Evaluating the effects of tannic acid on rabbit growth performance, digestibility, antioxidant status, intestinal morphology and caecal fermentation and microbiota.

The objective of this study was to assess the effects of dietary supplementation with tannic acid (TA) on the growth performance, digestibility, antioxidant status, intestinal morphology and the caecal fermentation and microbiota in rabbits. A total number of 120 Ira rabbits (30 days of age) were randomly allotted to four dietary treatment groups: TA 0 (control), TA 0.75, TA 1.5 and TA 3, administered basal diets with 0, 0.75, 1.5 and 3 g TA/kg of feed for 28 days. Compared to the control group, dietary 3 g TA/kg inclusion decreased the average daily feed intake (p < 0.05). No significant differences were found in the digestibility among the groups (p > 0.05). Serum total antioxidant capacity was significantly higher in the 3 g/kg TA group than in the other groups (p < 0.05). There was a significant increase in the concentration of propionic acid and butyric acid in the 3 g/kg TA group. The addition of TA had no effect on villus height and crypt depth of small intestine (p > 0.05). The 16S rRNA high-throughput sequencing results showed that at the phylum level, dietary 3 g/kg TA increased the abundance of Bacteroidetes in the caecum of rabbits (p < 0.05). Based on the results, dietary TA is effective in antioxidant capacity of rabbits, improving caecal fermentation and optimizing the caecal microflora. However, the appropriate dosage supplementation of TA in rabbits needs further research.

A novel simultaneous short-course nitrification, denitrification and fermentation process: bio-enhanced phenol degradation and denitrification in a single reactor.

The feasibility of a simultaneous nitrification, denitrification and fermentation process (SNDF) under electric stirrer agitation conditions was verified in a single reactor. Enhanced activated sludge for phenol degradation and denitrification in pharmaceutical phenol-containing wastewater under low dissolved oxygen conditions, additional inoculation with Comamonas sp. BGH and optimisation of co-metabolites were investigated. At a hydraulic residence time (HRT) of 28 h, 15 mg/L of substrate as strain BGH co-metabolised substrate degraded 650 ± 50 mg/L phenol almost completely and was accompanied by an incremental increase in the quantity of strain BGH. Strain BGH showed enhanced phenol degradation. Under trisodium citrate co-metabolism, strain BGH combined with activated sludge treated phenol wastewater and degraded NO2--N from 50 ± 5 to 0 mg/L in only 7 h. The removal efficiency of this group for phenol, chemical oxygen demand (COD) and TN was 99.67%, 90.25% and 98.71%, respectively, at an HRT of 32 h. The bioaugmentation effect not only promotes the degradation of pollutants, but also increases the abundance of dominant bacteria in activated sludge. Illumina MiSeq sequencing research showed that strain BGH promoted the growth of dominant genera (Acidaminobacter, Raineyella, Pseudarcobacter) and increased their relative abundance in the activated sludge system. These genera are resistant to toxicity and organic matter degradation. This paper provides some reference for the activated sludge to degrade high phenol pharmaceutical wastewater under the action of biological enhancement.

A Computation-guided Design of Highly Defined and Dense Bimetallic Active Sites on a Two-dimensional Conductive Metal-organic Framework for Efficient H2O2 Electrosynthesis.

Electrochemical synthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction (2e--ORR) provides an alternative method to the energy-intensive anthraquinone method. Metal macrocycles with precise coordination are widely used for 2e--ORR electrocatalysis, but they have to be commonly loaded on conductive substrates, thus exposing a large number of 2e--ORR-inactive sites that result in poor H2O2 production rate and efficiency. Herein, guided by first-principle predictions, a substrate-free and two-dimensional conductive metal-organic framework (Ni-TCPP(Co)), composed of Co-N4 sites in porphine(Co) centers and Ni2O8 nodes, is designed as a multi-site catalyst for H2O2 electrosynthesis. The approperiate distance between the CoN4 and Ni2O8 sites in Ni-TCPP(Co) weakens the electron transfer between them, thus ensuring their inherent activities and creating high-density active sites. Meanwhile, the intrinsic electronic conductivity and porosity of Ni-TCPP(Co) further facilitate rapid reaction kinetics. Therefore, outstanding 2e--ORR electrocatalytic performance has been achieved in both alkaline and neutral electrolytes (>90%/85% H2O2 selectivity within 0-0.8 V vs. RHE and >18.2/18.0 mol g-1 h-1 H2O2 yield under alkaline/neutral conditions), with confirmed feasibility for water purification and disinfection applications. This strategy thus provides a new avenue for designing catalysts with precise coordination and high-density active sites, promoting high-efficiency electrosynthesis of H2O2 and beyond.

