A state-of-art review on the redox activity of persistent free radicals in biochar.

Biochar-bound persistent free radicals (biochar-PFRs) attract much attention because they can directly or indirectly mediate the transformation of contaminants in large-scale wastewater treatment processes. Despite this, a comprehensive top-down understanding of the redox activity of biochar-PFRs, particularly consumption and regeneration mechanisms, as well as challenges in redox activity assessment, is still lacking. To tackle this challenge, this review outlines the identification and determination methods of biochar-PFRs, which serve as a prerequisite for assessing the redox activity of biochar-PFRs. Recent developments concerning biochar-PFRs are discussed, with a main emphasis on the reaction mechanisms (both non-free radical and free radical pathways) and their effectiveness in removing contaminants. Importantly, the review delves into the mechanism of biochar-PFRs regeneration, triggered by metal cations, reactive oxygen species, and ultraviolet radiations. Furthermore, this review thoroughly explores the dilemma in appraising the redox activity of biochar-PFRs. Components with unpaired electrons (particular defects and metal ions) interfere with biochar-PFRs signals in electron paramagnetic resonance spectra. Scavengers and extractants of biochar-PFRs also inevitably modify the active ingredients of biochar. Based on these analyses, a practical strategy is proposed to precisely determine the redox activity of biochar-PFRs. Finally, the review concludes by presenting current gaps in knowledge and offering suggestions for future research. This comprehensive examination aims to provide new and significant insights into the redox activity of biochar-PFRs.

The overlooked toxicity of environmentally persistent free radicals (EPFRs) induced by anthracene transformation to earthworms (Eisenia fetida).

Environmentally persistent free radicals (EPFRs) as intermediate products exist widely in the PAHs-contaminated soils, but toxicity assessment associated with EPFRs for terrestrial invertebrates remains unclear. Using the model organism Eisenia fetida, we compared the adverse effects among anthracene (ANT), anthraquinone (ANQ), and EPFRs induced by ANT transformation on clay surfaces. Our results showed that EPFRs-exposed earthworms experienced histopathological damage, which was more severe than ANT and ANQ-exposed earthworms. The source of EPFRs damage was associated with the obvious dysbiosis of reactive oxygen species in earthworms. Specifically, EPFRs trigged more severe antioxidant responses and oxidative damages (e.g., membrane lipid and DNA injury) in comparison with ANT and ANQ exposure, as evidenced by the values of integrated biomarker response (IBR) following the order of EPFRs (14.5) > ANT (12.8) > ANQ (10.9). Moreover, high-throughput sequencing found that EPFRs induced dramatic changes in the composition and structure of earthworm gut microbiota, which may involve immune and metabolism dysfunction, in turn aggravated EPFRs toxicity. Overall, the obtained information highlights the more severe injury of EPFRs to terrestrial organisms, deserving more attentions for the assessment of potential risks associated with radical intermediates in PAHs-contaminated soils.

Effect mechanism of litter extract from Alternanthera philoxeroides on the selective absorption of heavy metal ions by amphoteric purple soil.

Plant litter causes a serious waste of resources. Thus, plant litter extract (LE) should be used in the soil remediation of heavy metals. In this study, different proportions of LE from the Alternanthera philoxeroides were used to modify dodecyl dimethyl betaine (BS)-modified purple soil (P). The basic physicochemical properties of LE + BS-modified Ps (LE + BS-Ps) were determined, and the microscopic morphology of LE + BS-Ps was studied by using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, and specific surface area detection. The isothermal adsorption characteristics of heavy metal ions (Pb2+, Cu2+, and Cr6+) on different LE + BS-Ps were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and LE + BS-P's property were compared. Results showed that the cation exchange capacity and specific surface area of LE + BS-Ps increased, pH of LE + BS-Ps decreased, and TOC of LE + BS-Ps increased first and then decreased with increasing proportion of LE. FTIR, SEM, and EDS results proved that LE was modified on the surface of BS-P. Langmuir and Freundlich models could be used to describe the adsorption isotherms of heavy metal ions on different LE + BS-Ps, and the fitting correlation of the Langmuir model was higher than that of the Freundlich model. The maximum adsorption capacity (qm) of Pb2+, Cu2+, and Cr6+ were 107.60-295.66, 133.00-342.11, and 33.59-75.41 mmol/kg, respectively. The qm of Pb2+, Cu2+, and Cr6+ on LE + BS-Ps all increased first and then decreased with increasing proportion of LE, and the peak value was observed in 20%LE + BS-Ps. High pH improved Pb2+ and Cu2+ adsorption but inhibited Cr6+ adsorption. The adsorption amounts of Pb2+, Cu2+, and Cr6+ all increased first and then decreased with incresing ionic strength and were maintained at the maximum value of 0.1-0.2 mol/L. The Pb2+, Cu2+, and Cr6+ adsorption mechanisms on different LE + BS-Ps showed a positive temperature effect and presented spontaneous, exothermic and entropy-adding processes.

