Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function.

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin (CAP), the main component of chili pepper. Despite studies in several neurological diseases, the role of TRPV1 in demyelinating diseases remains unknown. Herein, we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone (CPZ)-induced demyelination mouse model. TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice, whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination. TRPV1 was predominantly expressed in Iba1+ microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions. TRPV1 deficiency decreased microglial recruitment to the corpus callosum, with an associated increase in the accumulation of myelin debris. Conversely, the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance. Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment. In addition, the expression of the scavenger receptor CD36 was increased, and that of the glycolysis regulators Hif1a and Hk2 was decreased. We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.

Secretagogin Mediates the Regulatory Effect of Electroacupuncture on Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Surgical Trauma.

Electroacupuncture (EA) improves hypothalamic-pituitary-adrenal (HPA) axis disorder by reducing corticotropin-releasing hormone (CRH) synthesis and release in the paraventricular nucleus (PVN). However, the potential mechanism underlying CRH regulation remains unclear. Secretagogin (SCGN) is closely related to stress and is involved in regulating the release of CRH. We hypothesized that SCGN in the PVN might trigger the HPA system and be involved in EA-mediated modulation of HPA dysfunction caused by surgical trauma. Serum CRH and adrenocorticotropic hormone (ACTH) and plasma corticosterone (CORT) levels at 6 h and 24 h after hepatectomy were determined by radioimmunoassay. CRH and SCGN protein levels in the PVN were detected by western blot and immunofluorescence, and CRH and SCGN mRNA levels in the PVN were determined by means of real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Our studies showed that serum CRH, ACTH, and CORT levels and PVN CRH expression were significantly increased at 6 h and 24 h after hepatectomy in the hepatectomy group compared with the control group, and those in the EA+hepatectomy group were decreased compared with those in the hepatectomy group. The protein and mRNA levels of SCGN in the PVN were also increased after hepatectomy, and their expression in the EA+hepatectomy group was decreased compared with that in the hepatectomy group. When SCGN expression in the PVN was functionally knocked down by a constructed CsCI virus, we found that SCGN knockdown decreased the serum CRH, ACTH, and CORT levels in the SCGN shRNA+hepatectomy group compared with the hepatectomy group, and it also attenuated CRH expression in the PVN. In summary, our findings illustrated that EA normalized HPA axis dysfunction after surgical trauma by decreasing the transcription and synthesis of SCGN.

MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1†.

Precocious puberty (PP) commonly results from premature activation of the hypothalamic-pituitary-gonadal axis (HPGA). Gonadotropin-releasing hormone (GnRH) is the initial trigger for HPGA activation and plays an important role in puberty onset. N-methyl-D-aspartate (NMDA) can promote pulsatile GnRH secretion and accelerates puberty onset. However, the mechanism of N-methyl-D-aspartate receptors (NMDARs) in PP pathogenesis remains obscure. We found that serum GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen (E2) levels, hypothalamic NMDAR1, and GnRH mRNA expression peaked at the vaginal opening (VO) day. Next, the hypothalamic NMDAR1 mRNA and protein levels in rats treated with danazol, a chemical commonly effecting on the reproductive system, were significantly increased at the VO day (postnatal day 24) compared to controls, accompanied by enhanced serum GnRH, LH, FSH, and E2 levels. Further, microRNA-664-2 (miR-664-2) was selected after bioinformatics analysis and approved in primary hypothalamic neurons, which binds to the 3'-untranslated regions of NMDAR1. Consistently, the miR-664-2 expression in hypothalamus of the Danazol group was decreased compared to Vehicle. Our results suggested that attenuated miR-664-2 might participate in PP pathogenesis through enhancing the NMDAR1 signaling.

A metal-organic zeolitic framework with immobilized urease for use in a tapered optical fiber urea biosensor.

A tapered single-mode coreless single-mode (SCS) structure with high sensitivity for sensing refractive index is described. In order to achieve high specificity of optical biosensors, here enzyme capsulation film was achieved by embedding urease in zeolitic imidazolate framework (ZIF-8/urease) through in situ growth approach on the coreless fibers. Determination of urea is achieved through online monitoring of its binding to the urease in zeolitic imidazolate framework. Refractive index change result in wavelength shifts of the optical fiber biosensor. The resonance wavelength exhibits a good linear relationship with urea concentration in the range of 1 to 10 mM with detection limit of 0.1 mM and sensitivity of 0.8 mM/RIU (refractive index unit) if operated with broadband light ranging from 1525 nm to 1590 nm. Final assessment of optical biosensor in real sample was performed where excellent performance in terms of sensitivity and selectivity was observed. Schematic representation of experimental setup and mechanism for urea detection. A tapered single-mode coreless single-mode (SCS) structure is placed between a broadband light source ranging (BBS) and optical spectrum analyzer (OSA). ZIF-8/urease composites are applied as a recognition layer for urea detection.

