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Abstract The integration of industrial robot application (IRA) into various sectors has catalyzed significant transformations in the labor market, reshaping the dynamics of individual migration decision (IMD). As industries increasingly adopt automation, the implications for workforce distribution and migration patterns become critical areas of study. Based on the conditional logit model and using CMDS data, this paper explores the relationship between IRA and IMD, as well as the heterogeneity effect and influencing mechanism. The findings indicate that IRA reduces the probability of the floating population choosing the city, and the results are robust after considering endogeneity and further robustness test. The impact of IRA on IMD is heterogeneous. Relatively speaking, the floating population with high education levels, health, younger, unmarried, female, agricultural household registration, state-owned enterprises, and non-routine task work does not over-think the impact of IRA during the migration process. In addition, the floating population also considers geographical location, city size, marketization level, wage level, and environmental quality when making migration decisions. the mechanism test shows that IRA attracts or suppresses the floating population through factors such as wage levels, housing price level, difficulty in finding a job, etc., depending on the result of individual utility maximization. These insights reveal the complex interplay between technological advancements in robotics and labor migration, emphasizing the need for comprehensive policy frameworks to manage these transformations effectively.

Food security has been long understudied in the context of Central Asia. We present an analysis examining household-level food demand for Tajikistan and assessing the magnitude of its food security changes during the COVID-19 pandemic. Based on an extensive household survey data set from Tajikistan, we estimate the expenditure, income, and price elasticities for nine food categories using the QUAIDS model. Then, we develop a microsimulation model using the estimated elasticities to assess the dual impact of declining remittance income and rising food prices stemming from the pandemic shock. There are significant differences in demand elasticities across food groups, with high elasticities observed for nutritious foods, such as meat, fruit, eggs, and milk, in rural households. Moreover, our findings show that changes in remittance income and food prices significantly negatively affected food security for rural households during the COVID-19 pandemic. These findings have important implications for policymakers concerned about rural livelihoods and food security in remittance-receiving economies during the post-pandemic period.

Abstract Air pollution poses a major threat to both the environment and public health. The air quality index (AQI), aggregate AQI, new health risk–based air quality index (NHAQI), and NHAQI-WHO were employed to quantitatively evaluate the characterization of air pollution and the associated health risk in Gansu Province before (P-I) and after (P-II) COVID-19 pandemic. The results indicated that AQI system undervalued the comprehensive health risk impact of the six criteria pollutants compared with the other three indices. The stringent lockdown measures contributed to a considerable reduction in SO2, CO, PM2.5, NO2 and PM10; these concentrations were 43.4%, 34.6%, 21.4%, 17.4%, and 14.2% lower in P-II than P-I, respectively. But the concentration of O3 had no obvious improvement. The higher sandstorm frequency in P-II led to no significant decrease in the ERtotal and even resulted in an increase in the average ERtotal in cities located in northwestern Gansu from 0.78% in P-I to 1.0% in P-II. The cumulative distribution of NHAQI-based population-weighted exposure revealed that 24% of the total population was still exposed to light pollution in spring during P-II, while the air quality in other three seasons had significant improvements and all people were under healthy air quality level.

Abstract Cancer cells generally exhibit ‘iron addiction’ phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic ‘ballooning’ phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death. Graphical Abstract

Objective: Mobile health applications (apps) have gained significant popularity and widespread utilization among patients with coronary heart disease (CHD). The objective of this study is to evaluate the effects of mHealth apps on clinical outcomes and health behaviors in patients with CHD. Methods: Databases were searched from inception until December 2023, including Cochrane Library, PubMed, EMBASE, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Service System (SinoMed), Wanfang Data, China Science and Technology Journal Database (VIP), for randomized controlled trials (RCTs) regarding the effectiveness of mHealth apps in patients with CHD. Two researchers conducted a comprehensive review of the literature, extracting relevant data and evaluating each study’s methodological quality separately. The meta-analysis was performed utilizing Review Manager v5.4 software. Results: A total of 34 RCTs were included, with 5,319 participants. The findings demonstrated that using mHealth apps could decrease the incidence of major adverse cardiac events (RR = 0.68, P = 0.03), readmission rate (RR = 0.56, P 0.05). Conclusion: Mobile health apps have the potential to lower the incidence of major adverse cardiac events (MACEs), readmission rates, and blood lipids in patients with CHD. They can also help enhance cardiac function, promote medication adherence, and alleviate symptoms of anxiety and depression. To further corroborate these results, larger-scale, multi-center RCTs with longer follow-up periods are needed.

