Implications for biological invasion of non-native plants for sale in the world's largest online market.

Internet trade is increasingly recognized as a dispersal pathway of non-native plant species that is difficult to monitor. We sought to identify non-native flora present in the Chinese online market, the largest e-commerce market globally, and to decipher the effect of existing trade regulations, among other variables, on e-trading patterns and to inform policy. We used a comprehensive list of 811 non-native plant species in China present in 1 of the 3 phases of the invasion continuum (i.e., introduced, naturalized, and invasive). The price, propagule types, and quantities of the species offered for sale were retrieved from 9 online stores, including 2 of the largest platforms. Over 30% of the non-native species were offered for sale in the online marketplaces; invasive non-native species dominated the list (45.53%). No significant price difference was observed across the non-native species of the 3 invasion categories. Among the 5 propagule types, a significantly higher number of non-native species were offered for sale as seeds. The regression models and path analyses consistently revealed a direct positive effect of the number of uses and species' minimum residence time and an indirect effect of biogeography on the pattern of trade in non-native plant species when minimal phylogenetic signal was detected. A review of the existing phytosanitary regulations in China revealed their inadequacy in managing e-trading of non-native plant species. To address the problem, we propose integration of a standardized risk assessment framework that considers perceptions of stakeholders and is adaptable based on continuous surveillance of the trade network. If implemented successfully, the measures could provide a template for other countries to strengthen trading regulations for non-native plant species and take proactive management measures.

La venta de plantas no nativas en el mercado virtual más grande y sus implicaciones para la invasión biológica Resumen El mercado virtual en internet se reconoce cada vez más como una vía de dispersión de especies vegetales no nativas difícil de controlar. Intentamos identificar la flora no nativa presente en el mercado virtual chino, el mayor mercado de comercio electrónico del mundo, para descifrar el efecto de las regulaciones comerciales vigentes, entre otras variables, en los patrones de comercio electrónico e informar a las políticas. Utilizamos una lista integral de 811 especies de plantas no nativas de China presentes en una de las tres fases de invasión (es decir, introducidas, naturalizadas o invasoras). El precio, los tipos de propágulos y las cantidades de las especies puestas a la venta se recuperaron de nueve tiendas en línea, incluidas dos de las mayores plataformas. Más del 30% de las especies no nativas se pusieron a la venta en los mercados en línea; las especies no nativas invasoras dominaron esta lista (45,53%). No se observaron diferencias significativas de precio entre las especies no nativas en las tres categorías de invasión. Entre los cinco tipos de propágulos, se puso a la venta un número significativamente mayor de especies no nativas en forma de semillas. Los modelos de regresión y los análisis de trayectoria revelaron un efecto positivo directo y constante del número de usos y del tiempo mínimo de residencia de las especies y un efecto indirecto de la biogeografía sobre el patrón de comercio de especies vegetales no nativas cuando se detectó una señal filogenética mínima. Una revisión de la normativa fitosanitaria vigente en China reveló su insuficiencia para gestionar el comercio electrónico de las especies vegetales no nativas. Para abordar el problema, proponemos la integración de un marco normalizado de evaluación de riesgos que tenga en cuenta las percepciones de los actores y sea adaptable en función de la vigilancia continua de la red comercial. Si se aplican con éxito, las medidas podrían servir de modelo para que otros países refuercen la normativa sobre comercio de especies vegetales no nativas y adopten medidas proactivas de gestión.

A longitudinal study on the effect of extreme temperature on non-accidental deaths in Hulunbuir City based on DLNM model.

