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The alpha subunit of type II calcium/calmodulin-dependent protein kinase (CAM II kinase-[Alpha]) plays an important role in longterm synaptic plasticity. We applied preembedding immunocytochemistry (for CAM II kinase-[Alpha]) and postembedding immunogold labeling [for glutamate or [Gamma]-aminobutyric acid (GABA)] to explore the subcellular relationships between transmitter-defined axon terminals and the kinase at excitatory and inhibitory synapses in thalamus and cerebral cortex. Many (but not all) axon terminals ending in asymmetric synapses contained presynaptic CAM II kinase-[Alpha] immunoreactivity; GABAergic terminals ending in symmetric synapses did not. Postsynaptically, CAM II kinase-[Alpha] immunoreactivity was associated with postsynaptic densities of many (but not all) glutamatergic axon terminals ending on excitatory neurons. CAM II kinase-[Alpha] immunoreactivity was absent at postsynaptic densities of all GABAergic synapses. The findings show that CAM II kinase-[Alpha] is selectively expressed in subpopulations of excitatory neurons and, to our knowledge, demonstrate for the first time that it is only associated with glutamatergic terminals pre- and postsynaptically. CAM II kinase-[Alpha] is unlikely to play a role in plasticity at GABAergic synapses.

Four previously undescribed hydroxypropionylated d-glucose derivatives, astrabhotins A–D (1–4), along with ten known compounds α-d-glucose (5), β-d-glucose (6), quebrachitol (7), 3-hydroxypropionic acid (8), oleic acid (9), isoliquiritigenin (10), liquiritigenin (11), odoratin (12), 7β-hydroxysitosterol (13) and daucosterol (14), were isolated from the roots of Astragalus bhotanensis. Their structures were elucidated based on the analyses of extensive spectroscopic data and physicochemical properties. Astrabhotin A (1) reduced the writhing response remarkably with 52.5% inhibition by acetic acid induced writhing test. The analgesic effect of 1 was stronger than the standard drug aspirin. In addition, compounds 1 and 3 showed significant antioxidant activities with IC50 values of 9.9 ± 0.2 and 7.9 ± 0.4 μg/mL, and exhibited weak or moderate cytotoxicity against HepG2 cells with IC50 values of 106.6 ± 2.7 and 42.0 ± 0.9 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

Abstract Background In 2003, Plasmodium vivax malaria has re-emerged in central eastern China including Yongcheng prefecture, Henan Province, where no case has been reported for eleven years. Our goals were to detect the space-time distribution pattern of malaria and to determine significant environmental variables contributing to malaria incidence in Yongcheng from 2006 to 2010, thus providing scientific basis for further optimizing current malaria surveillance and control programs. Methods This study examined the spatial and temporal heterogeneities in the risk of malaria and the influencing factors on malaria incidence using geographical information system (GIS) and time series analysis. Univariate analysis was conducted to estimate the crude correlations between malaria incidence and environmental variables, such as mosquito abundance and climatic factors. Multivariate analysis was implemented to construct predictive models to explore the principal environmental determinants on malaria epidemic using a Generalized Estimating Equation (GEE) approach. Results Annual malaria incidence at town-level decreased from the north to south, and monthly incidence at prefecture-level demonstrated a strong seasonal pattern with a peak from July to November. Yearly malaria incidence had a visual spatial association with yearly average temperature. Moreover, the best-fit temporal model (model 2) (QIC = 16.934, P2 = 0.818) indicated that significant factors contributing to malaria incidence were maximum temperature at one month lag, average humidity at one month lag, and malaria incidence of the previous month. Conclusions Findings supported the effects of environment factors on malaria incidence and indicated that malaria control targets should vary with intensity of malaria incidence, with more public resource allocated to control the source of infections instead of large scale An. sinensis control when malaria incidence was at a low level, which would benefit for optimizing the malaria surveillance project in China and some other countries with unstable or low malaria transmission.

