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BackgroundAcanthamoeba castellanii infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce.Case presentationWe present a case of Acanthamoeba castellanii infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed Acanthamoeba castellanii infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient’s symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy.ConclusionImmunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for Acanthamoeba castellanii infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.

Abstract Objective This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

Abstract Background Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status of cfDNA, such as cfDNA fragmentation profile. The fragmentation of cfDNA is non-random and may be related to cfDNA methylation. This study provides clinical evidence for the feasibility of inferring cfDNA methylation levels based on cfDNA fragmentation patterns. We performed whole-genome bisulfite sequencing and whole-genome sequencing (WGS) on both healthy individuals and cancer patients. Using the information of whole-genome methylation levels, we investigated cytosine–phosphate–guanine (CpG) cleavage profile and validated the method of predicting the methylation level of individual CpG sites using WGS data. Results We conducted CpG cleavage profile biomarker analysis on data from both healthy individuals and cancer patients. We obtained unique or shared potential biomarkers for each group and built models accordingly. The modeling results proved the feasibility to predict the methylation status of single CpG sites in cfDNA using cleavage profile model from WGS data. Conclusion By combining cfDNA cleavage profile of CpG sites with machine learning algorithms, we have identified specific CpG cleavage profile as biomarkers to predict the methylation status of individual CpG sites. Therefore, methylation profile, a widely used epigenetic biomarker, can be obtained from a single WGS assay for MCED.

Abstract Background The Hani people, who reside in Yuanyang County, Honghe Hani and Yi Autonomous Prefecture, Yunnan Province, rely on rice terrace farming as their primary livelihood. They utilize plants in various traditional ritual practices. The Hani people have categorized the value of plants based on their natural attributes and have refined the ways of using different plants in specific rituals through practical observations and experiences derived from their agricultural culture. Although the plants used in these rituals hold significant cultural value, they have yet to be studied from the perspective of ethnobotany. This study aims to approach the ritual plants using ethnobotanical methods. Methods Ethnobotanical fieldwork was conducted in 10 villages in Yuanyang County between 2021 and 2023. Data were collected from the local Hani people through semi-structured interviews and participatory observations and 41 informants were interviewed during the field investigations. The frequency of citation (FC) and relative frequency of citation (RFC) were utilized to evaluate the relative importance of ritual plants among the local communities. Results A total of 36 plant species, belonging to 18 families and 34 genera, were recorded as being used in 11 ritual practices by the Hani people. Rosaceae, Poaceae, and Fabaceae were found to have the highest number of species. Most of the ritual plants used by the Hani people were collected from the wild. FC and RFC analysis showed that the preferred plants for Hani rituals were Rhus chinensis Mill, Oryza sativa L., Phyllostachys sulphurea (Carr.) A. et C. Riv. and Musa basjoo Siebold & Zucc. ex Iinuma. The 11 rituals are all centered around the performance of people, crops and livestock. The Hani people use plants in different rituals mainly based on their biological attributes. Conclusions Many rituals of the Hani people are closely related to their production and livelihood, and the plants used in these rituals are deeply rooted in Hani’s traditional ecological knowledge and beliefs. The Hani people’s reverence for nature, respect for life, gratitude towards ancestors, and seeking blessings and disaster prevention for their families, crops, and livestock are all reflected in these rituals and their utilization of ritual plants. The Hani people showcase their agricultural culture in the Honghe Hani Rice Terraces through plant-based ritual performances. Studying ritual plants in the core area of the Hani Rice Terraces is of great significance for protecting the Hani Terrace farming culture. In the future, it is essential to pay more attention to the role of traditional knowledge in biodiversity conservation.

Abstract Background The Yi people are a sociolinguistic group living in Mile City, which is their typical settlement in southeastern Yunnan, China. Over the long history of using medicinal plants, the Yi people have accumulated and developed a wealth of traditional medicinal knowledge, which has played a vital role in their health care. However, only a few studies have been performed to systematically document the medicinal plants commonly used by the Yi people. This study provides fundamental data for the development and application of ethnomedicine as well as supports the conservation of the traditional medical knowledge of the Yi people. Methods This study was conducted from May 2020 to August 2022 and involved five townships in Mile. Information regarding medicinal plants was obtained through semistructured interviews, key informant interviews, and participatory observation. The collected voucher specimens were identified using the botanical taxonomy method and deposited in the herbarium. Ethnobotanical data were analyzed using informant consensus factor, relative frequency of citation, and fidelity level. Results In total, 114 informants distributed in five townships of Mile were interviewed. The Yi people used 267 medicinal plant species belonging to 232 genera and 104 families to treat various diseases. Asteraceae, Lamiaceae, and Fabaceae were the most commonly used plant families by the Yi people. In addition, herbs were most commonly used by the Yi people. Whole plants and roots were the preferred medicinal parts. Decoctions were the most common method of herbal medicine preparation. There are 49 different recorded diseases treated by Yi medicinal plants, and among them, respiratory diseases, rheumatism, traumatic injury, fractures, and digestive system diseases have the largest number of species used. A quantitative analysis demonstrated that plants such as Zingiber officinale, Lycopodium japonicum, Aconitum carmichaelii, Panax notoginseng, Cyathula officinalis, and Leonurus japonicus played crucial roles in disease prevention and treatment. Conclusion Traditional knowledge of medicinal plants is closely associated with the social culture of the local Yi people. The medicinal plants used for health care in the study area were diverse. Local healers were skilled at using medicinal plants to treat various diseases. Their treatment methods were convenient and unique, exhibiting distinctive regional characteristics. However, the inheritance of their traditional medicinal knowledge and protection of wild medicinal plant resources are facing serious challenges, including the decreasing number of local healers, aging of healers, lack of successors, and excessive harvesting of medicinal plant resources. This ethnobotanical survey provides a useful reference for the sustainable utilization and protection of medicinal plant resources in Mile and the inheritance of traditional medicinal knowledge of the Yi people.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. Methods Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. Results A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P