OBJECTIVE: To explore the frequency and effect of extreme temperature on the non-accidental death rate in Hulunbuir, a Chinese ice city. METHODS: From 2014 to 2018, mortality data of residents residing in Hulunbuir City were collected. The lag and cumulative effects of extreme temperature conditions on non-accidental death and respiratory and circulatory diseases were analyzed by distributed lag non-linear models (DLNM). RESULTS: The risk of death was the highest during high-temperature conditions, the RR value was 1.111 (95% CI 1.031 ~ 1.198). The effect was severe and acute. The risk of death during extreme low-temperature conditions peaked on the fifth day, (RR 1.057; 95% CI 1.012 ~ 1.112), then decreased and was maintained for 12 days. The cumulative RR value was 1.289 (95% CI 1.045 ~ 1.589). Heat significantly influenced the incidence of non-accidental death in both men (RR 1.187; 95% CI 1.059-1.331) and women (RR 1.252; 95% CI 1.085-1.445). CONCLUSIONS: Regardless of the temperature effect, the risk of death in the elderly group (≥ 65 years) was significantly higher than that of the young group (0-64 years). High-temperature and low-temperature conditions can contribute to the increased number of deaths in Hulunbei. While high-temperature has an acute effect, low-temperature has a lagging effect. Elderly and women, as well as people with circulatory diseases, are more sensitive to extreme temperatures.

Histo-epidemiological profile of breast cancers among women in the Central African Republic: about 174 cases.

BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide and leading cause of cancer deaths indeveloping countries. There is very limited data on BC in the Central African Republic. The purpose of this study was to describe the epidemiological and histopathological characteristics of BC in Bangui. METHODS: This retrospective study reviewed cancer data registries and medical records from the Pathology Unit of the National Laboratory in Bangui and the General Surgery and Gyneacology service from 2003 to 2015. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods. RESULTS: In total, 174 cases of BC were recorded, with an average annual frequency of13.4 cases per year. The age of the women at diagnosis varied from 16 to 90 years with a median of 45.5 years and InterQuartile range (IQR) 18 years. The age group of 45-54 years represented the majority of the study population (n = 51, 29.3%).About 25.9%ofthe patients were non-educated and 85.6% lived in cities. Over 48 % of the women were housewives with a moderate economic status (n = 99, 56.9%). Sixty nine percent of the specimens received at the pathology unit were pieces of breast tumour. Invasive ductal carcinoma (n = 113, 64.9%) was the main histological form and most of the tumours were of Grade III (n = 14, 46.7%). The only imaging assessment was ultrasound performed in (n = 53, 30.4%) women. Surgery was performed in (n = 166, 95.4%) patients, while (n = 159, 91.4%) received complementary chemotherapy. At the end of the study, 84.5%of the cases had died, 12.1% were alive and 3.4% were considered "lost to follow-up". CONCLUSION: BC is an important public health problem and affected most of the younger Central African women. Epidemiological and histological characteristics are more or less common to those described other developing countries. It is imperative to improve the awareness of health care institutions and women on the burden of BC, to carry out early screening of BC, and to strengthen the capacity of women's health care system.

High-speed true random number generation based on paired memristors for security electronics.

True random number generator (TRNG) is a critical component in hardware security that is increasingly important in the era of mobile computing and internet of things. Here we demonstrate a TRNG using intrinsic variation of memristors as a natural source of entropy that is otherwise undesirable in most applications. The random bits were produced by cyclically switching a pair of tantalum oxide based memristors and comparing their resistance values in the off state, taking advantage of the more pronounced resistance variation compared with that in the on state. Using an alternating read scheme in the designed TRNG circuit, the unbiasedness of the random numbers was significantly improved, and the bitstream passed standard randomness tests. The Pt/TaO x /Ta memristors fabricated in this work have fast programming/erasing speeds of ∼30 ns, suggesting a high random number throughput. The approach proposed here thus holds great promise for physically-implemented random number generation.

S-nitrosylation of NADPH oxidase regulates cell death in plant immunity.

Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection. However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals.

Reproductive risk factors associated with breast cancer in women in Bangui: a case-control study.

