Seeding alpine grasses in low altitude region increases global warming potential during early seedling growth.

Introduction of alpine grasses to low altitude regions has long been a crucial strategy for enriching germplasm diversity, cultivating and acclimating high-quality species, enhancing ecosystem resilience and adaptability, as well as facilitating ecosystem restoration. However, there is an urgent need to investigate the impacts of planting Gramineae seeds on greenhouse gas (GHG) emissions, particularly during the critical stage of early plant growth. In this study, four species of grass seeds (Stipa breviflora, Poa pratensis, Achnatherum splendens, Elymus nutans) were collected from 19 high-altitude regions surrounding the Qinghai-Tibet Plateau and sown at low-altitude. Measurements of GHG emissions at early seedling growth in the mesocosm experiment using static chamber method showed a strong increase in the cumulative emissions of CO2 (5.71%-9.19%) and N2O (11.36%-13.64%) (p < 0.05), as well as an elevated CH4 uptake (2.75%-5.50%) in sites where the four grass species were introduced, compared to bare soil. Consequently, there was a substantial rise in global warming potential (13.87%-16.33%) (p < 0.05) at grass-introduced sites. Redundancy analysis showed that seed traits, plant biomass, and seedling emergence percentage were the main driving biotic factors of three GHGs fluxes. Our study unveils the potential risk of escalating GHG emissions induced by introducing high altitude grasses to low altitude bare soil, elucidating the mechanism through linking seed traits with seedling establishment and environmental feedback. Furthermore, this offers a new perspective for assessing the impact of grass introduction on ecological environment of introduced site.

Ginsenosides and Polysaccharides from Ginseng Co-Fermented with Multi-Enzyme-Coupling Probiotics Improve In Vivo Immunomodulatory Effects.

The active components of ginseng, such as ginsenosides and polysaccharides, have high therapeutic value in treating cancer, decreasing obesity, and enhancing immunity. However, simple primary ginseng treatment cannot maximize this medicinal potential. Therefore, in this study, Panax ginseng was co-fermented with multi-enzyme-coupling probiotics to obtain a fermentation broth with higher levels of ginsenosides, polysaccharides, and probiotics. When compared to other treatment methods for cyclophosphamide-induced immunosuppression in mice, the results reveal that the P. ginseng fermentation broth treated with multi-enzyme-coupling probiotics could significantly improve the immune function of immunosuppressive mice and restore intestinal flora stability. Overall, this processing method will provide a novel strategy for promoting the application of ginseng and the relief of immunosuppression.

Microecosystem of yak rumen on the Qinghai-Tibetan Plateau is stable and is unaffected by soil or grass microbiota.

The rumen of livestock grazing on the Qinghai-Tibetan Plateau (QTP) acts as a transfer station for the circulation of soil, grass, faecal mineral elements and nutrients. Whether the microorganisms from the soil and grass could circulate through livestock rumen and excreted faeces. We studied the structural composition and interactive networks of microbiomes (bacteria and fungi) in soil, grass, and grazing yaks (rumen and faeces) on the QTP by using 16S rRNA gene and internally transcribed spacer (ITS) sequencing technology and to calculate the contribution rate of microorganisms from one habitat to another habitat using SourceTracker analysis. The meta-co-occurrence network revealed that soil, grass, rumen, and faeces comprise four independent habitats. The bacterial and fungal composition was significantly different in these four habitats. Soil microbiota showed the highest alpha diversity and microbial network complexity. Rumen microbiota demonstrated the highest microbial network stability and synergy, while grass endophytes showed the lowest microbial network complexity, stability, and synergy. According to the SourceTracker model, grass contributes 0.02% to the rumen microbes of yaks, while soil microorganisms do not circulate in the rumen. The soil and grass microbiota originating from faeces were 4.5% and 1.2%, respectively. The contribution of soil to grass was found to be 1.1%. Overall, the rumen microbiota of yaks is relatively stable and is only minimally influenced by the microbiota inhabiting the environment under natural grazing conditions. However, the contribution of yaks to soil and grass microbiota is relatively high when compared with the contribution of soil and grass to yaks microbiota.