Abstract Background The Bai people in Yunlong County, northwest Yunnan, China, have used medicinal plants and traditional remedies for ethnoveterinary practices. The Bai have mastered ethnoveterinary therapeutic methods in livestock breeding since ancient times. The Bai’s traditional ethnoveterinary knowledge is now facing extinction, and their unique ethnoveterinary practices have rarely been recorded. This study documented animal diseases, EMPs, and related traditional knowledge in Yunlong County, China. Methods Ethnobotanical fieldwork was conducted in six villages and townships of Yunlong County between 2021 and 2022. Data were obtained through semi-structured interviews, participatory observations, and keyperson interviews. A total of 68 informants were interviewed, and the informant consensus factor and use reports (URs) were used to evaluate the current ethnoveterinary practices among the local communities. Information on livestock diseases, medicinal plants, and traditional ethnoveterinary medicine knowledge were also obtained. Results A total of 90 plant species belong to 51 families, 84 genera were recorded as being used as EMPs by the Bai people, and Asteraceae plants are most frequently used. A total of 68 informants were interviewed, including 58 men (85.3%) and 10 women (14.7%). The most commonly used EMPs parts included the roots, whole plants, leaves, and stems, and the common livestock diseases identified in this field investigation included trauma and fracture, gastrointestinal disorders, respiratory disorders, parasitic diseases, miscellaneous, venomous snake bites, reproductive diseases, infectious diseases, skin disease, and urinary diseases. Most of the EMPs are herbs (77.78%). Courtyard is one of the habitats of medicinal plants in Yunlong County. Conclusion Traditional knowledge of ethnoveterinary medicine is related to the local sociocultural characteristics of the Bai. Plants are used in cultural traditions, which, in turn, nourish the plant culture. Cultural diversity and biodiversity are interdependent. This traditional knowledge is at risk of disappearance because of the increasing extension of Western veterinary medicine, lifestyle changes, and mainstream cultural influences. Therefore, it is important to continue research on ethnoveterinary practices.

Abstract Long noncoding RNAs (lncRNAs) play important roles in regulating HIV-1 infection and virus-host interactions. However, it is unclear whether and how ART alters lncRNAs in HIV-infected patients. In the present study, we investigated changes of lncRNAs in PBMCs from HIV-1 patients pre- and post-ART. We identified a total of 974 lncRNAs whose expression was restored to normal levels after ART. Cis-acting analysis showed that six lncRNAs have cis-regulated target genes, among which RP11-290F5.1 and interferon regulatory factor 2 (IRF2) were reported to promote HIV replication. Furthermore, we found that lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression in PBMCs from HIV-1 infected patients after ART, was significantly upregulated by RNA-seq and qRT-PCR assays. KEGG analysis of CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway and pathways related to cell cycle and DNA replication. Our findings thus reveal the dynamic change of lncRNAs in people living with HIV-1 pre- and post-ART and warrant further investigation of the role of lncRNAs in HIV-1 pathogenesis and treatment.

AbstractContext Dolichos trilobus Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.Objective To explore the therapeutic potential of doliroside B (DB) from D. trilobus and its disodium salt (DBDS) and the underlying mechanism in pain.Materials and methods In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS.Results DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABAA1 receptor.Discussion and conclusions DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.

Chinese sour bamboo shoot is a traditionally, spontaneous fermented food that is particularly popular due to its complex and distinctive flavor. The volatile compounds of sour bamboo shoot originate mainly from the raw materials and the microbial fermentation. To reveal the correlation between microorganisms and flavor, third-generation sequencing and Gas Chromatography-Ion Mobility Spectrometry were applied to analyze the dynamics of microbial communities at the species level and volatile compounds during sour bamboo shoot fermentation. The abundance of Lactobacillus acetotolerans and Lactobacillus fermentum increased during the fermentation, while Lactobacillus amyloliquefaciens decreased at first but then began to rise. At the end of fermentation, Lactobacillus amyloliquefaciens and Lactobacillus acetotolerans became the predominant species. A total of sixty-seven volatile compounds, which included twenty-three esters, nineteen alcohols, eight ketones, six aldehydes, six aromatic hydrocarbons, four acids and one ether, were identified. These compounds constituted the primary flavor of sour bamboo, which created a complex flavor of sour bamboo shoot. Among them, the contents of acetic acid, propionic acid, and isoamyl alcohol gradually increased during the fermentation process, and they became the main volatile compounds. Furthermore, the correlation between microorganisms and volatile compounds was investigated through two-way Orthogonal Partial Least Squares (O2PLS), which revealed a positive correlation between Lactobacillus amylolyticus and ethyl propanoate. Additionally, the abundance of Lactobacillus acetotolerans and Lactobacillus fermentum was found to be positively correlated with 2-heptenal. These findings provide a theoretical basis for understanding the formation mechanism of sour bamboo shoot flavor and the standardized production of high-quality sour bamboo shoots.