BACKGROUND: Breast cancer (breast Ca) is recognised as a major public health problem in the world. Data on reproductive factors associated with breast Ca in the Central African Republic (CAR) is very limited. This study aimed to identify reproductive variables as risk factors for breast Ca in CAR women. METHODS: A case-control study was conducted among 174 cases of breast Ca confirmed at the Pathology Unit of the National Laboratory in Bangui between 2003 and 2015 and 348 age-matched controls. Data collection tools included a questionnaire, interviews and a review of medical records of patients. Data were analysed using SPSS software version 20. Odd ratios and 95% confidence intervals (CI) for the likelihood of developing breast Ca were obtained using unconditional logistic regression. RESULTS: In total, 522 women with a mean age of 45.8 (SD = 13.4) years were enrolled. Women with breast Ca were more likely to have attained little or no education (AOR = 11.23, CI: 4.65-27.14 and AOR = 2.40, CI: 1.15-4.99), to be married (AOR = 2.09, CI: 1.18-3.71), to have had an abortion (AOR = 5.41, CI: 3.47-8.44), and to be nulliparous (AOR = 1.98, CI: 1.12-3.49). Decreased odds of breast Ca were associated with being employed (AOR = 0.32, CI: 0.19-0.56), living in urban areas (AOR = 0.16, CI: 0.07-0.37), late menarche (AOR = 0.18, CI: 0.07-0.44), regular menstrual cycles (AOR = 0.44, CI: 0.23-0.81), term pregnancy (AOR = 0.26, CI: 0.13-0.50) and hormonal contraceptive use (AOR = 0.62, CI: 0.41-0.93). CONCLUSION: Breast Ca risk factors in CAR did not appear to be significantly different from that observed in other populations. This study highlighted the risk factors of breast Ca in women living in Bangui to inform appropriate control measures.

Nitric oxide and S-nitrosoglutathione function additively during plant immunity.

Nitric oxide (NO) is emerging as a key regulator of diverse plant cellular processes. A major route for the transfer of NO bioactivity is S-nitrosylation, the addition of an NO moiety to a protein cysteine thiol forming an S-nitrosothiol (SNO). Total cellular levels of protein S-nitrosylation are controlled predominantly by S-nitrosoglutathione reductase 1 (GSNOR1) which turns over the natural NO donor, S-nitrosoglutathione (GSNO). In the absence of GSNOR1 function, GSNO accumulates, leading to dysregulation of total cellular S-nitrosylation. Here we show that endogenous NO accumulation in Arabidopsis, resulting from loss-of-function mutations in NO Overexpression 1 (NOX1), led to disabled Resistance (R) gene-mediated protection, basal resistance and defence against nonadapted pathogens. In nox1 plants both salicylic acid (SA) synthesis and signalling were suppressed, reducing SA-dependent defence gene expression. Significantly, expression of a GSNOR1 transgene complemented the SNO-dependent phenotypes of paraquat resistant 2-1 (par2-1) plants but not the NO-related characters of the nox1-1 line. Furthermore, atgsnor1-3 nox1-1 double mutants supported greater bacterial titres than either of the corresponding single mutants. Our findings imply that GSNO and NO, two pivotal redox signalling molecules, exhibit additive functions and, by extension, may have distinct or overlapping molecular targets during both immunity and development.

Encapsulation layer design and scalability in encapsulated vertical 3D RRAM.

Here we propose a novel encapsulated vertical 3D RRAM structure with each resistive switching cell encapsulated by dielectric layers, contributing to both the reliability improvement of individual cells and thermal disturbance reduction of adjacent cells due to the effective suppression of unwanted oxygen vacancy diffusion. In contrast to the traditional vertical 3D RRAM, encapsulated bar-electrodes are adopted in the proposed structure substituting the previous plane-electrodes, thus encapsulated resistive switching cells can be naturally formed by simply oxidizing the tip of the metal bar-electrodes. In this work, TaO x -based 3D RRAM devices with SiO2 and Si3N4 as encapsulation layers are demonstrated, both showing significant advantages over traditional unencapsulated vertical 3D RRAM. Furthermore, it was found thermal conductivity and oxygen blocking ability are two key parameters of the encapsulation layer design influencing the scalability of vertical 3D RRAM. Experimental and simulation data show that oxygen blocking ability is more critical for encapsulation layers in the relatively large scale, while thermal conductivity becomes dominant as the stacking layers scale to the sub-10 nm regime. Finally, based on the notable impacts of the encapsulation layer on 3D RRAM scaling, an encapsulation material with both excellent oxygen blocking ability and high thermal conductivity such as AlN is suggested to be highly desirable to maximize the advantages of the proposed encapsulated structure. The findings in this work could pave the way for reliable ultrahigh-density storage applications in the big data era.

Epidemiology of breast cancer: retrospective study in the Central African Republic.

