A Conductive 3D Dual-Metal π-d Conjugated Metal-Organic Framework Fe3 (HITP)2 /bpm@Co for Highly Efficient Oxygen Evolution Reaction.

Although 2D π-d conjugated metal-organic frameworks (MOFs) exhibit high in-plane conductivity, the closely stacked layers result in low specific surface area and difficulty in mass transfer and diffusion. Hence, a conductive 3D MOF Fe3 (HITP)2 /bpm@Co (HITP = 2,3,6,7,10,11-hexaiminotriphenylene) is reported through inserting bpm (4,4'-bipyrimidine) ligands and Co2+ into the interlayers of 2D MOF Fe3 (HITP)2 . Compared to 2D Fe3 (HITP)2 (37.23 m2  g-1 ), 3D Fe3 (HITP)2 /bpm@Co displays a huge improvement in the specific surface area (373.82 m2  g-1 ). Furthermore, the combined experimental and density functional theory (DFT) theoretical calculations demonstrate the metallic behavior of Fe3 (HITP)2 /bpm@Co, which will benefit to the electrocatalytic activity of it. Impressively, Fe3 (HITP)2 /bpm@Co exhibits prominent and stable oxygen evolution reaction (OER) performance (an overpotential of 299 mV vs RHE at a current density of 10 mA cm-2 and a Tafel slope of 37.14 mV dec-1 ), which is superior to 2D Fe3 (HITP)2 and comparable to commercial IrO2 . DFT theoretical calculation reveals that the combined action of the Fe and Co sites in Fe3 (HITP)2 /bpm@Co is responsible for the enhanced electrocatalytic activity. This work provides an alternative approach to develop conductive 3D MOFs as efficient electrocatalysts.

Regulating tumor glycometabolism and the immune microenvironment by inhibiting lactate dehydrogenase with platinum(iv) complexes.

Lactate dehydrogenase (LDH) is a key enzyme involved in the process of glycolysis, assisting cancer cells to take in glucose and generate lactate, as well as to suppress and evade the immune system by altering the tumor microenvironment (TME). Platinum(iv) complexes MDP and DDP were prepared by modifying cisplatin with diclofenac at the axial position(s). These complexes exhibited potent antiproliferative activity against a panel of human cancer cell lines. In particular, DDP downregulated the expression of LDHA, LDHB, and MCTs to inhibit the production and influx/efflux of lactate in cancer cells, impeding both glycolysis and glucose oxidation. MDP and DDP also reduced the expression of HIF-1α, ARG1 and VEGF, thereby disrupting the formation of tumor vasculature. Furthermore, they promoted the repolarization of macrophages from the tumor-supportive M2 phenotype to the tumor-suppressive M1 phenotype in the TME, thus enhancing the antitumor immune response. The antitumor mechanism involves reprogramming the energy metabolism of tumor cells and relieving the immunosuppressive TME.

An mHealth-based school health education system designed to scale up salt reduction in China (EduSaltS): A development and preliminary implementation study.

Background: High-salt diet is an important risk factor for several non-communicable diseases. School-based health education has been found effective in reducing salt intake among children and their families in China. However, no such interventions have been scaled up in the real world. For this purpose, a study was launched to support the development and scale-up of an mHealth-based system (EduSaltS) that integrated routine health education and salt reduction and was delivered through primary schools. This study aims to elaborate the framework, development process, features, and preliminary scaling-up of the EduSaltS system. Methods: The EduSaltS system evolved from previously successfully tested interventions to reduce family salt intake by empowering schoolchildren through school health education. EduSaltS was designed by following the WHO's conceptual framework for developing a scaling-up strategy which accounted for the nature of the innovation, the capacity of the implementing organizations, the characteristics of the environment, the resources available, and type of scaling up. The system was then developed step by step from determination of online platform architecture, definition of component interventions and activities, development of specific educational materials and tools, to the development of the online/offline hybridized system. The system was tested and refined by a pilot in two schools and a preliminary scale-up in two cities in China. Results: EduSaltS was developed as an innovative health education system, including an online WeChat-based education platform, a set of offline activities, and an actual administrative website showing the progress and setting the system. The WeChat platform could be installed on users' smartphones to automatically deliver 20 sessions of five-minute well-structured cartoon video classes, followed by other online interactive activities. It also helps support project implementation and real-time performance evaluation. As a first-stage roll-out, a one-year course has been successfully implemented among 54,538 children and their families from 209 schools in two cities, and the average course completion rate was 89.1%. Conclusion: As an innovative mHealth-based health education system, EduSaltS was developed based on successfully tested interventions and an appropriate framework for scaling up. The early-stage roll-out has shown its preliminary scalability, and further evaluation is ongoing.