High-titer production of staurosporine by heterologous expression and process optimization.

Staurosporine is the most well-known member of the indolocarbazole alkaloid family; it can induce apoptosis of many types of cells as a strong protein kinase inhibitor, and is used as an important lead compound for the synthesis of the antitumor drugs. However, the low fermentation level of the native producer remains the bottleneck of staurosporine production. Herein, integration of multi-copy biosynthetic gene cluster (BGC) in well characterized heterologous host and optimization of the fermentation process were performed to enable high-level production of staurosporine. First, the 22.5 kb staurosporine BGC was captured by CRISPR/Cas9-mediated TAR (transformation-associated recombination) from the native producer (145 mg/L), and then introduced into three heterologous hosts Streptomyces avermitilis (ATCC 31267), Streptomyces lividans TK24 and Streptomyces albus J1074 to evaluate the staurosporine production capacity. The highest yield was achieved in S. albus J1074 (750 mg/L), which was used for further production improvement. Next, we integrated two additional staurosporine BGCs into the chromosome of strain S-STA via two different attB sites (vwb and TG1), leading to a double increase in the production of staurosporine. And finally, optimization of fermentation process by controlling the pH and glucose feeding could improve the yield of staurosporine to 4568 mg/L, which was approximately 30-fold higher than that of the native producer. This is the highest yield ever reported, paving the way for the industrial production of staurosporine. KEYPOINTS: • Streptomyces albus J1074 was the most suitable heterologous host to express the biosynthetic gene cluster of staurosporine. • Amplification of the biosynthetic gene cluster had obvious effect on improving the production of staurosporine. • The highest yield of staurosporine was achieved to 4568 mg/L by stepwise increase strategy.

Enhancement of fungichromin production of Streptomyces sp. WP-1 by genetic engineering.

Fungichromin is a polyene macrolide antibiotic with potent killing activity against a broad range of agricultural pathogens and filamentous fungi and a wide range of potential applications. The production of fungichromin is still hampered by poor fermentation yield and high cost. In this study, the whole genome sequencing of fungichromin-producing Streptomyces sp. WP-1 was conducted, and the fungichromin biosynthetic gene cluster was identified. Comparative analysis revealed that the fungichromin biosynthetic gene cluster contains two regulatory genes, ptnF, and ptnR. The roles of ptnF and ptnR were determined through knockout and complementation. The yield of fungichromin was increased by overexpressing these two regulatory genes, as well as the crotonyl CoA reductase/carboxylase gene ptnB in Streptomyces sp. WP-1. The yield of fungichromin was increased to 8.5 g/L using a combination of genetic engineering and a medium optimization strategy, which is the highest fermentation titer recorded. KEY POINTS: • Confirmation of the positive regulation of ptnF and ptnR on fungichromin. • Improvement of fungichromin production by the construction of ptnF, ptnR, and ptnB overexpression strains. • Improvement of fungichromin production by the addition of soybean oil and copper ions at optimal concentration.

Enhancement of acarbose production by genetic engineering and fed-batch fermentation strategy in Actinoplanes sp. SIPI12-34.

BACKGROUND: Acarbose, as an alpha-glucosidase inhibitor, is widely used clinically to treat type II diabetes. In its industrial production, Actinoplanes sp. SE50/110 is used as the production strain. Lack of research on its regulatory mechanisms and unexplored gene targets are major obstacles to rational strain design. Here, transcriptome sequencing was applied to uncover more gene targets and rational genetic engineering was performed to increase acarbose production. RESULTS: In this study, with the help of transcriptome information, a TetR family regulator (TetR1) was identified and confirmed to have a positive effect on the synthesis of acarbose by promoting the expression of acbB and acbD. Some genes with low expression levels in the acarbose biosynthesis gene cluster were overexpressed and this resulted in a significant increase in acarbose yield. In addition, the regulation of metabolic pathways was performed to retain more glucose-1-phosphate for acarbose synthesis by weakening the glycogen synthesis pathway and strengthening the glycogen degradation pathway. Eventually, with a combination of multiple strategies and fed-batch fermentation, the yield of acarbose in the engineered strain increased 58% compared to the parent strain, reaching 8.04 g/L, which is the highest fermentation titer reported. CONCLUSIONS: In our research, acarbose production had been effectively and steadily improved through genetic engineering based on transcriptome analysis and fed-batch culture strategy.