Coexistence of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G and Neuronal or Glial Antibodies in the Central Nervous System: A Systematic Review.

BACKGROUND: Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) has been considered a diagnostic marker for patients with demyelinating disease, termed "MOG-IgG associated disorder" (MOGAD). Recently, the coexistence of MOG-IgG and other neuronal or glial antibodies has attracted extensive attention from clinicians. In this article, we systematically review the characteristics of MOG-IgG-related antibody coexistence syndrome. METHODS: Two authors independently searched PubMed for relevant studies published before October 2021. We also manually searched the references of each related article. The appropriateness of the included studies was assessed by reading the titles, abstracts, and full texts if necessary. RESULTS: Thirty-five relevant publications that met our inclusion criteria were finally included, of which fourteen were retrospective studies and twenty-one were case reports. A total of 113 patients were reported to show the coexistence of MOG-IgG and neuronal or glial antibodies. Additionally, 68.14% of patients were double positive for MOG-IgG and N-Methyl-D-Aspartate Receptor-IgG (NMDAR-IgG), followed by 23.01% of patients who were double positive for MOG-IgG and aquaporin4-IgG (AQP4-IgG). Encephalitis was the predominant phenotype when MOG-IgG coexisted with NMDAR-IgG, probably accompanied by imaging features of demyelination. Patients with dual positivity for MOG-IgG and AQP4-IgG experienced more severe disease and more frequent relapses. The coexistence of MOG-IgG and antibodies other than NMDAR-IgG and AQP4-IgG was extremely rare, and the clinical presentations were diverse and atypical. Except for patients who were double positive for MOG-IgG and AQP4-IgG, most patients with multiple antibodies had a good prognosis. CONCLUSIONS: MOG-IgG may coexist with neuronal or glial antibodies. Expanded screening for neuronal or glial antibodies should be performed in patients with atypical clinical and radiological features.

SERPINA5 Protein in Cumulus-Oocyte Complexes Increases the Fertilisation Ability of Mouse Sperm.

Obtaining high-quality sperm is key to improving the success rate of assisted reproductive technology (ART). Although cytokines secreted by cumulus-oocyte complexes (COCs) bind to sperm surface receptors to improve sperm quality, the effects of adding mouse COCs to human tubal fluid (HTF) medium on sperm capacitation have not yet been explored. Eight-week-old ICR mouse COCs were added to HTF medium and crushed to obtain the post-modified HTF medium. Compared with using HTF medium, the fertilisation rate and number of sperm combined with the zona pellucida significantly increased after in vitro capacitation using the post-modified HTF medium (P < 0.01). Proteomic and Western blotting analyses showed that the level of SERPINA5 in sperm increased significantly following in vitro capacitation with the post-modified HTF medium (P < 0.05). Immunohistochemical staining analysis demonstrated that SERPINA5 protein was expressed in mouse cumulus cells. A SERPINA5 antibody was added in the post-modified HTF medium to block the effects of SERPINA5 after in vitro capacitation, which significantly decreased the fertilisation rate and the number of sperm combined with the zona pellucida (P < 0.05). Recombinant mouse SERPINA5 protein (1 ~ 2 µg/ml) was added to HTF medium and the fertilisation rate and the number of sperm combined with the zona pellucida significantly increased (P < 0.01). Moreover, recombinant human SERPINA5 protein (5 µg/ml) was added before human semen freezing. Compared with adding no SERPINA5 protein, the percentage of normal sperm morphology and the intact acrosome significantly increased (P < 0.05). Our study provides a reference method for optimising sperm quality in the process of in vitro capacitation.

[Effect of Desmodium renifolium on ovariectomized rat model of osteoporosis via BMP-2/Smads signaling pathway].