BACKGROUND: Breast cancer is recognised as a major public health problem in developing countries; however, there is very limited evidence about its epidemiology in the Central African Republic. The aim of this study was to investigate the epidemiological and histopathological characteristics of breast cancer in Bangui. METHODS: This is a retrospective study based on the data collected from pathological anatomy records from 2003 to 2015 in Bangui. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods. RESULTS: The mean age was 45.83 (SD = 13.5) years. The age group of 45-54 years represented the majority of the study population (29.3%). Over 69.5% of the women were housewives with a moderate economic status (56.9%). Less than 14% of the study population had a level of academic degree and 85.6% lived in cities. The breast cancer prevalence was 15.27%. The age-standardized incidence and death by world population (ASW) were 11.19/100,000 and 9.97/100,000 respectively. 50-54 years were most affected. Left breast cancer is mainly common and the time between first symptoms and consultation is more than 48 months. Most (69%) of the samples analysed were lumpectomy. The most common morphology of breast cancer was invasive ductal carcinoma (64.9%). Scarff Bloom Richardson III was the main grade in both common pathological types, but their proportion showed no significant increase along with time (χ2 = 7.06, p = 0.54). Invasion of regional lymph node differed significantly among the pathological type of breast cancer (χ2 = 24.6, p = 0.02). Surgery and chemotherapy were appropriate treatment yet 84.5% of the cases died. CONCLUSION: The findings of this study showed that breast cancer is common and mostly affected women. Epidemiological trends are more or less common to those of developing countries with a predominance of invasive ductal carcinoma. However, most of the women studied live in an urban area and developed the disease in advanced stage. The establishment of an appropriate framework will effectively contribute to promoting the early detection and reducing the incidence of this disease in the population.

Optimizing vancomycin dosing in pediatrics: a machine learning approach to predict trough concentrations in children under four years of age.

BACKGROUND: Vancomycin trough concentration is closely associated with clinical efficacy and toxicity. Predicting vancomycin trough concentrations in pediatric patients is challenging due to significant inter-individual variability and rapid physiological changes during maturation. AIM: This study aimed to develop a machine learning model to predict vancomycin trough concentrations and determine optimal dosing regimens for pediatric patients < 4 years of age using ML algorithms. METHOD: A single-center retrospective observational study was conducted from January 2017 to March 2020. Pediatric patients who received intravenous vancomycin and underwent therapeutic drug monitoring were enrolled. Seven ML models [linear regression, gradient boosted decision trees, support vector machine, decision tree, random forest, Bagging, and extreme gradient boosting (XGBoost)] were developed using 31 variables. Performance metrics including R-squared (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) were compared, and important features were ranked. RESULTS: The study included 120 eligible trough concentration measurements from 112 patients. Of these, 84 measurements were used for training and 36 for testing. Among the seven algorithms tested, XGBoost showed the best performance, with a low prediction error and high goodness of fit (MAE = 2.55, RMSE = 4.13, MSE = 17.12, and R2 = 0.59). Blood urea nitrogen, serum creatinine, and creatinine clearance rate were identified as the most important predictors of vancomycin trough concentration. CONCLUSION: An XGBoost ML model was developed to predict vancomycin trough concentrations and aid in drug treatment predictions as a decision-support technology.

Alien flora are accumulating steadily in China over the last 80 years.

New alien species are increasingly introduced and established outside their native range. The knowledge of the spatiotemporal dynamics of their accumulation and the factors determining their residence time in the introduced range is critical for proactive management, especially in emerging economies. Based on a comprehensive time series dataset of 721 alien angiosperms in China, we show that new alien flora has been accumulating steadily in China, particularly in the coastal regions, for the last 80 years without saturation. The ability to occupy a large number of habitats facilitates the early introduction of alien flora, whereas a large naturalized range, greater number of uses, and multiple introduction pathways directly contribute to their naturalization and invasion. The temporal pattern is predicted to remain consistent in the foreseeable future. We propose upgrading the country's biosecurity infrastructure based on a standardized risk assessment framework to safeguard the country from ongoing and future invasions.

Elderly Fall Detection Based on GCN-LSTM Multi-Task Learning Using Nursing Aids Integrated with Multi-Array Flexible Tactile Sensors.