Fast and Robust Visual Tracking with Few-Iteration Meta-Learning.

Visual object tracking has been a major research topic in the field of computer vision for many years. Object tracking aims to identify and localize objects of interest in subsequent frames, given the bounding box of the first frame. In addition, the object-tracking algorithms are also required to have robustness and real-time performance. These requirements create some unique challenges, which can easily become overfitting if given a very small training dataset of objects during offline training. On the other hand, if there are too many iterations in the model-optimization process during offline training or in the model-update process during online tracking, it will cause the problem of poor real-time performance. We address these problems by introducing a meta-learning method based on fast optimization. Our proposed tracking architecture mainly contains two parts, one is the base learner and the other is the meta learner. The base learner is primarily a target and background classifier, in addition, there is an object bounding box prediction regression network. The primary goal of a meta learner based on the transformer is to learn the representations used by the classifier. The accuracy of our proposed algorithm on OTB2015 and LaSOT is 0.930 and 0.688, respectively. Moreover, it performs well on VOT2018 and GOT-10k datasets. Combined with the comparative experiments on real-time performance, our algorithm is fast and robust.

MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis.

Interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate T(H)-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a T(H)-17 cell-associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer T(H)-17 cells and mild EAE, and its overexpression led to more T(H)-17 cells and severe EAE. We also found that miR-326 promoted T(H)-17 differentiation by targeting Ets-1, a negative regulator of T(H)-17 differentiation. Our data show a critical role for microRNA in T(H)-17 differentiation and the pathogenesis of multiple sclerosis.

Interactive effects of exogenous melatonin and Rhizophagus intraradices on saline-alkaline stress tolerance in Leymus chinensis.

Melatonin, a ubiquitous molecule found in almost all organisms, is considered an important regulator in plant growth. However, little is known about the interactive effect of melatonin and arbuscular mycorrhizal (AM) fungi on plant resistance against soil salinity and alkalinity. To fill in such a gap in knowledge, we conducted three experiments to explore (1) whether exogenous melatonin and an AM fungus had interactive effects on plant response to saline-alkaline stress, (2) whether the influence of melatonin on mycorrhizal plant stress tolerance was attributable to effect on the AM fungus, and (3) whether the effect of melatonin application was due to changes in soil salinity and alkalinity. We found interactive effects between melatonin and the AM fungus on alleviating ROS burst, decreasing malondialdehyde content and protecting Leymus chinensis photosynthetic activity through activation of antioxidant enzyme and gene expression (superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase) in plant shoots and roots. Our results showed that exogenous melatonin promoted spore germination and hyphal length of the AM fungus under Petri-dish conditions. However, exogenous melatonin application did not exhibit significant effects on soil salinity and alkalinity. This study provides an insight into the beneficial effects of exogenous melatonin on saline-alkaline stress tolerance in mycorrhizal L. chinensis through regulating antioxidant systems, protecting photosynthetic activity, and promoting associated AM fungal growth without changing soil salinity and alkalinity. It also reveals potential applications of exogenous melatonin and AM fungi for the restoration of saline-alkaline degraded grassland.

Giant cell arteritis presenting as bilateral anterior ischemic optic neuropathy: a biopsy-proven case report in Chinese patient.

BACKGROUND: Giant cell arteritis (GCA) is a systemic vasculitis of medium and large-size vessels and can led to permanent visual loss in elderly patients. GCA is very rare among Asians. We report a Chinese patient presenting with acute bilateral anterior ischemic optic neuropathy, and the temporal artery biopsy proved the diagnose of GCA. CASE PRESENTATION: A 77-year-old Chinese man presented with sudden bilateral blindness for 5 days with a severe headache. Funduscopic examination revealed bilateral optic disc swollen with "chalky white" pallid appearance. The blood tests showed the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) elevated dramatically. The color duplex ultrasonography (CDUS) of the superficial temporal artery revealed the inflammation of the vessel wall as a "halo sign". The temporal artery biopsy was perfumed and the pathology revealed luminal occlusion with multinuclear giant cell infiltration. The patient was treated with intravenous methylprednisolone for 3 days and oral prednisone weaning for 12 months. The visual acuity remained no light perception at one year follow-up. CONCLUSIONS: Although very rare in Asian, GCA can led to permanent blindness in elderly Chinese caused by anterior ischemic optic neuropathy. The noninvasive CDUS might be a promising technique for diagnose GCA in highly suspected patients.

