Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

BACKGROUND: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear. METHODS: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node. RESULTS: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke. CONCLUSIONS: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.

Synergistic Effects of APOE and CLU May Increase the Risk of Alzheimer's Disease: Acceleration of Atrophy in the Volumes and Shapes of the Hippocampus and Amygdala.

BACKGROUND: The volume loss of the hippocampus and amygdala in non-demented individuals has been reported to increase the risk of developing Alzheimer's disease (AD). Many neuroimaging genetics studies mainly focused on the individual effects of APOE and CLU on neuroimaging to understand their neural mechanisms, whereas their synergistic effects have been rarely studied. OBJECTIVE: To assess whether APOE and CLU have synergetic effects, we investigated the epistatic interaction and combined effects of the two genetic variants on morphological degeneration of hippocampus and amygdala in the non-demented elderly at baseline and 2-year follow-up. METHODS: Besides the widely-used volume indicator, the surface-based morphometry method was also adopted in this study to evaluate shape alterations. RESULTS: Our results showed a synergistic effect of homozygosity for the CLU risk allele C in rs11136000 and APOEɛ4 on the hippocampal and amygdalar volumes during a 2-year follow-up. Moreover, the combined effects of APOEɛ4 and CLU C were stronger than either of the individual effects in the atrophy progress of the amygdala. CONCLUSION: These findings indicate that brain morphological changes are caused by more than one gene variant, which may help us to better understand the complex endogenous mechanism of AD.

[Impacts of climate and land use change on water and sediment load in the Northwest arid region, China: With Xiaonanchuan River Basin as a case.] / 西北干旱区气候和土地利用变化对水沙运移的影响­­ä»¥å°å—川流域为例.

Understanding regional water and sediment transport patterns and their responses to climate and land use changes can provide a theoretical basis for the prevention and control of soil erosion, and is an important prerequisite for the integrated development of land and water resources. Based on monthly monitoring meteorological, runoff, and sediment data from 1963 to 2013, combined with the land use data in the 1980s and 2000 and NDVI data, using the Mann-Kendall trend analysis and abrupt change test method, we systematically analyzed the long-term variations of the climate, runoff and sediment transport, with the changes of land use and vegetation coverage being identified in the Xiaonanchuan (XNC) River basin, a typical watershed in the Northwest arid region. Based on the analysis of single element change, the impacts of climate and land use change on water and sediment transport were quantified by the multiple linear regression analysis. Simultaneously, the key action factors were identified. Results showed that air temperature was developing to the polarization, the precipitation increased gradually. A generally warm and wet tendency of climate change and an increased frequency of extreme climate events were found in the XNC River basin. Moreover, the speed and magnitude of climate change were intensified after the 1990s, which was the abrupt change point of the climate. Since the 1980s, with economic and social development, the area of arable land and built land expanded, that of the forest area increased, and the ecological environments were improved in the XNC River basin. Under the dominant driving effects of land use and vegetation coverage change, the runoff and sediment load gradually reduced with the average rate of 1.7×106 m3·(10 a)-1 and 1.5×108 m3·(10 a)-1, respectively. Quantifying the influence of land use and climate change on the water and sediment transport indicated that vegetation cove-rage and mean daily maximum temperature were the two key factors affecting the runoff change, while the vegetation coverage and maximum daily precipitation were the two key factors affecting the sediment load change. Under the condition of current climate change, ecological restoration could be one of the most effective ways to prevent water and soil losses in the arid area.

[Toxoplasma gondii Infection in HIV-infected Individuals in Henan Province].

Genomic DNA was extracted from 1 038 peripheral blood samples from HIV-infected individuals in Henan Province. One-step single-tube nested PCR was performed to amplify the 529 bp repeating sequences of Toxoplasma gondii. Of the 1 038 samples （762 from males and 276 from females）, 66 showed positive PCR results, with a positive rate of 6.4%. The PCR positive rate in males and females was 6.3% （48/762） and 6.5% （18/276） respectively. The PCR positive rate in the married HIV individuals was 4.9%（25/508）, and that in unmarried, divorced and widowed HIV individuals was 7.7% （41/530）（χ2 = 3.451, P> 0.05）. The PCR positive rate in HIV individuals with a high-school educational level or above was 6.9%（34/489）, and that in those below the high-school level was 5.8% （32/549）（χ2 = 0.545, P> 0.05）. The highest infection rate was in the age group of 20-40 years（7.6%, 31/410）. In addition, the Toxoplasma infection rate in those with and without a history of venereal diseases, and those with an unknown history was 8.0%（9/113）, 6.5%（50/773） and 4.6%（7/152） respectively （χ2 = 0.355, P> 0.05）.

Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P.

Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.

Study on the transmission of Toxoplasma gondii by semen in rabbits.

OBJECTIVE: To confirm the transmission of Toxoplasma gondii by semen and to investigate the impact of vaginal status on the transmission of T. gondii in female rabbits. METHODS: Sixteen male rabbits were infected with T. gondii by intraperitoneal injection each with 1 x 10(5) RH tachyzoites. Eight rabbits died in 8-14 d after infection. unde Artificial vagina was used to collect semen from male rabbits weekly before and after infection for 8 weeks. If more than 2 portions of semen from 8 survived male rabbits were collected after infection, the collected semen was mixed weekly for later use. Twenty-seven female rabbits were divided into 4 groups: group 1 with normal vagina (7 rabbits), group 2 with wounded vagina (7), group 3 with trichomonas vaginitis (7) and group 4 with colpomycosis infection (6). Tachyzoites were found in mixed semen digested by trypsinate, and were used for endovaginal artificial insemination to female rabbits by uterine cavity tube once a week for 8 consecutive weeks. 2-3 d after every insemination, 2 ml blood was collected from helix vein of each rabbit, and stored at -40 degrees C for use. Anti-T. gondii antibody was examined by ELISA and the B1 gene of T. gondii was detected by PCR. RESULTS: Anti-T. gondii antibody was detected in some rabbits be (2, 3, 1, and 1 rabbits from each of the groups respectively) on the 16th day after the first insemination. The positive rate of ELISA was 25.9%. The amplification of B1 gene (200 bp) by PCR appeared positive from the blood samples on the 3rd day after the first insemination and the last positive one was proved on the 51th day after the first insemination. Number of positive samples was 2, 1, 3 and 1 in the 4 groups respectively, with an overall PCR positive rate of 18.5%. Only 3 of the 27 rabbits were positive by both ELISA and PCR. CONCLUSIONS: T. gondii can be transmitted by semen and the health status of vagina shows no impact on it.