Due to the frailty of elderly individuals' physical condition, falling can lead to severe bodily injuries. Effective fall detection can significantly reduce the occurrence of such incidents. However, current fall detection methods heavily rely on visual and multi-sensor devices, which incur higher costs and complex wearable designs, limiting their wide-ranging applicability. In this paper, we propose a fall detection method based on nursing aids integrated with multi-array flexible tactile sensors. We design a kind of multi-array capacitive tactile sensor and arrange the distribution of tactile sensors on the foot based on plantar force analysis and measure tactile sequences from the sole of the foot to develop a dataset. Then we construct a fall detection model based on a graph convolution neural network and long-short term memory network (GCN-LSTM), where the GCN module and LSTM module separately extract spatial and temporal features from the tactile sequences, achieving detection on tactile data of foot and walking states for specific time series in the future. Experiments are carried out with the fall detection model, the Mean Squared Error (MSE) of the predicted tactile data of the foot at the next time step is 0.0716, with the fall detection accuracy of 96.36%. What is more, the model can achieve fall detection on 5-time steps with 0.2-s intervals in the future with high confidence results. It exhibits outstanding performance, surpassing other baseline algorithms. Besides, we conduct experiments on different ground types and ground morphologies for fall detection, and the model showcases robust generalization capabilities.

Invasive alien plants are phylogenetically distinct from other alien species across spatial and taxonomic scales in China.

Introduction: Phylogenetic relatedness is one of the important factors in the community assembly process. Here, we aimed to understand the large-scale phylogenetic relationship between alien plant species at different stages of the invasion process and how these relationships change in response to the environmental filtering process at multiple spatial scales and different phylogenetic extents. Methods: We identified the alien species in three invasion stages, namely invasive, naturalized, and introduced, in China. The occurrence records of the species were used to quantify two abundance-based phylogenetic metrics [the net relatedness index (NRI) and the nearest taxon index (NTI)] from a highly resolved phylogenetic tree. The metrics were compared between the three categories of alien species. Generalized linear models were used to test the effect of climate on the phylogenetic pattern. All analyses were conducted at four spatial scales and for three major angiosperm families. Results: We observed significantly higher NRI and NTI values at finer spatial scales, indicating the formation of more clustered assemblages of phylogenetically closely related species in response to the environmental filtering process. Positive NTI values for the invasive and naturalized aliens suggested that the presence of a close relative in the community may help the successful naturalization and invasion of the introduced alien species. In the two-dimensional phylogenetic space, the invasive species communities significantly differed from the naturalized and introduced species, indicating that established alien species need to be phylogenetically different to become invasive. Positive phylogenetic measures for the invasive aliens across the spatial scales suggested that the presence of invasive aliens could facilitate the establishment of other invasive species. Phylogenetic relatedness was more influenced by temperature than precipitation, especially at a finer spatial scale. With decreased temperature, the invasive species showed a more clustered assemblage, indicating conservatism of their phylogenetic niche. The phylogenetic pattern was different at the family level, although there was a consistent tendency across families to form more clustered assemblages. Discussion: Overall, our study showed that the community assemblage became more clustered with the progression of the invasion process. The phylogenetic measures varied at spatial and taxonomic scales, thereby highlighting the importance of assessing phylogenetic patterns at different gradients of the community assembly process.

Multichannel Flexible Pulse Perception Array for Intelligent Disease Diagnosis System.

Pressure sensors with high sensitivity, a wide linear range, and a quick response time are critical for building an intelligent disease diagnosis system that directly detects and recognizes pulse signals for medical and health applications. However, conventional pressure sensors have limited sensitivity and nonideal response ranges. We proposed a multichannel flexible pulse perception array based on polyimide/multiwalled carbon nanotube-polydimethylsiloxane nanocomposite/polyimide (PI/MPN/PI) sandwich-structure pressure sensor that can be applied for remote disease diagnosis. Furthermore, we established a mechanical model at the molecular level and guided the preparation of MPN. At the structural level, we achieved high sensitivity (35.02 kPa-1) and a broad response range (0-18 kPa) based on a pyramid-like bilayer microstructure with different upper and lower surfaces. A 27-channel (3 × 9) high-density sensor array was integrated at the device level, which can extract the spatial and temporal distribution information on a pulse. Furthermore, two intelligent algorithms were developed for extracting six-dimensional pulse information and automatic pulse recognition (the recognition rate reaches 97.8%). The results indicate that intelligent disease diagnosis systems have great potential applications in wearable healthcare devices.