The protective layer formed by soil particles on plastics decreases the toxicity of polystyrene microplastics to earthworms (Eisenia fetida).

The recent discovery of microplastics contaminants in most ecosystems has raised major health issues, yet knowledge on their impact on soil organisms is limited, especially their toxicity evolution with aging. Herein, the toxicity of polystyrene microplastic (PS-MP) to earthworm (Eisenia fetida) along with aging was investigated. Results showed that the 28 d-LC50 (50% lethal concentration) of PS-MP was 25.67 g kg-1, whereas that increased to 96.47 g kg-1 after PS-MP initially aged in soil for 28 days, indicating the toxicity of PS-MP decreased with aging. Laser scanning confocal microscope and scanning electron microscope (SEM) found that the toxicity of PS-MP to earthworm may be due to the ingestion of PS-MP by earthworms and the physical damage (e.g., epidermis abrasion and setae loss) of PS-MP to earthworms. Similarly, the levels of reactive oxygen species, antioxidant enzyme activities and malondialdehyde content increased with PS-MP concentrations from 0.1 to 1.5 g kg-1, but decreased with aging from 7 to 28 days. The integrated biomarker response index also confirmed that the toxicity of PS-MP decreased with aging. SEM found that PS-MP were progressively covered by soil particles during soil aging, inducing the formation of protective layer and increasing the particle size of PS-MP, which prevented direct contact with earthworms and decreased the ingestion of PS-MP, in turn decreased PS-MP toxicity. Overall, our study provides valuable insights for elucidating the effect of aging on the toxicity of microplastics.

Hot carrier dynamics in MoS2/WS2heterostructure.

TMDs based heterostructure have drawn much attention for its potential application in photoelectric devices benefiting from the rapid and effective carrier separation and ultra-long interlayer exciton lifetime. Recent studies on carrier dynamics of TMDs based heterostructures are mainly focused on the transfer process of photo-generated carriers across the interface and lifetime of interlayer exciton but little attention is paid on the dynamics of hot carriers. Here, the carrier dynamics of hot carriers in MoS2/WS2heterostructure is investigated by transient absorption spectra. Rapid separation of electron and hole is observed. More importantly, hot carriers of C exciton, which contribute to the absorption of most of the visible light, could compensate for the carrier loss in the band edge exciton energy band through the intervalley transfer process. This re-injection process of hot carriers of C exciton could compensate for carrier depletion in photoelectric devices, thus may greatly improve the light utilization in optoelectronic devices.

T-2 Toxin Induces Oxidative Stress at Low Doses via Atf3ΔZip2a/2b-Mediated Ubiquitination and Degradation of Nrf2.