Objective: Respiratory viral diseases have posed a persistent threat to public health due to their high transmissibility. Influenza virus and SARS-Cov-2 are both respiratory viruses that have caused global pandemics. A zero-COVID-19 strategy is a public health policy imposed to stop community transmission of COVID-19 as soon as it is detected. In this study, we aim to examine the epidemiological characteristics of seasonal influenza in the past five years before and after the emergence of COVID-19 in China and observe the possible impact of the strategy on influenza. Methods: Data from two data sources were retrospectively analyzed. A comparison on influenza incidence rate between Hubei and Zhejiang provinces was conducted based on data from the Chinese Center for Disease Control and Prevention (CDC). Then a descriptive and comparative analysis on seasonal influenza based on data from Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital before and after the outbreak of SARS-CoV-2 was conducted. Results: From 2010–2017, both provinces experienced relatively low influenza activity until the 1st week of 2018, when they reached peak incidence rates of 78.16/100000PY, 34.05/100000PY respectively. Since then, influenza showed an obvious seasonality in Hubei and Zhejiang until the onset of COVID-19. During 2020 and 2021, there was a dramatic decline in influenza activity compared to 2018 and 2019. However, influenza activity seemed to rebound at the beginning of 2022 and surged in summer, with positive rates of 20.52% and 31.53% in Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital respectively as of the time writing this article. Conclusions: Our results reinforce the hypothesis that zero-COVID-19 strategy may impact the epidemiological pattern of influenza. Under the complex pandemic situation, implementation of NPIs could be a beneficial strategy containing not only COVID-19 but also influenza.

The study of functional traits and their relationship to trade-offs has provided valuable insights into how plants adapt to environmental changes. Nonetheless, further research is necessary to fully comprehend the subtropical montane trade-off patterns in moss functional traits and the impact of environmental gradients on the correlation of these traits. To address this gap, we conducted a study of 11 moss species (7 families, 9 genera) in 54 patches from two subtropical mountain ranges, examining 40 functional traits related to photosynthesis, nutrients, water retention, and architecture. Through principal component analysis (PCA) and bi-variate correlation analysis, our findings reveal a strong correlation between light capture and nutrient assimilation strategies, as evidenced by the coordination between the traits of light capture and nutrient per area along a main principal component. Interestingly, we observed a trend towards smaller leaves and leaf cells in species with higher capacity for photosynthesis and metabolism, consistent with global trait spectra in vascular plants. However, we found that the trade-off between light capture and nutrient assimilation strategies was independent of water-holding capacity at shoot levels. Instead, we found that water-holding capacity was closely associated with nutrient utilization, energy metabolism, chlorophyll synthesis, and the primary process of photosynthesis. Our results highlight the multiple dimensions of functional traits in subtropical montane mosses and demonstrate that variation in these traits is driven by water availability, slope, and canopy density. Overall, our study provides valuable insights into the co-variation of moss traits and how environmental changes may impact mosses and ecosystem function.

This study discusses the application of fuzzy adaptive PID and improved genetic algorithm (IGA) in motion control and path optimization of autonomous underwater vehicle (AUV). The fuzzy adaptive PID method is selected because it is considered to be a strongly nonlinear and coupled system. First, this study creates the basic coordinate system of the AUV, and then analyzes the spatial force from the AUV to obtain the control model of the heading angle, climb angle, and depth. Next, the knowledge of fuzzy adaptive PID and IGA technology on AVU are investigated, then fuzzy adaptive PID controllers and path optimization are established, and experimental simulations are carried out to compare and analyze the simulation results. The research results show that controllers and IGA can be used for the motion control and path optimization of AUV. The advantages of fuzzy adaptive PID control are less overload, enhanced system stability, and more suitable for motion control and path optimization of AUV.

Abstract To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X 2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods (X 2 = 54.206, P

Background and aimThe increased pancreatic enzymes have recently been reported in patients with severe fever with thrombocytopenia syndrome (SFTS). However, its significance has not been elucidated clearly. The aim of this study was to explore the prevalence, clinical characteristics of elevated pancreatic enzymes (amylase and lipase) and its association with AP in patients with SFTS.MethodsData of demographics, comorbid conditions, clinical symptoms, laboratory parameters and survival time of patients with SFTS were collected. Patients were assigned into the non-AP and AP groups according to the diagnostic criteria of AP. Patients in the non-AP group were divided into the normal (3×ULN) groups according to the serum amylase and lipase levels, and then their clinical data were compared.ResultsA total of 284 patients diagnosed with SFTS were retrospectively enrolled, including 248 patients in the non-AP group and 36 patients in the AP group. Patients in the non-AP group were composed of 48, 116 and 84 patients in the normal, EPE and HPE groups, respectively. Compared with patients in the normal and EPE groups, patients in the HPE group had higher serum levels of laboratory parameters referring to liver, kidney, heart and coagulation system injury, as well as higher viral load. The cumulative survival rate of patients in the HPE group was significantly lower than that of patients in the normal group. In addition, patients in the AP group also had higher serum levels of laboratory variables reflecting liver, heart, coagulation dysfunction and viral load than patients in the HPE group. The cumulative survival rate of patients in the AP group was significantly lower than that of patients in the HPE group.ConclusionThe increased pancreatic enzymes are very common in patients with SFTS, but they are not always associated with AP. Though AP accounts for the majority of deaths for patients with elevated pancreatic enzymes, patients with pancreatic enzymes >3×ULN except for AP also have a high in-hospital mortality rate.