TPN171H alleviates pulmonary hypertension via inhibiting inflammation in hypoxia and monocrotaline-induced rats.

Pulmonary hypertension (PH) is a progressive and life-threatening disease with poor prognosis despite many advances in medical therapy over the past 20 years. Novel therapies which target on the underlying pathology of PH are still urgent to be met. TPN171H is a recently found new compound that exhibits potent pharmacological effects in PH via inhibiting phosphodiesterase type 5 (PDE-5). However, as one icariin derivative, the anti-inflammatory effects of TPN171H for treating PH are not clear. The present study was designed to investigate the therapeutical effect of TPN171H against inflammation in PH and reveal the underlying mechanism. Hypoxia and monocrotaline (MCT)-induced PH rat models were established, which were treated by oral administration of TPN171H (5, 25 mg/kg/d) or sildenafil (25 mg/kg/d). The right ventricle systolic pressure (RVSP), right ventricle hypertrophy index (RVHI) and vascular remodeling were measured. The results suggested that TPN171H significantly reduced RVSP and RVHI, and reversed pulmonary vascular remodeling in rats with both models. Furthermore, in in vivo and in vitro research, our data suggested that TPN171H remarkably suppressed cathepsin B-mediated NLRP3 inflammasome activation, which may contribute to its therapeutical function for PH.

PKR deficiency alleviates pulmonary hypertension via inducing inflammasome adaptor ASC inactivation.

Pulmonary hypertension is a progressive fatal disease that currently has no specific therapeutic approaches. In this study, dsRNA-dependent protein kinase (PKR) was considered a candidate molecule in pulmonary hypertension. We demonstrated that PKR is activated in the endothelium of experimental pulmonary hypertension models. Deletion of PKR or treatment with the PKR activation inhibitor C16 inhibited the development of pulmonary hypertension. To explore the mechanism of PKR in pulmonary hypertension, we detected its downstream signaling and found that PKR knockout represses apoptosis-associated speck-like protein containing CARD (ASC) activation to inhibit high mobility group box 1 (HMGB1) and interleukin-1 beta release. To further explore whether ASC mediates the pro-pulmonary hypertension role of PKR, we used ASC deletion mice and found that ASC deletion inhibits the development of pulmonary hypertension and the release of HMGB1 and interleukin-1 beta. Furthermore, we co-cultured pulmonary arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells (PASMCs) and found that endothelial PKR promotes PASMCs proliferation through the release of HMGB1 and interleukin-1 beta. In conclusion, these data indicate that endothelial PKR promotes the excessive proliferation of PASMCs by inducing ASC activation to release HMGB1 and interleukin-1 beta, which lead to the development of pulmonary hypertension. Our study will provide a novel insight that PKR is a potential target in the future treatment of pulmonary hypertension.

Novel Pyrazolo[3,4-b] Pyridine Derivative (HLQ2g) Attenuates Hypoxic Pulmonary Hypertension via Restoring cGKI Expression and BMP Signaling Pathway.

Pulmonary hypertension (PH) is an extremely serious cardiopulmonary disease, finally leading to progressive right ventricular failure and death. Our previous studies have nominated HLQ2g, a pyrazolo[3,4-b] pyridine derivative stimulating soluble guanylate cyclase (sGC), as a new candidate for the treatment of PH, but the specific mechanism is still not clear. The PH model induced by hypoxia was established in rats. Right ventricular systolic pressure (RVSP) was assessed by jugular vein catheterization. RV weight was the index to evaluate RV hypertrophy. The protein levels of cGMP-dependent protein kinase type I (cGKI), bone morphogenetic protein receptor 2 (BMPR2), phosphorylated Smad1/5/8 (p-Smad1/5/8), and inhibitor of differention 1 (Id1) in pulmonary artery and human pulmonary artery smooth muscle cells (HPASMCs) were determined by western blotting. Cell proliferation and migration were evaluated. In the whole experiment, the first clinically available sGC stimulator Riociguat was used as the reference. In hypoxic PH rat model, elevated RVSP and RV hypertrophy were significantly reduced by HLQ2g treatment. Both Riociguat and HLQ2g attenuated vascular remodeling accompanied with up-regulated cGKI expression and BMP signaling pathway, which was characterized by elevated expression of BMPR2, p-Smad1/5/8, and Id1 in HPH rats. In addition, HLQ2g inhibited proliferation and migration of HPASMCs induced by hypoxia and platelet-derived growth factor (PDGF), restored BMPR2 signaling, which was recalled by Rp-8-Br-PET-cGMPS, the inhibitor of cGKI. In summary, the novel pyrazolo[3,4-b] pyridine derivative HLQ2g can alleviate HPH progression by up-regulating cGKI protein and BMP signaling pathway.