Abstract Background Characterizing the breeding site of Anopheles sinensis is of major importance for the transition from malaria control to elimination in China. However, little information is available especially regarding the characteristics and influencing factors of breeding sites of An. sinensis in Yongcheng City, a representative region of unstable malaria transmission in the Huang-Huai River region of central China. The aims of this study were to determine the breeding site characteristics of An. sinensis and related environmental and physicochemical parameters, to find out which breeding site characteristics could best explain the presence of An. sinensis larvae, and to determine whether the breeding habit of An. sinensis has changed or not. Methods Random repeated cross sectional study was undertaken in six villages of the Yongcheng city characterized by different levels of the historical incidence of P. vivax malaria. The potential breeding sites of An. sinensis larvae in each village were examined twice per month both in the household courtyards and the village surroundings. The larval sampling was done by the standard dipping method. Some important breeding site characterizations were recorded and characterized. The anopheline mosquito larvae and emerged adults were identified to the species level morphologically and to sub-species by the ribosomal DNA PCR technique. Chi-square analysis and logistic regression analysis were applied to determine the importance of factors for explaining the presence or absence of An. sinensis larvae. Results According to the ribosomal DNA PCR assay, all sampled anopheline mosquito larvae and emerged adults belonged to An. sinensis. Only 3 containers that were sampled from the household courtyards were found to contain An. sinensis larvae. There were no differences in the species composition of mosquito larvae among containers that contained water in the household courtyards (P > 0.05). An. sinensis larvae were shown to be present in a total of 60 breeding sites in the village surroundings, this included 8 (13.3%) river fringes, 26 (43.3%) ponds, 23 (38.3%) puddles, and 3 (5.0%) irrigation/drainage ditches. Logistic regression analysis revealed that the breeding site type, water depth, chemical oxygen demand (COD), ammonia nitrogen, and sulphate were found to be the key factors determining the presence of An. sinensis larvae. Approximately 94.9% of An. sinensis larvae inhabited relatively large and medium-sized water bodies, with depths between 0.5 m and 1.0 m (73.3%), COD lower than 2 mg/L (75%), ammonia nitrogen lower than 0.4 mg/L (86.7%), and sulphate lower than 150 mg/L (58.3%), respectively. Conclusion These results indicate that the majority of An. sinensis larval breeding sites were relatively large and medium-sized water bodies with depths between 0.5 m and 1.0 m, and containing low levels of COD, ammonia nitrogen, and sulphate, respectively. For effective An. sinensis larval control, the type of breeding site, water depth, COD, ammonia nitrogen, and sulphate should be given higher priority over other factors in areas where it is the primary vector.

Abstract Background The knowledge of mosquito species diversity and the level of anthropophily exhibited by each species in a region are of great importance to the integrated vector control. Culicine species are the primary vectors of Japanese encephalitis (JE) virus and filariasis in China. Anopheles sinensis plays a major role in the maintenance of Plasmodium vivax malaria transmission in China. The goal of this study was to compare the abundance and host-seeking behavior of culicine species and An. sinensis in Yongcheng city, a representative region of P. vivax malaria. Specifically, we wished to determine the relative attractiveness of different animal baits versus human bait to culicine species and An. sinensis. Results Culex tritaeniorhynchus was the most prevalent mosquito species and An. sinensis was the sole potential vector of P. vivax malaria in Yongcheng city. There were significant differences (P < 0.01) in the abundance of both An. sinensis and Cx. tritaeniorhynchus collected in distinct baited traps. The relative attractiveness of animal versus human bait was similar towards both An. sinensis and Cx. tritaeniorhynchus. The ranking derived from the mean number of mosquitoes per bait indicated that pigs, goats and calves frequently attracted more mosquitoes than the other hosts tested (dogs, humans, and chickens). These trends were similar across all capture nights at three distinct villages. The human blood index (HBI) of female An. sinensis was 2.94% when computed with mixed meals while 3.70% computed with only the single meal. 19:00~21:00 was the primary peak of host-seeking female An. sinensis while 4:00~5:00 was the smaller peak at night. There was significant correlation between the density of female An. sinensis and the average relative humidity (P < 0.05) in Wangshanzhuang village. Conclusions Pigs, goats and calves were more attractive to An. sinensis and Cx. tritaeniorhynchus than dogs, humans, and chickens. Female An. sinensis host-seeking activity mainly occurred from 19:00 to 21:00. Thus, we propose that future vector control against An. sinensis and Cx. tritaeniorhynchus in the areas along the Huang-Huai River of central China should target the interface of human activity with domestic animals and adopt before human hosts go to bed at night.

Objective To analyze the Aedes surveillance data of Chongqing in 2020, and we provide a basis for control of Aedes-borne diseases in Chongqing. Methods Wanzhou, Yubei and Shapingba districts with local dengue outbreaks, and Qianjiang, Dazu districts and Dianjiang county with no local dengue cases in Chongqing in 2019 were selected as investigation points. The larvae of Aedes mosquito were monitored by Breteau index method and mosquito ovitrap index method, adult Aedes mosquito was monitored by double net trap method. The surveillance data of larval and adult Aedes mosquitoes from six surveillance sites of Chongqing were analyzed using Excel 2010 software for a preliminary assessment of the risk of dengue transmission. Results In Apr.-Dec. 2020, the mean Breteau index (BI) of Aedes mosquitoes was 4.50. The BI of Chongqing from June to September were all >5, indicating a risk of dengue transmission; the BI of Shapingba in June, that of Yubei from June to July, and that of Wanzhou from July to August were >10, indicating a risk of dengue outbreak; the mean mosquito ovitrap index (MOI) was 2.15, the MOI of Yubei from July to August was >10, indicating a risk of dengue outbreak. The mean adult density of Aedes was 0.86 mosquitoes per net per hour. The net trap index of Aedes density in Shapingba district and Dianjiang county was 1.81 /(net⋅h) and 1.48 /(net⋅h), respectively, followed by Wanzhou district 1.04 /(net⋅h). The adult density of Aedes in Shapingba from June to September, that of Wanzhou from June to July, that of Dianjiang from May to June and August to September were higher than 2 mosquitoes per net per hour. Conclusion In 2020, the dengue transmission risk varies in different months in the six districts in Chongqing. Yubei, Shapingba and Wanzhou have higher risk than other investigative points. It is suggested that Aedes surveillance and risk assessment should be strengthened in key districts to ensure sustainable control of Aedes for the prevention and control of Aedes-borne diseases in Chongqing. [ABSTRACT FROM AUTHOR]

