Regulatory T 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 coronavirus disease 2019 (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 T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of 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 concerted nAb responses, which are shaped by both Treg and Tfh cells.

ELAVL1 regulates glycolysis in nasopharyngeal carcinoma cells through the HMGB3/ß-catenin axis.

BACKGROUND: The role of ELAVL1 in the progression of various tumors has been demonstrated. Our research aims to investigate how ELAVL1 controls the glycolytic process in nasopharyngeal carcinoma cells through the HMGB3/ß-catenin pathway. METHODS: The expression of ELAVL1 was detected in clinical tumor samples and nasopharyngeal carcinoma cell lines. A subcutaneous tumor model was established in nude mice to investigate the role of ELAVL1 in tumor progression. The relationship between HMGB3 and ELAVL1 was validated by RNA pull down and RIP assays. TOPFlash/FOPFlash reporter assay was used to detect ß-catenin activity. Assay kits were utilized to measure glucose consumption, lactate production, and G6PD activity in nasopharyngeal carcinoma cells. Western blot was conducted to detect the expression of glycolysis-related proteins. The glycolytic capacity was analyzed through extracellular acidification rate (ECAR). RESULTS: In both clinical samples and nasopharyngeal carcinoma cell lines, the expression levels of ELAVL1 mRNA and protein were found to be upregulated. Knockdown of ELAVL1 significantly inhibited the in vivo proliferation of nasopharyngeal carcinoma and suppressed the glycolytic capacity of nasopharyngeal carcinoma cells. ELAVL1 interacts with HMGB3, leading to an increase in the stability of HMGB3 mRNA. Overexpression of HMGB3 elevated the reduced ß-catenin activity caused by sh-ELAVL1 and reversed the inhibitory effect of sh-ELAVL1 on cellular glycolytic capacity. Treatment with ß-catenin inhibitor (FH535) effectively suppressed the promotion of glycolytic capacity induced by HMGB3 overexpression. CONCLUSIONS: ELAVL1 promotes glycolysis in nasopharyngeal carcinoma cells by interacting with HMGB3 to stabilize HMGB3 mRNA, thereby activating ß-catenin pathway. Therefore, targeting the ELAVL1-HMGB3-ß-catenin axis has the potential to be a novel approach for treating nasopharyngeal carcinoma.

Evaluation of sediment phosphorus dynamics in cascade reservoir systems: A case study of Weiyuan River, China.

Reservoirs tend to accumulate phosphorus (P) originating from agriculture, industry, and other upstream sources in sediment, with this stored P later released. However, the spatiotemporal dynamics of sediment P release in reservoirs remains unclear. This study investigated the spatiotemporal dynamics in P of the sediment and water of three cascade reservoirs in the Weiyuan River (Tuojiang tributary). The results showed elevated P in sediment [total P (TP): 1208.93 mg kg-1] and water (TP: 0.23 mg L-1) during the low-water season (LWS), which could be attributed to notably higher organic matter content (9.65%), finer particle size (20.95 µm), and extended hydraulic retention time (HRT: 13.13 days) downstream of the cascade reservoirs. Further study employing static in-situ diffusive gradient in thin films (DGT) and dynamic ex-situ adsorption kinetic experiments confirmed that the downstream release of P from sediments [diffusion flux (Fd): 1.67 mg m-2 d-1, equilibrium P concentrations (EPC0): 0.22 ± 0.10 mg L-1] greatly exceeded those upstream (-0.66 ± 0.17 mg m-2 d-1, 0.07 ± 0.001 mg L-1), Fe (II) was a critical factor in regulating sedimentary P release. The combined effects of high P in overlying water and sediment significantly stimulated downstream phytoplankton growth, particularly among cyanobacteria (26.48%) and green algae (8.33%). Further regulatory steps are needed to regulate LWS algal blooms downstream of cascade reservoirs.

[The role and the molecular mechanism of abietic acid in the proliferation, invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells].

