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).

Heating promoted super sensitive electrochemical detection of p53 gene based on alkaline phosphatase and nicking endonuclease Nt.BstNBI-assisted target recycling amplification strategy at heated gold disk electrode.

An ultrasensitive electrochemical biosensor for detecting p53 gene was fabricated based on heated gold disk electrode coupling with endonuclease Nt.BstNBI-assisted target recycle amplification and alkaline phosphatase (ALP)-based electrocatalytic signal amplification. For biosensor assembling, biotinylated ssDNA capture probes were first immobilized on heated Au disk electrode (HAuDE), then combined with streptavidin-alkaline phosphatase (SA-ALP) by biotin-SA interaction. ALP could catalyze the hydrolysis of ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA). While AA could induce the redox cycling to generate electrocatalytic oxidation current in the presence of ferrocene methanol (FcM). When capture probes hybridized with p53, Nt.BstNBI would recognize and cleave the duplexes and p53 was released for recycling. Meanwhile, the biotin group dropt from the electrode surface and subsequently SA-ALP could not adhere to the electrode. The signal difference before and after cleavage was proportional to the p53 gene concentration. Furthermore, with electrode temperature elevated, the Nt.BstNBI and ALP activities could be increased, greatly improving the sensitivity and efficiency for p53 detection. A detection limit of 9.5 × 10-17 M could be obtained (S/N = 3) with an electrode temperature of 40 °C, ca. four magnitudes lower than that at 25 °C.

Elevated postprandial triglyceride-rich lipoproteins in patients with diabetes and stable coronary artery disease correlated with early renal damage and systemic inflammation.

BACKGROUND: Dyslipidaemia is key in the development of coronary heart disease (CHD) in patients with diabetes mellitus (DM). Accumulated evidence supports that diabetic nephropathy increases the mortality risk of patients with CHD, while the influence of diabetic dyslipidaemia on renal damage in patients with DM and CHD remains unknown. Moreover, recent data indicate that postprandial dyslipidaemia has predictive value in terms of CHD prognosis, especially in patients with DM. The study aimed to determine the relationship of triglyceride-rich lipoproteins (TRLs) after daily Chinese breakfast on systemic inflammation and early renal damage in Chinese patients with DM and SCAD. METHODS: Patients with DM diagnosed with SCAD while in the Department of Cardiology of Shengjing Hospital from September 2016 to February 2017 were enrolled in this study. Fasting and 4-h postprandial blood lipids, fasting blood glucose, glycated haemoglobin, urinary albumin-to-creatinine ratio (UACR), serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) concentrations, and other parameters were measured. Fasting and postprandial blood lipid profiles and inflammatory cytokines were analysed using a paired t-test. The association between variables was analysed using Pearson or Spearman bivariate analysis. P < 0.05 was considered to be statistically significant. RESULTS: The study enrolled 44 patients in total. Compared with fasting state, postprandial total cholesterol high-density lipoprotein-cholesterol (HDL-C),low-density lipoprotein-cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (non-HDL-C) all showed no significant change. Postprandial serum triglyceride (TG) concentration increased significantly compared with that at fasting (1.40 ± 0.40 vs. 2.10 ± 0.94 mmol/L, P < 0.001), as did serum remnant lipoprotein-cholesterol (RLP-C) (0.54 ± 0.18 mmol/L vs. 0.64 ± 0.25 mmol/L). Pearson analysis revealed that serum TG and RLP-C positively correlated before and after breakfast. Moreover, during fasting, positive correlations were observed between TG and serum IL-6, TNF-α, and UACR. Positive correlations were observed between RLP-C and IL-6, UACR under fasting condition, while both TG and RLP-C were positively correlated with postprandial serum IL-6, TNF-α, and UACR concentrations. Finally, positive correlations were observed between UACR and IL-6 and TNF-α concentration under both fasting and postprandial conditions. CONCLUSIONS: An increase in postprandial TRLs was observed in Chinese patients with DM and SCAD after daily breakfast, and this increase may be related to early renal injury via the induction of systemic inflammation.

