Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 2 min. The RT-LAMP-VF assay was capable of detecting 2×101 copies/µl of synthesized RNA transcript and 1×101copies/µl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO),the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.
Chemokine receptor CXCR5-mediated control of B cell trafficking in the lymphoid tissues plays a central role in orchestrating the B cell function, which not only guides the colocalization of B cells with follicular helper T cells in the follicular mantle zone but also determines the position of germinal center dark and light zones. However, the mechanisms that regulate the expression of CXCR5 in B cells remain unclear. Here, we show that the expression level of CXCR5 in B cells was substantially reduced in vitro culture conditions, while being maintained in the presence of CD40 signals. Furthermore, CD40 signaling promotes CXCR5 expression in B cells at least partially through noncanonical NF- κ B signaling pathway activation. However, other non-B cells also contributed to the optimal expression of CXCR5 in B cells through cell-cell contact and cytokine secretion. Our findings suggest that CD40 signaling-mediated activation of the noncanonical NF- κ B pathway promotes the expression of CXCR5 in a B cell-intrinsic way to orchestrate the trafficking of B cells.
Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of the host. Schistosome eggs induce M2 macrophages-rich granulomas and these M2 macrophages play critical roles in the maintenance of granuloma and subsequent fibrosis. Reactive oxygen species (ROS), which are highly produced by stimulated macrophages during infection and necessary for the differentiation of M2 macrophages, are massively distributed around deposited eggs in the liver. However, whether ROS are induced by schistosome eggs to subsequently promote M2 macrophage differentiation, and the possible underlying mechanisms as well, remain to be clarified during S. japonicum infection. Herein, we observed that extensive expression of ROS in the liver of S. japonicum-infected mice. Injection of ROS inhibitor in infected mice resulted in reduced hepatic granulomatous responses and fibrosis. Further investigations revealed that inhibition of ROS production in S. japonicum-infected mice reduces the differentiation of M2, accompanied by increased M1 macrophage differentiation. Finally, we proved that S. japonicum egg antigens (SEA) induce a high level of ROS production via both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and mitochondria in macrophages. Our study may help to better understand the mechanism of schistosomiasis japonica-induced hepatic pathology and contribute to the development of potential therapeutic strategies by interfering with ROS production.
Ischemia stroke and epilepsy are two neurological diseases that have significant patient and societal burden, with similar symptoms of neurological deficits. However, the underlying mechanism of their co-morbidity are still unclear. In this study, we performed a combined analysis of six gene expression profiles (GSE58294, GSE22255, GSE143272, GSE88723, GSE163654, and GSE174574) to reveal the common mechanisms of IS and epilepsy. In the mouse datasets, 74 genes were co-upregulated and 7 genes were co-downregulated in the stroke and epilepsy groups. Further analysis revealed that the co-expressed differentially expressed genes (DEGs) were involved in negative regulation of angiogenesis and the MAPK signaling pathway, and this was verified by Gene Set Enrichment Analysis of human datasets and single cell RNA sequence of middle cerebral artery occlusion mice. In addition, combining DEGs of human and mouse, PTGS2, TMCC3, KCNJ2, and GADD45B were identified as cross species conserved hub genes. Meanwhile, molecular docking results revealed that trichostatin A and valproic acid may be potential therapeutic drugs. In conclusion, to our best knowledge, this study conducted the first comorbidity analysis of epilepsy and ischemic stroke to identify the potential common pathogenic mechanisms and drugs. The findings may provide an important reference for the further studies on post-stroke epilepsy.