Objective:To investigate the effects and molecular mechanisms of abietic acid in the cell proliferation, invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells. Methods:①Cisplatin-resistant C666/DDP cell line was constructed by increasing drug concentration method. ②The effects of abietic acid on proliferation, invasion and migration of C666/DDP cells were investigated by CCK-8 method, reactive oxygen species（ROS） and mitochondrial membrane potential（MMP） level assay and subcutaneous tumorigenesis assay in nude mice to detect the effects of abietic acid on proliferation and apoptosis of C666/DDP cells in vitro and in vivo. The effect of abietic acid on the proliferation and apoptosis of C666/DDP cells in vitro and in vivo was measured by Transwell assay. ③Western blot and IHC method to detect the expression of PI3K/AKT/mTOR pathway related proteins. Results:①The IC50 of cisplatin cytotoxicity to C666-1 was about 25 µmol/L. RI=25 µmol/L /4 µmol/L=6.25, resistance was obtained, and the C666-1-DDP resistant strain was successfully constructed. ②Abietic acid promoted apoptosis and inhibited proliferation of C666/DDP cells, and showed G2/M phase block; transwell showed that abietic acid inhibited C666/DDP cell migration and invasion, increased ROS level of C666/DDP cells and decreased MMP. Transwell showed that abietic acid inhibited the migration and invasion ability of C666/DDP cells, increased the ROS level of C666/DDP cells and decreased MMP. ③Animal experiments showed that abietic acid inhibited the proliferation of cisplatin-resistant nasopharyngeal carcinoma in vivo in a concentration gradient and suppressed the expression of PI3K/AKT/mTOR signaling pathway-related proteins. Conclusion:Abietic acid inhibits proliferation, invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells by a mechanism related to inhibition of PI3K/AKT/mTOR signaling pathway.

The influence of redox potential on phosphorus release from sediments in different water bodies.

Anthropogenic activities have significantly enriched P in sediments of many water bodies, with redox potential (Eh) being a key factor in controlling P adsorption or release.This study evaluates the impact of Eh on P release from sediments in the Weiyuan River, Honghu Lake, and Bao'enqiao Reservoir using reactor experiments. P speciation was further analyzed through SEDEX method. Results show that within an Eh range of -300 mV to +230 mV, more P is released from sediments into the water column. The P fractions CDB-P and Fe(II)-P exhibit the most significant changes, especially in reservoir sediments where ΔCDB-P (85.5 mg/kg) and ΔFe(II)-P (80.6 mg/kg) are the highest among the three water bodies, followed by lake sediments. Additionally, after redox oscillation, the EPC0 of lake and reservoir sediments increased to 16.2 and 18.8 times their initial values, respectively, significantly raising the risk of eutrophication.

m6A modification-mediated BATF2 suppresses metastasis and angiogenesis of tongue squamous cell carcinoma through inhibiting VEGFA.

The aim is to explore the underlying mechanism of basic leucine zipper ATF-like transcription factor 2 (BATF2) in tongue squamous cell carcinoma (TSCC). The expression of BATF2 in TSCC tissues and corresponding adjacent normal TSCC tissues, human TSCC cell lines (SCC-15 and CAL-27) and human normal tongue epithelial cells NTEC was detected. Then, SCC-15 cells with stable BATF2 knockdown and CAL-27 cells with BATF2 overexpression were established to investigate the functional effect of BATF2 on TSCC. Thereafter, the effect of BATF2 on TSCC angiogenesis and BATF2 m6A methylation was also examined. BATF2 was significantly downregulated in TSCC tissues and cell lines, and BATF2 overexpression could suppress growth, metastasis and angiogenesis of TSCC. Mechanistically, vascular endothelial growth factor A (VEGFA) was identified as a downstream gene of BATF2, and it was confirmed that BATF2 suppressed growth, metastasis and angiogenesis of TSCC via inhibiting VEGFA. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA mediated by METTL14 suppressed its expression in TSCC. METTL14/BATF2 axis could serve as a novel promising therapeutic candidate against angiogenesis for TSCC.

Impact of river dams on phosphorus migration: a case of the Pubugou Reservoir on the Dadu River in China.