Nonalcoholic Fatty Liver Disease as an Emerging Risk Factor and Potential Intervention Target for Atherosclerotic Cardiovascular Diseases.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is an underappreciated independent risk factor for atherosclerotic cardiovascular diseases (ASCVDs). In recent years, the risk of ASCVD has increased along with the prevalence of NAFLD. ASCVD events are highly prevalent and are the main contributor to death in patients with NAFLD. The association between NAFLD and ASCVD has been validated in numerous observational, cohort, and genetic studies. Most of these studies agree that NAFLD significantly increases the risk of developing atherosclerosis and ASCVD. In addition, the underlying proatherosclerotic mechanisms of NAFLD have been gradually revealed; both disorders share several common pathophysiologic mechanisms including insulin resistance, whereas systemic inflammation and dyslipidemia driven by NAFLD directly promote atherosclerosis. Recently, NAFLD, as an emerging risk enhancer for ASCVD, has attracted attention as a potential treatment target for ASCVD. This brief review aims to illustrate the potential mechanistic insights, present recent clinically relevant investigations, and further explore the emerging therapies such as novel antidiabetic and lipid-lowering agents that could improve NAFLD and reduce ASCVD risk.

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.

Tailoring carrier-free nanocombo of small-molecule prodrug for combinational cancer therapy.

The outcomes of monotherapy could not satisfy clinical cancer treatment owing to the challenges of tumor heterogeneity, multi-drug resistance, tumor metastasis and relapse. In response, the significance of combinational cancer therapy has been highlighted. Traditional combinational schemes usually utilize "free" drug for multi drug administration, independently. The diverse pharmacokinetics and biodistribution greatly hinder the antitumor effects and cause systematic toxicity. To tackle the hinderance, various nanoparticulate drug delivery systems (Nano-DDSs) have been developed. However, conventional Nano-DDSs encapsulate drugs into carrier materials through noncovalent interactions, resulting in low drug loading, fixed multi drug encapsulation ratio, chemical instability and carrier-associated toxicity. Recently, carrier-free nanocombos based on self-assembling small-molecule prodrugs (SPNCs) have emerged as a versatile Nano-DDSs for multiple drug delivery. Benefited by the self-assembly capability, SPNCs could be facilely fabricated with distinct merits of ultra-high drug loading, adjustable drug ratio and negligible carrier-associated toxicity. Herein, we summarize the latest trends of SPNCs. First, a basic review on self-assembling small-molecule prodrugs is presented. Additionally, facile techniques to prepare SPNCs are introduced. Furthermore, advanced combinational therapies based on SPNCs are spotlighted with special emphasis on synergistic mechanisms. Finally, future prospects and challenges are discussed.

Elevating Air Temperature May Enhance Future Epidemic Risk of the Plant Pathogen Phytophthora infestans.

Knowledge of pathogen adaptation to global warming is important for predicting future disease epidemics and food production in agricultural ecosystems; however, the patterns and mechanisms of such adaptation in many plant pathogens are poorly understood. Here, population genetics combined with physiological assays and common garden experiments were used to analyze the genetics, physiology, and thermal preference of pathogen aggressiveness in an evolutionary context using 140 Phytophthora infestans genotypes under five temperature regimes. Pathogens originating from warmer regions were more thermophilic and had a broader thermal niche than those from cooler regions. Phenotypic plasticity contributed ~10-fold more than heritability measured by genetic variance. Further, experimental temperatures altered the expression of genetic variation and the association of pathogen aggressiveness with the local temperature. Increasing experimental temperature enhanced the variation in aggressiveness. At low experimental temperatures, pathogens from warmer places produced less disease than those from cooler places; however, this pattern was reversed at higher experimental temperatures. These results suggest that geographic variation in the thermal preferences of pathogens should be included in modeling future disease epidemics in agricultural ecosystems in response to global warming, and greater attention should be paid to preventing the movement of pathogens from warmer to cooler places.

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.

Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude.

BACKGROUND: This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. METHODS: In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. RESULTS: A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8-2.3; χ2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 - 5.2; χ2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p < 0.001). The scores of gastrointestinal symptoms (F = 7.42, p < 0.001) and dizziness (F = 9.82, p < 0.001) but not headache (F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO2) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude (F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO2 (R = 0.38, p < 0.001), and SpO2 was moderately inversely correlated with the LLS (R = -0.48, p < 0.001). CONCLUSION: This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.

