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The role of CD39 pathway in Th1 cell function in tuberculosis (TB) is rarely elucidated. The present study aims to investigate the modulating mechanism of CD39 pathway during Mycobacterium tuberculosis (MTB) infection. CD39 expression was examined on host immune cells among patients with TB. The relationship between CD39 expression and Th1 cell function was analysed. Patients with TB displayed dramatically higher CD39 expression on Th1 cells than healthy controls, and a significantly increased expression of surface markers, including activation, exhaustion and apoptosis markers, were noted in CD39

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P

I read with interest the recent published article from Professor Robert L. Medcalf, entitled “Fibrinolysis and COVID‐19: a plasmin paradox” [1]. As an indirect marker of thrombin and plasmin activation, D‐dimer has been suggested to guide anticoagulant treat in COVID‐19 patients [2, 3]. However, D‐dimer may not be able to reflect accurate fibrinolysis status of COVID‐19 patients, and therefore can’t guide the possible antifibrinolysis or thrombolytic therapy in different stages of COVID‐19, as Professor Robert L. Medcalf discussed. Hence, we speculated that measuring direct markers of thrombin, plasmin and so on, may provide more therapeutic targets in COVID‐19 patients with coagulopathy.

Background A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, and the application of heparin in COVID-19 has been recommended by some expert consensus because of the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. Methods Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID-19 in Tongji hospital were retrospectively analyzed. The 28-day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis-induced coagulopathy (SIC) score or D-dimer result. Results There were 449 patients with severe COVID-19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D-dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28-day mortality in multivariate analysis. No difference in 28-day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P = .910). But the 28-day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P = .029), or D-dimer >6-fold of upper limit of normal (32.8% vs 52.4%, P = .017). Conclusions Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer.

Objectives This study aimed to determine the IgM and IgG responses against severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 in coronavirus disease 2019 (COVID‐19) patients with varying illness severities. Methods IgM and IgG antibody levels were assessed via chemiluminescence immunoassay in 338 COVID‐19 patients. Results IgM levels increased during the first week after SARS‐CoV‐2 infection, peaked 2 weeks and then reduced to near‐background levels in most patients. IgG was detectable after 1 week and was maintained at a high level for a long period. The positive rates of IgM and/or IgG antibody detections were not significantly different among the mild, severe and critical disease groups. Severe and critical cases had higher IgM levels than mild cases, whereas the IgG level in critical cases was lower than those in both mild and severe cases. This might be because of the high disease activity and/or a compromised immune response in critical cases. The IgM antibody levels were slightly higher in deceased patients than recovered patients, but IgG levels in these groups did not significantly differ. A longitudinal detection of antibodies revealed that IgM levels decreased rapidly in recovered patients, whereas in deceased cases, either IgM levels remained high or both IgM and IgG were undetectable during the disease course. Conclusion Quantitative detection of IgM and IgG antibodies against SARS‐CoV‐2 quantitatively has potential significance for evaluating the severity and prognosis of COVID‐19., In this study, we found that level of IgM was increased during the first week after SARS‐CoV‐2 infection and reached its peak level after 2 weeks, while IgG reached its peak in 3 weeks, which was maintained at a high level even over 48 days.

Summary B lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T cell-dependent, and CD4+ T cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4+ T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4+ T cells. Here, we addressed the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4+ T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease. TIGIT+ CD4+ T cells from both healthy individuals and SLE patients had a more activated phenotype than TIGIT- CD4+ T cells. Reversely, the activation, proliferation and cytokine production potential of TIGIT+ CD4+ T cells were significantly lower than those of TIGIT- CD4+ T cells. Furthermore, activation of TIGIT pathway by using CD155 could substantially down-regulate the activities of CD4+ T cells from SLE patients in vitro, and in vivo administration of CD155 resulted in a delayed development of SLE in MRL/lpr mice. TIGIT is a powerful negative regulator of CD4+ T cells in SLE, which suggests that TIGIT signaling pathway may be used as a potential therapeutic target for treating this disease. This article is protected by copyright. All rights reserved.

High groundwater salinity has become a major concern in the arid alluvial plain of the Dunhuang Basin in northwestern China because it poses a significant challenge to water resource management. Isotopic and geochemical analyses were conducted on 55 water samples from springs, boreholes and surface water to identify potential sources of groundwater salinity and analyse the processes that control increasing salinity. The total dissolved solid (TDS) content in the groundwater ranged from 400 to 41 000 mg/l, and high TDS values were commonly associated with shallow water tables and flow-through and discharge zones in unconfined aquifers. Various groundwater contributions from rainwater, agricultural irrigation, river water infiltration and lateral inflows from mountains were identified by major ions and δD and δ18O. In general, HCO3− and SO42− were the dominant anions in groundwater with a salinity of 2500 mg/l. The major ion concentrations indicated that mineral weathering, including carbonate and evaporite dissolution, primarily affected groundwater salinity in recharge areas. Evapotranspiration controlled the major ion concentration evolution and salinity distribution in the unconfined groundwaters in the flow-through and discharge areas, although it had a limited effect on groundwater in the recharge areas and confined aquifers. Agricultural irrigation increased the water table and enhanced evapotranspiration in the oasis areas of the basin. TDS and Cl became more concentrated, but H and O isotopes were not enriched in the irrigation district, indicating that transpiration dominated the increasing salinity. For other places in the basin, as indicated by TDS, Cl, δD and δ18O characteristics, evaporation, transpiration and water–rock interactions dominated at different hydrogeological zones, depending on the plant coverage and hydrogeological conditions. Groundwater ages of 3H, and δD and δ18O compositions and distributions suggest that most of the groundwaters in Dunhuang Basin have a paleometeoric origin and experienced a long residence time. These results can contribute to groundwater management and future water allocation programmes in the Dunhuang Basin. Copyright © 2015 John Wiley & Sons, Ltd.

