of CD4+ T cells in the mechanisms of COVID-19 related diarrhea. METHODS: We analyzed lymphocyte subsets in patients with COVID-19 and the expression of angiotensin-converting enzyme 2 (ACE2), the transmembrane protease serine 2, and CD4+ T cell-related indicators in the colon were compared between patients with and without diarrhea. Correlation analyses were performed for ACE2 and other indicators to identify the relationship between SARS-CoV-2 infection and CD4+ mediated inflammation. The expression and distribution of CD4+ T cell-associated chemokines and their receptors were detected to determine the possibility of migration of CD4+ T cells to inflammation sites. RESULTS: The CD4+ T cell counts and percentages and CD4/CD8 ratio showed the most significant differences between the 2 groups. The diarrhea group expressed higher levels of ACE2, T-box expressed in T cells (Tbet), and tumor necrosis factor-alpha (TNFα) at both the mRNA and protein levels, with no difference from the nondiarrhea group for the percentage of ACE2+TNFα+ cells, indicating an indirect association between ACE2 and TNFα. The mRNA expression of CXCL10, CXCL11, and CXCR3 and the number of CD4+CXCR3+T cells were increased in the diarrhea group. CONCLUSIONS: CD4+ T cell-mediated inflammation may contribute to COVID-19 related diarrhea. CXCR3+ mediated migration of CD4+ T cells into the gut may perpetuate inflammation.

Life in a New Normal with a Self-Care Routine: A Cross-Sectional Study of Older Adults' Daily Health Behaviors (DHB) Performance during the Initial Outbreak of COVID-19 in China.

For older adults, self-care begins with daily health behaviors (DHB), which refers to a series of basic behaviors beneficial to health in daily life; it is the foundation for promoting health, preventing disease, and maintaining health with or without the support of a healthcare provider. Thus, this study aimed to observe the changes in DHB among older adults when the COVID-19 pan-demic first erupted in China (at the beginning of 2020) and explore the impact factors on self-care routines in daily life. We applied a cross-sectional study among 1256 (83.7%) valid older Chinese from 19 February 2020 to 19 March 2020, the score of DHB changes (mean ± SD, 14.70 ± 2.140; range, 8-18) presented a significant growth (t1256 = 44.636, p < 0.001) during COVID-19. From 3 hierarchical linear regression models, the older Chinese who received a higher education include high school (ß = 0.403, 95% CI [0.009, 0.797], p = 0.045) and college degree and above (ß = 0.488, 95% CI [0.034, 0.943], p = 0.035), and lived in the eastern China (ß = 0.771, 95% CI [0.392, 1.151], p < 0.001) took DHB more frequently. However, the high-risk infection (ß = -0.740, 95% CI [-1.248, -0.231], p = 0.004), overweight/obese character (ß = -0.265, 95% CI [-0.526, -0.004], p = 0.047), and alcohol consumption (ß = -0.350, 95% CI [-0.634, -0.065], p = 0.016) are significant factors in decreasing a senior's DHB performance. For China, self-care offers a straightforward strategy among the range of measures required to combat COVID-19 and future health threats. In summary, findings in this study can build a foundation for developing healthcare policy and services for the relevant government and departments on prompting DHB and the importance of self-care among the older population.

Virome in the cloaca of wild and breeding birds revealed a diversity of significant viruses.

BACKGROUND: Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. RESULTS: Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). CONCLUSIONS: The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract.

Contact tracing period and epidemiological characteristics of an outbreak of the SARS-CoV-2 Delta variant in Guangzhou.

OBJECTIVES: An outbreak of the SARS-CoV-2 Delta variant occurred in Guangzhou in 2021. This study aimed to identify the transmission dynamics and epidemiological characteristics of the Delta variant outbreak to formulate an effective prevention strategy. METHODS: A total of 13102 close contacts and 69 index cases were collected. The incubation period, serial interval, and time interval from the exposure of close contacts to the symptom onset of cases were estimated. Transmission risks based on the exposure time and various characteristics were also assessed. RESULTS: The mean time from exposure to symptom onset among non-household presymptomatic transmission was 3.83 ± 2.29 days, the incubation period was 5 days, and the serial interval was 3 days. The secondary attack rate was high within 4 days before onset and 4-10 days after symptom onset. Compared with other contact types, household contact had a higher transmission risk. The transmission risk increased with the number and frequency of contact with index cases. Cycle threshold (Ct) values were associated with lower transmission risk (adjusted odds ratio [OR] 0.93 [95% CI 0.88-0.99] for ORF 1ab gene; adjusted OR 0.91 [95% CI 0.86-0.97] for N gene). CONCLUSION: The contact tracing period may need to be extended to 4 days before symptom onset. The low Ct value of index cases, the high number and frequency of contact with index cases, and household contacts were associated with a higher transmission risk of SARS-CoV-2 Delta.