Summary: All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the MERS-CoV Nsp1 bound to the human 40S ribosomal subunit. The extensive interactions between C-terminal domain of MERS-CoV Nsp1 and the mRNA entry channel of the 40S ribosomal subunit are critical for its translation inhibition function. This mechanism of MERS-CoV Nsp1 is strikingly similar to SARS-CoV and SARS-CoV-2 Nsp1, despite modest sequence conservation. Our results reveal that the mechanism of host translation inhibition is conserved across β-CoVs and highlight a potential therapeutic target for the development of antivirals that broadly restrict β-CoVs.

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis caused by a novel bunyavirus. Until recently, the SFTS related acute kidney injury (AKI) was largely unexplored. This study aimed to investigate the clinical characteristics and outcomes of AKI in patients with SFTS.MethodsThe non-AKI and AKI groups were compared in terms of general characteristics, clinical features, laboratory parameters and cumulative survival rate. The independent risk factors for in-hospital mortality in patients with SFTS were analyzed by multivariate logistic regression to identify the population with poor prognosis.ResultsA total of 208 consecutive patients diagnosed with SFTS were enrolled, including 153 (73.6%) patients in the non-AKI group and 55 (26.4%) patients in the AKI group. Compared with patients without AKI, patients with AKI were older and had a higher frequency of diabetes. Among these laboratory parameters, platelet count, albumin and fibrinogen levels of patients with AKI were identified to be significantly lower than those of patients without AKI, while ALT, AST, ALP, triglyceride, LDH, BUN, uric acid, creatine, Cys-C, β2-MG, potassium, AMY, lipase, CK-MB, TnI, BNP, APTT, thrombin time, D-dimer, CRP, IL-6, PCT and ESR levels were significantly higher in patients with AKI. A higher SFTS viral load was also detected in the AKI patients than in the non-AKI patients. The cumulative survival rates of patients at AKI stage 2 or 3 were significantly lower than those of patients without AKI or at AKI stage 1. However, there was no significant difference in the cumulative survival rates between patients without AKI and those with stage 1 AKI. Univariate and multivariate binary logistic regression analyses demonstrated that stage 2 or 3 AKI was an independent risk factor for in-hospital mortality in patients with SFTS.ConclusionAKI is associated with poor outcomes in patients with SFTS, especially patients at AKI stage 2 or 3, who generally have high mortality. Our findings support the importance of early identification and timely treatment of AKI in patients with SFTS.

Despite effective vaccines against SARS-CoV-2, therapeutic options such as anti-virals and neutralizing antibodies are critical in treating disease, especially given the breakthrough infections of emerging VOCs. Here, Peng et al. generate two potent monoclonal antibodies and a bispecific antibody with two antigenrecognition variable regions targeting SARS-CoV-2 spike, provide CryoEM structures and show in vitro and in vivo efficacy of a humanized antibody against wildtype virus and delta variant.

ObjectiveTo reveal the relationship between Body Mass Index(BMI), type 2 diabetes, and bone mineral density(BMD) using a mendelian randomization (MR) approach.MethodsGWAS data on BMI, type 2 diabetes, and BMD were selected from the IEU GWAS database at the University of Bristol.Univariable, multivariable, and mediated MR analyses were used to explore the relationship between BMI, type 2 diabetes, and BMD. beta(β) values were given, and three methods, including inverse variance weighting, MR-Egger regression, and weighted median, were used in this analysis.ResultsUnivariable mendelian randomization (UVMR) results showed that BMI and type 2 diabetes were positively associated with BMD. However, the association between BMI and BMD was insignificant in the multivariable Mendelian randomization (MVMR) analysis, while that between type 2 diabetes and BMD remained significant. Mediated MR analysis indicated that type 2 diabetes mediated the regulation of BMD by BMI.ConclusionThis study provides evidence supporting a positive causal association between BMI, type 2 diabetes, and BMD. Type 2 diabetes acts as a mediator in the regulation of BMD by BMI, indicating that both BMI and type 2 diabetes exert a protective influence on BMD.

Abstract Background Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. Methods This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X 2 test and t test. Results Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009–0.136; P 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4

Abstract Background SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 inhibitor, in the context of SAMHD1. Methods CNDAC was tested in 13 acute myeloid leukaemia (AML) cell lines, in 26 acute lymphoblastic leukaemia (ALL) cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation. Results Although the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance. Conclusion Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.