Covalent Organic Frameworks Enabling Site Isolation of Viologen-Derived Electron-Transfer Mediators for Stable Photocatalytic Hydrogen Evolution.

Electron transfer is the rate-limiting step in photocatalytic water splitting. Viologen and its derivatives are able to act as electron-transfer mediators (ETMs) to facilitate the rapid electron transfer from photosensitizers to active sites. Nevertheless, the electron-transfer ability often suffers from the formation of a stable dipole structure through the coupling between cationic-radical-containing viologen-derived ETMs, by which the electron-transfer process becomes restricted. Herein, cyclic diquats, a kind of viologen-derived ETM, are integrated into a 2,2'-bipyridine-based covalent organic framework (COF) through a post-quaternization reaction. The content and distribution of embedded diquat-ETMs are elaborately controlled, leading to the favorable site-isolated arrangement. The resulting materials integrate the photosensitizing units and ETMs into one system, exhibiting the enhanced hydrogen evolution rate (34600 µmol h-1 g-1 ) and sustained performances when compared to a single-module COF and a COF/ETM mixture. The integration strategy applied in a 2D COF platform promotes the consecutive electron transfer in photochemical processes through the multi-component cooperation.

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.

Regulation of Recurrent Inhibition by Asynchronous Glutamate Release in Neocortex.

The timing and size of inhibition are crucial for dynamic excitation-inhibition balance and information processing in the neocortex. The underlying mechanism for temporal control of inhibition remains unclear. We performed dual whole-cell recordings from pyramidal cells (PCs) and nearby inhibitory interneurons in layer 5 of rodent neocortical slices. We found asynchronous release (AR) of glutamate occurs at PC output synapses onto Martinotti cells (MCs), causing desynchronized and prolonged firing in MCs and thus imprecise and long-lasting inhibition in neighboring PCs. AR is much stronger at PC-MC synapses as compared with those onto fast-spiking cells and other PCs, and it is also dependent on PC subtypes, with crossed-corticostriatal PCs producing the strongest AR. Moreover, knocking out synaptotagmin-7 substantially reduces AR strength and recurrent inhibition. Our results highlight the effect of glutamate AR on the operation of microcircuits mediating slow recurrent inhibition, an important mechanism for controlling the timing and size of cortical inhibition.

National surveillance on Enterobius vermicularis infections among children at ages of 3 to 9 years in China from 2016 to 2018 / 中国血吸虫病防治杂志

Objective To understand the epidemic status of Enterobius vermicularis infections among children aged 3 to 9 years in China, so as to provide scientific basis for the formulation of the prevention and control strategies for enterobiasis. Methods The national surveillance of enterobiasis was performed in 736 national surveillance sites (counties) from 30 provinces (municipalities/autonomous regions) in China from 2016 to 2018. All surveillance sites were classified into parts according to the geographical directions, including the eastern, western, southern, northern and middle parts, and a township was randomly selected from each part. Then, an administrative village was randomly selected from the township, and 200 permanent residents at ages of over 3 years living in the administrative village were randomly selected using the cluster sampling method. A total of 1 000 residents were examined in each surveillance site. E. vermicularis infections were detected among children at ages of 3 to 9 years using the modified Kato-Katz technique and the adhesive cellophane-tape perianal swab method, and the prevalence of infections was calculated and compared. Results The prevalence of E. vermicularis infections was 2.50%, 2.84% and 2.46% among children at ages of 3 to 9 years in the 736 surveillance sites from 30 provinces (municipalities/autonomous regions) in China from 2016 to 2018, and there was no gender-specific prevalence of E. vermicularis infections (P > 0.05). Enterobiasis was main prevalent in the southern and southwestern part of China (Jiangxi, Guangxi, Guangdong, Sichuan, Fujian, Chongqing and Hainan), with 5.00% prevalence and greater, and the highest prevalence was seen in Jiangxi and Guangxi for successive 3 years. In addition, the prevalence of E. vermicularis infections was higher in children with the Han ethnicity than in those with the minority ethnicity, and a high prevalence was found in children at ages of 4 to 7 years, and a low prevalence seen in children at ages of 3, 8 and 9 years. Conclusions The prevalences of E. vermicularis infections have not changed much among children at ages of 3 to 9 years in China from 2016 to 2018, and high prevalence is seen in southern and southwestern China, which should be given a high priority.