The PERK/PKR-eIF2α Pathway Negatively Regulates Porcine Hemagglutinating Encephalomyelitis Virus Replication by Attenuating Global Protein Translation and Facilitating Stress Granule Formation

The replication of coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERSCoV), and the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is closely associated with the endoplasmic reticulum (ER) of infected cells. The unfolded protein response (UPR), which is mediated by ER stress (ERS), is a typical outcome in coronavirus-infected cells and is closely associated with the characteristics of coronaviruses. However, the interaction between virus-induced ERS and coronavirus replication is poorly understood. Here, we demonstrate that infection with the betacoronavirus porcine hemagglutinating encephalomyelitis virus (PHEV) induced ERS and triggered all three branches of the UPR signaling pathway both in vitro and in vivo. In addition, ERS suppressed PHEV replication in mouse neuro-2a (N2a) cells primarily by activating the protein kinase R-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) axis of the UPR. Moreover, another eIF2a phosphorylation kinase, interferon (IFN)-induced double-stranded RNA-dependent protein kinase (PKR), was also activated and acted cooperatively with PERK to decrease PHEV replication. Furthermore, we demonstrate that the PERK/PKR-eIF2a pathways negatively regulated PHEV replication by attenuating global protein translation. Phosphorylated eIF2a also promoted the formation of stress granules (SGs), which in turn repressed PHEV replication. In summary, our study presents a vital aspect of the host innate response to invading pathogens and reveals attractive host targets (e.g., PERK, PKR, and eIF2a) for antiviral drugs. [ FROM AUTHOR] Copyright of Journal of Virology is the property of American Society for Microbiology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

ESG Performance and Stock Price Volatility in Public Health Crisis: Evidence from COVID-19 Pandemic.

Unlike traditional financial crises, COVID-19 is a global public health crisis with a significant negative impact on the global economy. Meanwhile, the stock market has been hit hard, and corporate share prices have become more volatile. However, the stock prices of some enterprises with good performance of ESG (Environment, Social, and Governance) are relatively stable in the epidemic. This paper selects ESG rating data from MSCI (Morgan Stanley Capital International) with better differentiation, adopts multiple regression and dummy variables, and adopts the Differences-in-Differences (DID)model with the help of COVID-19, an exogenous event. Empirical test the impact of ESG performance on the company's stock price fluctuations. The results show that the stock price volatility of companies with good ESG performance is lower than that of companies with poor performance. Second, COVID-19 exacerbates volatility in company stock prices, but the increase in stock price volatility of companies with good ESG performance is small. That is, good ESG performance helps reduce the increase in stock price volatility due to COVID-19 shock, and plays a role in enhancing "resilience" and stabilizing stock prices. This paper provides new empirical evidence for the study of ESG performance and corporate stock price volatility, and puts forward relevant policy recommendations for enterprises and government departments.