To investigate the effect of gender on hepatic pathology and antibody-mediated immunity in Schistosoma japonicum-infected C57BL/6 mice.Female and male C57BL/6 mice were infected with S. japonicum, and the hepatic pathological changes were observed using HE and picrosirius red staining in mice 8 weeks post-infection. The serum specific IgG antibody levels against the soluble adult worm antigen (SWA) and soluble egg antigen (SEA) were measured in mice using enzyme-linked immunosorbent assay (ELISA), and the percentages of follicular helper T (Tfh) cells and regulatory T (Treg) cells were detected in mouse spleen and lymph nodes using flow cytometry.HE staining showed no significant difference in the mean area of a single hepatic egg granuloma between female and male mice 8 weeks post-infection with S. japonicum [(28.050 ± 3.576) × 104 μm2 vs. (26.740 ± 4.093) × 104 μm2; t = 0.241, P = 0.821], and picrosirius red staining revealed no statistical differences between female and male mice in terms of the mean proportion of picrosirius red stained hepatic tissues [(7.667 ± 1.856)% vs. (7.667 ± 1.764)%; t = 0, P = 1] or the mean optical density [(0.023 ± 0.003) vs. (0.027 ± 0.007); t = 0.447, P = 0.678]. ELISA detected no significant differences in the serum IgG antibody levels against SWA [(2.098 ± 0.037) vs. (1.970 ± 0.071); t = 1.595, P = 0.162] or SEA [(3.738 ± 0.039) vs. (3.708 ± 0.043); t = 0.512, P = 0.623] between female and male mice 8 weeks post-infection with S. japonicum. Flow cytometry detected significantly greater percentages of Tfh cells in the spleen [female mice, (8.645 ± 1.356)% vs. (1.730 ± 0.181)%, t = 5.055, P = 0.002; male mice, (8.470 ± 1.161)% vs. (1.583 ± 0.218)%, t = 5.829, P = 0.001] and lymph nodes [female mice, (3.218 ± 0.153)% vs. (1.095 ± 0.116)%, t = 11.040, P < 0.001; male mice, (3.673 ± 0.347)% vs. (0.935 ± 0.075)%, t = 8.994, P = 0.001) of both female and male mice 8 weeks post-infection with S. japonicum than in uninfected mice; however, no significant differences were seen between female and male mice 8 weeks post-infection with S. japonicum in terms of the percentages of Tfh cells in the spleen [(8.645 ± 1.356)% vs. (8.470 ± 1.161)%; t = 0.098, P = 0.925] or lymph nodes [(3.218 ± 0.153)% vs. (3.673 ± 0.347)%; t = 1.332, P = 0.241]. There was no significant difference in the proportion of Treg cells in the spleen of male mice between infected and uninfected mice [(10.060 ± 0.361)% vs. (10.130 ± 0.142)%; t = 0.174, P = 0.867], while a higher proportion of Treg cells was seen in the spleen of female mice 8 weeks post-infection with S. japonicum than in uninfected mice [(10.530 ± 0.242)% vs. (9.450 ± 0.263)%; t = 3.021, P = 0.023]. There was no significant difference in the proportion of Treg cells in the spleen between female and male mice infected with S. japonicum [(10.530 ± 0.242)% vs. (10.060 ± 0.361)%; t =1.077, P = 0.323]. In addition, the proportions of Treg cells were significantly greater in the lymph node of S. japonicum -infected female [(17.150 ± 0.805)% vs. (13.100 ± 0.265)%; t = 4.781, P = 0.003] and male mice [(18.550 ± 0.732)% vs. (12.630 ± 0.566)%; t = 6.402, P = 0.001] than in uninfected mice; however, no significant difference was seen between female and male mice 8 weeks post-infection [(17.150 ± 0.805)% vs. (18.550 ± 0.732)%; t = 1.287, P = 0.246].There are no gender-specific hepatic pathological changes or antibody-mediated immunity in C57BL/6 mice post-infection with S. japonicum.［摘要］目的 探讨性别因素对日本血吸虫感染所致C57BL/6小鼠肝脏病理及抗体免疫的影响。方法 雌、雄C57BL/6 小鼠分别感染日本血吸虫8周, 应用HE染色、天狼星红染色观察小鼠肝脏病理变化。采用酶联免疫吸附试验 (ELISA) 检测雌、雄C57BL/6小鼠血清抗可溶性成虫抗原 (SWA) 和可溶性虫卵抗原 (SEA) 特异性IgG抗体水平, 采用流式细胞术检测雌、雄C57BL/6小鼠脾脏、淋巴结中滤泡辅助性T (Tfh) 细胞和调节性T (Treg) 细胞水平。结果 感染日本血吸虫 8 周后, 雌 ([ 28.050 ± 3.576) × 104 μm2]、雄小鼠肝组织中平均单个虫卵肉芽肿面积 ([ 26.740 ± 4.093) × 104 μm2] 差异无统计学意义 (t = 0.241, P = 0.821); 天狼星红染色结果显示, 感染日本血吸虫雌、雄小鼠肝纤维化程度差异亦无统计学意义[天狼星红染色阳性区域平均比例： (7.667 ± 1.856) % vs. (7.667 ± 1.764) %; t = 0, P = 1; 平均光密度： (0.023 ± 0.003) vs. (0.027 ± 0.007); t = 0.447, P = 0.678]。ELISA检测结果显示, 雌、雄小鼠感染日本血吸虫 8 周后血清抗 SWA [ (2.098 ± 0.037) vs. (1.970 ± 0.071); t = 1.595, P = 0.162] 和SEA特异性IgG抗体水平 ([ 3.738 ± 0.039) vs. (3.708 ± 0.043); t = 0.512, P = 0.623] 差异均无统计学意义。流式细胞术检测结果表明, 感染日本血吸虫8周后雌、雄小鼠脾脏[雌鼠： (8.645 ± 1.356) % vs. (1.730 ± 0.181) %, t = 5.055, P = 0.002; 雄鼠： (8.470 ± 1.161) % vs. (1.583 ± 0.218) %, t = 5.829, P = 0.001]、淋巴结 [雌鼠： (3.218 ± 0.153) % vs. (1.095 ± 0.116) %, t = 11.040, P < 0.001; 雄鼠： (3.673 ± 0.347) % vs. (0.935 ± 0.075) %, t = 8.994, P < 0.001]中Tfh细胞比例均显著高于未感染小鼠, 但雌、雄小鼠脾脏 ([ 8.645 ± 1.356) % vs (. 8.470 ± 1.161) %; t = 0.098, P = 0.925]和淋巴结 ([ 3.218 ± 0.153) % vs. (3.673 ± 0.347) %; t = 1.332, P = 0.241]中Tfh细胞比例差异均无统计学意义。感染日本血吸虫8周雄鼠脾脏中Treg细胞比例与未感染小鼠无显著差异 ([ 10.060 ± 0.361) % vs. (10.130 ± 0.142) %; t = 0.174, P = 0.867], 而日本血吸虫感染雌鼠脾脏中Treg细胞比例显著高于未感染小鼠 ([10.530 ± 0.242) % vs. (9.450 ± 0.263) %; t = 3.021, P = 0.023], 但感染日本血吸虫雌、雄小鼠脾脏中Treg 细胞比例差异无统计学意义 ([ 10.530 ± 0.242) % vs. (10.060 ± 0.361) %; t =1.077, P = 0.323]; 日本血吸虫感染8周后, 雌 ([ 17.150 ± 0.805) % vs. (13.100 ± 0.265) %; t = 4.781, P = 0.003]、雄鼠淋巴结中Treg细胞比例均较未感染小鼠显著增加 ([ 18.550 ± 0.732) % vs. (12.630 ± 0.566) %; t = 6.402, P < 0.001], 但感染日本血吸虫雌、雄小鼠淋巴结中Treg 细胞比例差异无统计学意义 ([ 17.150 ± 0.805) % vs. (18.550 ± 0.732) %; t = 1.287, P = 0.246]。结论 利用C57BL/6小鼠研究日本血吸虫感染所致肝脏病理及抗体产生机制时, 不需要考虑性别因素。.