The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli.

Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of FIN in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. FIN reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of FIN does not primarily reflect changes in gonadal steroids. The effects of FIN on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that FIN impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus-pituitary-adrenal (HPA) axis.

Stable Radical Cation-Containing Covalent Organic Frameworks Exhibiting Remarkable Structure-Enhanced Photothermal Conversion.

The production of a radical cation-containing covalent organic framework (COF) has been accomplished by sequential in situ reactions, quaternization, and one-electron reduction of the 2,2'-bipyridine-based COFs. The acid-catalyzed COF formation enables the cis configuration of 2,2'-bipyridyl moieties in the structure, of which the stability arises from the eclipsed stacking of the two-dimensional layered structure. The postfunctionalization generates cyclic alkylated diquats as the sole products from the controlled quaternization. The reduction of diquat cations on the COF skeletons results in a large number of radical cations, which delocalize and uniaxially stack on top of one another by virtue of interlayered π-electronic couplings. The absorption of the near-infrared (NIR) region exhibited by the cationic radical COF is remarkably high owing to the intercharge transfer across the π-coupling interlayers. Also, the long-range array of extended and planar frameworks in such a COF leads to the extra stability of the radical cations against external stresses. The structure-enhanced performance of the COF material is witnessed with photothermal conversion efficiencies of as high as 63.8 and 55.2% when exposed to 808 and 1064 nm lasers, respectively. Further PEG modification on such a COF allows photoacoustic imaging and photothermal therapy in vivo under NIR light illumination to be manifested.

Temperature-Controllable Electrodes with a One-Parameter Calibration.

Electrically heated electrodes have been applied for various chemical and biological sensors. However, previous electrically heated electrodes, including microwires and microdiscs, are usually small and often suffer from the requirement of frequent calibrations of the electrode surface temperature ( Ts) at different environment temperatures. Here, we fabricate a temperature-controllable disk electrode (TCDE) with a conventional size (3-5 mm in diameter). A one-parameter temperature calibration is proposed using a temperature transfer coefficient α and a structural model ( Ts = Te + α ( Th - Te)) to estimate Ts ( Th and Te are the temperature of the heating element and environment, respectively). The value of α is unique for a TCDE and mainly dependent on the structure and materials of the electrodes and the solution in nature. Once α is experimentally determined, Ts can be calibrated and found to be applicable to wide fluctuations in room temperature (15.0-33.0 °C) with errors below 1.5% for three types of disk electrodes (gold, glassy carbon, and platinum). The required Ts can be obtained by just setting Th without thermal characterization between the heating power and Ts. A simple relationship for exploring the dependence of α on the height ( H) and radius ( R) of the electrode materials and other constants ( a, b, c, and R0), α = 1 - c - aH - b ( R - R0)2, is revealed by numerical simulations (COMSOL). The impact of the radii of both the insulating materials of the electrode and the electrochemical cells on Ts is also considered. The effect of the solution thermal conductivity on α is studied. TCDEs are expected to be used as a sensor platform with enhanced performance.

Alterations of Electrophysiological Properties and Ion Channel Expression in Prefrontal Cortex of a Mouse Model of Schizophrenia.

Maternal immune activation (MIA) and juvenile social isolation (SI) are two most prevalent and widely accepted environmental insults that could increase the propensity of psychiatric illnesses. Using a two-hit mouse model, we examined the impact of the combination of these two factors on animal behaviors, neuronal excitability and expressions of voltage-gated sodium (Nav) and small conductance calcium-activated potassium (SK) channels in the prefrontal cortex (PFC). We found that MIA-SI induced a number of schizophrenia-related behavioral deficits. Patch clamp recordings revealed alterations in electrophysiological properties of PFC layer-5 pyramidal cells, including hyperpolarized resting membrane potential (RMP), increased input resistance and enhanced medium after-hyperpolarization (mAHP). MIA-SI also increased the ratio of the maximal slope of somatodendritic potential to the peak slope of action potential upstroke, indicating a change in perisomatic Nav availability. Consistently, MIA-SI significantly increased the expression level of Nav1.2 and SK3 channels that contribute to the somatodendritic potential and the mAHP, respectively. Together, these changes may alter neuronal signaling in the PFC and behavioral states, representing a molecular imprint of environmental insults associated with neuropsychiatric illnesses.