Clinical and virological impact of single and dual infections with influenza A (H1N1) and SARS-CoV-2 in adult inpatients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimics the influenza A (H1N1) virus in terms of clinical presentation, transmission mechanism, and seasonal coincidence. Comprehensive data for the clinical severity of adult patients co-infected by both H1N1 and SARS-CoV-2, and, particularly, the relationship with PCR cycle threshold (Ct) values are not yet available. All participants in this study were tested for H1N1 and SARS-CoV-2 simultaneously at admission. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared among adults hospitalized for H1N1 infection, SARS-CoV-2 infection and co-infection with both viruses. Ct values for viral RNA detection were further compared within SARS-CoV-2 and co-infection groups. Score on seven-category ordinal scale of clinical status at day 7 and day 14 were assessed. Among patients with monoinfection, H1N1 infection had higher frequency of onset symptoms but lower incidence of adverse events during hospitalization than SAR-CoV-2 infection (P < 0.05). Co-infection had an increased odds of acute kidney injury, acute heart failure, secondary bacterial infections, multilobar infiltrates and admittance to ICU than monoinfection. Score on seven-category scale at day 7 and day 14 was higher in patients with coinfection than patients with SAR-CoV-2 monoinfection (P<0.05). Co-infected patients had lower initial Ct values (referring to higher viral load) (median 32) than patients with SAR-CoV-2 monoinfection (median 36). Among co-infected patients, low Ct values were significantly and positively correlated with acute kidney injury and ARDS (P = 0.03 and 0.02, respectively). Co-infection by SARS-CoV-2 and H1N1 caused more severe disease than monoinfection by either virus in adult inpatients. Early Ct value could provide clues for the later trajectory of the co-infection. Multiplex molecular diagnostics for both viruses and early assessment of SAR-CoV-2 Ct values are recommended to achieve optimal treatment for improved clinical outcome.

Mental Health Status of the Elderly Chinese Population During COVID-19: An Online Cross-Sectional Study.

Background: COVID-19 not only threatened the public's physical health but also brought unbearable psychological pressure, especially for those vulnerable groups like the elderly. However, studies on the psychological status of older adults during this public health emergency remained scant. This study aims to investigate the mental health status among the elderly Chinese population during COVID-19 pandemic and determine the influencing factors of psychological symptoms. Methods: From February 19 to March 19, 2020, an online survey was administered to Chinese older adults using a convenience sampling method. Information on demographic data, health status and other epidemic related factors were collected. Specifically, the study defined the psychological status as five primary disorder-depression, neurasthenia, fear, anxiety, and hypochondria-which were assessed by the Psychological Questionnaire for Emergent Event of Public Health (PQEEPH). Standard descriptive statistics and multiple logistic regression analyses were conducted to analyze the data. Results: Of 1,501 participants recruited from 31 provinces in China, 1,278 were valid for further analysis. Participants' scores on each sub-scale were described in median and interquartile [M(Q)]: depression [0.00 (0.33)], neurasthenia [0.00 (0.40)], fear [1.00 (0.83)], anxiety [0.00 (0.17)], hypochondria [0.00 (0.50)]. Chronic diseases (depression p = 0.001; neurasthenia p < 0.001; fear p = 0.023; anxiety p < 0.001; hypochondria p = 0.001) and the BMI index (depression p = 0.015; neurasthenia p = 0.046; fear p = 0.016; anxiety p = 0.015; hypochondria p = 0.013) had significant impacts on all of the five sub-scales. Specifically, the rural dwellers had a higher level of neurasthenia, fear, and hypochondria. Besides, education level (p = 0.035) and outbreak risk level (p = 0.004) had significant impacts on the depression. Higher household monthly income per capita (p = 0.031), and the community-level entry/exit control (p = 0.011) are factors against anxiety. Conclusions: Most elderly residents reported mild negative emotions during COVID-19 and more attention should be paid to the recognition and alleviation of fear. Our findings also identified factors associated with the mental health status of the elderly, which is of practical significance in the design and implementation of psychological interventions for this vulnerable population during COVID-19 and future emerging diseases.

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review.

Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

Association Between Metabolic Syndrome and Mild Parkinsonian Signs Progression in the Elderly.

Background: This study investigated the impact of metabolic syndrome on the progression from mild parkinsonian signs (MPS) to Parkinson's disease (PD). Methods: A total of 1,563 participants with MPS completed 6 years of follow-up. The diagnosis of metabolic syndrome was made according to Adult Treatment Panel III of the National Cholesterol Education Program. The evaluations of MPS and PD were based on the motor portion of the Unified Parkinson's Disease Rating Scale. Cox proportional hazard models were used to identify the association between metabolic syndrome and PD conversion. Results: Of the 1,563 participants, 482 (30.8%) with MPS developed PD at the end of the follow-up. Metabolic syndrome (HR: 1.69, 95% CI: 1.29-2.03) was associated with the risk of PD conversion. Metabolic syndrome was associated with the progression of bradykinesia (HR: 1.85, 95% CI: 1.43-2.34), rigidity (HR: 1.36, 95% CI: 1.19-1.57), tremor (HR: 1.98, 95% CI: 1.73-2.32), and gait/balance impairment (HR: 1.66, 95% CI: 1.25-2.11). The effect of metabolic syndrome on the progression of bradykinesia and tremor was nearly two fold. Participants treated for two or three to four components of metabolic syndrome, including high blood pressure, high fasting plasma glucose, hypertriglyceridemia, and low HDL-C, had a lower risk of PD conversion. Conclusion: Metabolic syndrome increased the risk of progression from MPS to PD. Participants treated for two or more components of metabolic syndrome had a lower risk of PD conversion.

