Analysis of unsuccessful tests and the effect of prolonged clinical sample preprocessing in the GeneXpert MTB/RIF assay.

Background: The GeneXpert MTB/RIF (Xpert) assay is a widely used technology for detecting Mycobacterium tuberculosis (MTB) in clinical samples. However, the study on the failure of the Xpert assay during routine implementation and its potential solutions is limited.

Methods: We retrospectively analyzed the records of unsuccessful tests in the Xpert and the GeneXpert MTB/RIF Ultra (Ultra) assays between April 2017 and April 2021 at the Shanghai Public Health Clinical Center.

Trends in and Risk Factors for Drug Resistance in in HIV-Infected Patients.

Trends in and risk factors for drug resistance in () in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture.

Population pharmacokinetics and pharmacodynamics of nirmatrelvir in Chinese patients with COVID-19.

Background: The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of nirmatrelvir (NMV) are unknown in Chinese patients with COVID-19.

Objectives: To understand the PK, as well as PK-PD characteristics of NMV for optimizing the dose in Chinese patients with COVID-19.

Methods: We enrolled 141 participants who received NMV 300 mg/ritonavir (RTV) 100 mg b.

A biphenotypic lymphocyte subset displays both T- and B-cell functionalities.

T cell/B cell mixed phenotypic lymphocytes have been observed in different disease contexts, yet their presence and function in physiological conditions remain elusive. Here, we provide evidence for the existence of a lymphocyte subset endogenously expressing both T- and B-cell lineage markers in mice. The majority of these T/B phenotypic lymphocytes (CD3CD19) show an origin of pro/pre B cells and distribute widely in mouse bone marrow, lymph nodes, spleen, and peripheral blood.

A new double-antigen sandwich test based on the light-initiated chemiluminescent assay for detecting anti-hepatitis C virus antibodies with high sensitivity and specificity.

Objectives: The aim of this study was to evaluate the performance of a new double-antigen sandwich test that is based on the light-initiated chemiluminescent assay (LiCA) for detecting anti-hepatitis C virus antibodies (anti-HCV) in comparison to Architect.

Methods: Analytical characteristics and diagnostic performance were tested using seroconversion panels and large pools of clinical samples. Positive results were validated by the strip immunoblot assay (RIBA) and HCV RNA.

Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis.

Coronavirus disease 2019 (COVID-19) severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples from 300 in-hospital COVID-19 patients, collected at the time of admission.

SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity.

Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition.

The impacts of vaccination status and host factors during early infection on SARS-CoV-2 persistence:a retrospective single-center cohort study.

Background: Viral persistence is a crucial factor that influences the transmissibility of SARS-CoV-2. However, the impacts of vaccination and physiological variables on viral persistence have not been adequately clarified.

Methods: We collected the clinical records of 377 COVID-19 patients, which contained unvaccinated patients and patients received two doses of an inactivated vaccine or an mRNA vaccine.

Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity.

The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse.

Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice.

Interleukin-12 receptor β1 (IL12RB1)-deficient individuals show increased susceptibilities to local or disseminated BCG infection and environmental mycobacteria infection. However, the low clinical penetrance of IL12RB1 deficiency and low recurrence rate of mycobacteria infection suggest that protective immunity still exists in this population. In this study, we investigated the mechanism of tuberculosis suppression using the IL12RB1-deficient mouse model.

Molecular Epidemiology and Antifungal Resistance of From Human Immunodeficiency Virus-Negative and Human Immunodeficiency Virus-Positive Patients in Eastern China.

Cryptococcosis is an opportunistic and potentially lethal infection caused by and complex, which affects both immunocompromised and immunocompetent people, and it has become a major public health concern worldwide. In this study, we characterized the molecular epidemiology and antifungal susceptibility of 133 isolates from East China Invasive Fungal Infection Group (ECIFIG), 2017-2020. Isolates were identified to species level by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed by sequencing.

Identification and validation of a metabolism-related gene signature for the prognosis of colorectal cancer: a multicenter cohort study.

Objective: Cell metabolism plays a vital role in the proliferation, metastasis and sensitivity to chemotherapy drugs of colorectal cancer. The purpose of this multicenter cohort study is to investigate the potential genes indicating clinical outcomes in colorectal cancer patients.

Methods: We analyzed gene expression profiles of colorectal cancer to identify differentially expressed genes then used these differentially expressed genes to construct prognostic signature based on the least absolute shrink-age and selection operator Cox regression model.

DNA-templated silver nanoclusters light up tryptophan for combined detection of plasma tryptophan and albumin in sepsis.

