Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.

Prevalence and risk factors of anal human papillomavirus infection among men with anal condyloma acuminata by HIV status in ShenZhen, Southeast China: A retrospective cohort study.

Patients with anal condyloma acuminatum (CA) are at risk of developing anal cancer which is associated with oncogenic human papillomavirus (HPV) infection. Investigation of anal HPV prevalence and risk factors can provide effective strategies for the prevention of anal cancer. A retrospective study was conducted among 549 patients with anal CA in the Third People's Hospital of Shenzhen between January 2019 and October 2021. HPV prevalence and HIV antibodies were detected by fluorescent PCR and ELISA, respectively. Logistic regression model and structural equation modeling (SEM) were conducted to analyzed the risk factors of oncogenic HPV infection. The overall prevalence of HPV was 96.72%. Both HPV6 (N = 285, 51.91%) and HPV11 (N = 300, 54.64%) were more than half infected and the most frequent Hr-HPV genotype was HPV16 (N = 138, 25.14%). HIV-positive (AOR: 5.02, 95% CI: 2.98-8.60, p < 0.0001) and history of syphilis (AOR: 4.24, 95% CI: 2.31-8.46, p < 0.0001) were independent risk factors statistically associated with oncogenic HPV infection. Ever had anal sex (AOR: 3.40, 95% CI: 1.28-11.81, p = 0.0267) and age 35 years and older (AOR: 2.79, 95% CI: 1.53-5.15, p = 0.0009) were associated with HPV16 and HPV52, respectively. SEM analyses showed that HIV-positive (b = 1.549, p < 0.001) and history of syphilis (b = 1.450, p < 0.001) had significant positive effects on oncogenic HPV infection. Ever had anal sex (b = 1.243, p = 0.025) and Age (b = 0.043, p = 0.002) positively drived HPV16 and HPV52 infection, respectively. Anal CA patients who are HIV-positive, have a history of syphilis, or at least 35 years old should be considered for Hr-HPV, cytology and other anal cancer related tests to reduce the risk of cancer development.

The performance of electrode ultrafiltration membrane bioreactor in treating cosmetics wastewater and its anti-fouling properties.

The membrane fouling problem of the membrane bioreactor (MBR) for wastewater treatment reduces the membrane flux and the pollutants removal efficiencies, which is the major obstacle limiting its application and should be properly solved. The combination of membrane and electricity can effectively slow down the membrane fouling rate due to electric repulsion between the pollutants and the membrane. In this study, the performance and the membrane fouling features of an electrode ultrafiltration membrane bioreactor (EMBR) fed with cosmetics wastewater were compared with a conventional ultrafiltration membrane bioreactor (UMBR). The results showed the COD removal efficiency increased by 4.43% and the transmembrane pressure (TMP) reduced by 50% in the EMBR as compared with the UMBR. The specific surface areas of electrode ultrafiltration membrane and conventional ultrafiltration membrane declined by 56.9% and 78.8% after 90 days of operation, respectively. The Protein (PN), polysaccharide (PS) and humic acids (HA) in the cake layer of EMBR were only 61.27%, 78.37% and 34.85% of that of UMBR, which contributed to its loose and porous structure and thus decreased the growth rate of TMP and extended the operation cycle. Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory calculation proved that the energy barrier between the electrode ultrafiltration membrane and the pollutants was 50% higher than that between the conventional ultrafiltration membrane and the pollutants. Therefore, the strong anti-fouling property of the electrode ultrafiltration membrane could reduce the chemicals dosage and manpower consumption for membrane cleaning and could be preferred for the treatment of cosmetics or alike wastewater containing high concentrations of surfactants and fatty acids.

Effect of Fe3+ on the sludge properties and microbial community structure in a lab-scale A2O process.

During biological wastewater treatment, ferric salt (Fe3+) usually serves as an inorganic flocculant to improve the agglomeration and sedimentation of suspended solids, and thus the removal efficiency of pollutants to meet the increasing strictly regulated wastewater discharge standards. In this study, we investigated the effects of Fe3+ on the removal efficiencies of pollutants, sludge properties, dominant flora and metabolic pathways of bacterial community in a classical anaerobic-anoxic-oxic (A2O) process. The results showed that a Fe3+ concentration lower than 10 mg·L-1 could improve the removal efficiencies of chemical oxygen demand (COD) and total nitrogen (TN), while an inhibition effect was exerted at concentration higher than 10 mg·L-1. The maximum removal efficiencies of COD and TN were 97% and 89%, respectively, under the critical Fe3+ concentration of 10 mg·L-1. Total phosphorous (TP) removal was constantly positively correlated with Fe3+ concentration, due to the enhanced adsorption of phosphorus on activated sludge with the increase of surface roughness. Thauera displayed the highest relative abundance, and certain bacteria in Proteobacteria, Dehloromonas and Candidatus-Competibacter exhibited good adaptability to high concentration of Fe3+. In the context of metabolic collaterals, the most abundant functional gene families were identified to be Carbohydrate Metabolism, Amino Acid Metabolism, Cell Motility, Membrane Transport, and Replication and Repair. This study provides an extensive mechanistic insight into the impact of Fe3+ on the A2O process, which is of fundamental significance to exploit the contributions of inorganic salts to biological wastewater treatment.

Effects of graphite particles/Fe3+ on the properties of anoxic activated sludge.

In order to improve the sludge flocculation, the combination of graphite particles/Fe3+ was used to change the sludge properties and accelerate the electron transfer rate. The effects of Fe3+ on the properties of graphite particles were investigated and the synergistic effects of graphite particles/Fe3+ on the sludge properties were analyzed using N2-adsorption/desorption, scanning electron microscopy-X-ray energy dispersive analysis (SEM-EDX), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The results showed that the operation time affected the specific surface area and pore size of graphite particles. The addition of Fe3+ reduced the specific surface area and increased the pore size of graphite particles, but it did not change the crystal structure of the graphite particles and the group structure of the sludge. Under the function of graphite particles/Fe3+, Zeta potential were improved and the relative hydrophobicity of the sludge was weakened. The contact angle was slightly lowered and flocculation ability (FA) was increased. Therefore, graphite particles/Fe3+ played an important role in the charge transfer and bioflocculation improvement.

Effects of K+ salinity on the sludge activity and the microbial community structure of an A2O process.

Salt ions are ubiquitous in wastewater and have significant impacts on the microbial activity and nitrogen and phosphorus removal in biological wastewater treatment processes. The effects of KCl salinity on the removal of COD, TN and PO43--P were investigated in a lab-scale A2O process. Meanwhile, the effects of K+ concentration on the composition of extracellular polymeric substances (EPS) and the microbial community structure were demonstrated. The results showed that the pollutant removal efficiencies and the bioactivity of the activated sludge decreased and the EPS content enhanced under high concentration of K+, which resulted in the deterioration of sludge compactness and settleability. The microbial diversity reduced after K+ addition and the microbial community structure was distinct between the system with (10 g L-1 and 40 g L-1) and without K+ addition. The relative abundance of Candidatus-Competibacter, Acinetobacter and Azoarcus decreased in the anoxic zone with the increase of K+ concentration, which might led to the decrease in denitrifying phosphorus removal capacity. However, the relative abundance of some genera of Firmicutes (such as Fusibacter, Acetoanaerobium, Planococcus and Exiguobacterium) increased, which was coincident with the enhanced microbial salt-tolerance capacity. Proteobacteria, Bacteroides, Chloroflexi and Firmicutes were the dominant phyla irrespective of the salinity changed, which guaranteed the removal of organic compounds, nitrogen and phosphorus in salty environment.