Viral Transmission and Clinical Features in Asymptomatic Carriers of SARS-CoV-2 in Wuhan, China.

We report the clinical characteristics, viral shedding duration, and contact tracing for asymptomatic carriers of SARS-CoV-2 in Wuhan, China. The asymptomatic carriers were relatively young (median age: 34.5 years). Chest computed tomography showed no abnormalities. The nasopharyngeal swab was an optimum specimen for RNA testing. The median viral shedding duration was 11.5 days. Notably, 2 months of viral shedding duration were reported in two nurses, which was much longer than previously reported or than usually thought. The transmissibility of SARS-CoV-2 by asymptomatic carriers during the studied period in Wuhan appeared to be weak. Only one patient (1/12) was found to have transmitted the virus to another person. Early asymptomatic carrier detection, isolation, and contact tracing could be useful to mitigate the spread of the disease.

The global emergence of a novel Streptococcus suis clade associated with human infections.

Streptococcus suis, a ubiquitous bacterial colonizer in pigs, has recently extended host range to humans, leading to a global surge of deadly human infections and three large outbreaks since 1998. To better understand the mechanisms for the emergence of cross-species transmission and virulence in human, we have sequenced 366 S. suis human and pig isolates from 2005 to 2016 and performed a large-scale phylogenomic analysis on 1,634 isolates from 14 countries over 36 years. We show the formation of a novel human-associated clade (HAC) diversified from swine S. suis isolates. Phylogeographic analysis identified Europe as the origin of HAC, coinciding with the exportation of European swine breeds between 1960s and 1970s. HAC is composed of three sub-lineages and contains several healthy-pig isolates that display high virulence in experimental infections, suggesting healthy-pig carriers as a potential source for human infection. New HAC-specific genes are identified as promising markers for pathogen detection and surveillance. Our discovery of a human-associated S. suis clade provides insights into the evolution of this emerging human pathogen and extend our understanding of S. suis epidemics worldwide.

Clinical characterization and therapeutic targets of vitamin A in patients with hepatocholangiocarcinoma and coronavirus disease.

Recent reports indicate that patients with hepatocholangiocarcinoma (CHOL) have a higher morbidity and mortality rate for coronavirus disease (COVID-19). Anti-CHOL/COVID-19 medicines are inexistent. Vitamin A (VA) refers to a potent nutrient with anti-cytotoxic and anti-inflammatory actions. Therefore, this study aimed to determine the potential functions and molecular mechanisms of VA as a potential treatment for patients with both CHOL and COVID-19 (CHOL/COVID-19). The transcriptome data of CHOL patients were obtained from the Cancer Genome Analysis database. Furthermore, the network pharmacology approach and bioinformatics analysis were used to identify and reveal the molecular functions, therapeutic biotargets, and signaling of VA against CHOL/COVID-19. First, clinical findings identified the medical characteristics of CHOL patients with COVID-19, such as susceptibility gene, prognosis, recurrence, and survival rate. Anti-viral and anti-inflammatory pathways, and immunopotentiation were found as potential targets of VA against CHOL/COVID-19. These findings illustrated that VA may contribute to the clinical management of CHOL/COVID-19 achieved by induction of cell repair, suppression of oxidative stress and inflammatory reaction, and amelioration of immunity. Nine vital therapeutic targets (BRD2, NOS2, GPT, MAPK1, CXCR3, ICAM1, CDK4, CAT, and TMPRSS13) of VA against CHOL/COVID-19 were identified. For the first time, the potential pharmacological biotargets, function, and mechanism of action of VA in CHOL/COVID-19 were elucidated.