As the first barrier for food against pollution, food packaging plays a crucial role in food production, which greatly impacts both the quality and safety of food. Recently, the increasing use of conventional plastic packaging has posed a significant threat to the environment. Meanwhile, cases of foodborne poisoning caused by microbial contamination emerge endlessly. On this background, biodegradable antimicrobial film prepared with natural biological materials has a broad application in future food packaging materials. This article reviews the research progress of biodegradable and antimicrobial films based on biological materials (polysaccharides, proteins, and lipids) and their application in food packaging. And introduces the application of different antimicrobial agents (Synthetic and natural antimicrobial agents) in antimicrobial films. Moreover, discusses the effect of the addition of antibacterial agents on the properties of packing and the antibacterial activities of films. Finally, the shortcomings of food packaging-related fields are discussed. The development of biodegradable antimicrobial food packaging films in the future is prospected.

BackgroundNonadherence to medication among patients with cardiovascular diseases undermines the desired therapeutic outcomes. eHealth interventions emerge as promising strategies to effectively tackle this issue. ObjectiveThe aim of this study was to conduct a network meta-analysis (NMA) to compare and rank the efficacy of various eHealth interventions in improving medication adherence among patients with cardiovascular diseases (CVDs). MethodsA systematic search strategy was conducted in PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure Library (CNKI), China Science and Technology Journal Database (Weipu), and WanFang databases to search for randomized controlled trials (RCTs) published from their inception on January 15, 2024. We carried out a frequentist NMA to compare the efficacy of various eHealth interventions. The quality of the literature was assessed using the risk of bias tool from the Cochrane Handbook (version 2.0), and extracted data were analyzed using Stata16.0 (StataCorp LLC) and RevMan5.4 software (Cochrane Collaboration). The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. ResultsA total of 21 RCTs involving 3904 patients were enrolled. The NMA revealed that combined interventions (standardized mean difference [SMD] 0.89, 95% CI 0.22-1.57), telephone support (SMD 0.68, 95% CI 0.02-1.33), telemonitoring interventions (SMD 0.70, 95% CI 0.02-1.39), and mobile phone app interventions (SMD 0.65, 95% CI 0.01-1.30) were statistically superior to usual care. However, SMS compared to usual care showed no statistical difference. Notably, the combined intervention, with a surface under the cumulative ranking curve of 79.3%, appeared to be the most effective option for patients with CVDs. Regarding systolic blood pressure and diastolic blood pressure outcomes, the combined intervention also had the highest probability of being the best intervention. ConclusionsThe research indicates that the combined intervention (SMS text messaging and telephone support) has the greatest likelihood of being the most effective eHealth intervention to improve medication adherence in patients with CVDs, followed by telemonitoring, telephone support, and app interventions. The results of these network meta-analyses can provide crucial evidence-based support for health care providers to enhance patients’ medication adherence. Given the differences in the design and implementation of eHealth interventions, further large-scale, well-designed multicenter trials are needed. Trial RegistrationINPLASY 2023120063; https://inplasy.com/inplasy-2023-12-0063/