Soil-transmitted helminthiasis in mainland China from 2016 to 2020: a population-based study.

Background: Soil-transmitted helminthiasis is epidemic in China and many other countries of the world, and has caused substantial burdens to human health. We conducted successive national monitoring in China from 2016 to 2020 to analyze the prevalence, changing trends, and factors influencing soil-transmitted helminthiasis, which provided a reference for future control strategies. Methods: Soil-transmitted helminth monitoring was carried out in 31 provinces (autonomous regions or municipalities, herein after referred to as "provinces") throughout China. Each province determined the number and location of monitoring sites (counties), and a unified sampling method was employed. At least 1,000 subjects were investigated in each monitoring county. Stool samples were collected and the modified Kato-Katz thick smear method was employed for stool examination. Infection data and the details of factors influencing soil-transmitted helminthiasis from 2016 to 2020 were collected from national monitoring sites. Additional influencing factors such as environment, climate and human activities were obtained from authoritative websites. Prevalence of soil-transmitted helminths was presented by species, province, sex, and age group. ArcGIS software was used to conduct spatial autocorrelation and hotspot analysis on the infection data. A Poisson distribution model and SaTScan software were used to analyze the infection data with retrospective spatiotemporal scan statistics. A database was built by matching village-level infection rate data with influencing factors. Subsequently, machine learning methods, including a Linear Regression (LR), a Random Forest (RF), a Gradient Boosted Machine (GBM), and an Extreme gradient boosting (XGBOOST) model was applied to construct a model to analyze the main influencing factors of soil-transmitted helminthiasis. Findings: The infection rates of soil-transmitted helminths at national monitoring sites from 2016 to 2020 were 2.46% (6,456/262,380), 1.78% (5,293/297,078), 1.29% (4,200/326,207), 1.40% (5,959/424,766), and 0.84% (3,485/415,672), respectively. The infection rate of soil-transmitted helminths in 2020 decreased by 65.85% compared to that in 2016. From 2016 to 2020, the infection rate of soil-transmitted helminthiasis was relatively high in southern and southwestern China, including Hainan, Yunnan, Sichuan, Guizhou, and Chongqing. In general, the infection rate was higher in females than in males, with the highest rate in the population aged 60 years and above, and the lowest in children aged 0-6 years. Global autocorrelation and hotspot analyses revealed spatial aggregation in both the national and local distribution of soil-transmitted helminthiasis in China from 2016 to 2020. The hotspots were concentrated in southwestern China. The spatiotemporal scanning analysis revealed aggregation years from 2016 to 2017 located in southwestern China, including Yunnan, Sichuan, Chongqing, Guizhou and Guangxi. The RF model was the best fit model for the infection rate of soil-transmitted helminths in China. The top six influencing factors of this disease in the model were landform, barefoot farming, isothermality, temperature seasonality, year, and the coverage of sanitary toilets. Interpretation: The overall infection rate of soil-transmitted helminths in China showed a decreasing trend from 2016-2020 due to the implementation of control measures and the economic boom in China. However, there are still areas with high infection rates and the distribution of such areas exhibit spatiotemporal aggregation. As a strategic next step, control measures should be adjusted to local conditions based on the main influencing factors and the prevalence of different sites to aid in the control and elimination of soil-transmitted helminthiasis. Funding: This research was funded by the National Key Research and Development Program of China (Grant Nos. 2021YFC2300800 and 2021YFC2300804) and the National Natural Science Foundation of China (Grant No. 32161143036).

Epidemiological Profile and Spatial Patterns of Enterobiasis in Children Aged 3-9 Years in China from 2016 to 2020.

