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Abstract Heart failure (HF), with its high morbidity and mortality, remains a global public health issue. Right ventricular (RV) dysfunction is a sign of deterioration in the natural history of HF, and a thorough evaluation of the relationship between RV contractility and its afterload through RV–pulmonary arterial (RV–PA) coupling can aid in accurately assessing overall RV function. The ratio of RV end‐systolic elastance (Ees) to pulmonary arterial elastance (Ea) invasively measured by right heart catheterization served as the gold standard for evaluating RV–PA coupling. An echocardiographic index termed tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) has been shown to correlate well with Ees/Ea. TAPSE/PASP is recognized as a non‐invasive surrogate of RV–PA coupling and has been extensively studied in patients with HF. This review briefly describes the methods of assessing RV–PA coupling, mainly discussing echocardiography, summarizes the clinical utility of TAPSE/PASP in patients with different HF types, and provides an overview of the available literature.

The present study took L2 English learners of different levels in China as subjects to investigate the relationship between collocational familiarity and collocational frequency as well as L1-L2 congruency, and then explored the development of the above relationship as L2 proficiency develops. The results showed that: a moderate positive correlation existed between familiarity and frequency, and the correlation increased with proficiency; a moderate positive correlation also existed between familiarity and congruency, but the correlation decreased with proficiency. Based on previous studies and the present findings, the research group infer that: low familiarity collocations tend to be represented and processed in analytic way and same-translation effect helps accelerate the semantic access of congruent collocations in this process; with the increase in learners’ proficiency, collocation familiarity develops from low to high with frequency effect; high familiarity collocations tend to be represented and processed in holistic way to have direct semantic access; furthermore, learners of two levels have two kinds of collocational representation and semantic access, but low-level learners show more analytic representation and indirect semantic access because of having more low familiarity collocations in the mental lexicon.

Abstract Purpose This study evaluates biochar from crop residues as a solution to soil degradation in continuous monoculture within greenhouse agriculture, focusing on its impact on soil microbial communities and cucumber plant growth. Methods We analyzed biochar derived from tomato straw (TSB), sweet pepper straw (SPSB), and eggplant straw (ESB), assessing their nutrient content, cation exchange capacity, and adsorption rates. This study examined the effects of three concentrations (2.5%, 5%, and 7.5% w/w) of the more promising SPSB on soil properties and cucumber growth. Results SPSB showed significantly higher levels of nitrogen, phosphorus, and potassium, along with superior adsorption capacity compared to TSB and ESB. The 5% w/w SPSB concentration notably improved cucumber growth, increasing plant height by 13.01%, stem thickness by 20.79%, leaf area by 50.26%, and dry weight by 58.56% relative to the control. High-throughput sequencing revealed this concentration significantly altered soil microbial community structure, enhancing bacterial and fungal diversity. It increased beneficial bacterial groups (Firmicutes, Actinobacteria, Bacillus) and modified fungal communities, with a decrease in Ascomycota and Aspergillus and shifts in Penicillium abundance. Functional genomic analysis indicated enrichment in bacterial metabolic pathways and fungal replication and expression genes. Conclusion SPSB, especially at a 5% w/w concentration, emerges as an effective soil amendment in greenhouses affected by continuous monoculture. This approach represents a sustainable method to enhance soil health and crop productivity.

Abstract Motivated by the effect of symmetry breaking in cuprates superconductors YBa $$_2$$ 2 Cu $$_3$$ 3 O $$_{7-\delta }$$ 7 - δ , we employ the renormalized mean-field theory to study the presence of uniform superconducting and charge-ordered states in two anisotropic t–J–U models, either with hopping strength anisotropy or antiferromagnetic interaction anisotropy. In the case of uniform superconducting state, compared with the isotropic t–J–U model with only $$d_{x^2-y^2}$$ d x 2 - y 2 -wave superconducting state, there is an additional s-wave superconducting state in the model with hopping strength anisotropy. Meanwhile, the hopping anisotropy may enhance the critical Coulomb interaction $$U_c$$ U c at the Mott insulator to the Gossamer superconductor transition point, and strong hopping anisotropy may weaken the superconducting state. In the case of a charge-ordered state, hopping anisotropy may suppress the amplitude of the charge density waves and pair density waves, which originate from local Coulomb interactions. These results indicate that the effects of hopping anisotropy and local Coulomb interactions are competitive. Moreover, the antiferromagnetic interaction anisotropy only weakly suppresses the superconducting gap and density wave amplitude. Our results show that the t–J–U model with hopping anisotropy is qualitatively consistent with experimental superconducting pair symmetry and charge density waves in the YBa $$_2$$ 2 Cu $$_3$$ 3 O $$_{7-\delta }$$ 7 - δ system.