T-2 toxin is mainly produced by Fusarium species, which is an extremely toxic mycotoxin to humans and animals. It is well known that T-2 toxin induces oxidative stress, but the molecular mechanism is still unknown. In this study, we found that T-2 toxin significantly promoted reactive oxygen species (ROS) accumulation in MCF-7 cells at low doses which maintains cell viability at least 80%. Further analysis showed that T-2 toxin downregulated the expression of the master regulator of antioxidant defense gene, nuclear factor erythroid 2-related factor (Nrf2), and its targeted antioxidant genes. Overexpression of Nrf2 or its target gene heme oxygenase 1 (HO1) significantly blocked the ROS accumulation in MCF-7 cells under T-2 toxin treatment. Moreover, we found that T-2 toxin downregulated the antioxidant genes via inducing the expression of ATF3ΔZip2a/2b. Importantly, overexpression of ATF3ΔZip2a/2b promoted the ubiquitination and degradation of Nrf2. Altogether, our results demonstrated that T-2 toxin-induced ROS accumulation via ATF3ΔZip2a/2b mediated ubiquitination and degradation of Nrf2, which provided a new insight into the mechanism of T-2 toxin-induced oxidative stress.

Minimize the Xylitol Production in Saccharomyces cerevisiae by Balancing the Xylose Redox Metabolic Pathway.

Xylose is the second most abundant sugar in lignocellulose, but it cannot be used as carbon source by budding yeast Saccharomyces cerevisiae. Rational promoter elements engineering approaches were taken for efficient xylose fermentation in budding yeast. Among promoters surveyed, HXT7 exhibited the best performance. The HXT7 promoter is suppressed in the presence of glucose and derepressed by xylose, making it a promising candidate to drive xylose metabolism. However, simple ectopic expression of both key xylose metabolic genes XYL1 and XYL2 by the HXT7 promoter resulted in massive accumulation of the xylose metabolic byproduct xylitol. Through the HXT7-driven expression of a reported redox variant, XYL1-K270R, along with optimized expression of XYL2 and the downstream pentose phosphate pathway genes, a balanced xylose metabolism toward ethanol formation was achieved. Fermented in a culture medium containing 50 g/L xylose as the sole carbon source, xylose is nearly consumed, with less than 3 g/L xylitol, and more than 16 g/L ethanol production. Hence, the combination of an inducible promoter and redox balance of the xylose utilization pathway is an attractive approach to optimizing fuel production from lignocellulose.

Overexpression of SFA1 in engineered Saccharomyces cerevisiae to increase xylose utilization and ethanol production from different lignocellulose hydrolysates.

Here, an engineered Saccharomyces cerevisiae strain SFA1OE was constructed by overexpressing SFA1 in a reported WXY70 with effective six-gene clusters. Under simulated maize hydrolysate, SFA1OE produced an ethanol yield of 0.492 g/g totalsugars within 48 h. The productivity of SFA1OE was comprehensively evaluated in typical hydrolysates from stalks of maize, sweet sorghum, wheat and Miscanthus. Within 48 h, SFA1OE achieved an ethanol yield of 0.489 g/g totalsugars in the optimized hydrolysate of alkaline-distilled sweet sorghum bagasse derived from Advanced Solid-State Fermentation process. By crossing SFA1OE with a DQ1-derived haploid strain, we obtained an evolved diploid strain SQ-2, exhibiting improved ethanol production and thermotolerance. This study demonstrates that overexpressing SFA1 enables efficient fermentation performance in different lignocellulosic hydrolysates, especially in the hydrolysate of alkaline-distilled sweet sorghum bagasse. The increased cellulosic bioethanol production of SFA1OE provides a promising platform for efficient biorefineries.

Development of an inactivated vaccine candidate for SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.

Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects.