Low-molecular-weight (LMW) thiols are produced in all living cells in different forms and concentrations. Glutathione (GSH), coenzyme A (CoA), bacillithiol (BSH), mycothiol (MSH), ergothioneine (ET) and trypanothione T(SH)2 are the main LMW thiols in eukaryotes and prokaryotes. LMW thiols serve as electron donors for thiol-dependent enzymes in redox-mediated metabolic and signaling processes, protect cellular macromolecules from oxidative and xenobiotic stress, and participate in the reduction of oxidative modifications. The level and function of LMW thiols, their oxidized disulfides and mixed disulfide conjugates in cells and tissues is tightly controlled by dedicated oxidoreductases, such as peroxiredoxins, glutaredoxins, disulfide reductases and LMW thiol transferases.This review provides the first summary of the current knowledge of structural and functional diversity of transferases for LMW thiols, including GSH, BSH, MSH and T(SH)2. Their role in maintaining redox homeostasis in single-cell and multicellular organisms is discussed, focusing in particular on the conjugation of specific thiols to exogenous and endogenous electrophiles, or oxidized protein substrates. Advances in the development of new research tools, analytical methodologies, and genetic models for the analysis of known LMW thiol transferases will expand our knowledge and understanding of their function in cell growth and survival under oxidative stress, nutrient deprivation, and during the detoxification of xenobiotics and harmful metabolites. The antioxidant function of CoA has been recently discovered and the breakthrough in defining the identity and functional characteristics of CoA S-transferase(s) is soon expected.

Summary: It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/μL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/μL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.

【Objective】Sri Lankan cassava mosaic virus (SLCMV) is a circular single-stranded DNA virus, containing two components of DNA-A and DNA-B. SLCMV is a member of the genus Begomovirus in the family Geminiviridae, which is a persistent threat to the world's cassava industry. In 2018, the SLCMV was found and reported for the first time in cassava from Fujian and Hainan provinces, China. However, the viral resistance of cassava varieties in domestic was unknown and the germplasm resources for disease resistance was lacking. To further explore the genetic background of domestic cassava germplasm resources resistance to mosaic disease and the mechanism of interaction between virus and host, SLCMV infectious clone was constructed and verified.【Method】In this study, SLCMV TVM3 strain was used as the object, and its 1.10 mer DNA-A and 1.08 mer DNA-B components were respectively constructed into pCAMBIA1301 vector, and the viral infectious clone vectors pCAMBIA1301-DNA-A (pDNA-A) and pCAMBIA1301-DNA-B (pDNA-B) were obtained. Agrobacterium tumefacien GV3101 mediated pDNA-A and pDNA-B co-infected tobacco and Arabidopsis plants.【Result】At 14 d post inoculation, the systematic leaves of tobacco plants produced severe mosaic and distortion symptoms, while the systematic leaves of Arabidopsis plants showed mild distortion at 18 d post inoculation. Total DNA was extracted from SLCMV infected tobacco and Arabidopsis plants leaves, and viral DNA-A and DNA-B components were detected by PCR method. In addition, the virus infection rate of tobacco plants was 100%, while the virus infection rate of Arabidopsis plants was only 40%, and the difference between the two group was significant (P < 0.05).【Conclusion】The SLCMV infectious clone have been successfully constructed, which could infect tobacco and Arabidopsis plants, and the viral infection rate reached 96.67% in tobacco plants. Furthmore, the DNA sequences of infectious clone in pDNA-A and pDNA-B are 1.10 mer and 1.08 mer length of the original virus genomic DNA-A and DNA-B components, respectively, whichdid not contain repetitive coding region sequences. This study provides an important basis for the further explore the genetic background of domestic cassava germplasm resources resistance to mosaic disease and the pathogenesis of virus.