The probability integral method is one of the most widely used methods for predicting surface subsidence induced by underground mining in China. In its parameter calculation, the least square algorithm is commonly employed for fitting parameters. However, in the process of fitting parameters, the results are easily affected by ill-conditioned normal matrices and the interference of outliers, resulting in divergent problems. To solve these problems, the principle of robust ridge estimation was introduced in this paper, and a parameter calculation model for the probability integral method based on this principle (hereafter referred to as the established model) was established. Besides, a parameter calculation experiment with manual intervention was conducted in combination with engineering examples. The results demonstrate that the parameter calculation method based on robust ridge estimation can suppress the interference of outliers, overcome the problem of ill-conditioned matrix, and ensure the effectiveness and reliability of parameter estimation results. Compared with the conventional least squares method, the robust ridge estimation method demonstrates greater accuracy in predicting surface subsidence parameters, which validates its rationality and accuracy in underground mining engineering. The research findings provide technical support for obtaining similar parameters for surface subsidence in mining areas and hold significant engineering application value.

BackgroundImmune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs.MethodsThis study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves.ResultsA total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008).ConclusionLower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

Abstract Purpose Incorporating crop residues into the soil is considered a sustainable and valuable method to alleviate soil deterioration caused by continuous monoculture in greenhouse production. However, the effect of vegetable residues retention on soil amendments is poorly understood. In the present study, we investigated the impacts of sweet pepper, tomato, and cucumber plant residues on soil microbial communities and plant growth of continuously cropped cucumber in a solar greenhouse. Methods The 16S rRNA and ITS1 rRNA genes were amplified, and high-throughput sequencing was performed to explore the impacts of vegetable residues incorporation on soil microbial communities. Additionally, soil chemical properties, cucumber root vigor, and fruit yield were measured to assess the impacts of vegetable residues incorporation on continuously cropped soil and cucumber growth. Results The results showed that incorporating vegetable residues could improve soil buffering capacity, increase the content of soil organic matter and available nutrients, and increased the diversity of soil microorganisms and improved community structure; vegetable residues increased the abundance of beneficial bacteria such as Actinobacteria, Firmicutes, Proteobacteria, and Chloroflexi, while reducing the quantity of soil-borne pathogens such as Bacillariophyta and Acidobacteria. Similar results were observed for the fungal communities: the relative abundance of Ascomycota was decreased to varying degrees, while the relative abundance of Rozellomycota and Basidiomycota was raised. The results demonstrated that vegetable residues incorporation significantly increased cucumber root vigor and enhanced fruit yield. The effects of different types of residues on improving soil properties were ordered sweet pepper plant residues > cucumber plant residues > tomato plant residues, and 20% of sweet pepper plant residues incorporation had the most significant effect on crop yield. Conclusion In summary, returning vegetable residues alleviated soil continuous cropping obstacles by improving the soil fertility and the diversity and community structure of soil microorganisms, and consequently promoting the growth and yield of greenhouse-grown cucumbers. The findings demonstrated that returning vegetable residues was an effective and sustainable measure for soil amendment during continuous cropping in greenhouse production.

Background: Rotator cuff tear has become one of the diseases affecting people's living quality. Conventional anchor materials such as titanium alloy and poly-lactic acid can lead to postoperative complications like bone defects and aseptic inflammation. Magnesium (Mg)-based implants are biodegradable and biocompatible, with strong potential to be applied in orthopaedics. Methods: In this study, we developed a high-purity (HP) Mg suture anchor and studied its mechanical properties and degradation behavior in vitro. Furthermore, we described the use of high-purity Mg to prepare suture anchor for the rotator cuff repair in sheep. Results: The in vitro tests showed that HP Mg suture anchor possess proper degradation behavior and appropriate mechanical property. Animal experiment indicated that HP Mg suture anchor provided reliable anchoring function in 12 weeks and showed no toxic effect on animal organs. Conclusion: In summary, the HP Mg anchor presented in this study had favorable mechanical property and biosecurity.The translational potential of this article: The translational potential of this article is to use high-purity Mg to develop a degradable suture anchor and verify the feasibility of the application in animal model. This study provides a basis for further research on the clinical application of biodegradable high-purity Mg suture anchor.