Steroidal saponin SSPH I induces ferroptosis in HepG2 cells via regulating iron metabolism.

Hepatocellular carcinoma (HCC) is a common type of solid liver carcinoma. Regulating ferroptosis is important for the treatment of HCC. SSPH I is an anti-HCC steroidal saponin isolated from Schizocapsa plantaginea Hance. In this study, we found that SSPH I exerted significant anti-proliferation and anti-migration effects on HepG2 cell, ferroptosis inhibitor ferrostatin-1 or iron chelator ciclopirox partly attenuated the effect of SSPH I. SSPH I also induced apoptosis and G2/M phase cell cycle arrest. ROS accumulation, glutathione depletion and malondialdehyde accumulation were detected after SSPH I treatment, which leads to lipid peroxidation. Ferrostatin-1 or ciclopirox showed a significant antagonist effect towards SSPH I induced lipid peroxidation. Furthermore, typical morphologic changes of ferroptosis, such as increasing density of mitochondrial membrane and reduction of mitochondrial cristae were observed in HepG2 cells after SSPH I treatment. SSPH I does not regulate the xCT protein. Interestingly, SSPH I elevated the expression levels of SLC7A5, which is the negative regulator of ferroptosis. In contrast, SSPH I upregulated the expression of TFR and Fpn proteins, leading to the accumulation of Fe2+. Ferrostatin-1 and ciclopirox presented a similar antagonist effect on SSPH I. In conclusion, our research first reveals that SSPH I induced ferroptosis in HepG2 cells. In addition, our results suggest that SSPH I induces ferroptosis by causing iron overload in HepG2 cells.

Model-Based Transfer Reinforcement Learning Based on Graphical Model Representations.

Reinforcement learning (RL) plays an essential role in the field of artificial intelligence but suffers from data inefficiency and model-shift issues. One possible solution to deal with such issues is to exploit transfer learning. However, interpretability problems and negative transfer may occur without explainable models. In this article, we define Relation Transfer as explainable and transferable learning based on graphical model representations, inferring the skeleton and relations among variables in a causal view and generalizing to the target domain. The proposed algorithm consists of the following three steps. First, we leverage a suitable casual discovery method to identify the causal graph based on the augmented source domain data. After that, we make inferences on the target model based on the prior causal knowledge. Finally, offline RL training on the target model is utilized as prior knowledge to improve the policy training in the target domain. The proposed method can answer the question of what to transfer and realize zero-shot transfer across related domains in a principled way. To demonstrate the robustness of the proposed framework, we conduct experiments on four classical control problems as well as one simulation to the real-world application. Experimental results on both continuous and discrete cases demonstrate the efficacy of the proposed method.

The value of process evaluation for public health interventions: field-case studies for non-communicable disease prevention and management in five countries.

Complex interventions are needed to effectively tackle non-communicable diseases. However, complex interventions can contain a mix of effective and ineffective actions. Process evaluation (PE) in public health research is of great value as it could clarify the mechanisms and contextual factors associ-ated with variation in the outcomes, better identify effective components, and inform adaptation of the intervention. The aim of this paper is to demonstrate the value of PE through five case studies that span the research cycle. The interven-tions include using digital health, salt reduction strategies, use of fixed dose combinations, and task shifting. Insights of the methods used, and the implications of the PE findings to the project, were discussed. PE of complex interventions can refute or confirm the hypothesized mechanisms of action, thereby enabling intervention refinement, and identifying implementation strategies that can address local contextual needs, so as to improve service delivery and public health outcomes.

Identification of Phthalates from Artificial Products in Chinese Kindergarten Classrooms and the Implications for Preschool Children's Exposure Assessments.