Sugar substitutes, which generally refer to a class of food additives, mostly have vibration frequencies within the terahertz (THz) band. Therefore, THz technology can be used to analyze their molecular properties. To understand the characteristics of sugar substitutes, this study selected mannitol and erythritol as representatives. Firstly, PXRD and Raman techniques were used to determine the crystal structure and purity of mannitol and erythritol. Then, the THz time-domain spectroscopy (THz-TDS) system was employed to measure the spectral properties of the two sugar substitutes. Additionally, density functional theory (DFT) was utilized to simulate the crystal configurations of mannitol and erythritol. The experimental results showed good agreement with the simulation results. Finally, microfluidic chip technology was used to measure the THz spectroscopic properties of the two sugar substitutes in solution. A comparison was made between their solid state and aqueous solution state, revealing a strong correlation between the THz spectra of the two sugar substitutes in both states. Additionally, it was found that the THz spectrum of a substance in solution is related to its concentration. This study provides a reference for the analysis of sugar substitutes.

Summary: Saccharides are essential organic compounds that perform critical functions in sustaining life processes. As biomolecules, their vibrational frequencies predominantly fall in the terahertz (THz) range, making them amenable to analysis using THz techniques. In this study, L-sorbose and D-melibiose were measured using a THz time-domain spectroscopy system covering a frequency range of 0.1–2.0 THz, and their crystal structures were simulated using density functional theory. The experimental results demonstrated significant agreement with the simulation findings. In addition, the spectral properties of the two saccharides in solution were determined using microfluidic chip technology, thereby facilitating a comparison between the solid and aqueous states. The results demonstrate that the intramolecular and intermolecular interactions of the saccharides were weakened by the presence of water molecules, and the THz absorption spectrum of the same substance solution was found to be correlated with its concentration and temperature.

BackgroundWith the intensification of global climate warming, extreme low temperature events such as cold spells have become an increasingly significant threat to public health. Few studies have examined the relationship between cold spells and mortality in multiple Chinese provinces.MethodsWe employed health impact functions for temperature and mortality to quantify the health risks of the first winter cold spell in China on November 26th, 2022, and analyzed the reasons for the stronger development of the cold spell in terms of the circulation field.ResultsThis cold spell was a result of the continuous reinforcement of the blocking high-pressure system in the Ural Mountains, leading to the deepening of the cold vortex in front of it. Temperature changes associated with the movement of cold fronts produced additional mortality risks and mortality burdens. In general, the average excess risk (ER) of death during the cold spell in China was 2.75%, with a total cumulative excess of 369,056 deaths. The health risks associated with temperatures were unevenly distributed spatially in China, with the ER values ranging from a minimum of 0.14% to a maximum of 5.72%, and temperature drops disproportionately affect southern regions of China more than northern regions. The cumulative excess deaths exibited the highest in eastern and central China, with 87,655 and 80,230 respectively, and the lowest in northwest China with 27,474 deaths. Among the provinces, excess deaths pronounced the highest in Shandong with 29,492 and the lowest in Tibet with only 196.ConclusionThe study can provide some insight into the mortality burden of cold spells in China, while emphasising the importance of understanding the complex relationship between extreme low temperature events and human health. The outcomes could provide valuable revelations for informing pertinent public health policies.

We designed a linear polarization converter based on metasurface and simulated its functionality. It has a broad bandwidth and operates in the terahertz frequency range (0.4–1.2 THz). The polarization converter consists of a polyimide substrate, a metal grating and a bimetallic split ring resonator. In a bimetallic split ring resonator, the gaps between the rings are rotated by 90° from one another. The structure is simulated by commercial software CST STUDIO SUITE. The results show that the device successfully converts the polarization of terahertz wave from y to x. This structure also has high stability in terms of incidence angle and operates efficiently in the range of 0° to 45°.This kind of polarization converter has a wide application prospect in satellite communication, radar detection, 3D imaging of displays, and other fields.

