B Cell Dysfunction Associated With Aging and Autoimmune Diseases

Impaired humoral responses, as well as an increased propensity for autoimmunity, play an important role in the development of immune system dysfunction associated with aging. Accumulation of a subset of atypical B cells, termed age-associated B cells (ABCs), is one of the key age-related changes in B cell compartments. ABCs are characterized by their distinct phenotypes, gene expression profiles, special survival requirements, variations in B cell receptor repertoires, and unique functions. Here, we summarize recent progress in the knowledge base related to the features of ABCs, their potential role in immune senescence, and their relationship with autoimmune diseases

Relationship between histone demethylase LSD family and development and prognosis of gastric cancer

Objectiveto elucidate the correlation between histone demethylase and gastric cancerResearch objecthistone demethylase and gastric cancerResultsAs one of the important regulatory mechanisms in molecular biology and epigenetics, histone modification plays an important role in gastric cancer including downstream gene expression regulation and epigenetics effect. Both histone methyltransferase and histone demethylases are involved in the formation and maintaining different of histone methylation status, which in turn through a variety of vital molecules and signaling pathways involved in the recognition of histone methylation modification caused by the downstream biological process, eventually participate in the regulation of chromatin function, and with a variety of important physiological activities, especially closely related to the occurrence of gastric cancer and embryonic development.ConclusionThis paper intends to review the research progress in this field from the aspects of histone methylation modification and the protein structure, catalytic mechanism and biological function of the important histone demethylases LSD1 and LSD2, in order to provide the theoretical reference for further understanding and exploration of histone demethylases in development and prognosis of gastric cancer

B cell intrinsic and extrinsic factors impacting memory recall responses to SRBC challenge

MBCs (MBCs) generated in T-dependent immune responses can persist for a lifetime and rapidly react upon secondary antigen exposure to differentiate into plasma cells (PCs) and/or to improve the affinity of their BCR through new rounds of hypermutation in germinal centers (GCs). The fate of a MBC in secondary immune reactions appears to depend upon multiple parameters, whose understanding is mandatory for the design of efficient vaccine strategies. We followed the behavior of MBCs in recall responses to SRBCs using an inducible AID fate mapping mouse model in which B cells engaged in a germinal center (GC) response are irreversibly labeled upon simultaneous tamoxifen ingestion and immunization. We used different schemes of mouse immunization and tamoxifen feeding in adoptive-transfer experiments of total splenic B cells into congenic mice that have been pre-immunized or not, to assess the contribution of the different effector subsets in a physiological competitive context. We were able to show that naive B cells can differentiate into GC B cells with kinetics similar to MBCs in the presence of previously activated T follicular helper (TFH) cells and a primed microenvironment. We also showed that MBCs are recruited into secondary GCs, together with naive B cells. In contrast, PC differentiation, which dominated secondary MBC responses, was not dependent upon a previous TFH activation. We observed that the presence of persisting germinal centers and circulating antibody levels are key factors determining the germinal center versus plasma cell fate in a recall response. Notably, disruption of persistent germinal center structures by a lymphotoxin beta-receptor fusion protein or a longer timing between the prime and the boost, which correlated with reduced antigen-specific immunoglobulin levels in serum, were two conditions with an opposite impact, respectively inhibiting or promoting a GC fate for MBCs. Altogether, these studies highlight the complexity of recall responses, whose outcome varies according to immunization contexts

Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort

Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens

Dynamic analysis on fluid-structure interaction of an elastically mounted square cylinder at low Reynolds numbers

Fluid-structure interaction of an elastically mounted rigid square cylinder of low non-dimensional mass immersed in fluid flow is investigated numerically in the Reynolds numbers range of 60≤Re≤250. The square cylinder is allowed to freely vibrate only in the transverse direction perpendicular to the incoming flow. The two-dimensional incompressible Reynolds-averaged Navier-Stokes equations are solved by the finite volume method for the fluid flow. The equation of motion is solved for the vibration of the square cylinder. The results show that abrupt both the frequency and amplitude ratios curves experience sudden change at Re=90 and 168, which marks the onset of the lock-in and galloping regime, respectively. Thus, four regimes can be divided in the present study and which are the initial regime, the lock-in regime, the lower branch and galloping regime. A local peak value is observed in the force coefficients curve and the maximum value is reached at Re=231. It is found that the peak oscillating amplitude of the lock-in regime is reached at 0.22D and the width of lock-in region with sharp corner is very narrow. In the galloping regime, the peak amplitude of the oscillating square cylinder is close to 0.70D at Re=231. Typical 2S vortex structure is observed in the initial regime, the lock-in regime, and the lower branch. While in the galloping regime, 2P, 2P+2S and more complicated vortex patterns are observed as Re increases