Phthalates are typical chemical pollutants in kindergarten classrooms since numerous artificial products (e.g., polyvinyl chloride (PVC) floorings, soft polymers and plastic toys) that might contain phthalates are widely distributed in kindergarten classrooms. Although Chinese preschool children spend a considerable amount of their waking hours (>8 h/day) in kindergartens, phthalate exposure in such indoor environment has not been given much attention. In this study, the mass fractions of six phthalates in twenty-six artificial products (fifteen flat decoration materials and eleven plastic toys) commonly found in Chinese kindergarten classrooms were measured. Di-2-ethylhexyl phthalate (DEHP) was the most predominant compound in all materials. The emission characteristics of the DEHP from these materials were further investigated. The measured emission characteristics were used for predicting multi-phase DEHP concentrations in kindergarten classrooms by applying a mass transfer model. The modeled concentrations were comparable with those measured in the real environment, indicating that these products might be the major sources of DEHP in Chinese kindergarten classrooms. Preschool children's exposure to DEHP was found to be 0.42 µg/kg/day in kindergartens under baseline conditions, accounting for 18% of the total exposure to DEHP in Chinese indoor environments.

Process Evaluation of an Application-Based Salt Reduction Intervention in School Children and Their Families (AppSalt) in China: A Mixed-Methods Study.

Background: Salt reduction is a cost-effective, and rather challenging public health strategy for controlling chronic diseases. The AppSalt program is a school-based multi-component mobile health (mhealth) salt reduction program designed to tackle the high salt intake in China. This mixed-methods process evaluation was conducted to investigate the implementation of this program across sites, identify factors associated with the implementation, and collect evidence to optimize the intervention design for future scale-up. Methods: Mixed methods were used sequentially to collect data regarding five process evaluation dimensions: fidelity, dose delivered, dose received, reach, and context. Quantitative data were collected during the intervention process. Participation rate of intervention activities was calculated and compared across cities. The quantitative data was used for the selection of representative intervention participants for the qualitative interviews. Qualitative data were collected in face-to-face semi-structured interviews with purposively selected students (n = 33), adult family members (n = 33), teachers (n = 9), heads of schools (n = 9), key informants from local health, and education departments (n = 8). Thematic analysis technique was applied to analyze the interview transcripts using NVivo. The qualitative data were triangulated with the quantitative data during the interpretation phase. Results: The total number of families recruited for the intervention was 1,124. The overall retention rate of the AppSalt program was 97%. The intervention was implemented to a high level of fidelity against the protocol. About 80% of intervention participants completed all the app-based salt reduction courses, with a significant difference across the three cities (Shijiazhuang: 95%; Luzhou: 73%; Yueyang: 64%). The smartphone app in this program was perceived as a feasible and engaging health education tool by most intervention participants and key stakeholders. Through the interviews with participants and key stakeholders, we identified some barriers to implementing this program at primary schools, including the left-behind children who usually live with their grandparents and have limited access of smartphones; perceived adverse effects of smartphones on children (e.g., eyesight damage); and overlooked health education curriculum at Chinese primary schools. Conclusion: This process evaluation demonstrated the feasibility and acceptability of using smartphone applications delivered through the education system to engage families in China to reduce excessive salt intake. Clinical Trial Registration: The AppSalt study was registered at www.chictr.org.cn, identifier: ChiCTR1800017553. The date of registration is August 3, 2018.

App based education programme to reduce salt intake (AppSalt) in schoolchildren and their families in China: parallel, cluster randomised controlled trial.