Abstract Trip destination prediction plays an important role in exploring urban travel patterns. Accurate prediction can improve the efficiency of traffic management and the quality of location‐based services. Here, a deep learning structure that contains three components: travel information extraction, classification learning mechanism, and output module is proposed. Three types of information (the partial trajectory of on‐going trips, historical trajectories, and related external information) are extracted in the first component. Then, the classification learning mechanism chooses different methods (i.e. Long Short‐Term Memory network and Embedding technology) according to the characteristic of variables. Finally, an output layer that integrates the prior information about destinations is constructed. Two open‐source trajectory datasets are used to validate the effectiveness of the proposed model. Results show that the proposed model outperforms benchmark models using only part of the information or using all of the information but ignore the classification learning mechanism. The performance of the proposed model under different call types and travel durations is further explored. The result of this study will help understand travel behaviour in urban cities.

Abstract Comorbidities are important for the disease outcome of COVID‐19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID‐19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID‐19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID‐19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan‐Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS‐CoV‐2 virus clearance, however, the use of Angiotensin‐Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID‐19 patients.

Abstract Background The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear. Methods In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA). For in vitro verification, we performed cell cloning, flow cytometry and transwell experiments to verify the proliferation and invasion ability of CRC cells after knocking down CBX2. Results Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis. Conclusions Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

To systematically analyze the spatiotemporal heterogeneity, diurnal variation characteristics, and influencing factors of karst cave microclimate environments in Mahuang Cave, a cave in the Shuanghe Cave National Geological Park in Guizhou Province, China, was investigated. Monthly monitoring of meteorological and environmental parameters, such as wind speed, air pressure, humidity, and temperature indicators inside the cave and atmospheric temperature and precipitation outside the cave, was conducted from 2019 to 2021, as well as encrypted monitoring in August and December 2019. The results showed that: (1) The meteorological parameters of Mahuang Cave exhibited seasonal characteristics and cyclical interannual variation. Cave wind speed, relative humidity, and temperature were high in summer and autumn and lowest in winter, whereas cave air pressure was high in winter and low in summer. The atmospheric temperature outside the cave was the main controlling factor. (2) On a short time scale, the dewpoint and temperature of Mahuang Cave did not change significantly, and an abrupt change phenomenon occurred mostly around noon. The warm season was more sensitive than the cold season, and the closer to the entrance of the cave, the stronger the response. (3) In terms of spatial distribution, the overall microclimate factors of Mahuang Cave became increasingly stable and entered a constant state with the increasing depth of the cave passage. The related effects of cave morphology and structure, the physical environment of the cave passage, air movement, and groundwater dynamics were important factors leading to an abrupt change phenomenon in cave microclimates. Local meteorological conditions and cave geometry controlled the temporal variability and spatial heterogeneity of the cave microclimate environment.

SIRT6 has been reported to have multiple functions in inflammation and metabolism. In the present study, we explored the regulatory effects and mechanisms of SIRT6 in thioacetamide (TAA)-induced mice acute liver failure (ALF) models. The SIRT6 activator UBCS039 was used in this animal and cell experiments. We observed that UBCS039 ameliorated liver damage, including inflammatory responses and oxidative stress. Further study of mechanisms showed that the upregulation of SIRT6 inhibited the inflammation reaction by suppressing the nuclear factor-κB (NF-κB) pathway in the TAA-induced ALF mice model and lipopolysaccharide-stimulated macrophages. In addition, the upregulation of SIRT6 alleviated oxidative stress damage in hepatocytes by regulating the Nrf2/HO-1 pathway. These findings demonstrate that pharmacologic activator of SIRT6 could be a promising target for ALF.

The umbrella-shaped bolt (U-bolt) is a novel type of mechanical bolt used for rock reinforcement. It is made of a smooth steel bar, hinges, rigid rods, and sliding blocks. During installation and operation, the tension of the bolt is converted into the extrusion force on the rock mass deep in slope, so that the higher compressive strength of the rock mass is used to obtain the greater friction force and anchoring force. In this article, the structural and mechanical analysis results of the U-bolt is provided, and the relation between penetration and point normal stress is discussed. Based on these analyses, a simulation method for the U-bolt is proposed. The bolt elements are identified at first, then the penetration on the rock mass is calculated, and the tensile strength of bolt elements is increased to a reasonable value. Meanwhile, the method is applied to deep-buried rock reinforcement and a rock slope, and simulation results reveal that the U-bolt can alleviate the fracturing degree and reduce the depth and displacement of the excavation damaged zone (EDZ), and decrease the landslide distance.

The membrane fusion mechanism of SARS-CoV-2 offers an attractive target for the development of small molecule antiviral inhibitors. Fusion involves an initial binding of the crown-like trimeric spike glycoproteins of SARS-CoV-2 to the receptor angiotensin II-converting enzyme 2 (ACE2) on the permissive host cellular membrane and a prefusion to post-fusion conversion of the spike trimer. During this conversion, the fusion peptides of the spike trimer are inserted into the host membrane to bring together the host and viral membranes for membrane fusion in highly choreographic events. However, geometric constraints due to interactions with the membranes remain poorly understood. In this study, we build structural models of super-complexes of spike trimer/ACE2 dimers based on the molecular structures of the ACE2/neutral amino acid transporter B(0)AT heterodimer. We determine the conformational constraints due to the membrane geometry on the enzymatic activity of ACE2 and on the viral fusion process. Furthermore, we find that binding three ACE2 dimers per spike trimer is essential to open the central pore as necessary for triggering productive membrane fusion through an elongation of the central stalk. The reported findings thus provide valuable insights for targeting the membrane fusion mechanism for drug design at the molecular level.