This study aimed to investigate the effect of Desmodium renifolium(Linn.) Schindl on ovariectomized rat model of osteoporosis and explore the underlying mechanism. Rats were randomized into a sham group, a model group, a Xianlin Gubao group, and low-, medium-, and high-dose D. renifolium groups. Bilateral oophorectomy was performed in other groups except sham group(removal of bilateral peri-ovarian adipose tissue). The sham group and model group were administrated with equal volume of 0.5% CMC-Na, Xianlin Gubao group with Xianlin Gubao, and D. renifolium groups with different concentrations of alcoholic extract of D. renifolium once a day for 14 weeks. The body weight of rats were recorded during the experiment. The levels of estradiol(E_2), 1,25-dihydroxyvitamin D_3 [1,25(OH)_2D_3], calcium(Ca), and phosphorus(P) in serum were determined after the administration. The femur microstructure was analyzed via micro-CT. RT-PCR and Western blot were employed to respectively determine the mRNA and protein levels of bone morphogenetic protein 2(BMP-2), Runt-related transcription factor 2(Runx2), and osterix(OSX) in the tibia of rats. The results indicated that D. renifolium significantly inhibited the weight growth, improved the uterus appearance, elevated the levels of E_2, Ca, P, and 1,25(OH)_2D_3 in serum, increased the number and reduced the fracture of bone trabeculae, ameliorated the bone microstructure parameters, and up-regulated the mRNA and protein levels of BMP-2, Runx2, and OSX. All the results demonstrated that D. renifolium had significant protective effect on the ovariectomized rat model of osteoporosis by regulating the BMP-2/Smads signaling pathway.

Effectiveness and Safety of Rituximab for Refractory Myasthenia Gravis: A Systematic Review and Single-Arm Meta-Analysis.

Background and Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Nearly 10-30% of patients with MG are refractory to conventional therapy. Rituximab (RTX), a monoclonal antibody targeting CD20, is increasingly used in autoimmune disorders. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of RTX for refractory MG. Methods: Studies published between January 1, 2000 and January 17, 2021 were searched in PubMed, EMBASE, Cochrane Library, and ClincalTrails.gov. Primary outcomes included proportion of patients achieving minimal manifestation status (MMS) or better and quantitative MG (QMG) score change from baseline. Secondary outcomes were glucocorticoids (GC) doses change from baseline and proportion of patients discontinuing oral immunosuppressants. Results: A total of 24 studies involving 417 patients were included in the meta-analysis. An overall 64% (95% confidence interval, 49-77%) of patients achieved MMS or better. The estimated reduction of QMG score was 1.55 (95% confidence interval, 0.88-2.22). The mean reduction of GC doses was 1.46 (95% confidence interval, 1.10-1.82). The proportion of patients discontinuing oral immunosuppressants was 81% (95% confidence interval, 66-93%). Subgroup analyses showed that the proportion of patients achieving MMS or better and discontinuing oral immunosuppressants was higher in MuSK-MG group than those in AChR-MG group. Improvement was more pronounced in patients with mild to moderate MG compared to those with severe MG. Moreover, the efficacy appeared to be independent of the dose of RTX. 19.6% of patients experienced adverse events, most of which were mild to moderate. Only one patient developed progressive multifocal leukoencephalopathy. Conclusions: RTX can alleviate the symptom of weakness, decrease QMG score and reduce the doses of steroids and non-steroid immunosuppressive agents in refractory MG. It is well-tolerated with few severe adverse events. Randomized controlled trials are urgently needed to study the efficacy of RTX in treating refractory MG and to identify the characteristics of patients who might respond well to RTX.

Aberrant expression of miR-199a in newborns with hypoxic-ischemic encephalopathy and its diagnostic and prognostic significance when combined with S100B and NSE.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a disorder mainly due to asphyxia during the perinatal period, and late diagnosis leads to high mortality. In this study, the expression of microRNA-199a (miR-199a) in HIE newborns was investigated, as well as its clinical significance in HIE diagnosis and prognosis. Circulating levels of S100B and NSE in HIE newborns were measured using enzyme-linked immunosorbent assay, and the expression of miR-199a was analyzed using quantitative real-time PCR. The diagnostic value of miR-199a, S100B and NSE was evaluated using the receiver operating characteristic (ROC) analysis, and their prognostic value was assessed by the evaluation of Gesell intellectual development of the HIE newborns. HIE newborns possessed significantly increased levels of S100B and NSE and decreased miR-199a (all P < 0.01). The Neonatal Behavioral Neurological Assessment (NBNA) score of HIE newborns was negatively correlated with S100B and NSE, while was positively correlated miR-199a. The ROC analysis results showed the diagnostic value of serum miR-199a, and the combined detection of miR-199a, S100B and NSE could obtained the highest diagnostic accuracy in HIE newborns. miR-199a expression was lowest in newborns with severe HIE, and it had diagnostic potential to distinguish HIE cases with different severity. Regarding the prognosis of neonatal HIE, the correlation of miR-199a, S100B, NSE with Gesell intellectual development was found in HIE newborns. The decreased miR-199a in HIE newborns serves as a potential diagnostic biomarker and may help to improve the diagnostic and prognostic value of S100B and NSE in neonatal HIE.