Reservoirs in agricultural catchments retain large proportions of inflowing phosphorus (P). However, the effects of reservoirs on the P cycle and related biogeochemical processes remain unclear. Therefore, this study investigated the degree to which a typical river-transition-reservoir in Southwest China retains both inflowing particulate phosphorus (PP) and dissolved total phosphorus (DTP) and various forms of P in sediments over different water seasons [normal-water season (NWS), low-water season (LWS), and high-water season (HWS)]. The proportions of inflowing PP and DTP retained were 37% and 27%, respectively. This result could be attributed to the absorption of DTP by the large load of intercepted sediment in the dam and the interception of PP itself. The rank of water seasons in terms of the proportion and load of inflowing TP retained was LWS (79%, 336 t P yr-1) > NWS (21%, 43 t P yr-1) > HWS (4%, 27 t P yr-1), which might be due to the high P concentration 0.78 mg L-1 and long hydraulic retention time (HRT) 780 d during the LWS. In the long-term, there was a high rate of retention of bioavailable phosphorus (BAP) in sediments (63%). This result could be attributed to the combined effect of fine sediment particles and organic matter (OM). In addition, HRT (R2 = 0.89, p < 0.05) affected the retention of P more significantly than P concentration (R2 = 0.56, p < 0.05). Dam interception during the LWS resulted in high BAP contents (280 mg kg-1) in sediments, high P concentrations (0.78 mg L-1), and weak hydrodynamics (HRT: 780 d) in overlying water. Therefore, further regulatory measures are urgently demanded during the LWS to prevent reservoir algal blooms.

Effects of non-invasive brain stimulation on walking and balance ability in Parkinson's patients: A systematic review and meta-analysis.

Objective: To investigate and contrast the effects of non-invasive brain stimulation (NIBS), including repeated transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), on walking and balance ability in patients with Parkinson's disease (PD). Methods: The PubMed, Embase, Medline, Cochrane, CNKI, and Chinese WanFang databases were searched up to June 2022. Quality assessment was performed using the Cochrane Collaboration's risk-of-bias guidelines, and the standardized mean differences (SMD) or mean differences (MD) for each outcome were calculated. Results: Among 32 eligible studies, including 1,586 participants were analyzed in this meta-analysis. The results of the meta-analysis showed that NIBS was effective in improving UPDRS-III scores (MD = -2.07; 95% CI, -2.62 to -1.53; P < 0.00001; I 2 = 6%) and variables associated with the ability of walk such as step width (SMD = 0.35; 95% CI, 0.16-0.55; P = 0.0005; I 2 = 38%), cadence (SMD = 0.3; 95% CI, 0.05 to 0.55; P = 0.02; I 2 = 25%), and 6MWT (MD = 62.86; 95% CI, 39.43-86.29; P < 0.00001; I 2 = 0%). In subgroup analyses across intervention types, UPDRS-III scores (rTMS: MD = -2.54; 95% CI, -3.16 to -1.92; P < 0.00001; I 2 = 0%; tDCS: MD = -1.20; 95% CI, -1.99 to -0.40; P = 0.003; I 2 = 0%) and TUGT time (rTMS: MD = -4.11; 95% CI, -4.74 to -3.47; P < 0.00001; I 2 = 0%; tDCS: MD = -0.84; 95% CI, -1.48 to -0.21; P = 0.009; I 2 = 0%) significantly improved. Moreover, our results also showed that compared to tDCS, rTMS was more significant in improving UPDRS-III scores and TUGT time (p < 0.05). Conclusion: NIBS benefits some walking ability variables but not balance ability in 36 patients with PD. The rTMS significantly improved UPDRS-III scores and TUGT time compared to tDCS. Further studies are needed to determine the optimal protocol and to illuminate effects based on the ideal target brain regions, stimulation intensity, timing, and type of intervention. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022350782.

[Comparison of acellular dermal allograft and tragus cartilage perichondrium in type â tympanoplasty under otoendoscopy].