In addition to the traditional long-distance and bulk power transmission application, the HVDC system can bring additional benefits to the system by providing ancillary service. The high-voltage direct-current transmission (HVDC) system can regulate its power flow in a very short time and can be used to provide emergency support to rescue the disturbed system from very bad conditions. However, because traditional generators cannot meet the great power demand of the HVDC system in a short time, the fast response of the HVDC system may cause severe power-unbalance events in the power supporting system. In this paper, a combination frequency response control (CFRC) is proposed for the fast frequency response (FFR) and HVDC system coordinating under the contingency. With the proposed combination frequency response control, the most use of the frequency response capacity of the HVDC system could be made. Meanwhile, the coordination between the HVDC system and fast frequency response could prevent the frequency of the power-source-provided system from dropping to an unacceptable level. The simulation study is conducted on a highly reduced power system model of the three North American interconnections. The simulation verification shows the effectiveness and feasibility of the proposed combination frequency response control and indicates that the frequency stability for both side systems of the HVDC system could be significantly improved with the proposed combination frequency response control. In the future, the communication delay between energy storage and HVDC will be considered in the strategy to further improve the accuracy of fast frequency response.

Analog compute schemes and compute-in-memory (CIM) have emerged in an effort to reduce the increasing power hunger of convolutional neural networks (CNNs), which exceeds the constraints of edge devices. Memristive device types are a relatively new offering with interesting opportunities for unexplored circuit concepts. In this work, the use of memristive devices in cascaded time-domain CIM (TDCIM) is introduced with the primary goal of reducing the size of fully unrolled architectures. The different effects influencing the determinism in memristive devices are outlined together with reliability concerns. Architectures for binary as well as multibit multiply and accumulate (MAC) cells are presented and evaluated. As more involved circuits offer more accurate compute result, a tradeoff between design effort and accuracy comes into the picture. To further evaluate this tradeoff, the impact of variations on overall compute accuracy is discussed. The presented cells reach an energy/OP of 0.23 fJ at a size of $1.2~{\mu{ }}\text{m}^{2}$ for binary and 6.04 fJ at $3.2~\mu \text{m}^{2}$ for $4\times 4$ bit MAC operations.

Background: Previous studies have demonstrated that activated endothelial epithelial sodium channel (EnNaC) impairs vasodilatation, which contributes to salt-sensitive hypertension. Here, we investigate whether mesenteric artery (MA) EnNaC is involved in cold exposure–induced hypertension (CIH) and identify the underlying mechanisms in SD rats.Methods: One group of rats was housed at room temperature and served as control. Three groups of rats were kept in a 4°C cold incubator for 10 h/day; among which two groups were administrated with either benzamil (EnNaC blocker) or eplerenone (mineralocorticoid receptor antagonist, MR). Blood pressure (BP), vasodilatation, and endothelial function were measured with tail-cuff plethysmography, isometric myograph, and Total Nitric Oxide (NO) Assay kit, respectively. A cell-attached patch-clamp technique, in split-open MA, was used to determine the role of EnNaC in CIH rats. Furthermore, the plasma aldosterone levels were detected using an ELISA kit; and Western blot analysis was used to examine the relative expression levels of Sgk1 and Nedd4-2 proteins in the MA of SD rats.Results: We demonstrated that cold exposure increased BP, impaired vasodilatation, and caused endothelial dysfunction in rats. The activity of EnNaC significantly increased, concomitant with an increased level of plasma aldosterone and activation of Sgk1/Nedd4-2 signaling. Importantly, CIH was inhibited by either eplerenone or benzamil. It appeared that cold-induced decrease in NO production and impairment of endothelium-dependent relaxation (EDR) were significantly ameliorated by either eplerenone or benzamil in MA of CIH rats. Moreover, treatment of MAs with aldosterone resulted in an activation of EnNaC, a reduction of NO, and an impairment of EDR, which were significantly inhibited by either eplerenone or GSK650394 (Sgk1 inhibitor) or benzamil.Conclusion: Activation of EnNaC contributes to CIH; we suggest that pharmacological inhibition of the MR/Sgk1/Nedd4-2/EnNaC axis may be a potential therapeutic strategy for CIH.