The Association Between Apolipoprotein E Gene Polymorphism and In-Stent Restenosis After Extracranial and Intracranial Artery Stenting.

BACKGROUND AND PURPOSE: Neo-atherosclerosis plays a vital role in the incidence of in-stent restenosis (ISR) after extracranial and intracranial artery stenting, and Apolipoprotein (ApoE) gene polymorphism has been reported to be closely related to the occurrence and development of atherosclerosis. The present study aims to investigate the association between ApoE gene polymorphism and ISR after extracranial and intracranial artery stenting. METHODS: A total of 169 patients with successful stent implantation were included in this study. ApoE genotypes were obtained during the postoperative follow-up. Color Doppler ultrasonography of cervical artery or head and neck CT angiography (CTA) was performed on the 1,3,6 and 12 months and then yearly in the clinical follow-up. Multivariate Cox regression analysis of independent risk factors was performed to evaluate the ISR. Kaplan-Meier curves were generated to compare the restenosis -free rate among the patients with different ApoE genotypes. RESULTS: Of the 169 patients, 43 (43/169, 25.4%) developed ISR after a mean follow-up period of 10.4 months (1-35 months). Multivariate analysis showed that genotype E4/E4 (hazard ratio 3.305, P = 0.031, 95% confidence interval 1.118-9.773) and degree of stenosis >90% (hazard ratio 5.083, P = 0.001, 95% confidence interval 1.938-13.327) were significant determinants of ISR. CONCLUSION: ApoE gene polymorphism is closely related to the incidence of ISR after extracranial and intracranial artery stenting, and the genotype E4/E4 is an independent risk factor for ISR.

Deregulated miR-384 serves as a biomarker in neonatal hypoxic-ischemic encephalopathy and alleviates microglia-mediated neuroinflammation.

Microglia-mediated neuroinflammation is important in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). This study aimed to investigate the expression of microRNA-384 (miR-384) in HIE newborns and evaluate the clinical and functional role of miR-384 in HIE diagnosis and neuroinflammation. The expression of miR-384 was estimated using quantitative real-time PCR. The levels of proinflammatory cytokines were examined using ELISA. Receiver operating characteristic (ROC) analysis was applied to evaluate the diagnostic performance of miR-384. The oxygen-glucose deprivation (OGD) experiment was adopted to activate primary neonatal microglia. A putative target of miR-384 was analyzed by bioinformatics prediction and a luciferase reporter assay. The expression of miR-384 was decreased in the serum of HIE newborns and OGD-induced activated microglia. Serum miR-384 had relatively high diagnostic accuracy for the screening of HIE cases from healthy newborns and the differentiation between newborns with different HIE severities. The OGD-induced increase in microglial neuroinflammation was significantly attenuated by the overexpression of miR-384, and AKT3, as a downstream target of miR-384, was inhibited by miR-384 in activated microglia. The data of this study demonstrated that decreased serum miR-384 expression may be a novel noninvasive biomarker for the diagnosis and progression of neonatal HIE. miR-384 can inhibit the neuroinflammation in activated microglia, which may be mediated by targeting AKT3.

Ginsenoside Rd attenuates blood-brain barrier damage by suppressing proteasome-mediated signaling after transient forebrain ischemia.