Facile Fabrication of Large-Scale Silver Nanowire Bilayer Films and Its Application as Sensitive and Reproducible Surface-Enhanced Raman Scattering Substrates.

The homogeneous surface-enhanced Raman scattering (SERS) active hot spots on a SERS substrate is the most crucial factor in ensuring their application as reproducible and ultrasensitive sensing platforms. In this paper, we report on a simply shaking-assisted liquid­liquid (water-chloroform) interfacial assembly process for fabricating aligned Ag nanowire (AgNW) bilayer films on solid substrates. A scalable fabrication process can be easily realized by using a large size of container. These AgNW bilayer films can be used as ideal SERS active substrates for chemical and biomolecular detection with highly sensitivity and excellent reproducibility. Significantly, sensitive and quantitative detection of carbaryl with a detection limit of 0.1 ppm using these SERS substrates to demonstrate potential applications for environmental pollutant analysis.

Short-Circuit Fault Detection and Classification Using Empirical Wavelet Transform and Local Energy for Electric Transmission Line.

In order to improve the classification accuracy of recognizing short-circuit faults in electric transmission lines, a novel detection and diagnosis method based on empirical wavelet transform (EWT) and local energy (LE) is proposed. First, EWT is used to deal with the original short-circuit fault signals from photoelectric voltage transformers, before the amplitude modulated-frequency modulated (AM-FM) mode with a compactly supported Fourier spectrum is extracted. Subsequently, the fault occurrence time is detected according to the modulus maxima of intrinsic mode function (IMF2) from three-phase voltage signals processed by EWT. After this process, the feature vectors are constructed by calculating the LE of the fundamental frequency based on the three-phase voltage signals of one period after the fault occurred. Finally, the classifier based on support vector machine (SVM) which was constructed with the LE feature vectors is used to classify 10 types of short-circuit fault signals. Compared with complementary ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and improved CEEMDAN methods, the new method using EWT has a better ability to present the frequency in time. The difference in the characteristics of the energy distribution in the time domain between different types of short-circuit faults can be presented by the feature vectors of LE. Together, simulation and real signals experiment demonstrate the validity and effectiveness of the new approach.

Blocking A2B adenosine receptor alleviates pathogenesis of experimental autoimmune encephalomyelitis via inhibition of IL-6 production and Th17 differentiation.

Adenosine is a key endogenous signaling molecule that regulates immune responses. A(2B) adenosine receptor (AR) is a relatively low-affinity receptor for adenosine, and the activation of A(2B)AR is believed to require pathological level of adenosine that is associated with ischemia, inflammation, trauma, or other types of stress. The role of A(2B)AR in the pathogenesis of multiple sclerosis (MS) is still unclear. In this study, we discovered that A(2B)AR was upregulated both in the peripheral blood leukocytes of MS patients and the peripheral lymphoid tissues of experimental autoimmune encephalomyelitis (EAE) mice. A(2B)AR-specific antagonists, CVT-6883 and MRS-1754, alleviated the clinical symptoms of EAE and protected the CNS from immune damage. A(2B)AR-knockout mice also developed less severe EAE. Further study indicated that blocking or deleting A(2B)AR inhibited Th17 cell differentiation by blocking IL-6 production from APCs such as dendritic cells. In dendritic cells, A(2B)AR was also upregulated during the development of EAE. CVT-6883 and genetic deletion of A(2B)AR significantly reduced adenosine-mediated IL-6 production. The phospholipase Cß-protein kinase C and p38 MAPK pathways were found to be involved in the A(2B)AR-mediated IL-6 production. Our findings not only revealed the pathological role of A(2B)AR in EAE, but also suggested that this receptor might be a new therapeutic target for the development of anti-MS drugs.

A Generalized Coordination Engineering Strategy for Single-Atom Catalysts toward Efficient Hydrogen Peroxide Electrosynthesis.