CD137-targeting immune therapy, which activates anti-tumor T effector cell responses, seems to be an attractive concept in clinical oncology. Recent evidence has demonstrated that tumor cells besides T cells and antigen-presenting cells are able to express CD137 and CD137L. Here we aimed to identify CD137/CD137L expression in established colon cancer cell lines and primary tumors (UICC stages I-IV) from patients with documented long-term follow-up. CD137/CD137L expression was highly upregulated in early to late-stage tumors while the inverse was observed in patient-derived peripheral blood mononuclear cells. High CD137L expression within primary tumors was mediated by tumor cells and significantly correlated with the occurrence of distant metastases and shortened survival in advanced stages of disease (UICC stage IV). Interestingly, induced tumor cell signaling via CD137L on its surface in vitro resulted in dual effects: (i) reduced tumor cell proliferation suggesting inhibitory signaling in all investigated cancers and (ii) increased epithelial-to-mesenchymal transition signaling events. Taken together CD137/CD137L expression was stage-dependently upregulated with shortened survival in patients with highly CD137L-expressing tumors. Our clinical and experimental data suggest that colon cancer cells predominantly express CD137L and thereby have negative impact on overall survival through a process of reverse signaling. Beside agonistic CD137 antibody therapy to foster T effector cell responses, CD137L-mediated intervention strategies may become instrumental to circumvent relapsed tumor growth through induced epithelial-to-mesenchymal transition and consecutive metastases formation.

The axis of local cardiac endogenous Klotho-TGF-ß1-Wnt signaling mediates cardiac fibrosis in human.

BACKGROUND: Cardiovascular fibrosis is a major contributor to cardiovascular disease, the primary cause of death in patients with chronic kidney disease (CKD). We previously reported expression of endogenous Klotho in human arteries, and that CKD is a state of Klotho deficiency, resulting in vascular calcification, but myocardial expression of Klotho is poorly understood. This study aimed to further clarify endogenous Klotho's functional roles in cardiac fibrosis in patients with underlying CKD. METHODS AND RESULTS: Human atrial appendage specimens were collected during cardiac surgery from individuals with or without CKD. Cardiac fibrosis was quantified using trichrome staining. For endogenous Klotho functional studies, primary human cardiomyocytes (HCMs) were treated with uremic serum from CKD patients or recombinant human TGF-ß1. The effects of endogenous Klotho in HCMs were studied using Klotho-siRNA and Klotho-plasmid transfection. Both gene and protein expression of endogenous Klotho are found in human heart, but decreased Klotho expression is clearly associated with the degree of cardiac fibrosis in CKD patients. Moreover, we show that endogenous Klotho is expressed by HCMs and cardiac fibroblasts (HCFs) but that HCM expression is suppressed by uremic serum or TGF-ß1. Klotho knockdown or overexpression aggravates or mitigates TGF-ß1-induced fibrosis and canonical Wnt signaling in HCMs, respectively. Furthermore, co-culture of HCMs with HCFs increases TGF-ß1-induced fibrogenic proteins in HCFs, but overexpression of endogenous Klotho in HCMs mitigates this effect, suggesting functional crosstalk between HCMs and HCFs. CONCLUSIONS: Our data from analysis of human hearts as well as functional in vitro studies strongly suggests that the loss of cardiac endogenous Klotho in CKD patients, specifically in cardiomyocytes, facilitates intensified TGF-ß1 signaling which enables more vigorous cardiac fibrosis through upregulated Wnt signaling. Upregulation of endogenous Klotho inhibits pathogenic Wnt/ß-catenin signaling and may offer a novel strategy for prevention and treatment of cardiac fibrosis in CKD patients.

Safety, immunogenicity, and lot-to-lot consistency of live attenuated varicella vaccine in 1-3 years old children: a double-blind, randomized phase III trial.

The study was to evaluate the safety, immunogenicity and lot-to-lot consistency of live attenuated varicella vaccine in Chinese population aged 1-3 years. The double-blind, randomized phase III trial was conducted in Henan Province, China. In total, 1197 subjects were included in this study. Subjects were randomly assigned into four groups in a 2:2:2:1 ratio to receive one of the three lots of commercial scale (CS) vaccine or the licensed pilot scale (LPS) vaccine. Seroconversion rate and neutralizing antibody titers (NATb) were assessed at day 0 pre-vaccination and at day 30 post-vaccination. Safety data were recorded for 30 days post-vaccination. After vaccination, the geometric mean titers (GMTs) of the three CS groups were 25.04 (95% confidence interval [CI], 22.85 to 27.44), 24.47 (95% CI, 22.35 to 26.78) and 25.88 (95% CI, 23.61 to 28.36), respectively (P= 0.6928). The ratio of GMTs adjusted for covariates of each pair of lots were all between 0.67 to 1.50 in susceptible subjects. The difference of seroconversion rate between pooled CS group and LPS group was 3.82 (95% CI, 0.55 to 8.81). Meanwhile, the percentage of solicited local, systemic and unsolicited adverse reactions showed no difference across the four groups, and most of the adverse reactions were mild or moderate in intensity. The CS group was comparable to the LPS group in safety and immunogenicity. The consistency of three consecutive CS lots was reliable. Moreover, the CS group was non-inferior to the LPS group.