Ischemic stroke damages the blood-brain barrier (BBB), which leads to brain edema and increases the risk of intracranial hemorrhage. Proteasome inhibition has been found to protect the BBB against cerebral ischemia by suppressing neuroinflammation-mediated matrix metalloproteases-9 (MMP-9) activation. We recently showed that ginsenoside Rd (Rd), a major active ingredient of Panax ginseng, could suppress proteasome-mediated inflammation and be efficient for treating ischemic stroke but downstream mechanisms were still unidentified. For this purpose, Sprague-Dawley rats were subjected to focal cerebral ischemic injury. The activity of proteasome and its downstream effectors nuclear factor-kappa B (NF-κB) and MMP-9 were evaluated. Rd reduced the activity of 20S proteasome in a cell-free assay and inhibited proteasome activity in brain lysates after ischemic stroke. Rd administration suppressed ischemic injury-induced NF-κB activity and IκB degradation mediated by the proteasome. Moreover, Rd reduced the activity and level of MMP-9, a downstream effector of NF-κB, and protected against BBB damage as evidenced by reduced Evan's Blue leakage and brain edema after cerebral ischemic injury. Jointly, these data demonstrate that ginsenoside Rd attenuates the pathogenesis of cerebral ischemia-induced BBB damage, probably by inhibiting proteasome activity and sequentially suppressing NF-κB/MMP-9 pathway.

RPC-Based Orthorectification for Satellite Images Using FPGA.

Conventional rational polynomial coefficients (RPC)-based orthorectification methods are unable to satisfy the demands of timely responses to terrorist attacks and disaster rescue. To accelerate the orthorectification processing speed, we propose an on-board orthorectification method, i.e., a field-programmable gate array (FPGA)-based fixed-point (FP)-RPC orthorectification method. The proposed RPC algorithm is first modified using fixed-point arithmetic. Then, the FP-RPC algorithm is implemented using an FPGA chip. The proposed method is divided into three main modules: a reading parameters module, a coordinate transformation module, and an interpolation module. Two datasets are applied to validate the processing speed and accuracy that are achievable. Compared to the RPC method implemented using Matlab on a personal computer, the throughputs from the proposed method and the Matlab-based RPC method are 675.67 Mpixels/s and 61,070.24 pixels/s, respectively. This means that the proposed method is approximately 11,000 times faster than the Matlab-based RPC method to process the same satellite images. Moreover, the root-mean-square errors (RMSEs) of the row coordinate (ΔI), column coordinate (ΔJ), and the distance ΔS are 0.35 pixels, 0.30 pixels, and 0.46 pixels, respectively, for the first study area; and, for the second study area, they are 0.27 pixels, 0.36 pixels, and 0.44 pixels, respectively, which satisfies the correction accuracy requirements in practice.

Lessons on malaria control in the ethnic minority regions in Northern Myanmar along the China border, 2007-2014.

BACKGROUND: For many countries where malaria is endemic, the burden of malaria is high in border regions. In ethnic minority areas along the Myanmar-China border, residents have poor access to medical care for diagnosis and treatment, and there have been many malaria outbreaks in such areas. Since 2007, with the support of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), a malaria control project was introduced to reduce the malaria burden in several ethnic minority regions. METHODS: A malaria control network was established during the period from 2007 to 2014. Multiple malaria interventions, including diagnosis, treatment, distribution of LLINs and health education, were conducted to improve the accessibility and quality of malaria control services for local residents. Annual cross-sectional surveys were conducted to evaluate intervention coverage and indicators of malaria transmission. RESULTS: In ethnic minority regions where a malaria control network was established, both the annual malaria incidence (19.1 per thousand per year, in 2009; 8.7, in 2014) and malaria prevalence (13.6 % in 2008; 0.43 % in 2014) decreased dramatically during the past 5-6 years. A total of 851 393 febrile patients were detected, 202 598 malaria cases (including confirmed cases and suspected cases) were treated, and 759 574 LLINs were delivered to populations at risk. Of households in 2012, 73.9 % had at least one ITNs/LLINs (vs. 28.3 %, in 2008), and 50.7 % of children less than 5 years and 50.3 % of pregnant women slept under LLINs the night prior to their visit. Additionally, malaria knowledge was improved in 68.4 % of residents. CONCLUSION: There has been great success in improving malaria control in these regions from 2007 to 2014. Malaria burdens have decreased, especially in KOK and WA. The continued maintenance of sustainable malaria control networks in these regions may be a long-term process, due to regional conflicts and the lack of funds, technology, and health workers. Furthermore, information and scientific support from the international community should be offered to these ethnic minority regions to uphold recent achievements.

