Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.

The efficacy assessment of convalescent plasma therapy for COVID-19 patients:a multi-center case series

Convalescent plasma(CP)transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections.However,the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019(COVID-19).We aimed to explore the potential efficacy of CP therapy,and to assess the possible factors associated with its efficacy.We enrolled eight critical or severe COVID-19 patients from four centers.Each patient was transfused with 200–400mL of CP from seven recovered donors.The primary indicators for clinical efficacy assessment were the changes of clinical symptoms,laboratory parameters,and radiological image after CP transfusion.CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody(NAb)level.No adverse events were observed during and after CP transfusion.Following CP transfusion,six out of eight patients showed improved oxygen support status;chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days;the viral load was decreased to a negative level in five patients who had the previous viremia;other laboratory parameters also tended to improve,including increased lymphocyte counts,decreased C-reactive protein,procalcitonin,and indicators for liver function.The clinical efficacy might be associated with CP transfusion time,transfused dose,and the NAb levels of CP.This study indicated that CP might be a potential therapy for severe patients with COVID-19.

DNAzyme@CuSNPs dual mimic enzyme probe-amplified chemiluminescent imaging array immunosensor for multiple chicken cytokines detection

The detection of cytokines plays an important role in clinical diagnosis and immune mechanism research of chicken diseases.In this work,a novel and ultrasensitive chemiluminescent(CL)imaging array immunosensor was proposed to detect multiple chicken cytokines based on DNAzyme@CuS nanoparticles(DNAzyme@CuSNPs)dual mimic enzyme signal amplification strategy.DNAzyme@CuSNPs owns excellent peroxidase property,which was modified with second antibody(Ab_(2))to prepare DNAzyme@CusNPs detection probe,and demonstrated high catalysis CL imaging signal due to synergistic catalysis.Chicken interleukin-4(ChIL-4)and chicken interferon-y(ChIFN-y)were used as model analysis samples,the DNAzyme@CusSNPs-based CL imaging immunosensor achieved simultaneous and high-throughput detection of ChIL-4 and ChIFN-y with wide linear range of 10^(-3)-10^(2) ng/mL,and the detection limits are 0.41 pg/mL and 0.36 pg/mL,respectively.The multiplex chicken cytokines CL imaging array immunosensor shows a high sensitivity,wide linear range,excellent specificity and acceptable stability.This research opens dual mimic enzyme signal-amplified strategy to develop sensitive CL imaging immunoassay for chicken diseases detection application.

A multiplexed circulating tumor DNA detection platform engineered from 3D-coded interlocked DNA rings

Circulating tumor DNA(ctDNA)is a critical biomarker not only important for the early detection of tumors but also invaluable for personalized treatments.Currently ctDNA detection relies on sequencing.Here,a platform termed three-dimensional-coded interlocked DNA rings(3D-coded ID rings)was created for multiplexed ctDNA identification.The ID rings provide a ctDNA recognition ring that is physically interlocked with a reporter ring.The specific binding of ctDNA to the recognition ring initiates target-responsive cutting via a restriction endonuclease;the cutting then triggers rolling circle amplification on the reporter ring.The signals are further integrated with internal 3D codes for multiplexed readouts.ctDNAs from non-invasive clinical specimens including plasma,feces,and urine were detected and validated at a sensitivity much higher than those obtained through sequencing.This 3D-coded ID ring platform can detect any multiple DNA fragments simultaneously without sequencing.We envision that our platform will facilitate the implementation of future personalized/precision medicine.