Source-grid-load-storage has represented an interactive characteristic in the active distribution network (ADN). Moreover, power electronic devices have been widely used for source-grid-load-storage with the rapid development of power electronics technology. In this condition, the large-scale distributed source may cause voltage quality degradation, while the application of large-scale power electronics equipment may also lead to serious harmonic distortion. Power quality has become one of the most important issues in the development of ADN. In this paper, the source-grid-load-storage interactive power quality characteristic of the ADN is analyzed. Firstly, considering the source-grid-load-storage interaction in ADN, the voltage deviation and fluctuation are analyzed and the degrees are further quantified. Then, the source-load-storage harmonic models for the power electronic components are built, which is the basis for harmonic analysis. Moreover, the decoupled harmonic power flow algorithm for ADN is proposed to analyze the system harmonic distributions. Finally, considering the location and capacity of photovoltaic and energy storage, the interaction and power quality are analyzed in the IEEE 33-bus distribution system. With the access of energy storage, more than 20% of the voltage deviation and more than 6% of the voltage fluctuation caused by photovoltaics are effectively suppressed, while the harmonic distortion may be further increased.

To investigate the transmission dynamics and temporal and spatial migration characteristics of HIV spread among men who have sex with men (MSM) in China, a total of 1012 HIV-1 partial pol sequences, including five subtypes, were studied. Bayesian analysis were applied for each subtype to infer its dynamic characters including the effective reproductive number (Re) and migration process. The mean curve of each Re was almost always greater than 1 (even the 95% highest posterior density (HPD) lower value) along with time, which supports the necessity for a comprehensive study about risk behaviors among young MSM group in China. We also should reappraise the free treatment strategy, especially the therapeutic effect during the free treatment policy.

The oral route is the most preferred route for systemic and local drug delivery. However, the oral drug delivery system faces the harsh physiological and physicochemical environment of the gastrointestinal tract, which limits the bioavailability and targeted design of oral drug delivery system. Innovative pharmaceutical approaches including nanoparticulate formulations, biomimetic drug formulations, and microfabricated devices have been explored to optimize drug targeting and bioavailability. In this review, the anatomical factors, biochemical factors, and physiology factors that influence delivering drug via oral route are discussed and recent advance in conventional and novel oral drug delivery approaches for improving drug bioavailability and targeting ability are highlighted. We also address the challenges and opportunities of oral drug delivery systems in future.

The atmospheric vapour pressure deficit (VPD) has been demonstrated to be a significant environmental factor inducing plant water stress and affecting plant photosynthetic productivity. Despite this, the rate-limiting step for photosynthesis under varying VPD is still unclear. In the present study, tomato plants were cultivated under two contrasting VPD levels: high VPD (3–5 kPa) and low VPD (0.5–1.5 kPa). The effect of long-term acclimation on the short-term rapid VPD response was examined across VPD ranging from 0.5 to 4.5 kPa. Quantitative photosynthetic limitation analysis across the VPD range was performed by combining gas exchange and chlorophyll fluorescence. The potential role of abscisic acid (ABA) in mediating photosynthetic carbon dioxide (CO2) uptake across a series of VPD was evaluated by physiological and transcriptomic analyses. The rate-limiting step for photosynthetic CO2 utilisation varied with VPD elevation in tomato plants. Under low VPD conditions, stomatal and mesophyll conductance was sufficiently high for CO2 transport. With VPD elevation, plant water stress was gradually pronounced and triggered rapid ABA biosynthesis. The contribution of stomatal and mesophyll limitation to photosynthesis gradually increased with an increase in the VPD. Consequently, the low CO2 availability inside chloroplasts substantially constrained photosynthesis under high VPD conditions. The foliar ABA content was negatively correlated with stomatal and mesophyll conductance for CO2 diffusion. Transcriptomic and physiological analyses revealed that ABA was potentially involved in mediating water transport and photosynthetic CO2 uptake in response to VPD variation. The present study provided new insights into the underlying mechanism of photosynthetic depression under high VPD stress.