Autapses enhance bursting and coincidence detection in neocortical pyramidal cells.

Autapses are synaptic contacts of a neuron's axon onto its own dendrite and soma. In the neocortex, self-inhibiting autapses in GABAergic interneurons are abundant in number and play critical roles in regulating spike precision and network activity. Here we examine whether the principal glutamatergic pyramidal cells (PCs) also form functional autapses. In patch-clamp recording from both rodent and human PCs, we isolated autaptic responses and found that these occur predominantly in layer-5 PCs projecting to subcortical regions, with very few in those projecting to contralateral prefrontal cortex and layer 2/3 PCs. Moreover, PC autapses persist during development into adulthood. Surprisingly, they produce giant postsynaptic responses (∼5 fold greater than recurrent PC-PC synapses) that are exclusively mediated by AMPA receptors. Upon activation, autapses enhance burst firing, neuronal responsiveness and coincidence detection of synaptic inputs. These findings indicate that PC autapses are functional and represent an important circuit element in the neocortex.

Cadmium induces inflammatory cytokines through activating Akt signaling in mouse placenta and human trophoblast cells.

INTRODUCTION: Several reports demonstrated that cadmium (Cd) had proinflammatory activities. The present study aimed to investigate whether Cd induces inflammatory cytokines in mouse placenta and human trophoblast cells. METHODS: Human JEG-3 cells were treated with different concentration of CdCl2 (0-50 µM) or CdCl2 (25 µM) for different times. The pregnant mice were administered with CdCl2 (3.0 mg/kg, i.p.) on GD15. RESULTS: TNF-α, IL-8 and IL-6 mRNAs were elevated in CdCl2-treated JEG-3 cells. Several inflammatory cytokines were up-regulated in Cd-treated placenta of mice. Moreover, keratinocyte chemokine (KC), a functional analogue of human IL-8, was increased in maternal serum and amniotic fluid from CdCl2-exposed mice. Additional experiment showed that gestational Cd exposure activated Akt signaling in mouse placenta. Co-culture with CdCl2 elevated pAkt level in JEG-3 cells in concentration- and time-dependent manners. LY294002, a specific inhibitor of PI3K, blocked CdCl2-evoked Akt phosphorylation in JEG-3 cells. Concomitantly, LY294002 inhibited CdCl2-induced IL-8 in JEG-3 cells. N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, blocked CdCl2-evoked Akt phosphorylation in mouse placenta and human trophoblast cells. Additionally, NAC attenuated Cd-induced up-regulation of KC in amniotic fluid. DISCUSSION: Cd induces inflammatory cytokines partially through activating Akt signaling in mouse placenta and human trophoblast cells. NAC may be exploited for prevention of Cd-induced placental inflammation.

N-acetylcysteine alleviates cadmium-induced placental endoplasmic reticulum stress and fetal growth restriction in mice.

Cadmium (Cd) is a developmental toxicant that induces fetal growth restriction (FGR). Placental endoplasmic reticulum (ER) stress is associated with FGR. This study investigated the effects of N-acetylcysteine (NAC) on Cd-induced placental ER stress and FGR. Pregnant mice were intraperitoneally injected with CdCl2 daily from gestational day (GD)13 to GD17. As expected, Cd reduced fetal weight and crown-rump length. Cd decreased the internal space of blood vessels in the placental labyrinth layer and inhibited placental cell proliferation. Several genes of growth factors, such as Vegf-a, placental growth factor, Igf1 and Igf1r, and several genes of nutrient transport pumps, such as Glut1, Fatp1 and Snat2, were down-regulated in placenta of Cd-treated mice. Moreover, Cd evoked placental ER stress. Of interest, NAC alleviated Cd-induced FGR. Additional experiment showed that NAC inhibited Cd-induced impairment of placental development and placental ER stress. Therefore, NAC may be exploited for prevention of Cd-induced placental insufficiency and FGR.