(1) Background: Enterobius vermicularis infection causes a significant health burden in children. The infection occurs throughout the country and remains a serious public concern in China. Therefore, it is necessary to know the situation of E. vermicularis infection, to provide a scientific basis for the disease control and the optimum conditions for children's growth. (2) Methods: Descriptive epidemiological analysis was implemented to demonstrate the status and changing trend of E. vermicularis infection from 2016 to 2020, while the spatial distribution characteristics and spatial-temporal clustering were illuminated by spatial autocorrelation analysis and spatio-temporal scanning analysis. (3) Results: The infection of E. vermicularis showed a fluctuating downward trend with a decline of 32.00% in 2020 compared to that in 2016 and was concentrated in central and southern China. There was no significant difference in infection rate between boys and girls, while the high infection rate was presented in 4-, 5- and 6- year-old children. The hotspots and spatial clustering areas were mainly concentrated in southern China. (4) Conclusions: From 2016 to 2020, the infection rate of E. vermicularis in children aged 3 to 9 years in China demonstrated a declining trend, and its distribution showed spatial clustering, mainly in southern China. Therefore, it is necessary to strengthen surveillance and implement control measures in combination with health education and environmental improvement.

National surveillance of hookworm disease in China: A population study.

BACKGROUND: Hookworm disease is endemic in China and is widespread globally. The disease burden to humans is great. METHODS: The study described the national surveillance of hookworm implemented in 31 provinces/autonomous regions/municipalities (P/A/Ms) of China in 2019. Each P/A/M determined the number and location of surveillance spots (counties). A unified sampling method was employed, and at least 1000 subjects were investigated in each surveillance spot. The modified Kato-Katz thick smear method was employed for stool examination. Fifty samples positive with hookworm eggs were cultured in each surveillance spot to discriminate species between A. duodenale and N. americanus. Twenty-five soil samples were collected from each surveillance spot and examined for hookworm larva. The 2019 surveillance results were analyzed and compared with that of 2016-2018. RESULTS: A total of 424766 subjects were investigated in 31 P/A/Ms of China in 2019, and the overall hookworm infection rate was 0.85% (3580/424766). The weighted infection and standard infection rates were 0.66% (4288357/648063870) and 0.67% (4343844/648063870), respectively. Sichuan province had the highest standard infection rate (4.75%) in 2019, followed by Chongqing (2.54%) and Hainan (2.44%). The standard infection rates of other P/A/Ms were all below 1%, with no hookworm detected in 15 P/A/Ms. The standard hookworm infection rate in the males and the females were 0.61% (2021216/330728900) and 0.71% (2267141/317334970), respectively, with a significant difference between different genders ([Formula: see text] = 17.23, P<0.0001). The highest standard hookworm infection rate (1.97%) was among age ≥ 60 years, followed by 45~59 years (0.77%), 15~44 years (0.37%), and 7~14 years (0.20%). The lowest standard infection rate was among the 0~6 years age group (0.12%). A significant difference was observed among different age groups ([Formula: see text] = 2 305.17, P<0.0001). The constitute ratio for N. americanus, A. duodenale, and coinfection was 78.70% (1341/1704), 2.03% (346/1704), and 1.00% (17/1704), respectively. The detection rate of hookworm larva from soil was 3.45% (71/2056). CONCLUSION: The national surveillance showed that the hookworm infection rate has been decreasing annually from 2016 to 2019, and it is now below 1%. China has made significant progress in controlling hookworm. The national surveillance system is an important way to understand the endemic status and provide important information in this process and thus needs to be continually optimized.

GluN2A/ERK/CREB Signaling Pathway Involved in Electroacupuncture Regulating Hypothalamic-Pituitary-Adrenal Axis Hyperactivity.

The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis caused by stress will inevitably disrupt the homeostasis of the neuroendocrine system and damage physiological functions. It has been demonstrated that electroacupuncture (EA) can modulate HPA axis hyperactivity during the perioperative period. As the initiating factor of the HPA axis, hypothalamic corticotrophin-releasing hormone (CRH) is the critical molecule affected by EA. However, the mechanism by which EA reduces CRH synthesis and secretion remains unclear. Activated N-methyl-D-aspartate receptor (NMDAR) has been linked to over-secretion of hypothalamic CRH induced by stress. To determine whether NMDAR is involved in EA regulating the over-expression of CRH, a surgical model of partial hepatectomy (HT) was established in our experiment. The effect of EA on hypothalamic NMDAR expression in HT mice was examined. Then, we investigated whether the extracellular regulated protein kinases (ERK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway mediated by NMDAR was involved in EA regulating HPA axis hyperactivity. It was found that surgery enhanced the expression of hypothalamic CRH and caused HPA axis hyperactivity. Intriguingly, EA effectively suppressed the expression of CRH and decreased the activation of GluN2A (NMDAR subunit), ERK, and CREB in HT mice. GluN2A, ERK, and CREB antagonists had similar effects on normalizing the expression of CRH and HPA axis function compared with EA. Our findings suggested that surgery enhanced the activation of the hypothalamic GluN2A/ERK/CREB signaling pathway, thus promoting the synthesis and secretion of CRH. EA suppressed the phosphorylation of GluN2A, ERK, and CREB in mice that had undergone surgery, indicating that the GluN2A/ERK/CREB signaling pathway was involved in EA alleviating HPA axis hyperactivity.