OBJECTIVE: To determine whether a smartphone application based education programme can lower salt intake in schoolchildren and their families. DESIGN: Parallel, cluster randomised controlled trial, with schools randomly assigned to either intervention or control group (1:1). SETTING: 54 primary schools from three provinces in northern, central, and southern China, from 15 September 2018 to 27 December 2019. PARTICIPANTS: 592 children (308 (52.0%) boys; mean age 8.58 (standard deviation 0.41) years) in grade 3 of primary school (about 11 children per school) and 1184 adult family members (551 (46.5%) men; mean age 45.80 (12.87) years). INTERVENTION: Children in the intervention group were taught, with support of the app, about salt reduction and assigned homework to encourage their families to participate in activities to reduce salt consumption. MAIN OUTCOME MEASURES: Primary outcome was the difference in salt intake change (measured by 24 hour urinary sodium excretion) at 12 month follow-up, between the intervention and control groups. RESULTS: After baseline assessment, 297 children and 594 adult family members (from 27 schools) were allocated to the intervention group, and 295 children and 590 adult family members (from 27 schools) were allocated to the control group. During the trial, 27 (4.6%) children and 112 (9.5%) adults were lost to follow-up, owing to children having moved to another school or adults unable to attend follow-up assessments. The remaining 287 children and 546 adults (from 27 schools) in the intervention group and 278 children and 526 adults (from 27 schools) in the control group completed the 12 month follow-up assessment. Mean salt intake at baseline was 5.5 g/day (standard deviation 1.9) in children and 10.0 g/day (3.5) in adults in the intervention group, and 5.6 g/day (2.1) in children and 10.0 g/day (3.6) in adults in the control group. During the study, salt intake of the children increased in both intervention and control groups but to a lesser extent in the intervention group (mean effect of intervention after adjusting for confounding factors -0.25 g/day, 95% confidence interval -0.61 to 0.12, P=0.18). In adults, salt intake decreased in both intervention and control groups but to a greater extent in the intervention group (mean effect -0.82 g/day, -1.24 to -0.40, P<0.001). The mean effect on systolic blood pressure was -0.76 mm Hg (-2.37 to 0.86, P=0.36) in children and -1.64 mm Hg (-3.01 to -0.27, P=0.02) in adults. CONCLUSIONS: The app based education programme delivered through primary school, using a child-to-parent approach, was effective in lowering salt intake and systolic blood pressure in adults, but the effects were not significant in children. Although this novel approach could potentially be scaled up to larger populations, the programme needs further strengthening to reduce salt intake across the whole population, including schoolchildren. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800017553.

Engaging Female Community Health Volunteers (FCHVs) for cardiovascular diseases risk screening in Nepal.

INTRODUCTION: Non-Communicable Diseases (NCDs) have become the leading public health problems worldwide and the cardiovascular diseases (CVDs) is one of the major NCDs. Female Community Health Volunteers (FCHVs) in Nepal are the key drivers to implementing frontline health services. We explored the potential for engaging FCHVs for CVD risk screening at the community level in Nepal. METHODS: We used multiple approaches (quantitative and qualitative) for data collection. The trained FCHVs administered CVD risk screening questionnaire among 491 adults in rural and urban areas and calculated the CVD risk scores. To maintain consistency and quality, a registered medical doctor also, using the same risk scoring chart, independently calculated the CVD risk scores. Kappa statistics and concordance coefficient were used to compare these two sets of risk screening results. Sensitivity and specificity analyses were conducted. Two focus group discussions among the FCHVs were conducted to determine their experiences with CVD risk screening and willingness to engage with CVD prevention and control efforts. RESULTS: The mean level of agreement between two sets of risk screening results was 94.5% (Kappa = 0.77, P<0.05). Sensitivity of FCHV screening was 90.3% (95% CI: 0.801-0.964); and the specificity was 97% (95% CI: 0.948, 0.984). FCHVs who participated in the FGDs expressed a strong enthusiasm and readiness to using the CVD risk screening tools. Despite their busy workload, all FCHVs showed high level of motivation and willingness in using CVD risk screening tools and contribute to the prevention and control efforts of NCDs. The FCHVs recommended needs for providing additional training and capacity building opportunities. CONCLUSION: We conclude that there is a potential for engaging FCHVs to use simple CVD risk screening tools at the community level. The findings are promising, however, further studies engaging larger number of FCHVs and larger population would warrant feasibility of such tools within the existing healthcare systems in Nepal.

Association of Sodium, Potassium and Sodium-to-Potassium Ratio with Urine Albumin Excretion among the General Chinese Population.

Mixed evidence was published regarding the association of sodium, potassium and sodium-to-potassium ratio (Na/K ratio) with renal function impairment. This study was conducted to further explore the relationship between sodium, potassium, NA/K ratio and kidney function in the general adult Chinese population. We performed a cross-sectional analysis using the baseline data from the Action on Salt China (ASC) study. 5185 eligible general adult participants from the baseline investigation of the ASC study were included in this analysis. Sodium, potassium and albumin excretion were examined from 24-h urine collection. Albuminuria was defined as albumin excretion rate (AER) greater than or equal to 30 mg/24-h. Mixed linear regression models, adjusted for confounders, were fitted to analyze the association between sodium, potassium and Na/K ratio, and natural log transformed AER. Mixed effects logistic regression models were performed to analyze the odds ratio of albuminuria at each quintile of sodium, potassium and Na/K ratio. The mean age of the participants was 49.5 ± 12.8 years, and 48.2% were male. The proportion of albuminuria was 7.5%.The adjusted mixed linear models indicated that sodium and Na/K ratio was positively associated with natural log transformed AER (Sodium: ß = 0.069, 95%CI [0.050, 0.087], p < 0.001; Na/K ratio: ß = 0.026, 95%CI [0.012, 0.040], p < 0.001). Mixed effects logistic regression models showed that the odds of albuminuria significantly increased with the quintiles of sodium (p < 0.001) and Na/K ratio (p = 0.001). No significant association was found between potassium and the outcome indicators. Higher sodium intake and higher Na/K ratio are associated with early renal function impairment, while potassium intake was not associated with kidney function measured by albumin excretion.