The Buyi are a socio-linguistic group in Yunnan Province of southwest China that have a long history of using medicinal plants as part of their indigenous medical system. Given the limited written documentation of the Buyi indigenous medical system, the objective of this paper is to document the medicinal plants of the Buyi and associated traditional knowledge and transmission. Field research was conducted in four villages in Lubuge Township of Luoping County in Yunnan Province using ethnobotanical methodologies including participatory observation, semi-structured interviews, key informant interviews, and focus group discussions to elicit information on medicinal plants. In total, 120 informants (including 15 key informants who are healers) were interviewed. This study found that a total of 121 medicinal plant species belonging to 64 families are used by the Buyi including by local healers to treat different diseases. Among the medicinal plants recorded in this study, 56 species (46%) have not previously been documented in the scientific literature as having medicinal value, highlighting the pressing need for ethnobotanical documentation in indigenous communities. The most frequently used medicinal part was the leaf (24.9% of documented plants), and the most common preparation method was decoction (62.8% of medicinal). Medicinal plants were mainly used to treat rheumatism (12.4% of plants), trauma and injuries (9.6%). The documented plants are also used for other non-medicinal purposes including food, fodder, fencing, and ornamental. In addition, 35 of the medicinal plants are considered poisonous and are used by local Buyi healers for medicine. The traditional Buyi beliefs and practices associated with the documented medicinal plants likely contributes to their conservation in the environments and around Buyi communities. This study further highlights that ethnomedicinal knowledge of the Buyi is at risk of disappearing due to increased introduction and use of modern medicine in Buyi communities, livelihood changes, rapid modernization, and urbanization. Research, policy, and community programs are urgently needed to conserve the biocultural diversity associated with the Buyi medical system including ethnobotanical knowledge towards supporting both environmental and human wellbeing.

Abstract Background AIDS-related KS generally involves cutaneous lesions, that slowly progress over months to years. Neither rapidly progressing of KS nor KS complicated with hemophagocytic syndrome (HPS) has rarely been reported. Case presentation We report a rare case of rapid progression of Kaposi’s sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection. The symptoms of this patient were atypical, showing only persistent high fever and rapid progressed to hemophagocytic syndrome. This patient was successfully treated with antiretroviral therapy combined with liposomal doxorubicin. Conclusions The condition of the KS patient could deteriorate rapidly over a period of days and even developeded into HPS, which was life-threatening. However, chemotherapy initiated in a timely manner might improve prognosis.

ABSTRACT The effect of antiretroviral therapy (ART) on CD4+/CD25hi/CD127low T lymphocyte changes in people living with HIV/AIDS (PLWHA) is still a matter of debate. From October 2015 to December 2019, peripheral blood from 70 cases of PLWHA were collected for the detection of CD4+/CD25hi/CD127low T lymphocytes by flow cytometry. Statistical analysis was performed to detect changes of CD4+/CD25hi/CD127low T lymphocytes in patients with different duration of ART and different treatment effects. We found that the number of CD4+/CD25hi/CD127low T lymphocytes in ART-naive PLWHA were lower than those in healthy volunteers (10.3±٦.٠ cells/uL vs 31.7±8.0 cells/uL, P < 0.05). CD4+/CD25hi/CD127low T lymphocyte counts increased to 17.8±٤.٠ cells/uL 6 months post-ART and 25.0±١١.٩ cells/uL 9 months post-ART, respectively (P < 0.05). There was no significant difference in CD4+/CD25hi/CD127low T lymphocyte counts between PLWHA who reached a complete immune reconstruction after ART and healthy volunteers. The growth of CD4+/CD25hi/CD127low T lymphocyte counts in patients who had baseline CD4 > 200 cells/uL was greater than those who had baseline CD4 ≤ 200 cells/uL (12.6±٤.٦ cells/uL vs 5.6±٥.٠ cells/uL, P = 0.027). CD4+/CD25hi/CD127low T lymphocyte counts were positively correlated with CD4+ T lymphocyte counts (r = 0.923, P < 0.001) and CD4+/CD8+ ratio (r = 0.741, P < 0.001), but were negatively correlated with HIV-VL (r = −0.648, P = 0.000). In conclusion, the results of the present study showed that changes in CD4+/CD25hi/CD127low T lymphocyte counts can be used to assess the effect of ART in PLWHA.

We found that all 5 asymptomatic household contacts of a Wuhan, China, physician with coronavirus disease had severe acute respiratory syndrome coronavirus 2 detected by PCR. The index patient and 2 contacts also had abnormal chest computed tomography scans. Asymptomatic infected household contacts of healthcare workers with coronavirus disease might be underrecognized.