Estimation of Mean Variation in Prediction Probability for Prevalence of Hypertension in Middle-Aged and Older Chinese Using Probit Model.

The aims of this study are to estimate the mean change in the predicted probability and identify the most important predictors of diagnosed, measured, total, and undiagnosed hypertension among aged 45+ adults in China. We used data collected from the fourth wave (2015) of the China Health and Retirement Longitudinal Study (n = 12 236). First, we estimated the prevalence of diagnosed, measured, total, and undiagnosed hypertension. Second, we used probit models to identify the factors that were associated with hypertension, and we estimated average marginal effects of variables in probit models. Among Chinese people aged 45+, the prevalence of diagnosed, measured, total, and undiagnosed hypertension were 23.1%, 32.7%, 42.6%, and 19.5%, respectively. The probability of total hypertension is higher for overweight and obesity than normal body mass index (10.4% and 19.3%, respectively), higher for past smokers and current smokers than nonsmokers (5.9% and 3.8%, respectively), higher for urban population than rural population (4.0%), and lower for married individuals than unmarried/single (-7.1%). Our results suggest that continued strengthening for smoking prevention is needed to reduce smoking-related hypertension and greater focus on prevention of hypertension are necessary for overweight or obesity and in urban areas among middle-aged and older adults in China.

Forward genetics identifies a novel sleep mutant with sleep state inertia and REM sleep deficits.

Switches between global sleep and wakefulness states are believed to be dictated by top-down influences arising from subcortical nuclei. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterized by a substantially reduced propensity to transition between wake and sleep states with an especially pronounced deficit in initiating rapid eye movement (REM) sleep episodes. The causative mutation, an Ile102Asn substitution in the synaptic vesicular protein, VAMP2, was associated with morphological synaptic changes and specific behavioral deficits, while in vitro electrophysiological investigations with fluorescence imaging revealed a markedly diminished probability of vesicular release in mutants. Our data show that global shifts in the synaptic efficiency across brain-wide networks leads to an altered probability of vigilance state transitions, possibly as a result of an altered excitability balance within local circuits controlling sleep-wake architecture.

Body mass index moderates the relationship between C-reactive protein and depressive symptoms: evidence from the China Health and Retirement Longitudinal Study.

The present study aimed to investigate the role of abnormal body mass index (BMI, kg/m2) in the depression-CRP (C-reactive protein) relationship in a healthy middle-aged and elderly Chinese population. Analytical samples were drawn from the China Health and Retirement Longitudinal Study (CHARLS), and participants were categorized by different BMI levels. Depressive subtypes were evaluated both at baseline and follow-up using the Center for Epidemiology Studies Depression scale. Hs-CRP and other variables were measured at baseline. Multiple linear regression analyses were used to evaluate the cross-sectional and longitudinal relationship between depression and baseline hs-CRP. Depression was significantly negatively associated with BMI (ρ = -0.077, p < 0.0001), with underweight associated with worse depressive symptoms than other BMI groups. Both cross-sectional and longitudinal associations between serum hs-CRP and depressive subtypes were significantly positive in the underweight group (p < 0.05). However, in the other BMI groups (from normal weight to obesity), the CRP-depression relationship was no longer significant (p > 0.05). The significant relationship between CRP and depression in the underweight group suggested that not only obesity but also a low BMI could explain a substantial portion of the inflammation-depression link.