Effectiveness and impact of the cross-border healthcare model as implemented by non-governmental organizations: case study of the malaria control programs by health poverty action on the China-Myanmar border.

BACKGROUND: In the Yunnan province of China, 18 counties in six prefectures border Myanmar. Due to its particular combination of geographic features, climate conditions, and cultural landscape, the area provides a suitable environment for the spread of insect-borne diseases such as malaria. In five identified Myanmar Special Regions along the China-Myanmar border, economic development is lagging, people live in extreme poverty, and the healthcare system is fragile. Coupled with political and other reasons, this precludes malaria control work to be effectively carried out in Myanmar, resulting in a heavy burden of the disease. Frequent population movements and favorable conditions for malaria transmission on the border fuel difficulties in controlling and eliminating the spread of the disease in the area. CASE PRESENTATION: To reduce the prevalence of malaria in the China-Myanmar border area and improve healthcare services for local residents in this particular environment, Health Poverty Action (HPA) has provided malaria aid in the area since the beginning of 2006, as a sub-recipient of the China Global Fund Malaria Programs. In this case study, we examined HPA's activities as part of its malaria control programs in the area, analyzed and summarized the effectiveness and impact of the cross-border healthcare model as implemented by non-governmental organizations, and put forward suggestions for cross-border health aid models and for the prevention of malaria transmission in the Greater Mekong Subregion. CONCLUSIONS: HPA had carried out a great quantity of successful malaria control activities in border areas between China and Myanmar, strengthened the partnership and established the collaboration, coordination and cooperation channels among stakeholders. HPA has laid good groundwork and developed its valuable model that could be highlighted and referenced.

Investigation and control of a Plasmodium falciparum malaria outbreak in Shan Special Region II of Myanmar along the China-Myanmar Border from June to December 2014.

BACKGROUND: From 2007 to 2013, intensive control measures reduced malaria burden by 90 % along the China-Myanmar border. However, despite these measures a P. falciparum malaria outbreak was reported in the Shan Special Region II of Myanmar in June of 2014. METHODS: Epidemiological, parasitological and entomological investigations were performed. Dihydroartemisinin piperaquine (DAPQ) was immediately administered to treat parasite positive individuals. Long lasting insecticidal nets (LLIN), indoor residual spraying (IRS) with insecticides and behavior change communication (BCC) were also provided for outbreak control. An embedded efficacy study was conducted evaluating DP. Molecular genotyping via polymerase chain reaction (PCR) was performed on the Kelch gene on chromosome 13. RESULTS: All infections were identified as Plasmodium falciparum by RDT and microscopy. Two fatalities resulted from the outbreak. The attack rate was 72.8 % (67/92) and the incidence density rate was 14.2 per 100 person-weeks. The positive rate of rapid diagnostic test (RDT) was 72.2 % (65/90) and microscopically-determine parasite rate 42.2 % (38/90). Adjusted odds ratio (OR) of multivariate logistic regression analysis for aged <15 years, 15-45 years, inappropriate treatment from a private healer and lack of bed nets were 13.51 (95 % confidence interval, 2.21-105.89), 7.75 (1.48-44.97), 3.78 (1.30-46.18) and 3.21(1.21-15.19) respectively. In the six surrounding communities of the outbreak site, positive RDT rate was 1.2 % (4/328) and microscopically-determine parasite rate 0.6 % (2/328). Two light traps collected a total of 110 anopheline mosquitoes including local vectors, An. minimus, An. sinensis and An. maculates. After intensive control, the detection of malaria attacks, parasites and antigen were reduced to zero between July 1 and December 1, 2014. The cure rate of P. falciparum patients at day 42 was 94.3 % (95 % CI, 80.8-99.3 %). The PCR did not detect K13-propeller mutations. CONCLUSION: Imported P. falciparum caused the outbreak. Age, seeking inappropriate treatment and lack of bed nets were risk factors for infection during the outbreak. P. falciparum was sensitive to treatment with DAPQ. The integrated measures controlled the outbreak and prevented the spread of P. falciparum effectively. The results of this study indicate that malaria control on the China-Myanmar border, especially among special populations, needs further collaboration between China, Myanmar and international societies.

Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis.

The paradigm that B cells are nonphagocytic was taken for granted for a long time until phagocytic B cells were found in early vertebrate animals. Thereafter, limited evidence has shown that human B cells may also internalize bacteria. However, whether human B cells can actively phagocytose bacteria has been less extensively investigated; in particular, the mechanisms and significance of the phagocytosis require clarification. Here, we show that the human Raji B cell line can phagocytose both live and dead Mycobacterium tuberculosis (Mtb), and the phagocytosed Mtb in turn affects the immune functions of the B cells. After incubation of Raji cells with Mtb, our confocal microscopy, electron microscopy and flow cytometry data showed that Raji cells effectively engulfed Mtb as well as latex beads. The phagocytic rate was proportional to the incubation time and the amount of Mtb or beads added. Additionally, we found that normal human serum could enhance the ability of Raji cells to phagocytose Mtb, while heat-inactivated serum reversed this promoting effect. The phagocytic process of B cells could partially be inhibited by cytochalasin B, an actin inhibitor. Importantly, the phagocytosed Mtb could regulate B cell immune functions, such as stimulating IgM production and upregulating the expression of the antigen-presenting costimulatory molecules CD80 and CD86. Therefore, our results provide the first evidence that human B cells can phagocytose Mtb in an active manner that is independent of bacterial viability, and phagocytosed Mtb can in turn regulate the immune activation of B cells.

Ginsenoside Rd Is Efficacious Against Acute Ischemic Stroke by Suppressing Microglial Proteasome-Mediated Inflammation.

A great deal of attention has been paid to neuroprotective therapies for cerebral ischemic stroke. Our two recent clinical trials showed that ginsenoside Rd (Rd), a kind of monomeric compound extracted from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious for the treatment of ischemic stroke. In this study, we conducted a pooled analysis of the data from 199 patients with acute ischemic stroke in the first trial and 390 in the second to reanalyze the efficacy and safety of Rd. Moreover, animal stroke models were carried out to explore the possible molecular mechanisms underlying Rd neuroprotection. The pooled analysis showed that compared with placebo group, Rd could improve patients' disability as assessed by modified Rankin Scale (mRS) score on day 90 post-stroke and reduce neurologic deficits on day 15 or day 90 post-stroke as assessed by NIH Stroke Scale (NIHSS) and Barthel Index (BI) scores. For neuroprotective mechanisms, administration of Rd 4 h after stroke could inhibit ischemia-induced microglial activation, decrease the expression levels of various proinflammatory cytokines, and suppress nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation. An in vitro proteasome activity assay revealed a significant inhibitory effect of Rd on proteasome activity in microglia. Interestingly, Rd was showed to have less side effects than glucocorticoid. Therefore, our study demonstrated that Rd could safely improve the outcome of patients with ischemic stroke, and this therapeutic effect may result from its capability of suppressing microglial proteasome activity and sequential inflammation.

Treatment of Rivaroxaban versus Aspirin for Non-disabling Cerebrovascular Events (TRACE): study protocol for a randomized controlled trial.