Designing non-noble metal single-atom catalysts (M-SACs) for two-electron oxygen reduction reaction (2e-ORR) is attractive for the hydrogen peroxide (H2O2) electrosynthesis, in which the coordination configuration of the M-SACs essentially affects the reaction activity and product selectivity. Though extensively investigated, a generalized coordination engineering strategy has not yet been proposed, which fundamentally hinders the rational design of M-SACs with optimized catalytic capabilities. Herein, a generalized coordination engineering strategy is proposed for M-SACs toward H2O2 electrosynthesis via introducing heteroatoms (e.g., oxygen or sulfur atoms) with higher or lower electronegativity than nitrogen atoms into the first sphere of metal-N4 system to tailor their electronic structure and adjust the adsorption strength for *OOH intermediates, respectively, thus optimizing their electrocatalytic capability for 2e-ORR. Specifically, the (O, N)-coordinated Co SAC (Co-N3O) and (S, N)-coordinated Ni SAC (Ni-N3S) are precisely synthesized, and both present superior 2e-ORR activity (Eonset: ≈0.80 V versus RHE) and selectivity (≈90%) in alkaline conditions compared with conventional Co-N4 and Ni-N4 sites. The high H2O2 yield rates of 14.2 and 17.5 moL g-1 h-1 and long-term stability over 12 h are respectively achieved for Co-N3O and Ni-N3S. Such favorable 2e-ORR pathway of the catalysts is also theoretically confirmed by the kinetics simulations.

Simultaneous regeneration of activated carbon and removal of adsorbed atrazine by ozonation process: From laboratory scale to pilot studies.

A novel treatment technique by coupling granular activated carbon (GAC) adsorption and ozone regeneration was constructed for long-lasting water decontamination. The GAC adsorption showed high performance for atrazine (ATZ) removal (99.9 %), and the ozone regeneration ensured the recyclability of GAC for water purification. The regeneration process was evaluated via several paths to assist the efficient adsorption process. Employing ozone micro-nano bubbles (O3-MNBs) for regenerating GAC showed superior performance compared to traditional ozone. Meantime, inhibiting the formation of bromate (BrO3-). ATZ adsorption process suffered from the pore-filling, hydrogen bonding effect and π-π EDA interaction. The surface phenolic hydroxyl group, carboxyl group and pyridine nitrogen benefitted the triggering of ozone to generate reactive oxygen species, and regenerate the GAC surface. The superior performance of the adsorption and regeneration process was verified via a long-term running by a pilot study. It significantly improved the removal of organic micropollutants, UV254 and permanganate index. Additionally, the intermittent O3-MNBs regeneration process resulted in efficient decontamination within the pores structure of GAC, which also effectively preserved the pore structure from destruction. For actual application, the cost of water production can be saved around 0.63 kWh m-3. This work proposed new ideas and theoretical support for economic water production.

Construction and validation of a deep learning prognostic model based on digital pathology images of stage III colorectal cancer.

BACKGROUND: TNM staging is the main reference standard for prognostic prediction of colorectal cancer (CRC), but the prognosis heterogeneity of patients with the same stage is still large. This study aimed to classify the tumor microenvironment of patients with stage III CRC and quantify the classified tumor tissues based on deep learning to explore the prognostic value of the developed tumor risk signature (TRS). METHODS: A tissue classification model was developed to identify nine tissues (adipose, background, debris, lymphocytes, mucus, smooth muscle, normal mucosa, stroma, and tumor) in whole-slide images (WSIs) of stage III CRC patients. This model was used to extract tumor tissues from WSIs of 265 stage III CRC patients from The Cancer Genome Atlas and 70 stage III CRC patients from the Sixth Affiliated Hospital of Sun Yat-sen University. We used three different deep learning models for tumor feature extraction and applied a Cox model to establish the TRS. Survival analysis was conducted to explore the prognostic performance of TRS. RESULTS: The tissue classification model achieved 94.4 % accuracy in identifying nine tissue types. The TRS showed a Harrell's concordance index of 0.736, 0.716, and 0.711 in the internal training, internal validation, and external validation sets. Survival analysis showed that TRS had significant predictive ability (hazard ratio: 3.632, p = 0.03) for prognostic prediction. CONCLUSION: The TRS is an independent and significant prognostic factor for PFS of stage III CRC patients and it contributes to risk stratification of patients with different clinical stages.

Strong mitonuclear discordance in the phylogeny of Neodermata and evolutionary rates of Polyopisthocotylea.