Objective:To compare the therapeutic effect of otoendoscopic tympanoplasty with acellular dermal allograft（AlloDerm） and tragus cartilage perichondrium. Method:121 patients who underwent type Ⅰ tympanoplasty under otoscope were retrospectively analyzed. According to the grafts used, they were divided into two groups: AlloDerm group （56 cases） and tragus cartilage perichondrium group （65 cases）. The operative time, postoperative tympanic membrane healing rate, and hearing recovery were compared between two groups. The follow-up time was twelve months. Result:The operative time in the AlloDerm group were lower than those in the tragus cartilage perichondrium group（P<0.05）. The successful closure rates between the acellular dermal allograft group and tragus cartilage perichondrium group at 1-month follow-up were 92.86% and 92.31% respectively, while the closure rates between two groups at 6-month follow-up were drop to 91.07% and 90.77% respectively, the closure rates between two groups at 12-month follow-up were also 91.07% and 90.77% respectively,the was no statistically difference between two groups（P>0.05）. The difference in pre-and post-operative air bone gap（ABG） values between two groups was no statistically significant（P>0.05）. Conclusion:Both the AlloDerm and the tragus cartilage perichondrium tympanoplasty can achieve satisfactory healing rate of the tympanic membrane and audiologic improvement. However, AlloDerm has a short operation time, no need to obtain materials and less trauma, and is worth of promotion and application.

Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein-Barr virus associated nasopharyngeal carcinoma.

Exosomes have emerged as novel vehicles for proteins and other contents in cancer progression. Cyclophilin A (CYPA) is a pivotal member of immunophilin family. Whether CYPA can be detected in sera of nasopharyngeal carcinoma (NPC) patients remains to be explored. Epstein-Barr virus (EBV) is the first identified human tumor virus and is a causative agent of NPC. The antibody of EBV capsid antigen immunoglobulin A (EBV-VCA-IgA) is a known biomarker of NPC, with a proportion of no more than 70% being detected positively. Hence, novel biomarkers need to be discovered for early diagnosis, prognosis, and monitoring of EBV-associated NPC. A total of 110 NPC and 36 normal control serum samples were collected. Exosomes from these samples were extracted. The mRNA and protein expression levels of the above samples were validated by reverse transcription -quantitative polymerase chain reaction, Western blotting, or enzyme-linked immunosorbent assay (ELISA). Finally, the results demonstrated that both the serum and exosomal CYPA levels of NPC patients were significantly higher than that of normal cases. In addition, exosomal CYPA had a much higher level than that in the whole sera. The positive rate of EBV-VCA-IgA antibody was 68.2% in NPC sera, and noticeably, among the cases with EBV-VCA-IgA negative, 80% of them presented high levels of CYPA above the standard (cutoff value). In particular, CYPA in exosomes was uniformly with higher significance than that in whole sera. Combined analysis of CYPA protein and EBV-VCA-IgA antibody showed a greatly higher discriminatory ability in diagnosis of NPC. Moreover, exosomal CYPA level had a positive correlation with that of the EBV-encoded latent membrane protein 1 (LMP1) in exosomes. EBV-positive cancer cells secreted significantly higher levels of exosomal CYPA. This study established the utility of circulating exosomal CYPA as a potential noninvasive diagnostic biomarker for EBV-associated NPC.

Targeting Exosomal EBV-LMP1 Transfer and miR-203 Expression via the NF-κB Pathway: The Therapeutic Role of Aspirin in NPC.

Nasopharyngeal carcinoma (NPC) is an invasive head-and-neck tumor with Epstein-Barr virus (EBV) as an important etiological cause. The EBV oncoprotein Latent membrane protein 1 (LMP1) can be trafficked into exosomes with unclear roles, and this trafficking is a potential problem in NPC control. MicroRNA-203 (miR-203) was found by us to be downregulated by LMP1, and it functions as a tumor suppressor in NPC. In this study, aspirin reversed the epithelial-mesenchymal transition (EMT) by promoting miR-203 expression in cells, and, remarkably, it repressed exosomal LMP1 (exo-LMP1) secretion from EBV-positive cells. Nuclear factor κB (NF-κB) activation was required for the exo-LMP1 production. The exo-LMP1 uptake influenced the EMT potential of EBV-negative recipient NPC cells. The exo-LMP1 level was upregulated in clinical NPC plasma samples. Aspirin treatment observably inhibited NPC lung metastasis in nude mice. The study revealed that aspirin is a promising drug for NPC therapy via its targeting of exo-LMP1 transfer and the regulatory effect of LMP1 on miR-203 expression. EBV can regulate its own tumorigenesis via the LMP1/NF-κB/exo-LMP1 axis, opening a new avenue for understanding the pathogenesis of this tumor virus. Our study also provides a rationale for the use of exo-LMP1 or exosomal miR-203 (exo-miR203) in EBV-targeted therapy by aspirin in invasive NPC.

