Anti-CD20 treatment attenuates Th2 cell responses: implications for the role of lung follicular mature B cells in the asthmatic mice.

BACKGROUND: B cells were believed to act as antigen-presenting cells (APCs) to promote T helper type 2 (Th2) cell responses. However, the role of lung B cells and its subpopulations in Th2 cell responses in asthma remains unclear. OBJECTIVE: We leveraged an anti-CD20 monoclonal antibody (mAb) treatment that has been shown to selectively deplete B cells in mice and investigated whether this treatment modulates Th2 cell responses and this modulation is related to lung follicular mature (FM) B cells in a murine model of asthma. METHODS AND RESULTS: We used a house dust mite (HDM)-induced asthma mouse model and found that anti-CD20 mAb treatment attenuates Th2 cell responses. Meanwhile, anti-CD20 mAb treatment did dramatically reduce the number of B cells, especially FM B cells in the lungs, but did not impact the frequency of other immune cell types, including lung T cells, dendritic cells, natural killer cells, and regulatory T cells in wild-type mice. Moreover, we found that the suppressive effect of anti-CD20 mAb treatment on Th2 cell responses could be reversed upon adoptive transfer of lung FM B cells, but not lung CD19+ B cells without FM B cells in asthmatic mice. CONCLUSIONS: These findings reveal that anti-CD20 mAb treatment alleviates Th2 cell responses, possibly by depleting lung FM B cells in a Th2-driven asthma model. This implies a potential therapeutic approach for asthma treatment through the targeting of lung FM B cells.

The Antiproliferative and Proapoptotic Effects of Cucurbitacin B on BPH-1 Cells via the p53/MDM2 Axis.

Cucurbitacin B (Cu B), a triterpenoid compound, has anti-inflammatory and antioxidant activities. Most studies only focus on the hepatoprotective activity of Cu B, and little effort has been geared toward exploring the effect of Cu B on the prostate. Our study identified that Cu B inhibited the proliferation of the benign prostatic hyperplasia epithelial cell line (BPH-1). At the molecular level, Cu B upregulated MDM2 and thrombospondin 1 (THBS1) mRNA levels. Immunocytochemistry results revealed that the protein expressions of p53 and MDM2 were upregulated in BPH-1 cells. Furthermore, Cu B upregulated THBS1 expression and downregulated COX-2 expression in the BPH-1 cell supernatant. Altogether, Cu B may inhibit prostate cell proliferation by activating the p53/MDM2 signaling cascade and downregulating the COX-2 expression.

Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation.

Background: It is unclear what the causal relationship is between the gut microbiota and sepsis. Therefore, we employed Mendelian randomization (MR) to determine whether a causal link exists between the two. Methods: This study used publicly available genome-wide association studies (GWAS) summary data of gut microbiota, sepsis, sepsis (critical care), and sepsis (28-day death in critical care) to perform a two-sample MR analysis. To ensure the robustness of the results, we also conducted a sensitivity analysis. Results: For sepsis susceptibility, inverse variance weighted (IVW) estimates revealed that Victivallales (OR = 0.86, 95% CI, 0.78-0.94, p = 0.0017) was protective against sepsis, while Lentisphaerae (OR = 0.89, 95% CI, 0.80-0.99), Gammaproteobacteria (OR = 1.37, 95% CI, 1.08-1.73), Clostridiaceae1 (OR = 1.21, 95% CI, 1.04-1.40), RuminococcaceaeUCG011 (OR = 1.10, 95% CI, 1.01-1.20), Dialister (OR = 0.85, 95% CI, 0.74-0.97), and Coprococcus2 (OR = 0.81, 95% CI, 0.69-0.94) presented a suggestive association with the development of sepsis (all p < 0.05). For sepsis (critical care), IVW estimates indicated that Lentisphaerae (OR = 0.70, 95% CI, 0.53-0.93), Victivallales (OR = 0.67, 95% CI, 0.50-0.91), Anaerostipes (OR = 0.49, 95% CI, 0.31-0.76), LachnospiraceaeUCG004 (OR = 0.51, 95% CI, 0.34-0.77), and Coprococcus1 (OR = 0.66, 95% CI, 0.44-0.99) showed a suggestive negative correlation with sepsis (critical care) (all p < 0.05). For sepsis (28-day death in critical care), IVW estimates suggested that four bacterial taxa had a normally significant negative correlation with the risk of sepsis-related death, including Victivallales (OR = 0.54, 95% CI, 0.30-0.95), Coprococcus2 (OR = 0.34, 95% CI, 0.14-0.83), Ruminiclostridium6 (OR = 0.43, 95% CI, 0.22-0.83), and Coprococcus1 (OR = 0.45, 95% CI, 0.21-0.97), while two bacterial taxa were normally significantly positively linked to the risk of sepsis-related death, namely, Mollicutes (OR = 2.03, 95% CI, 1.01-4.08) and Bacteroidales (OR = 2.65, 95% CI, 1.18-5.96) (all p < 0.05). The robustness of the above correlations was verified by additional sensitivity analyses. Conclusion: This MR research found that several gut microbiota taxa were causally linked to the risk of sepsis, sepsis in critical care, and sepsis-related 28-day mortality in critical care.

Neural correlates of impaired learning and recognition of novel faces in mild cognitive impairment.

OBJECTIVE: Face memory impairment significantly affects social interactions and daily functioning in individuals with mild cognitive impairment (MCI). While deficits in recognizing familiar faces among individuals with MCI have been reported, their ability to learn and recognize unfamiliar faces remains unclear. This study examined the behavioral performance and event-related potentials (ERPs) of unfamiliar face memorization and recognition in MCI. METHODS: Fifteen individuals with MCI and 15 healthy controls learned and recognized 90 unfamiliar neutral faces. Their performance accuracy and cortical ERPs were compared between the two groups across the learning and recognition phases. RESULTS: Individuals with MCI had lower accuracy in identifying newly learned faces than healthy controls. Moreover, individuals with MCI had reduced occipitotemporal N170 and central vertex positive potential responses during both the learning and recognition phases, suggesting impaired initial face processing and attentional resources allocation. Also, individuals with MCI had reduced central N200 and frontal P300 responses during the recognition phase, suggesting impaired later-stage face recognition and attention engagement. CONCLUSION: These findings provide neurobehavioral evidence for impaired learning and recognition of unfamiliar faces in individuals with MCI. SIGNIFICANCE: Individuals with MCI may have face memory deficits in both early-stage face processing and later-stage recognition .

Ferroelectric Order Evolution in Freestanding PbTiO3 Films Monitored by Optical Second Harmonic Generation.

The demand for low-dimensional ferroelectric devices is steadily increasing, however, the thick substrates in epitaxial films impede further size miniaturization. Freestanding films offer a potential solution by eliminating substrate constraints. Nevertheless, it remains an ongoing challenge to improve the stability in thin and fragile freestanding films under strain and temperature. In this work, the structure and ferroelectric order of freestanding PbTiO3 (PTO) films are investigated under continuous variation of the strain and temperature using nondestructive optical second harmonic generation (SHG) technique. The findings reveal that there are both out-of-plane and in-plane domains with polarization along out-of-plane and in-plane directions in the orthorhombic-like freestanding PTO films, respectively. In contrast, only out-of-plane domains are observed in the tetragonal epitaxial PTO films. Remarkably, the ferroelectricity of freestanding PTO films is strengthened under small uniaxial tensile strain from 0% up to 1.66% and well-maintained under larger biaxial tensile strain up to 2.76% along the [100] direction and up to 4.46% along the [010] direction. Moreover, a high Curie temperature of 630 K is identified in 50 nm thick freestanding PTO films by wide-temperature-range SHG. These findings provide valuable understanding for the development of the next-generation electronic nanodevices with flexibility and thermostability.

Age-related differences in long-term potentiation-like plasticity and short-latency afferent inhibition and their association with cognitive function.

Background: The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood. Aims: To reveal the differences in long-term potentiation (LTP)-like plasticity and short-latency afferent inhibition (SAI) between older and younger individuals, alongside their correlation with cognitive function using transcranial magnetic stimulation (TMS). Methods: The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80. All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS. Cognitive function assessments included evaluations of global cognitive function, language, memory and executive function. The neurophysiological assessment included LTP-like plasticity and SAI. Results: The findings of this study revealed a decline in LTP among the older adults compared with the younger adults (wald χ2=3.98, p=0.046). Subgroup analysis further demonstrated a significant reduction in SAI level among individuals aged 70-80 years in comparison to both the younger adults (SAI(N20): (t=-3.37, p=0.018); SAI(N20+4): (t=-3.13, p=0.038)) and those aged 60-70 (SAI(N20): (t=-3.26, p=0.025); SAI(N20+4): (t=-3.69, p=0.006)). Conversely, there was no notable difference in SAI level between those aged 60-70 years and the younger group. Furthermore, after employing the Bonferroni correction, the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function (r=0.61, p<0.001) in the younger group remained statistically significant. Conclusions: During the normal ageing process, a decline in synaptic plasticity may precede cholinergic system dysfunction. In individuals over 60 years of age, there is a reduction in LTP-like plasticity, while a decline in cholinergic system function is observed in those over 70. Thus, the cholinergic system may play a vital role in preventing cognitive decline during normal ageing. In younger individuals, LTP-like plasticity might represent a potential neurophysiological marker for language function.