Differential expression patterns of housekeeping genes increase diagnostic and prognostic value in lung cancer.

BACKGROUND: Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these "housekeeping genes" (HKGs) could separate one normal human tissue type from another. Current focus on identifying "specific disease markers" is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers. METHODS: Microarray and RNA-seq data for normal lungs, lung adenocarcinomas (AD), squamous cell carcinomas of the lung (SQCLC), and small cell carcinomas of the lung (SCLC) were collected from online databases. Using 374 of 451 HKGs, differentially expressed genes between pairs of sample types were determined via two-sided, homoscedastic t-test. Principal component analysis and hierarchical clustering classified normal lung and lung cancers subtypes according to relative gene expression variations. We used uni- and multi-variate cox-regressions to identify significant predictors of overall survival in AD patients. Classifying genes were selected using a set of training samples and then validated using an independent test set. Gene Ontology was examined by PANTHER. RESULTS: This study showed that the differential expression patterns of 242, 245, and 99 HKGs were able to distinguish normal lung from AD, SCLC, and SQCLC, respectively. From these, 70 HKGs were common across the three lung cancer subtypes. These HKGs have low expression variation compared to current lung cancer markers (e.g., EGFR, KRAS) and were involved in the most common biological processes (e.g., metabolism, stress response). In addition, the expression pattern of 106 HKGs alone was a significant classifier of AD versus SQCLC. We further highlighted that a panel of 13 HKGs was an independent predictor of overall survival and cumulative risk in AD patients. DISCUSSION: Here we report HKG expression patterns may be an effective tool for evaluation of lung cancer states. For example, the differential expression pattern of 70 HKGs alone can separate normal lung tissue from various lung cancers while a panel of 106 HKGs was a capable class predictor of subtypes of non-small cell carcinomas. We also reported that HKGs have significantly lower variance compared to traditional cancer markers across samples, highlighting the robustness of a panel of genes over any one specific biomarker. Using RNA-seq data, we showed that the expression pattern of 13 HKGs is a significant, independent predictor of overall survival for AD patients. This reinforces the predictive power of a HKG panel across different gene expression measurement platforms. Thus, we propose the expression patterns of HKGs alone may be sufficient for the diagnosis and prognosis of individuals with lung cancer.

Tumor necrosis factor receptor-associated factor (TRAF) 6 inhibition mitigates the pro-inflammatory roles and proliferation of rheumatoid arthritis fibroblast-like synoviocytes.

BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs. METHODS: Synovium were collected by closed needle biopsy from inflamed knees of active RA patients, and FLSs were isolated by modified tissue culture method. Expression of TRAF6 and CD55 in RA synivium was tested by double immunofluorescence (IF) staining. TRAF6 in RA-FLSs was inhibited using Lentiviral-TRAF6-shRNA transfection. Real-time PCR and ELISA were used to detect the mRNA expression and secretion of matrix metalloproteinase (MMP) and pro-inflammatory cytokines. Cell Counting Kit-8 was used to detect cell proliferation, flow cytometry was used to detect cell cycle, and Annexin V assay was used to detect cell apoptosis. RESULTS: We showed that in the intimal and subintimal area of RA synovium, TRAF6 was expressed obviously not only in CD55+ cells, but also in some other CD55- cells. TRAF6 expression in RA-FLSs was suppressed effectively by Lentiviral-TRAF6-shRNA transfection. Inhibition of TRAF6 in RA-FLSs mitigated the mRNA levels and secretion of pro-inflammatory cytokines and MMPs, such as IL-1ß, IL-8, IL-6, TNF-α, MMP-13, and MMP-3. In addition, it decreased the proliferation of RA-FLSs, blocked RA-FLSs in G0/G1-phase, and inhibited the cells to go into S-phase and G2/M-phase, but not facilitated apoptosis of RA-FLSs. CONCLUSION: TRAF6 plays direct roles in the pro-inflammatory effects and proliferation of RA-FLSs. TRAF6 may serve as a potential treatment target in RA.