Tryptophan (Trp) as an essential amino acid plays critical roles in regulating multiple cell activities, and the changes of its circulating level usually indicate disease status such as the severity of acute inflammation sepsis. However, the current technology for Trp detection mostly relies on chromatography that cannot meet the rapid and simple detection requirement in monitoring sepsis. Herein, a label-free fluorescent nanosensor was constructed to detect Trp and its carrier protein - human serum albumin (HSA) in plasma.

Successive Site Translocating Inoculation Improved T Cell Responses Elicited by a DNA Vaccine Encoding SARS-CoV-2 S Protein.

A variety of methods have been explored to increase delivery efficiencies for DNA vaccine. However, the immunogenicity of DNA vaccines has not been satisfactorily improved. Unlike most of the previous attempts, we provided evidence suggesting that changing the injection site successively (successively site-translocated inoculation, SSTI) could significantly enhance the immunogenicity of DNA vaccines in a previous study.

Monocytic MDSCs homing to thymus contribute to age-related CD8+ T cell tolerance of HBV.

Hepatitis B virus exposure in children usually develops into chronic hepatitis B (CHB). Although hepatitis B surface antigen (HBsAg)-specific CD8+ T cells contribute to resolve HBV infection, they are preferentially undetected in CHB patients. Moreover, the mechanism for this rarely detected HBsAg-specific CD8+ T cells remains unexplored.

Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples.

The detection of samples at ultralow concentrations (one to ten copies in 100 μl) in biofluids is hampered by the orders-of-magnitude higher amounts of 'background' biomolecules. Here we report a molecular system, immobilized on a liquid-gated graphene field-effect transistor and consisting of an aptamer probe bound to a flexible single-stranded DNA cantilever linked to a self-assembled stiff tetrahedral double-stranded DNA structure, for the rapid and ultrasensitive electromechanical detection (down to one to two copies in 100 μl) of unamplified nucleic acids in biofluids, and also of ions, small molecules and proteins, as we show for Hg, adenosine 5'-triphosphate and thrombin. We implemented an electromechanical biosensor for the detection of SARS-CoV-2 into an integrated and portable prototype device, and show that it detected SARS-CoV-2 RNA in less than four minutes in all nasopharyngeal samples from 33 patients with COVID-19 (with cycle threshold values of 24.

Ultraprecise Antigen 10-in-1 Pool Testing by Multiantibodies Transistor Assay.

Effective screening of infectious diseases requires a fast, cheap, and population-scale testing. Antigen pool testing can increase the test rate and shorten the screening time, thus being a valuable approach for epidemic prevention and control. However, the overall percent agreement (OPA) with polymerase chain reaction (PCR) is one-half to three-quarters, hampering it from being a comprehensive method, especially pool testing, beyond the gold-standard PCR.

Rapid SARS-CoV-2 Nucleic Acid Testing and Pooled Assay by Tetrahedral DNA Nanostructure Transistor.

Direct SARS-CoV-2 nucleic acid testing with fast speed and high frequency is crucial for controlling the COVID-19 pandemic. Here, direct testing of SARS-CoV-2 nucleic acid is realized by field-effect transistors (FETs) with an electro-enrichable liquid gate (LG) anchored by tetrahedral DNA nanostructures (TDNs). The applied gate bias electrostatically preconcentrates nucleic acids, while the liquid gate with TDNs provides efficient analyte recognition and signal transduction.

Quality Management for Point-Of-Care Testing of Pathogen Nucleic Acids: Chinese Expert Consensus.

COVID-19 continues to circulate globally in 2021, while under the precise policy implementation of China's public health system, the epidemic was quickly controlled, and society and the economy have recovered. During the pandemic response, nucleic acid detection of SARS-CoV-2 has played an indispensable role in the first line of defence. In the cases of emergency operations or patients presenting at fever clinics, nucleic acid detection is required to be performed and reported quickly.

Identifying Risk Factors for Secondary Infection Post-SARS-CoV-2 Infection in Patients With Severe and Critical COVID-19.

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection.

Direct SARS-CoV-2 Nucleic Acid Detection by Y-Shaped DNA Dual-Probe Transistor Assay.

Rapid screening of infected individuals from a large population is an effective means in epidemiology, especially to contain outbreaks such as COVID-19. The gold standard assays for COVID-19 diagnostics are mainly based on the reverse transcription polymerase chain reaction, which mismatches the requirements for wide-population screening due to time-consuming nucleic acid extraction and amplification procedures. Here, we report a direct nucleic acid assay by using a graphene field-effect transistor (g-FET) with Y-shaped DNA dual probes (Y-dual probes).

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2 subjects.

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2 subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink.