TREG cells and CXCR3+ circulating TFH cells concordantly shape the neutralizing antibody responses in individuals who have recovered from mild COVID-19.

Regulatory T (TREG) cells are involved in the antiviral immune response in patients with COVID-19; however, whether TREG cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of TREG cells and lower frequencies of CXCR3+ circulating TFH (cTFH) cells than healthy controls. Furthermore, TREG and CXCR3+ cTFH cells were negatively and positively correlated with the nAb responses, respectively, and TREG cells was inversely associated with CXCR3+ cTFH cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, TREG cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTFH cells, especially CXCR3+ cTFH cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits a concerted nAb responses which are shaped by both TREG and TFH cells.

SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals.

Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb) and B cell differentiation are tightly regulated by T follicular help (TFH) cells. However, the longevity and functional role of TFH cell subsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection and inactivated vaccine elicited both spike-specific CXCR3+ TFH cell and CXCR3- TFH cell responses, which showed distinct response patterns. Spike-specific CXCR3+ TFH cells exhibit a dominant and more durable response than CXCR3- TFH cells that positively correlated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3+ TFH cell subset induced by two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells have a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3- TFH cells. In conclusion, the persistent and functional role of spike-specific CXCR3+ TFH cells following SARS-CoV-2 infection and vaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. The findings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immune memory.

Synthesis and biological evaluation of substituted 3-(2'-benzimidazolyl)coumarin platinum(II) complexes as new telomerase inhibitors.

Eight new platinum(II) complexes Pt1-Pt8 with substituted 3­(2'­benzimidazolyl) coumarins were successfully synthesized and characterized by single crystal X-ray diffraction analysis, nuclear magnetic resonance spectroscopy (NMR), electrospray ionization-mass spectrometry (ESI-MS), infrared spectrophotometry (IR) and elemental analysis. Crystallographic data of these Pt1-Pt8 complexes showed that the Pt(II) has distorted four-coordinated square planar geometry. Pt1-Pt8 were found to display high cytotoxic activity in vitro against the cisplatin-resistant SK-OV-3/DDP cancer cells with a low IC50 from 1.01-10.32 µM, but low cytotoxicity on the normal HL-7702 cells. Further studies revealed that Pt1-Pt3 induced apoptosis in SK-OV-3/DDP cancer cells via mitochondria dysfunction signaling pathways. Our findings also indicated that Pt1 was a telomerase inhibitor targeting c-myc promoter elements.

Lipase-immobilized biocatalytic membranes for biodiesel production.

Microbial lipase from Candida rugosa (Amano AY-30) has good transesterification activity and can be used for biodiesel production. In this study, polyvinylidene fluoride (PVDF) membrane was grafted with 1,4-diaminobutane and activated by glutaraldehyde for C. rugosa lipase immobilization. After immobilization, the biocatalytic membrane was used for producing biodiesel from soybean oil and methanol via transesterification. Response Surface Methodology (RSM) in combination with a 5-level-5-factor central composite rotatable design (CCRD) was employed to evaluate the effects of reaction time, reaction temperature, enzyme amount, substrate molar ratio and water content on the yield of soybean oil methyl ester. By ridge max analysis, the predicted and experimental yields under the optimum synthesis conditions were 97% and 95%, respectively. The lipase-immobilized PVDF membrane showed good reuse ability for biodiesel production, enabling operation for at least 165 h during five reuses of the batch, without significant loss of activity.