[The historical materials of stomatology in the oracle bone inscriptions of the Yin-Shang Dynasties].

Some oracle bone inscriptions of the Yin-Shang Dynasties were related to the stomatology, including special terms of diseases of the mouth, tongue and teeth which were classified, and proper nouns of some special diseases. Moreover, witch doctors' exploration for the causes of oral diseases, the observation on different stages of oral diseases, and the records of oral disease treatment were also involved. All of these reflected the sprouting stage of stomatology in the Yin-Shang Dynasties in ancient China.

Mycetocola miduiensis sp. nov., a psychrotolerant bacterium isolated from Midui glacier.

An aerobic, asporous, flagellated, Gram-stain-positive, rod-shaped bacterium MD-T1-10-2(T) was isolated from the topsoil of Midui Glacier, Tibet Province, China. Phylogenetic analysis based on 16S rRNA gene sequence analysis placed the strain in a clade containing Mycetocola manganoxydans CCTCC AB 209002(T), Mycetocola reblochoni DSM 18580(T), Mycetocola tolaasinivorans JCM 11656(T), Mycetocola lacteus JCM 11654(T) and Mycetocola saprophilus JCM 11655(T), with the sequence similarities of 99.2, 98.1, 96.7, 96.6 and 96.4 %, respectively. DNA-DNA hybridization analysis indicated that strain MD-T1-10-2(T) represented a new member of this genus. The optimal ranges of temperature and pH for growth were 20-25 °C and 7.0-9.0, respectively; the strain could even grow at 0 °C. The major cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The predominant menaquinones were MK-10 and MK-11. The cell wall amino acids were lysine, alanine, glycine and glutamic acids. The DNA G+C content was 65.9 mol%. Based on the genotypic and phenotypic data, strain MD-T1-10-2(T) for which the name Mycetocola miduiensis sp. nov. is proposed; the type strain is MD-T1-10-2(T) ( = CGMCC 1.11101(T) = NBRC 107877(T)).

The association between hepatitis B virus infection and disease activity, synovitis, or joint destruction in rheumatoid arthritis.

The prevalence of chronic hepatitis B virus (HBV) infection in China is high. Four percent of patients with HBV infection can present with polyarthritis and positive rheumatic factor similar to rheumatoid arthritis (RA). Here, we investigated the association between HBV infection and serological, radiological, or histological disease status in RA. According to HBV infection status, 223 consecutive hospitalized Chinese patients with RA were divided into the groups of chronic HBV infection, past HBV infection, and no HBV infection. Clinical data and hand radiographs were collected. Synovium was obtained by closed-needle biopsy, and serial tissue sections were stained immunohistochemically for HBV surface antigen (HBsAg) and cluster of differentiation (CD) markers. (1) The prevalence of HBsAg positivity and chronic hepatitis B in RA was consistent with the age-matched general Chinese population (11.2 vs. 8.7 %, 1.7 vs. 1.0 %, respectively, P > 0.05). (2) Clinical parameters, disease activity score in 28 joints, or Sharp scores showed no significant difference among the three groups in 206 RA or 140 treatment-naïve patients, both with active disease (all P > 0.05). (3) Synovial immunohistochemical staining showed negative HBsAg in ten RA patients with HBV carrier status and ten RA patients with past HBV infection. Except for higher subintimal CD3+ cell density in the past HBV infection group, Krenn's synovitis score, mean densities of subintima positive-staining cells (CD20, CD38, CD79a, and CD68), and CD34+ microvessel counts showed no significant difference among RA patients with HBV carrier status, past HBV infection, or no HBV infection (all P > 0.05). Chronic HBV infection may have no significant effect on disease activity, synovitis, or joint destruction in RA.