The genomic evolution of Polyopisthocotylea remains poorly understood in comparison to the remaining three classes of Neodermata: Monopisthocotylea, Cestoda, and Trematoda. Moreover, the evolutionary sequence of major events in the phylogeny of Neodermata remains unresolved. Herein we sequenced the mitogenome and transcriptome of the polyopisthocotylean Diplorchis sp., and conducted comparative evolutionary analyses using nuclear (nDNA) and mitochondrial (mtDNA) genomic datasets of Neodermata. We found strong mitonuclear discordance in the phylogeny of Neodermata. Polyopisthocotylea exhibited striking mitonuclear discordance in relative evolutionary rates: the fastest-evolving mtDNA in Neodermata and a comparatively slowly-evolving nDNA genome. This was largely attributable to its very long stem branch in mtDNA topologies, not exhibited by the nDNA data. We found indications that the fast evolution of mitochondrial genomes of Polyopisthocotylea may be driven both by relaxed purifying selection pressures and elevated levels of directional selection. We identified mitochondria-associated genes encoded in the nuclear genome: they exhibited unique evolutionary rates, but not correlated with the evolutionary rate of mtDNA, and there is no evidence for compensatory evolution (they evolved slower than the rest of the genome). Finally, there appears to exist an exceptionally large (≈6.3 kb) nuclear mitochondrial DNA segment (numt) in the nuclear genome of newly sequenced Diplorchis sp. A 3'-end segment of the 16S rRNA gene encoded by the numt was expressed, suggesting that this gene acquired novel, regulatory functions after the transposition to the nuclear genome. In conclusion, Polyopisthocotylea appears to be the lineage with the fastest-evolving mtDNA sequences among all of Bilateria, but most of the substitutions were accumulated deep in the evolutionary history of this lineage. As the nuclear genome does not exhibit a similar pattern, the circumstances underpinning this evolutionary phenomenon remain a mystery.

The antiepileptic drug valproic acid restores T cell homeostasis and ameliorates pathogenesis of experimental autoimmune encephalomyelitis.

Maintaining a constant number and ratio of immune cells is one critical aspect of the tight regulation of immune homeostasis. Breakdown of this balance will lead to autoimmune diseases such as multiple sclerosis (MS). The antiepileptic drug valproic acid (VPA) was reported to regulate the growth, survival, and differentiation of many cells. However, its function in T cell homeostasis and MS treatment remains unknown. In this study, VPA was found to reduce spinal cord inflammation, demyelination, and disease scores in experimental autoimmune encephalomyelitis, a mouse model of MS. Further study indicated that VPA induces apoptosis in activated T cells and maintains the immune homeostasis. This effect was found to be mainly mediated by the caspase-8/caspase-3 pathway. Interestingly, this phenomenon was also confirmed in T cells from normal human subjects and MS patients. Considering the long history of clinical use and our new findings, we believe VPA might be a safe and effective therapy for autoimmune diseases, such as multiple sclerosis.

Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis.

BACKGROUND: The effective treatment of neuromyelitis optica (NMO) with rituximab has suggested an important role for B cells in NMO pathogenesis. OBJECTIVE: To explore the antibody-independent function of B cells in NMO and relapsing-remitting multiple sclerosis (RRMS). METHODS: Fifty-one NMO patients and 42 RRMS patients in an acute relapse phase and 37 healthy controls (HC) were enrolled in the study. The B cell expression of B cell activating factor receptor (BAFF-R), CXCR5 and very late antigen-4 (VLA-4), the B cell production of interleukin (IL)-10 and interferon (IFN)-γ and the proportion of circulating memory and CD19(+)CD24(high)CD38(high) regulatory B cells were evaluated by flow cytometry. The cerebrospinal fluid (CSF) levels of BAFF and CXCL13 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The CD19(+)CD24(high)CD38(high) regulatory B cell levels and the B cell expression of IL-10 were significantly lower in NMO patients than in RRMS patients and the HC. In aquaporin-4 antibody (AQP4-ab)-positive NMO patients, the B cell IL-10 production and CD19(+)CD24(high)CD38(high) regulatory B cell levels were even lower than in AQP4-ab-negative NMO patients. The CSF BAFF and CXCL13 levels were significantly higher in NMO patients than in patients with RRMS and other non-inflammatory neurologic diseases (ONDs). CONCLUSIONS: The immuno-regulatory properties of B cells are significantly impaired in NMO patients and particularly in AQP4-ab-positive NMO patients. The elevated CSF levels of BAFF and CXCL13 in NMO suggest an enhanced intrathecal B cell recruitment and activation. Our results further define the distinct immunological nature of NMO and RRMS from the B cell perspective.