Overviewing human’s history of literature, we could see the bud of sports literature in ancient Greek’s myths and the beginning of it in Homer’s Epic and China’s ancient poems collection The book of Songs. In the revival of modern Olympic Games, Coubertin’s Ode to the Sports shows vivid description of sports images and events from aesthetic perspective. The author made a comprehensive retrieve towards 42,863 poems in The Whole Collection of Tang Poetry and offered people a new perspective to appreciate sports and literature.
Deer antler blastema progenitor cells (ABPCs) are promising for regenerative medicine due to their role in annual antler regeneration, the only case of complete organ regeneration in mammals. ABPC-derived signals show great potential for promoting regeneration in tissues with limited natural regenerative ability. Our findings demonstrate the capability of extracellular vesicles from ABPCs (EVsABPC) to repair spinal cord injury (SCI), a condition with low regenerative capacity. EVsABPC significantly enhanced the proliferation of neural stem cells (NSCs) and activated neuronal regenerative potential, resulting in a 5.2-fold increase in axonal length. Additionally, EVsABPC exhibited immunomodulatory effects, shifting macrophages from M1 to M2. Engineered with activated cell-penetrating peptides (ACPPs), EVsABPC significantly outperformed EVs from rat bone marrow stem cells (EVsBMSC) and neural stem cells (EVsNSC), promoting a 1.3-fold increase in axonal growth, a 30.6% reduction in neuronal apoptosis, and a 2.6-fold improvement in motor function recovery. These findings support ABPC-derived EVs as a promising therapeutic candidate for SCI repair.
Abstract Adult mammals are unable to regenerate bulky bone tissues, making large bone defects clinically challenging. Deer antler represents an exception to this rule, exhibiting the fastest bony growth in mammals, offering a unique opportunity to explore novel strategies for rapid bone regeneration. Here, a bone graft exploiting the biochemical, biophysical, and structural characteristics of antlers is constructed. It is decellularized antler cancellous bone (antler‐DCB) to obtain a bone scaffold. Then, an antler‐based bone graft is constructed by integrating antler‐DCB with antler‐derived biological signals, delivered by extracellular vesicles (EVs) from antler blastema progenitor cells (ABPCs), a novel stem cells responsible for antlerogenesis is discovered. The antler‐based bone graft transformed bone marrow stromal cells into cells with an ABPC‐like phenotype and transcriptomic signature. In vivo, the antler‐based graft triggered rapid bone formation in a rat model, with doubled volume of newly formed bones than commercial DCBs. In addition, the antler‐based graft orchestrated a coordinated process of vascularization, neurogenesis, and immunomodulation during osteogenesis, partially imitating early antlerogenesis. These findings provide practical insights to develop a therapeutic intervention for treating severe bone defects.
To evaluate the mid-term effectiveness of the medium-and-long-term programme for prevention and control of schistosomiasis in Anhui Province.In the programme, the comprehensive measures were carried out, including the schistosomiasis detection and chemotherapy for residents and livestock, snail control, health education, and infectious source control. The mid-term effectiveness of the programme was observed and evaluated longitudinally.From 2004 to 2009, 750 798 schistosomiasis patients and 547 069 persons with the history of infested water contacting were treated. The number of positive cattle treated was 8 462 cattle-times and the number of cattle with history of infested water contact treated was 117 023 cattle-times. The area with snails control by molluscicides was 30 532.0 hm2, and the area with snails control by environmental modification was 13 979.5 hm2. The number of persons who received health education was 31.73 million person-times. The infectious source control measures were carried out in 40% of endemic villages with human infection rate being more than 1%. Up to 2009, the infection rates of population and cattle, and the incidence rate of acute schistosomiasis reduced to 0.51%, 1.25% and 0.30/100 000, respectively. During the period of 2004-2009, the areas with snails fluctuated from 29 065.4 to 29 740.3 hm2. The densities of living snails and infected snails both showed a declining trend in general. During these years, the whole province reached the criteria of infection control, 4 counties reached the criteria of transmission control, and 4 counties reached the criteria of transmission interruption.The effect of the comprehensive strategy of schistosomiasis control is remarkable.
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