Soil-Transmitted Helminthiasis - China, 2018.

What is already known about this topic? Soil-transmitted helminthiasis (STH) is distributed widely in China and a large number of the population is afflicted. However, trends of STH infections are decreasing. What is added by this report? The most recent data indicates that the overall prevalence of STH was 1.29% in 2018 in China, which was based on the national sentinel surveillance and demonstrates a continuous decline pattern. What are the implications for public health practice? Considering the current prevalence in China and various endemic statuses in different regions, precision control measures should be implemented for the control and elimination of STH in China.

Engagement of the National Institute of Parasitic Diseases in control of soil-transmitted helminthiasis in China.

Soil-transmitted helminthiases (STHs) have been widely transmitted in China and the control of STHs was initiated by NIPD-CTDR since its foundation. Three national surveys on STHs have been carried out in China, and the infection rate has dropped from 53.58% in the first national survey (1988-92) to 4.49% in the third national survey (2014-16) due to strong interventions including mass drug administration, health education and environment improvement. National surveillance of STHs started in 2006 and has been implemented successively until now, which allows to understand the endemic status and trends of STHs prevalence in China. Surveillance has been expanded to 30 provinces of China since 2016. Integrated pilot programmes have been implemented between 2006 and 2009, in which an integrated strategy, with health education and control of infection sources as key components, was adopted. Since 2019, new control pilots have been started, which will be continued for five successive years to further explore appropriate control strategies in the current "new era". With the decline of infection rate of STHs, China is approaching the elimination stage for STHs. In order to achieve this final target, poverty alleviation programmes should be integrated with precise control measures, according to real situations.

Enzyme-Embedded Metal-Organic Framework Colloidosomes via an Emulsion-Based Approach.

Improving the activity and stability of enzymes is significant in enzyme immobilization. Here a facile approach to prepare ring-like ZIF-8 colloidosomes and spherical catalase-embedded ZIF-8 colloidosomes is developed via one-step emulsion-based technique at the water/butanol interface. The influence of the concentrations of ZIF-8 nanocrystals and Pluronic F127 as well as the oil-water ratio was investigated. Compared with in situ biomineralization, the colloidosomes prepared via the pickering emulsion method show successful encapsulation of positively charged enzymes. By using catalase as an immobilized model, the immobilized catalase exhibits high biocatalytic activity, stability and recyclability compared with free catalase.

Electroacupuncture Alleviates Surgical Trauma-Induced Hypothalamus Pituitary Adrenal Axis Hyperactivity Via microRNA-142.

Electroacupuncture (EA) could improve the hyperactivity of the hypothalamus pituitary adrenal (HPA) axis induced by hepatectomy. However, its underlying mechanism still remains largely unclear. Here, we found that hypothalamic corticotrophin releasing hormone (CRH) modulates the function of the HPA axis, while hepatectomy induced an HPA axis disorder and EA application could regulate the hypothalamic CRH. We first demonstrated that microRNAs (miRNAs) target on CRH via bioinformatics analysis and screened them in the primary hypothalamic neurons. MicroR-142 (miR-142) and miR-376c were identified to inhibit CRH at the mRNA and protein levels, and a dual luciferase reporter assay confirmed their binding to the 3'-untranslated regions (3'-UTR) of CRH. Further analyses revealed a decrease in hypothalamic miR-142 expression in the hepatectomy rats and an increase in miR-142 and miR-376c after EA intervention. Importantly, the improvement effect of EA on the HPA axis regulatory function in hepatectomy rats was blocked by miR-142 antagomir. Our findings illustrated that EA could up-regulate hypothalamic miR-142 expression and decrease the CRH level to alleviate the hyperactivity of the HPA axis induced by hepatectomy.