[The expression and clinical significance of BATF2 in oral tongue squamous cell carcinoma].

OBJECTIVES: To investigate the expression and clinical significance of BATF2 in the oral tongue squamous cell carcinoma (OTSCC). METHODS: Expression of BATF2 mRNA and protein in 16 paired OTSCC tissues and adjacent non-tumor mucosa were examined using quantitative PCR, western blotting analysis and immunohistochemistry assays, and the relation between BATF2 expression and clinical pathologic factor and prognosis was analyzed. RESULTS: In 16 paired tissues, expression of BATF2 mRNA in 13 OTSCC tissues and expression of BATF2 protein in 14 OTSCC tissues were significantly lower than that in adjacent non-tumor mucosa. In 202 paraffin-embedded OTSCC samples, BATF2 was not expressed in 20 cases (9.9%), low expressed in 104 cases (51.5%) and highly expressed in 78 (38.6%). BATF2 expression level was significantly correlated with histological differentiation (P = 0.002). Patients with low BATF2 expression had significantly poorer overall survival and disease-free survival than those with high BATF2 expression (P < 0.001). CONCLUSIONS: BATF2 was low expressed in OTSCC and related to tumor differentiation and prognosis and may serve as a prognostic biomarker and potential therapeutic target for this disease.

Decreased expression of BATF2 is significantly associated with poor prognosis in oral tongue squamous cell carcinoma.

BATF2, also called SARI, is associated with several cancer types, and loss of BATF2 expression is frequently detected in aggressive and metastatic cancers. The expression of BATF2 was previously shown to slow the growth rate of malignant tumor cells injected into athymic nude mice, and decreased expression of BATF2 has been correlated to poor prognosis in hepatocellular carcinoma. However, the functional role of BATF2 in oral tongue squamous cell carcinoma (OTSCC) remains unknown. In the present study, we examined BATF2 expression in 16 fresh, paired OTSCC and adjacent non-tumor tissues, as well as in a normal tongue epithelial cell line and in 5 OTSCC cell lines by quantitative PCR and western blot analysis. We also evaluated BATF2 expression in 202 paraffin­embedded OTSCC and 30 adjacent non-tumor samples by immunohistochemistry, and its relationship with clinicopathological features and prognosis was investigated. We found that BATF2 expression was significantly reduced in the majority of the 16 OTSCC tumor tissues and the 5 OTSCC cell lines when compared with the non-tumor tissues and the normal tongue epithelial cell line, respectively. Consistent with these results, our immunohistochemistry analysis revealed that decreased BATF2 expression was present in 124 of the 202 cases and was significantly correlated with poor tumor differentiation (P=0.002). Patients with decreased BATF2 expression showed reduced survival when compared to those with high expression (P<0.001). Multivariate analysis revealed that BATF2 expression is an independent predictor of overall survival (P=0.001). These results demonstrate that BATF2 plays a tumor-suppressor role in the development of OTSCC and that BATF2 may serve as a prognostic biomarker and potential therapeutic target for this disease.

[Epidemiology investigation of allergic rhinitis in urban and rural areas of Ningbo and Yongzhou].

OBJECTIVE: To investigate the epidemiological characteristics of allergic rhinitis (AR) in urban and rural areas of Ningbo and Yongzhou. METHOD: Fifteen fields in the two cities from October 2006 to June 2007 were randomly selected. Cases suspected with symptoms of AR by a self-administered and interview questionnaire were recommended to special examinations for confirmed diagnosis. RESULT: 1. A total of 9969 individuals from 3803 families were surveyed, of whom 303 suffered with AR. 2. The prevalence rate was 4.10% in Ningbo and 1.65% in Yongzhou (the sex-adjusted rate was 4.10% and 1.64% respectively, and the age-adjusted rate was 4.33% and 1.58%); the population of island inhabitants had the lowest prevalence rate of 0.73%. 3. The prevalence rate in patients with asthma and that with family genetic history was 8% and 12% respectively. CONCLUSION: It demonstrates that the prevalence rate is higher in Ningbo than in Yongzhou, in urban than in rural and in adolescent than in other ages. Allergic rhinitis may be associated with asthma and related to genetic factors. Allergic rhinitis may be curable.