There is considerable interest in naturalizing flow regime on managed rivers to slow the spread of saltcedar (Tamarix ramosissima) invasion in southwestern USA or to preserve riparian forests dominated by saltcedar and other species in northwestern China. However, little is known about the responses of established saltcedar in water sources to frequent intra‐annual fluctuation of water table resulting from this new, more dynamic flow regime. This study investigates how saltcedar at a riparian site in the middle reaches of the Heihe River, northwest China, responds in water sources use to intra‐annual water table fluctuations. Stable oxygen isotope was employed to determine accurate depth at which saltcedar obtains its water supply, and soil moisture monitoring was used to determine sources of plant‐available soil water. We found that the primary zone of water uptake by saltcedar were stable at 25–60 cm depth, but the water sources used by saltcedar switched between groundwater and soil moisture with the water table fluctuations. Saltcedar derived its water from groundwater when water table was at depth less than 60 cm but switched to soil moisture at 25–60 cm depth when water table declined. It is supposed that the well‐developed clay layer at 60–80 cm depth constrained lateral roots of saltcedar to the soil layers above 60 cm, while the fine‐textured soils at this site, which were periodically resaturated by rising groundwater before the stored soil moisture had become depleted, provided an important water reservoir for saltcedar when groundwater dropped below the primary zone of fine roots. The root distribution of saltcedar may also be related to local groundwater history. The quick decline in water table in the early 1980s when the riparian saltcedar had established may strand its roots in the shallow unsaturated zone. We suggested that raising the water table periodically instead of maintaining it invariably above the rooting depth could sustain desired facultative phreatophytes while maximizing water deliveries. Copyright © 2015 John Wiley & Sons, Ltd.

Human NK cells display extensive phenotypic and functional heterogeneity among healthy individuals, but the mechanism responsible for this variation is still largely unknown. Here, we show that a novel immune receptor, T-cell immunoglobulin and ITIM domain (TIGIT), is expressed preferentially on human NK cells but shows wide variation in its expression levels among healthy individuals. We found that the TIGIT expression level is related to the phenotypic and functional heterogeneity of NK cells, and that NK cells from healthy individuals can be divided into three categories according to TIGIT expression. NK cells with low levels of TIGIT expression show higher cytokine secretion capability, degranulation activity, and cytotoxic potential than NK cells with high levels of TIGIT expression. Blockade of the TIGIT pathway significantly increased NK-cell function, particularly in NK cells with high levels of TIGIT expression. We further observed that the TIGIT expression level was inversely correlated with the IFN-γ secretion capability of NK cells in patients with cancers and autoimmune diseases. Importantly, we propose a novel mechanism that links TIGIT expression with NK-cell functional heterogeneity, and this mechanism might partially explain why individuals have different susceptibilities to infection, autoimmune disease, and cancer.

Glucagon-like peptide-1 (GLP-1) plays an important role in the regulation of postprandial insulin release. Here, we used the split DnaB mini-intein system to produce recombinant human GLP-1/7-36 (rhGLP-1) in Escherichia coli. The C-terminal domain of DnaB mini-intein (IntC) was genetically fused at the N-terminus of rhGLP-1 to produce IntC-GLP-1. IntC-GLP-1 and N-terminal domain of DnaB mini-intein (IntN) protein were prepared in a denatured buffer of pH 8.0. IntC-GLP-1 was diluted 1:8 into the phosphate buffer of pH 6.6. IntN was added into the diluted solution of IntC-GLP-1 at the molar ratio of 1:2. Then, rhGLP-1 was released from IntC-GLP-1 via inducible C-terminal peptide-bond cleavage by shifting pH from 8.0 to 6.6 at 25 °C for 24-H incubation. Then, the supernatant was applied to a Ni-Sepharose column, and the pass through fraction was collected. About 5.34 mg of rhGLP-1 with the purity of 97% was obtained from 1 L of culture medium. Mass spectrometry showed the molecular weight of 3,300.45 Da, which was equal to the theoretical value of GLP-1/7-36. The glucose-lowering activity of rhGLP-1 was confirmed by the glucose tolerance test in mice. In conclusion, the reported method was an efficient strategy to produce rhGLP-1 without using enzyme or chemical reagents, which could also be used for other similar peptides.

A mutant of alpha-lactalbumin was expressed and purified, in which His32, Thr33, Glu49, Ile59, Val99, and Tyr103 were substituted by Leu32, Glu33, Asp49, Trp59, Asn99, and Ala103, respectively, to create a catalytic site of lysozyme in alpha-lactalbumin. The mutant catalyzed hydrolysis of the synthetic substrate, pNP-(NAcGlc)(3), with a K(M) and k(cat) of 0.160 +/- 0.00986 mmol/L and 3.39 +/- 0. 0456 x10(-5) min(-1), respectively, which was comparable with those of chicken lysozyme of 0.137 +/- 0.0153 mmol/L and 5.25 +/- 0.115 x10(-4) min(-1). By using the Isothermal Titration Calorimetre (ITC), the average binding enthalpy of the mutant or chicken lysozyme with the substrate (chitopentaose) was measured, which was 49.22 KJ/mol for the mutant and 105.47 KJ/mol for chicken lysozyme. In conclusion, the six point mutations occurring in alpha-lactalbumin could be converted into an enzyme that was 17.5-fold less efficient than chicken lysozyme but nevertheless capable of hydrolyzing the glycosidic bond.