Abstract Background The development of the corticospinal tract (CST) in higher vertebrates relies on a series of axon guidance decisions along its long projection pathway. Several guidance molecules are known to be involved at various decision points to regulate the projection of CST axons. However, previous analyses of the CST guidance defects in mutant mice lacking these molecules have suggested that there are other molecules involved in CST axon guidance that are yet to be identified. In this study, we investigate the role of plexin signaling in the guidance of motor CST axons in vivo. Results Expression pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in the developing cerebral cortex when the motor CST axons originating from layer V cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we show that motor CST axons that turn dorsally to cross the midline at the pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other CST guidance defects are found in neuropilin-1 mutants, this dorsal turning defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting that the local cues that activate plexin signaling at the dorsal turning point are membrane-bound semaphorins. Further expression pattern study and mutant analysis indicate that Sema6A is one of the local cues for motor CST axon turning at the pyramidal decussation. Conclusion Dorsal turning and midline crossing at the pyramidal decussation is a crucial step to properly direct CST axons into the dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and Sema6A is at least partially required for dorsal turning of the CST axons, while neuropilin-1 is required for proper fasciculation of the tract at midline crossing. Together with previous reports, these results demonstrate that several guidance cues are specifically utilized to regulate the dorsal turning and midline crossing of developing CST axons.

The aim of the present study was to investigate the effects of atorvastatin against heart ischemia/reperfusion (I/R) injury and its potential underlying mechanism. Rats were allocated into the following groups: Sham, I/R, atorvastatin (10 mg/kg daily), fasudil (10 mg/kg daily) and atorvastatin + fasudil in combination. Drugs were administered for 2 weeks prior to I/R injury. I/R was established by ligating the left anterior descending branch (LAD) for 30 min and releasing the ligature for 180 min. The I/R group was found to have increased myocardial infarct size, cardiomyocyte apoptosis, levels of plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-α, superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels and Rho-kinase activity compared with the other treatment groups (P<0.05). Moreover, pretreatment with atorvastatin significantly attenuated Rho-kinase activity, myocardial infarct size, cardiomyocyte apoptosis, levels of plasma IL-6 and TNF-α, SOD activity and MDA levels, and upregulated nitric oxide production. It was also indicated that the specific Rho-kinase inhibitor, fasudil, had the same effects as atorvastatin in I/R. Therefore, the present results suggested atorvastatin may lead to cardiovascular protection, which may be mediated by Rho-kinase inhibition in heart I/R injury. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument have been widely used by scholars around the world to assess the methodological quality of clinical practice guidelines (CPGs). We sought to identify items or domains that are commonly scored low in the assessment, and to systematically review the issues that emerged when evaluators used the AGREE II tool for guideline quality assessment.A systematic search was conducted to identify articles published in medically relevant databases from 2022 to 2023 regarding the use of the AGREE II tool for the assessment of CPGs. We extracted six quality domains and overall quality assessment data of CPGs included in the literature, and processed the data using descriptive statistical analysis, difference analysis, regression analysis, and correlation analysis. A seven‐point Likert scale was used to assess the reporting quality of the included articles.151 relevant publications were identified, including 2081 guidelines published between 1990 and 2022. The results of the regression analysis showed a statistically significant impact of all domains on overall guideline quality (p < 0.001; R2 = 0.777). Domain 1, 2, 3, 4, and 6 scores differed significantly over time (p < 0.001) and were increasing. The score was good for Domain 4 (median 78.00 [IQR: 62.75–89.00]; mean 74.34 [SD 18.85]) and Domain 1 (median 78.00 [IQR: 61.00–90.00]; mean 73.57 [SD 21.12]). Scores were generic for Domain 6 (median 58.33 [IQR: 25.00–83.33]; mean 53.98 [SD 34.13]), Domain 2 (median 53.00 [IQR: 33.30–72.10]; mean 53.30 [SD 24.52]) and Domain 3 (median 51.00 [IQR: 26.02–73.00]; mean 50.44 [SD 27.19]). The score was poor for Domain 5 (median 36.20 [IQR: 20.20–58.32]; mean 40.21 [SD 24.90]). In addition, the quality evaluation results of the included articles showed that 33.1% were evaluated as low and 11.9% as very low.AGREE II tools have facilitated the development of methodological quality for CPGs. Although the quality of CPGs has improved over time, some general low‐quality problems still exist, and solving these problems will be an effective way for developers to upgrade the quality of guidelines. In addition, addressing critical issues in the evaluation of guidelines to present high‐quality study reports would be another way to guide guideline development. [ABSTRACT FROM AUTHOR]