Traditional methods of quantifying epidemic spread are based on surveillance data. The most widely used surveillance data are normally incidence data from case reports and hospital records, which are normally susceptible to human error, and sometimes, they even can be seriously error-prone and incomplete when collected during a destructive epidemic. In this manuscript, we introduce a new method to study the spread of infectious disease. We gave an example of how to use this method to predict the virus spreading using the HIV gene sequences data of China. First, we applied Bayesian inference to gene sequences of two main subtypes of the HIV virus to infer the effective reproduction number (GRe(t)) to trace the history of HIV transmission. Second, a dynamic model was established to forecast the spread of HIV medication resistance in the future and also obtain its effective reproduction number (MRe(t)). Through fitting the two effective reproduction numbers obtained from the two separate ways above, some crucial parameters for the dynamic model were obtained. Simply raising the treatment rate has no impact on lowering the infection rate, according to the dynamics model research, but would instead increase the rate of medication resistance. The negative relationship between the prevalence of HIV and the survivorship of infected individuals following treatment may be to blame for this. Reducing the MSM population’s number of sexual partners is a more efficient strategy to reduce transmission per the sensitivity analysis.

BackgroundHyperhomocysteinemia (HHcy) causes cardiovascular diseases via regulating inflammatory responses. We investigated whether and how the epithelial sodium channel (ENaC), a recently identified ion channel in endothelial cells, plays a role in HHcy-induced endothelial dysfunction.MethodsCell-attached patch-clamp recording in acute split-open aortic endothelial cells, western blot, confocal imaging, and wire myograph combined with pharmacological approaches were used to determine whether HHcy-mediated inflammatory signaling leads to endothelial dysfunction via stimulating ENaC.ResultsThe data showed that 4 weeks after L-methionine diet the levels of plasma Hcy were significantly increased and the ENaC was dramatically activated in mouse aortic endothelial cells. Administration of benzamil, a specific ENaC blocker, ameliorated L-methionine diet-induced impairment of endothelium-dependent relaxation (EDR) and reversed Hcy-induced increase in ENaC activity. Pharmacological inhibition of NADPH oxidase, reactive oxygen species (ROS), cyclooxygenase-2 (COX-2)/thromboxane B2 (TXB2), or serum/glucocorticoid regulated kinase 1 (SGK1) effectively attenuated both the Hcy-induced activation of endothelial ENaC and impairment of EDR. Our in vitro data showed that both NADPH oxidase inhibitor and an ROS scavenger reversed Hcy-induced increase in COX-2 expression in human umbilical vein endothelial cells (HUVECs). Moreover, Hcy-induced increase in expression levels of SGK-1, phosphorylated-SGK-1, and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 (p-Nedd4-2) in HUVECs were significantly blunted by a COX-2 inhibitor.ConclusionWe show that Hcy activates endothelial ENaC and subsequently impairs EDR of mouse aorta, via ROS/COX-2-dependent activation of SGK-1/Nedd4-2 signaling. Our study provides a rational that blockade of the endothelial ENaC could be potential method to prevent and/or to treat Hcy-induced cardiovascular disease.

We have shown that cholesterol regulates the activity of ion channels in mouse cortical collecting duct (CCD) mpkCCDc14 cells and that the transient receptor potential melastatin 4 (TRPM4) channel is expressed in these cells. However, whether TRPM4 channel is regulated by cholesterol remains unclear. Here, we performed inside-out patch-clamp experiments and found that inhibition of cholesterol biosynthesis by lovastatin significantly decreased, whereas enrichment of cholesterol with exogenous cholesterol significantly increased, TRPM4 channel open probability (Po) by regulating its sensitivity to Ca2+ in mpkCCDc14 cells. In addition, inside-out patch-clamp data show that acute depletion of cholesterol in the membrane inner leaflet by methyl-β-cyclodextrin (MβCD) significantly reduced TRPM4 Po, which was reversed by exogenous cholesterol. Moreover, immunofluorescence microscopy, Western blot, cell-surface biotinylation, and patch clamp analysis show that neither inhibition of intracellular cholesterol biosynthesis with lovastatin nor application of exogenous cholesterol had effect on TRPM4 channel protein abundance in the plasma membrane of mpkCCDc14 cells. Sucrose density gradient centrifugation studies demonstrate that TRPM4 was mainly located in cholesterol-rich lipid rafts. Lipid-protein overlay experiments show that TRPM4 directly interacted with several anionic phospholipids, including PI(4,5)P2. Depletion of PI(4,5)P2 with either wortmannin or PGE2 abrogated the stimulatory effects of exogenous cholesterol on TRPM4 activity, whereas exogenous PI(4,5)P2 (diC8-PI(4,5)P2, a water-soluble analog) increased the effects. These results suggest that cholesterol stimulates TRPM4 via a PI(4,5)P2-dependent mechanism.