BACKGROUND: Transient ischemic attack (TIA) or minor ischemic stroke represents the largest group of cerebrovascular disease, and those patients have a high risk of early recurrent stroke. Over decades, anticoagulation therapy has been used prudently in them for likely increasing the risk of intra-/extra-cranial hemorrhagic complications. However, recently rivaroxaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants, while carrying significantly less risk of intracranial hemorrhage. Therefore, we assumed that patients may benefit from rivaroxaban if treated soon after TIA or minor stroke, and designed this adequately powered randomized study, TRACE. METHODS AND DESIGN: The Treatment of Rivaroxaban versus Aspirin in Non-disabling Cerebrovascular Events (TRACE) study is a randomized, double-blind clinical trial with a target enrollment of 4400 patients. A 14-days regimen of rivaroxaban 10 mg daily or a 14-days regimen of aspirin 100 mg daily will be administrated to randomized participants with acute TIA or minor stroke, defined as National Institute of Health Stroke Scale scores ≤ 3. The primary efficacy end point is percentage of patients with any stroke (ischemic or hemorrhage) at 14 days. Study visits will be performed at the day of randomization, day 14 and day 90. DISCUSSION: Even though the new oral anticoagulants seem to be both safe and effective, few clinical trials have been carried out to test their effect on non-disabling cerebrovascular events. Treatment with rivaroxaban may prevent more cerebrovascular events with an acceptable risk profile after TIA or minor stroke, compared with aspirin, thus helping to improve the outcome of the disease. TRIAL REGISTRATION: No. NCT01923818.

Involvement of cannabinoid receptors in infrasonic noise-induced neuronal impairment.

Excessive exposure to infrasound, a kind of low-frequency but high-intensity sound noise generated by heavy transportations and machineries, can cause vibroacoustic disease which is a progressive and systemic disease, and finally results in the dysfunction of central nervous system. Our previous studies have demonstrated that glial cell-mediated inflammation may contribute to infrasound-induced neuronal impairment, but the underlying mechanisms are not fully understood. Here, we show that cannabinoid (CB) receptors may be involved in infrasound-induced neuronal injury. After exposure to infrasound at 16 Hz and 130 dB for 1-14 days, the expression of CB receptors in rat hippocampi was gradually but significantly decreased. Their expression levels reached the minimum after 7- to 14-day exposure during which the maximum number of apoptotic cells was observed in the CA1. 2-Arachidonoylglycerol (2-AG), an endogenous agonist for CB receptors, reduced the number of infrasound-triggered apoptotic cells, which, however, could be further increased by CB receptor antagonist AM251. In animal behavior performance test, 2-AG ameliorated the infrasound-impaired learning and memory abilities of rats, whereas AM251 aggravated the infrasound-impaired learning and memory abilities of rats. Furthermore, the levels of proinflammatory cytokines tumor necrosis factor alpha and interleukin-1ß in the CA1 were upregulated after infrasound exposure, which were attenuated by 2-AG but further increased by AM251. Thus, our results provide the first evidence that CB receptors may be involved in infrasound-induced neuronal impairment possibly by affecting the release of proinflammatory cytokines.

MicroRNAs as Potential Biomarkers for Diagnosing Cancers of Central Nervous System: a Meta-analysis.

Recent studies have shown abnormal microRNA (miRNA) expression levels in the central nervous system (CNS) of cancer patients, suggesting that miRNAs may serve as promising biomarkers for cancers of CNS. However, other studies have arrived at conflicting results. Therefore, this meta-analysis aims to systematically measure the potential diagnostic value of miRNAs for CNS cancers. Electronic databases as well as other sources were searched until to April 12, 2014 for relevant articles. Data from different studies were pooled using the random-effects model. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and area under the SROC curve (AUC) value were used to estimate overall diagnostic performance. Twenty-three studies from 6 articles were included in the current meta-analysis with a total of 299 CNS cancer patients and 418 controls. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.85 (95% CI, 0.80-0.89), 0.83 (95% CI, 0.76-0.88), 5.1 (95% CI, 3.4-7.5), 0.18 (95% CI, 0.12-0.26), 28 (95% CI, 14-58), and 0.91 (95% CI, 0.88-0.93), respectively. Subgroup analyses showed that cerebrospinal fluid (CSF)-based miRNAs assays yielded more accurate results and seemed to be more sensitive in diagnosing of primary central nervous system lymphoma (PCNSL). In conclusion, miRNAs may be suitable for serving as noninvasive biomarkers for CNS cancers detection. However, further validation based on a larger sample of patients and controls is still required.