Sodium and Potassium Excretion of Schoolchildren and Relationship with Their Family Excretion in China.

This cross-sectional study aimed to assess 24-h urinary sodium and potassium excretion in children and the relationships with their family excretion. Using the baseline data of a randomized trial conducted in three cities of China in 2018, a total of 590 children (mean age 8.6 ± 0.4 years) and 1180 adults (mean age 45.8 ± 12.9 years) from 592 families had one or two complete 24-h urine collections. The average sodium, potassium excretion and sodium-to-potassium molar ratio of children were 2180.9 ± 787.1 mg/d (equivalent to 5.5 ± 2.0 g/d of salt), 955.6 ± 310.1 mg/d and 4.2 ± 1.7 respectively, with 77.1% of the participants exceeding the sodium recommendation and 100% below the proposed potassium intake. In mixed models adjusting for confounders, every 1 mg/d increase in sodium excretion of adult family members was associated with a 0.11 mg/d (95% CI: 0.06 to 0.16, p < 0.0001) increase in sodium excretion of children. The family-child regression coefficient corresponds to 0.20 mg/d (95% CI: 0.15 to 0.26, p < 0.0001) per 1 mg/d in potassium and to 0.36 (95% CI: 0.26 to 0.45, p < 0.0001) in sodium-to-potassium molar ratio. Children in China are consuming too much sodium and significantly inadequate potassium. The sodium, potassium excretion and sodium-to-potassium ratio of children are associated with their family excretions in small to moderate extent. Efforts are warranted to support salt reduction and potassium enhancement in children through comprehensive strategies engaging with families, schools and food environments.

TREM1 Blockade Ameliorates Lipopolysaccharide-Induced Acute Intestinal Dysfunction through Inhibiting Intestinal Apoptosis and Inflammation Response.

OBJECTIVE: The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. METHODS: Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1ß were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. RESULTS: LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1ß levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. CONCLUSION: LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.

App-Based Salt Reduction Intervention in School Children and Their Families (AppSalt) in China: Protocol for a Mixed Methods Process Evaluation.

BACKGROUND: The app-based salt reduction intervention program in school children and their families (AppSalt) is a multicomponent mobile health (mHealth) intervention program, which involves multiple stakeholders, including students, parents, teachers, school heads, and local health and education authorities. The complexity of the AppSalt program highlights the need for process evaluation to investigate how the implementation will be achieved at different sites. OBJECTIVE: This paper presents a process evaluation protocol of the AppSalt program, which aims to monitor the implementation of the program, explain its causal mechanisms, and provide evidence for scaling up the program nationwide. METHODS: A mixed methods approach will be used to collect data relating to five process evaluation dimensions: fidelity, dose delivered, dose received, reach, and context. Quantitative data, including app use logs, activity logs, and routine monitoring data, will be collected alongside the intervention process to evaluate the quantity and quality of intervention activities. The quantitative data will be summarized as medians, means, and proportions as appropriate. Qualitative data will be collected through semistructured interviews of purposely selected intervention participants and key stakeholders from local health and education authorities. The thematic analysis technique will be used for analyzing the qualitative data with the support of NVivo 12. The qualitative data will be triangulated with the quantitative data during the interpretation phase to explain the 5 process evaluation dimensions. RESULTS: The intervention activities of the AppSalt program were initiated at 27 primary schools in three cities since October 2018. We have completed the 1-year intervention of this program. The quantitative data for this study, including app use log, activity logs, and the routine monitoring data, were collected and organized during the intervention process. After completing the intervention, we conducted semistructured interviews with 32 students, 32 parents, 9 teachers, 9 school heads, and 8 stakeholders from local health and education departments. Data analysis is currently underway. CONCLUSIONS: Using mHealth technology for salt reduction among primary school students is an innovation in China. The findings of this study will help researchers understand the implementation of the AppSalt program and similar mHealth interventions in real-world settings. Furthermore, this process evaluation will be informative for other researchers and policy makers interested in replicating the AppSalt program and designing their salt reduction intervention. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19430.