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) via activation of NADPH oxidase p47phox, serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell–expressed developmentally downregulated protein 4–2 (p-Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, ß-, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of H2S which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.

BackgroundChina's National Free Antiretroviral Treatment Program (NFATP) has substantially reduced morbidity and HIV/AIDS incidence since 2003. However, HIV resistance to antiretroviral drugs (ARVs) has been a major challenge for the current treatment of HIV/AIDS in China.MethodsIn the current study, we established a nested dynamic model to predict the multi-drug resistance dynamics of HIV among the heterosexual population and evaluated the impact of intervention measures on the transmission of drug resistance. We obtained an effective reproductive number [Formula: see text] from each sub-model held at different stages of the dynamic model. Meanwhile, we applied Bayesian phylogenetic methods to infer the weighted average effective reproductive number [Formula: see text] from four HIV subtypes that sampled from 912 HIV-positive patients in China. It is an original and innovative method by fitting [Formula: see text] to [Formula: see text] by Markov Chain Monte Carlo (MCMC) to generate unknown parameters in [Formula: see text].ResultsBy analyzing the HIV gene sequences, we inferred that the most recent common ancestor of CRF01AE, CRF07BC, CRF08BC, and CRFBC dated from 1994, 1990, 1993 and 1990, respectively. The weighted average effective reproductive number [Formula: see text] dropped from 1.95 in 1994 to 1.73 in 2018. Considering different interventions, we used a macro dynamic model to predict the trend of HIV resistance. The results show that the number of new infections and total drug resistance under the baseline parameter (S1) are 253,422 and 213,250 in 2025, respectively. Comparing with the numbers under the target treatment rate (S2), they were 219,717 and 236,890, respectively. However, under the ideal treatment target (S3, the treatment rate reaches 90% and the treatment success rate reaches 90%), the number of new infections shows a declining trend and will decrease to 46,559 by 2025. Compared with S1 and S2, the total number of resistance also decreased to 160,899 in 2025.ConclusionWith the promotion of NFATP in China, HIV resistance to ARVs is inevitable. The strategy of increasing the treatment rate would not only ineffectively curb the epidemic, but also deteriorate drug resistance issue. Whereas, a combination of intervention strategies (the treatment rate reaches 90% and the treatment success rate reaches 90%) can greatly reduce both infection and drug resistance rate than applying one strategy alone.

Abstract Background Gastric cancer (GC) is one of the most common malignant gastrointestinal tumors with the high morbidity and mortality, affecting the quality of human life. This study aimed to identify the role of heart rate variability (HRV) in patients with GC. Methods From January 2010 to June 2014, 383 consecutive patients diagnosed with GC were enrolled in this study. Clinical and pathological information from each patient were retrospectively recorded. HRV, including standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive differences (RMSSD), were measured by electrocardiography. Results The results showed that the SDNN and RMSSD in GC patients were 19.02 ± 13.58 ms and 21.64 ± 17.57 ms, respectively. HRV decreased with advanced clinical stage (P 0.05). C-reactive protein (CRP) was higher in the low HRV group than that in high HRV group (P = 0.008). Conclusions GC patients showed a lower HRV that was correlated with tumor stage. HRV decreased with tumor progression, which may be related to a mechanism involving vagal nerve excitement inhibiting the inflammatory reaction.