Abstract Background The Buyi (Bouyei) people in Qianxinan Buyi and Miao Autonomous Prefecture, Southwest Guizhou, China, have used medicinal plants and traditional remedies for ethnoveterinary practices, such as treating domestic animals during livestock breeding, since ancient times. However, the unique ethnoveterinary practices of the Buyi have rarely been recorded. This study aimed to identify the plants used in their traditional ethnoveterinary practices, and to propose suggestions for future conservation and sustainable use of this knowledge. Methods Ethnobotanical fieldwork was conducted in 19 villages/townships in Qianxinan Prefecture between 2017 and 2018. Data were collected from the local Buyi people through semi-structured interviews and participatory observations. The informant consensus factor (FIC) and use reports (URs) were utilized to evaluate the consent of the current ethnoveterinary practices among the local communities, and 83 informants were interviewed during the field investigations. Plant samples and voucher specimens were collected for taxonomic identification. Results A total of 122 plant species, belonging to 60 families and 114 genera, were recorded as being used in ethnoveterinary practices by the Buyi people. The most used ethnoveterinary medicinal plant (EMP) parts included the roots, whole plant, and bulb, and the most common preparation methods included decoction, crushing, and boiling. Some EMPs, such as Quisqualis indica and Paris polyphylla, have special preparation methods. The informant consensus factor (FIC) and use reports (URs) of the EMP species were analyzed. Twenty EMP species with the highest URs were noted as having particular importance in the daily lives of Buyi people in Qianxinan Prefecture. Conclusion In this study, we identified traditional ethnoveterinary knowledge of the medicinal plants among the Buyi communities in Qianxinan Prefecture. This knowledge has previously been limited to local vets, herders, and aged community members. Plants with important medicinal uses need to be validated phytochemically and pharmacologically in the future, to develop new alternative drugs for veterinary purposes.

Abstract Background The Yi is the largest ethnic group in Yunnan Province (China), with a population of five million. The Yi people tend to live in mountainous areas, and their culture includes a unique dietary system for treating and protecting people against illnesses. Medicinal plants occupy an essential place in the Yi diet because they play a key role in health and the prevention and treatment of diseases. However, few studies have addressed these medicinal dietary plants and their importance in the Yi’s daily lives. The aim of this study was to (1) investigate the medicinal dietary plants used by the Yi in Mile City, (2) document the traditional knowledge held about these plants, (3) identify species with important cultural significance to the Yi in Mile City, and (4) analyze the special preparation methods and consumption habits of these plants. Methods Field investigations were performed in six villages in Mile City, Honghe Hani and Yi Autonomous Prefecture, Yunnan, from July 2017 to May 2018. Information was collected using direct observation, semi-structured interviews, key informant interviews, individual discussions, and focus group discussions. The use value (UV) and frequency of utilization index (FUI) of these plants were analyzed. Plant samples and voucher specimens were collected for taxonomic identification. Results This study documented 124 species belonging to 62 families and 102 genera. These plants included angiosperms (117 spp.), gymnosperms (3), pteridophytes (2), lichen (1), and fungus (1). The 20 species with the highest UV were noted as being particularly important to the Yi people’s daily life in Mile City. The primary medicinal preparation method for plants recorded in the study was decoction. The most commonly used plant parts were fruits and roots. The most frequently used edible parts were fruits, and the most frequently used medicinal parts were roots. The medicinal parts were used to treat diseases such as rheumatism, edemas, kidney deficiency, spleen deficiency, gastritis, parasites, and so on. Conclusion A wide variety of medicinal dietary plants are used by the Yi people in Mile City. Those plants, which have both rich nutritional and medicinal value, occupy an essential part of the Yi dietary and medicine culture. Ethnobotanical surveys of medicinal dietary plants provide a theoretical reference for the conservation and sustainable use of the plant resources and could contribute to the protection of the Yi food culture and traditional medicine in Mile City. In addition, this information provides a sound basis for developing and using Yi ethnic medicine and health products.

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan. The virus is highly infectious. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. Case presentation We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital. Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019 (COVID-2019) and survived from the viral infection. They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors. Cases 2 and 4 suffered from severe type of COVID-19, and Case 2 was dead owning to the advanced age, uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases. The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4, who suffered from hepatitis B related hepatocellular carcinoma. However, Case 4 was recovered from COVID-19 after a combination therapy against virus, bacteria and fungi, and also respiratory support. Nearly all patients showed a decrease in lymphocytes including total CD3+ T cells, B cells, and natural killer cells after infection of the virus. Conclusions The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients. And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.

Many pathogens manipulate ubiquitin-mediated signaling to evade host cell defense. Here, the authors characterize the structure and enzymatic activity of a deubiquitylase domain from the causative pathogen of scrub typhus, providing evidence for a distinct mechanism of ubiquitin chain selectivity.

Abstract In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

ABSTRACTCirculating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.

ABSTRACTQuantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27–55%), 100% (95% CI: 54–100%), 100%, 16% (95% CI: 13–19%), 0.6 (95% CI: 0.48–0.75) and 47% (95% CI: 33–60%) for RT-PCR to 94% (95% CI: 83–99%), 100% (95% CI: 48–100%), 100%, 63% (95% CI: 36–83%), 0.06 (95% CI: 0.02–0.18), and 95% (95% CI: 84–99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5–12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.