Flavobacterium noncentrifugens sp. nov., a psychrotolerant bacterium isolated from glacier meltwater.

A non-motile, Gram-stain-negative bacterium, designated R-HLS-17(T), was isolated from the meltwater of Hailuogou Glacier located in Sichuan province, south-west China. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate belonged to the genus Flavobacterium, with the closest relatives being Flavobacterium antarcticum JCM 12383(T) (95.5% 16S rRNA gene sequence similarity), F. omnivorum JCM 11313(T) (95.0%) and F. fryxellicola LMG 22022(T) (95.2%). Growth occurred at 0-29 °C (optimum, 10-20 °C) and pH 6.0-8.5 (optimum, 7.0-8.0). The DNA G+C content was 46.5 mol%. The major cellular fatty acids were iso-C15:0, iso-C15:1 G, summed feature 9 (comprising iso-C17:1ω9c and/or 10-methyl C16:0), iso-C17:0 3-OH and iso-C15:0 3-OH. The predominant menaquinone was MK-6. Based on the genotypic and phenotypic characteristics, we propose that strain R-HLS-17(T) represents a novel species of the genus Flavobacterium, Flavobacterium noncentrifugens sp. nov. The type strain is R-HLS-17(T) (=CGMCC 1.10076(T)=NBRC 108844(T)).

Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovitis severity in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Focal bone erosion is due to excess bone resorption of osteoclasts. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the critical mediators both in inflammatory signal pathway and differentiation and resorption activity of osteoclasts. Here we aimed to investigate TRAF6 expression in RA synovium and its correlation with histological synovitis severity and radiological joint destruction in RA. METHODS: Synovitis score was determined in needle biopsied synovium from 44 patients with active RA. Synovium from nine patients with osteoarthritis (OA) and seven with orthopedic arthropathies (Orth.A) were enrolled as "less inflamed" disease controls. Serial sections were stained immunohistochemically for TRAF6 as well as CD68 (macrophage), CD3 (T cell), CD20 (B cell), CD38 (plasmocyte), CD79a (B lineage cells from pre-B cell to plasmocyte stage), and CD34 (endothelial cell). Double immunofluorescence staining of TRAF6 and CD68 were tested. Densities of positive staining cells were determined and correlated with histological disease activity (synovitis score) and radiographic joint destruction (Sharp score). RESULTS: TRAF6 expression was found in the intimal and subintimal area of RA synovium, with intense staining found in the endochylema and nucleus of intimal synoviocytes and subintimal inflammatory cells. Double immunofluorescence staining showed TRAF6 was expressed in most of the intimal cells and obviously expressed in CD68+ cells and some other CD68- cells in subintimal area. Synovial TRAF6 was significantly over-expressed in the RA group compared with the OA and Orth.A group (2.53 ± 0.94 vs. 0.72 ± 0.44 and 0.71 ± 0.49, P < 0.0001). Synovial TRAF6 expression in RA correlated significantly with synovitis score (r = 0.412, P = 0.006), as well as the inflammatory cell infiltration (r = 0.367, P = 0.014). Significant correlation was detected between synovial TRAF6 expression and intimal CD68+ cells, as well as the cell density of subintimal CD68+ cells, CD3+ cells, CD20+ cells, CD38+ cells, and CD79a+ cells (all P < 0.05). CONCLUSIONS: Elevated synovial TRAF6 expression correlated with synovitis severity and CD68+ cell density in RA. It is, therefore, hypothesized that synovial TRAF6 is involved in the pathogenesis of synovial inflammation and osteoclast differentiation in RA.

Synovial infiltration with CD79a-positive B cells, but not other B cell lineage markers, correlates with joint destruction in rheumatoid arthritis.

OBJECTIVE: The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA. METHODS: Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score). RESULTS: Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman's rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA. CONCLUSION: Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.