As proposed in the UNAIDSs 2014 report, to end global AIDS epidemic by 2030, 90% of people living with HIV need to be diagnosed, 90% of the diagnosed need to receive antiretroviral therapy (ART), and 90% of those on treatment need to achieve viral suppression (90-90-90 strategy). The strategies focus on the reservoir. It controls HIV spreading by reducing infectiousness of HIV infected individuals via diagnosis and treatment. In this manuscript, we compared the effects of HIV/AIDS interventions that focus on different individuals in MSM population through a dynamics model. Our results showed that, the success or not of the ”90-90-90” strategies depends on a very important factor: the infectious strength among individuals taking ART. Without highly effective HIV treatment, the ”90-90-90” strategies are likely to fail. Therefore, we call for the combination of both primary prevention among the susceptible with the 90-90-90 strategy among the infected to curb the HIV epidemic in Chinese MSM. Keywords: HIV/AIDS, Dynamics model, Prevention and treatment strategies, 2010 MSC: 39A11, 92D30

Human Immunodeficiency Virus (HIV) is able to persist in cellular and/or anatomical viral reservoirs, despite the effective inhibition of virus replication by the antiretroviral therapy (ART). Here we develop a mathematical model to gain some insights of HIV persistence relevant to the lymphocyte recirculation network of immune system and the central nervous system (CNS). Our simulations and analyses illustrate the role of the CNS as a virus reservoir to prevent antiretroviral drugs from penetrating the blood-brain (or blood-testis) barrier, and we examine the long-term impact of this reservoir on the transmissibility of an infected individual. We observe numerically that level of HIV in peripheral blood may not accurately reflect the true mechanisms occurring within other organs. Keywords: HIV reservoirs, Blood-brain barrier, Dynamical model, Lymphocyte recirculation network, 2010 MSC: 39A11, 92D30

Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli.

Necrotic cell death is a hallmark feature of ischemic stroke and it may facilitate inflammation by releasing intracellular components after cell-membrane rupture. Previous studies reported that β-caryophyllene (BCP) mitigates cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanism remains unclear. We explored whether BCP exerts a neuroprotective effect in cerebral I/R injury through inhibiting necroptotic cell death and inflammation. Primary neurons with and without BCP (0.2, 1, 5, 25 μM) treatment were exposed to oxygen-glucose deprivation and re-oxygenation (OGD/R). Neuron damage, neuronal death type and mixed lineage kinase domain-like (MLKL) protein expression were assessed 48 h after OGD/R. Furthermore, mice underwent I/R procedures with or without BCP (8, 24, 72 mg/kg, ip.). Neurologic dysfunction, cerebral infarct volumes, cell death, cytokine levels, necroptosis core molecules, and HMGB1-TLR4 signaling were determined at 48 h after I/R. BCP (5 μM) significantly reduced necroptotic neurons and MLKL protein expression following OGD/R. BCP (24, 72 mg/kg, ip.) reduced infarct volumes, neuronal necrosis, receptor-interaction protein kinase-1 (RIPK1), receptor-interaction protein kinase-3 (RIPK3) expression, and MLKL phosphorylation after I/R injury. BCP also decreased high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Thus, BCP alleviates ischemic brain damage potentially by inhibiting necroptotic neuronal death and inflammatory response. This study suggests a novel application for BCP as a neuroprotective agent.

To project the impact of partner reduction on preventing new HIV infections among men who have sex with men (MSM) under varying conditions of enhanced HIV testing and treatment (T&T) and condom use in Beijing, China.A complex network model was fitted to predict the number of new HIV infections averted from 2014 to 2023 under four scenarios of sexual behavior risk reduction (S)-S1: Male sexual partners decrease (reduced by a random value m from 1-50) while condom use increases (risk constant p is a random value between 0.2 and 1]); S2: Both sexual partners and condom use decrease (m 1, 50; p 1, 1.8); S3: Sexual partners reduce (m 1, 10) while condom use increases or decreases (p 0.2, 1.8); S4: Only MSM with ≥100 male sexual partners reduce their partners (m 1, 50) while condom use increases (p 0.2, 1). HIV prevalence will reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three most influential factors are: T&T coverage; partner reduction (m); and the background risk (p). Under scenarios 1-4 of sexual behavioral changes with enhanced T&T interventions, the cumulative HIV new infections prevented over the 10 years will be 46.8% for S1 (interquartile range [IQR] 32.4%, 60.1%); 29.7% for S2 (IQR 18.0%, 41.4%), 23.2% for S3 (IQR 12.2%, 37.0%) and 11.6% for S4 (IQR 4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if there were a substantial reduction of male sexual partners and/or expanded condom use.Partner reduction is a vital factor within HIV combination interventions to reduce HIV incidence among Beijing MSM, with substantial additional benefits derived from condom use. T&T without substantial partner reduction and increased condom use is less promising unless its implementation were extremely (and improbably) efficient.