ABSTRACTDifferent primers/probes sets have been developed all over the world for the nucleic acid detection of SARS-CoV-2 by quantitative real time polymerase chain reaction (qRT-PCR) as a standard method. In our recent study, we explored the feasibility of droplet digital PCR (ddPCR) for clinical SARS-CoV-2 nucleic acid detection compared with qRT-PCR using the same primer/probe sets issued by Chinese Center for Disease Control and Prevention (CDC) targeting viral ORF1ab or N gene, which showed that ddPCR could largely minimize the false negatives reports resulted by qRT-PCR [Suo T, Liu X, Feng J, et al. ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens. medRxiv [Internet]. 2020;2020.02.29.20029439. Available from: https://medrxiv.org/content/early/2020/03/06/2020.02.29.20029439.abstract]. Here, we further stringently compared the performance of qRT-PCR and ddPCR for 8 primer/probe sets with the same clinical samples and conditions. Results showed that none of 8 primer/probe sets used in qRT-PCR could significantly distinguish true negatives and positives with low viral load (10−4 dilution). Moreover, false positive reports of qRT-PCR with UCDC-N1, N2 and CCDC-N primers/probes sets were observed. In contrast, ddPCR showed significantly better performance in general for low viral load samples compared to qRT-PCR. Remarkably, the background readouts of ddPCR are relatively lower, which could efficiently reduce the production of false positive reports.

From cellular deposition of the HIV-1 capsid to integration of the viral genome, the capsid constitutes a primary target of a variety of host proteins that work to either promote or inhibit HIV-1 infection. Successful progression of HIV-1 infection depends on interactions between the capsid and host factors involved in stability, cellular transport, nuclear import, and genome integration. The virus must also guard its reverse-transcribing genome inside the capsid from host restriction factors that bind the capsid and suppress infection. Understanding the structure and dynamics of the capsid protein (CA) component and the assembled capsid sheds light on the molecular underpinnings of overall capsid stability, architecture, and flexibility that govern HIV-1 capsid–host interactions. The vast majority of these interactions are mediated through recognition of higher order interfaces only present in the assembled capsid lattice. Patterns formed at these interfaces serve as signposts for capsid-binders. Here we provide a graphical summary of the intricate interactions between host factors and the HIV-1 capsid while highlighting recent research. Insights into how host proteins interact with the capsid is crucial for understanding the HIV-1 replication cycle and developing antiviral therapeutics to prevent viral genome integration.

Abstract Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B‐lymphocyte (SIBC) lines from HIV‐infected patients with and without Non‐Hodgkin's Lymphoma (AIDS‐NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV‐infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV‐SIBC were generated from HIV‐infected patients without AIDS‐NHL (10%, 8/77), while 14 SIBCs named AIDS‐NHL‐SIBC were from 13 of the AIDS‐NHL patients (32.5%, 13/40). Among the 14 AIDS‐NHL‐SIBCs, 12 were derived from AIDS‐NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3‐CD20+CD27+) with EBV infection. Moreover, AIDS‐NHL‐SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV‐SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV‐SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS‐NHL patients and can be isolated from HIV‐infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV‐infected patients.

Coronaviruses have brought severe challenges to public health all over the world in the past 20years. SARS-CoV-2, the causative agent of the COVID-19 pandemic that has led to millions of deaths, belongs to the genus beta-coronavirus. Alpha- and beta-coronaviruses encode a unique protein, nonstructural protein 1 (Nsp1) that both suppresses host immune responses and reduces global gene expression levels in the host cells. As a key pathogenicity factor of coronaviruses, Nsp1 redirects the host translation machinery to increase synthesis of viral proteins. Through multiple mechanisms, coronaviruses impede host protein expression through Nsp1, while escaping inhibition to allow the translation of viral RNA. In this review, we discuss current data about suppression of the immune responses and inhibition of protein synthesis induced by coronavirus Nsp1, as well as the prospect of live-attenuated vaccine development with virulence-attenuated viruses with mutations in Nsp1.

In this paper, we take a water quality testing Unmanned Surface Vessel (USV) as the research object. We propose a heading keeping strategy based on Human Simulated Intelligent Control (HSIC) algorithm and a trajectory tracking strategy under line-of-sight (LOS) algorithm. The practicality of the proposed control strategies was verified by combining simulations and experiments. The main contents were constructed with three parts: Firstly, we designed a complete control system of a water quality inspection unmanned boat with Arduino microcontroller as the core processor. Secondly, we derived the mathematical model of motion after reasonable simplification. Combined with the cycle experiment, the mapping relation between virtual rudder angle and motor speed was established. Then, the USV heading direction control strategy of HSIC was presented and the reliability of the proposed strategy was verified by the course control experiment of USV. Finally, aiming at the defects and shortcomings of the upper-level trajectory tracking LOS algorithm in practical application, we propose the trajectory correction and precise steering control strategies, and the practicality of the improved algorithm was verified by multi-point trajectory tracking experiments. The autonomous fixed-point water quality testing experiment was designed and verified the effectiveness of the proposed strategies.

COVID-19 is a global crisis of unimagined dimensions. Currently, Remedesivir is only fully licensed FDA therapeutic. A major target of the vaccine effort is the SARS-CoV-2 spike-hACE2 interaction, and assessment of efficacy relies on time consuming neutralization assay. Here, we developed a cell fusion assay based upon spike-hACE2 interaction. The system was tested by transient co-transfection of 293T cells, which demonstrated good correlation with standard spike pseudotyping for inhibition by sera and biologics. Then established stable cell lines were very well behaved and gave even better correlation with pseudotyping results, after a short, overnight co-incubation. Results with the stable cell fusion assay also correlated well with those of a live virus assay. In summary we have established a rapid, reliable, and reproducible cell fusion assay that will serve to complement the other neutralization assays currently in use, is easy to implement in most laboratories, and may serve as the basis for high throughput screens to identify inhibitors of SARS-CoV-2 virus-cell binding and entry.