Immunogenicity and cytotoxicity of a platinum(IV) complex derived from capsaicin.

Platinum-based anticancer drugs constitute the cornerstone of chemotherapy for various cancers. Although cytotoxic agents are considered to have immunosuppressive effects, increasing evidence suggests that some cytotoxic compounds can effectively stimulate the antitumor immune response by inducing a special type of apoptosis called immunogenic cell death (ICD). A platinum(iv) complex (DCP) modified with the derivative of synthetic capsaicin (nonivamide) was designed to elicit ICD. The complex exhibited high cytotoxicity against a panel of human cancer cell lines including pancreas (PANC-1), breast (MCF-7), and liver (HepG2) cancer cells, and osteosarcoma (MG-63) cells. In addition to causing DNA damage, DCP also triggered the translocation of calreticulin (CRT) as well as the release of ATP and HMGB1 protein in PANC-1 cells, thus manifesting an efficient ICD-inducing effect on cancer cells. Furthermore, the DCP-treated PANC-1 cell-conditioned culture medium promoted the release of IFN-γ and TNF-α to induce the immune response of human peripheral blood mononuclear cells, thereby increasing their cytotoxicity to cancer cells. Concurrently, the phagocytosis of PANC-1 cells by macrophages was also augmented by DCP. The results demonstrate that DCP is an effective inducer of ICD and a potential agent for chemoimmunotherapy of cancers.

A Parallel Framework of Adaptive Dynamic Programming Algorithm With Off-Policy Learning.

In this article, a model-free online adaptive dynamic programming (ADP) approach is developed for solving the optimal control problem of nonaffine nonlinear systems. Combining the off-policy learning mechanism with the parallel paradigm, multithread agents are employed to collect the transitions by interacting with the environment that significantly augments the number of sampled data. On the other hand, each thread agent explores the environment with different initial states under its own behavior policy that enhances the exploration capability and alleviates the correlation between the sampled data. After the policy evaluation process, only one step update is required for policy improvement based on the policy gradient method. The stability of the system under iterative control laws is guaranteed. Moreover, the convergence analysis is given to prove that the iterative Q-function is monotonically nonincreasing and finally converges to the solution of the Hamilton-Jacobi-Bellman (HJB) equation. For implementing the algorithm, the actor-critic (AC) structure is utilized with two neural networks (NNs) to approximate the Q-function and the control policy. Finally, the effectiveness of the proposed algorithm is verified by two numerical examples.

Systematic Review on International Salt Reduction Policy in Restaurants.

As the catering sector has increasingly contributed to population-level salt intake, many countries have begun developing salt-reduction strategies for restaurants. This paper aims to provide an overview of global salt reduction policies in restaurants. Scientific papers and website materials were systematically searched from Web of Science, Science Direct, and PubMed, as well as official websites of government departments and organizations. A total of 78 full-text papers and grey literature works were included. From 58 countries and regions, 62 independent policies were identified, 27 of which were mandatory (3 with fines). The most common strategy was menu labeling, which was a component of 40 policies. Target setting (n = 23) and reformulation (n = 13) of dishes were also widely implemented. Other salt-reduction strategies included education campaign, chef training, toolkits delivery, table salt removal, media campaign, and government assistance such as free nutrition analysis and toolkits distribution. Most policies focused on chain restaurants. Evaluations of these policies were limited and showed inconsistent results, and more time is needed to demonstrate the clear long-term effects. Attention has been paid to salt reduction in restaurants around the world but is still at its early stage. The feasibility and effectiveness of the strategies need to be further explored.

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX-2 and PD-L1.

Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes. Cyclooxygenase-2 (COX-2) plays a vital role in the progression of BC, correlating with the expression of programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells, and its blockade would stimulate anticancer immunity. Two multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells. DNP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX; moreover, it displayed potent antitumor activity and almost no general toxicity in mice bearing triple-negative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo, inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells. These findings demonstrate that DNP is capable of intervening in inflammatory, immune, and metastatic processes of BC, thus presenting a new mechanism of action for anticancer platinum(IV) complexes. The multispecificity offers a special superiority for DNP to treat TNBC by combining chemotherapy and immunotherapy in one molecule.