We construct a four-leg spin-1/2 t – J type model to simulate a doped two-leg spin-1 antiferromagnetic Heisenberg ladder. Employing renormalized mean-field theory with simple Gutzwiller factors, we obtain three degenerate superconducting states with different pairing symmetry. Through improving the Gutzwiller factors, we find that the state C with inter-layer modified ${d}_{{y}^{2}-{z}^{2}}$ -wave pairing has the lowest energy in a large doping range. Besides, we use the density matrix renormalization group method to solve the model. The negative binding energy reveals the pairing tendency, and the pair–pair correlation functions exhibit a slowly decaying behavior on certain types of bonds. From the pair correlations, we confirm the inter-layer modified ${d}_{{y}^{2}-{z}^{2}}$ -wave superconducting state as the ground state of the model.

To project the HIV/AIDS epidemics among men who have sex with men (MSM) under different combinations of HIV testing and linkage to care (TLC) interventions including antiretroviral therapy (ART) in Beijing, China.Mathematical modeling.Using a mathematical model to fit prevalence estimates from 2000-2010, we projected trends in HIV prevalence and incidence during 2011-2020 under five scenarios: (S1) current intervention levels by averaging 2000-2010 coverage; (S2) increased ART coverage with current TLC; (S3) increased TLC/ART coverage; (S4) increased condom use; and (S5) increased TLC/ART plus increased condom use.The basic reproduction number based upon the current level of interventions is significantly higher than 1 (R0 = 2.09; 95% confidence interval (CI), 1.83-2.35), suggesting that the HIV epidemic will continue to increase to 2020. Compared to the 2010 prevalence of 7.8%, the projected HIV prevalence in 2020 for the five prevention scenarios will be: (S1) Current coverage: 21.4% (95% CI, 9.9-31.7%); (S2) Increased ART: 19.9% (95% CI, 9.9-28.4%); (S3) Increased TLC/ART: 14.5% (95% CI, 7.0-23.8%); (S4) Increased condom use: 13.0% (95% CI, 9.8-28.4%); and (S5) Increased TLC/ART and condom use: 8.7% (95% CI, 5.4-11.5%). HIV epidemic will continue to rise (R0 > 1) for S1-S4 even with hyperbolic coverage in the sensitivity analysis, and is expected to decline (R0 = 0.93) for S5.Our transmission model suggests that Beijing MSM will have a rapidly rising HIV epidemic. Even enhanced levels of TLC/ART will not interrupt epidemic expansion, despite optimistic assumptions for coverage. Promoting condom use is a crucial component of combination interventions.

From February to May, 2013, 132 human avian influenza H7N9 cases were identified in China resulting in 37 deaths. We developed a novel, simple and effective compartmental modeling framework for transmissions among (wild and domestic) birds as well as from birds to human, to infer important epidemiological quantifiers, such as basic reproduction number for bird epidemic, bird-to-human infection rate and turning points of the epidemics, for the epidemic via human H7N9 case onset data and to acquire useful information regarding the bird-to-human transmission dynamics. Estimated basic reproduction number for infections among birds is 4.10 and the mean daily number of human infections per infected bird is 3.16*10-5 [3.08*10-5, 3.23*10-5]. The turning point of 2013 H7N9 epidemic is pinpointed at April 16 for bird infections and at April 9 for bird-to-human transmissions. Our result reveals very low level of bird-to-human infections, thus indicating minimal risk of widespread bird-to-human infections of H7N9 virus during the outbreak. Moreover, the turning point of the human epidemic, pinpointed at shortly after the implementation of full-scale control and intervention measures initiated in early April, further highlights the impact of timely actions on ending the outbreak. This is the first study where both the bird and human components of an avian influenza epidemic can be quantified using only the human case data.