Enhancing the Antibacterial Properties and Biocompatibility of Ti-Cu Alloy by Roughening and Anodic Oxidation

Although Ti-Cu alloys have been shown to possess good antibacterial properties, they are still biologically inert. In this study, sandblasting and acid etching combined with anodic oxidation were applied to roughen the surface as well as to form a TiO2/CuO/Cu2O composite film, which would benefit both the antibacterial properties and the biocompatibility. The surface morphology, the phase composition, and the physicochemical properties were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Electrochemical testing and inductively coupled plasma spectrometry (ICP) were used to determine the corrosion resistance and Cu ion release, the plate counting method was used to evaluate the antibacterial performance, and the CCK-8 method was used to evaluate the cytocompatibility. It was revealed that a rough surface with densely porous double layer composed of TiO2/CuO/Cu2O was produced on Ti-Cu alloy surface after the combined surface modification, which enhanced the corrosion resistance significantly. The plate counting results demonstrated that the modified sample had strong long-term antibacterial performance (antibacterial rate > 99%), which was attributed to the formation of TiO2/CuO/Cu2O composite film. The cell compatibility evaluation results indicated that the surface modification improved the cytocompatibility. It was demonstrated that the combined modification provided very strong antibacterial ability and good cytocompatiblity, potentially making it a good candidate surface modification technique for Ti-Cu alloy for biomedical applications

ZnS-embedded porous carbon for peroxydisulfate activation: Enhanced electron transfer for bisphenol A degradation

Transition metal sulfides have garnered increasing attention for their role in persulfate activation, a crucial process in environmental remediation. However, the function of metal sulfides without reversible valence changes, such as ZnS, remains largely unexplored in this context. Here we report ZnS-embedded porous carbon (ZnS-C), synthesized through the pyrolysis of Zn-MOF-74 and dibenzyl disulfide. ZnS-C demonstrates remarkable activity in activating peroxydisulfate (PDS) across a wide pH range, enabling the efficient mineralization removal of bisphenol A (BPA). Through electrochemical investigation and theoretical simulations of charge density distributions, we unveil that the electron transfer from BPA to PDS mediated by the ZnS-C catalyst governs the reaction. This study, both in theory and experiment, demonstrates metal sulfide as electron pump that enhances electron transfer efficiency in PDS activation. These findings redefine the role of metal sulfide catalysts, shedding new light on their potential for regulating reaction pathways in PDS activation processes

THQ–Xanthene: An Emerging Strategy to Create Next‐Generation NIR‐I/II Fluorophores

Abstract Near‐infrared fluorescence imaging is vital for exploring the biological world. The short emissions (100 nm) for THQ‐modified xanthene dyes is established. Thus, a timely discussion of THQ–xanthene and its applications is extensive. Hence, the advent, working principles, development trajectory, and biological applications of THQ–xanthene dyes, especially in the fields of fluorescence probe‐based sensing and imaging, cancer theranostics, and super‐resolution imaging, are introduced. It is envisioned that the THQ modification tactic is a simple yet exceptional approach to upgrade the performance of conventional xanthene dyes. THQ–xanthene will advance the strides of xanthene‐based potentials in early fluorescent diagnosis of diseases, cancer theranostics, and imaging‐guided surgery

The effects of triclosan on pluripotency factors and development of mouse embryonic stem cells and zebrafish.

Triclosan (TCS) poses potential risks to reproduction and development due to its endocrine-disrupting properties. However, the mechanism of TCS's effects on early embryonic development is little known. Embryonic stem cells (ESC) and zebrafish embryos provide valuable models for testing the toxic effects of environmental chemicals on early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their morphology was evaluated. In mESC, alkaline phosphatase staining was significantly decreased after treatment with the highest concentration of TCS (50 μM). Although the expression levels of Sox2 mRNA were not changed, the mRNA levels of Oct4 and Nanog in TCS-treated groups were significantly decreased compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an expression inhibitor of pluripotency markers, was significantly increased in TCS-treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls had developed to the late stage of somitogenesis, while embryos exposed to 300 μg/L of TCS were still at the early stage of somitogenesis, and three genes (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the controls. The two models demonstrated that TCS may affect early embryonic development by disturbing the expression of the pluripotency markers (Oct4, Sox2 and Nanog)