Twenty-Four-Hour Urinary Sodium and Potassium Excretion and Their Associations With Blood Pressure Among Adults in China: Baseline Survey of Action on Salt China.

This study aimed to assess current level of sodium and potassium intake and their associations with blood pressure (BP) using the 24-hour urinary data in a large sample of China. Data from participants aged 18 to 75 years were collected as the baseline survey of Action on Salt China in 2018. Of 5454 adults, 5353 completed 24-hour urine collection. The average sodium, potassium excretion, and sodium-to-potassium molar ratio were 4318.1±1814.1 mg/d (equivalent to 11.0±4.6 g/d of salt), 1573.7±627.1 mg/d, and 5.0±2.1, respectively. After adjusting for potential confounding factors and correcting for regression dilution, each 1000-mg increase in sodium excretion was associated with increased systolic BP (1.32 mm Hg [95% CI, 0.92-1.81]) and diastolic BP (0.34 mm Hg [95% CI, 0.09-0.60]). Each 1000-mg increase in potassium excretion was inversely associated with systolic BP (-3.19 mm Hg [95% CI, -4.38 to -2.20]) and diastolic BP (-1.56 mm Hg [95% CI, -2.29 to -0.90]). Each unit increase in sodium-to-potassium molar ratio was associated with an increase of systolic BP by 1.21 mm Hg (95% CI, 0.91-1.60) and diastolic BP by 0.44 mm Hg (95% CI, 0.24-0.64). The relationships between sodium and BP mostly increase with the rise of BP quantiles. Potassium shows the opposite trend. The current sodium intake in Chinese adults remains high and potassium intake is low. Sodium and sodium-to-potassium ratio were positively associated with BP, whereas potassium was inversely associated with BP. Registration- URL: https://tinyurl.com/vdr8rpr; Unique identifier: ChiCTR1800017553. URL: https://tinyurl.com/w8c7x3w; Unique identifier: ChiCTR1800016804. URL: https://tinyurl.com/s3ajldw; Unique identifier: ChiCTR1800018119.

Anti-migraine effect of wine-processed Radix scutellariae: Pharmacodynamic verification in nitroglycerin-induced rats and correlation study between compounds dissolution and the fractal dimension.

ETHNOPHARMACOLOGICAL RELEVANCE: Wine-processed Radix scutellariae (RS) is the processed product of RS, which is the dried root of Scutellaria baicalensis Georgi. It is recorded in Chinese traditional formula that wine-processed RS has the effect of anti-migraine, while the effect has not been confirmed and the possible mechanism remains unclear. AIM OF THE STUDY: To verify the anti-migraine effect of wine-processed RS in nitroglycerin (NTG)-induced rats and explore the correlation between compounds dissolution and the pore structure based on fractal theory. MATERIALS AND METHODS: In the validation of pharmacodynamics, the effects of wine-processed RS on migraines were firstly evaluated by observing the number of head-scratching of rats, then investigated by determining the levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP) and the expression of c-Fos in the brain of NTG-induced rat models using ELISA and immunohistochemical assessments. In the correlation study, the stir-frying time of RS was set to 5 min, 10 min and 15 min. The scanning electron microscope (SEM) and mercury intrusion method were used to explore the pore structure and main parameters of the pore structure including pore size distribution, pore volume, porosity, surface area and fractal dimension. The compounds dissolution of total flavonoids and five major components containing baicalein, baicalin, scutellarin, wogonin and wogonoside was determined by UV-Vis spectrophotometry and HPLC separately. RESULTS: The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p < 0.01) and markedly decrease the levels of NO (p < 0.01), CGRP (p < 0.05) and the expression of c-Fos (p < 0.01) compared with model group. The data indicated that wine-processing would affect the dissolution of compounds by changing the pore structure of RS. The order of positive correlation between pore structure parameters and compounds' dissolution was total surface area > fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r < 0). Compared with the other sample groups (p < 0.05), the wine-processed RS stir-fried for 10 min had a pore structure which was more favorable for compounds dissolution. CONCLUSIONS: Wine-processing could strengthen the anti-migraine effect of RS by changing the pore structure of RS, which is linked to the dissolution of compounds. The RS stir-fried for 10 min may be more effective in treating migraine.