BackgroundCancer as a global public health problem, imposes a heavy disease burden. With the rapid development of oral anti-neoplastic drugs, there has been a paradigm shift in the treatment of cancer from intravenous to oral administration.ObjectiveThis study was conducted to investigate the trends and prescribing patterns of oral anti-neoplastic drugs in an academic tertiary hospital in China.MethodsA single-center and retrospective analysis was performed based on the prescriptions of outpatients treated with oral anti-neoplastic drugs from 2017 to 2022. Yearly prescriptions and expenditure were calculated according to their pharmacological classes, and trends were further analyzed. Defined daily doses (DDDs) and defined daily cost (DDC) of oral targeted anti-neoplastic drugs were also determined.ResultsBoth the number of prescriptions and expenditure of oral anti-neoplastic drugs increased progressively. There was a significant upward trend in the number and proportion of prescriptions for the older adult group, male group, and patients with gynecologic/genitourinary and respiratory cancer. Hormonal therapy agents accounted for the highest proportion of prescriptions, and letrozole was initially the most frequently prescribed drug. The number of DDDs of total oral targeted anti-neoplastic drugs showed a continuously ascending trend, primarily driven by the usage of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and BCR-ABL TKIs.ConclusionThe prescriptions and expenditure of oral anti-neoplastic drugs, and the number of DDDs of oral targeted anti-neoplastic drugs all showed a progressively ascending trend. Further studies are needed to evaluate the long-term health and financial outcomes, and the factors influencing these prescribing patterns.

Depression is a common mental illness. Ferroptosis is a form of cell death that may be responsible for neurological disease, but the role of ferroptosis in depression remains unclear. tRNA-derived small RNA (tsRNA) is an emerging non-coding small RNA, making it an important medium for studying neurological diseases. Chronic unpredictable mild stress (CUMS) was used to construct the depression model in mice, which was treated with ferrostatin-1 (Fer-1). Classical behavioral test, immunofluorescence and small RNA sequencing were used to detect depression-like behaviors, neuronal proliferation and the expression profile of tsRNAs in mice, respectively. The primary neuronal cell damage model was constructed by corticosterone (CORT), and the function of key tsRNA was investigated by quantitative real-time PCR, western blot and CCK-8 assays. Here, Fer-1 reduced the depression-like behavior of CUMS-induced mice and promoted neuronal growth. In addition, CUMS caused the disorder of tsRNA expression profile in hippocampal tissues of mice, and Fer-1 alleviated the abnormal tsRNA expression, among which tsRNA-3029b was an effective target. In vitro experiments manifested that ROS accumulation and decreased expression of SLC7A11 and GPX4 were found in CORT-induced depression-like cell model, suggesting that ferroptosis was involved in neuronal injury. However, inhibition of tsRNA-3029b suppressed neuronal cell ferroptosis and facilitated neuronal regeneration. In conclusion, Fer-1 showed an antidepressant effect in CUMS-induced mice and alleviated the abnormal expression profile of tsRNA. tsRNA-3029b was a key target in depression, and silencing of tsRNA-3029b reduced the occurrence of ferroptosis and protected neurons from injury, which may provide novel target for the treatment of depression.

Background The competencies of medical staff in the public health emergency system and evaluated the effects of system-based professional training were investigated. Material and Methods A competency model for individuals in a public health emergency management system was developed, which contained 33 items with 5 domains. A competency-based intervention was performed. A total of 68 participants from 4 health emergency teams in Xinjiang, China were recruited and randomly divided into 2 groups: the intervention (N = 38) and control groups (N = 30). Participants in the intervention group received competency-based training, while those in the control group received no training. All participants responded to the COVID-19 activities. The competencies of medical staff in the 5 domains were then analyzed in the pre-intervention, post-first training, and post-COVID-19 intervention using a self-designed questionnaire. Results Participants’ competencies were at the middle level at baseline. After the first training, competencies in the 5 domains significantly improved in the intervention group; in the control group, there was a significant increase in professional quality compared in the pre-training. After the response to COVID-19, the mean scores of competencies in the 5 domains significantly increased in both the intervention and control groups compared with those in the post-first training. Psychological resilience scores were higher in the intervention group than in the control group, whereas no significant differences in competencies were found in other domains. Conclusions Competency-based interventions provided practice and showed a positive effect on improving the competencies of medical staff in public health teams. Med Pr. 2023;74(1):19–26

Provisioning services are essential components of ecosystem services. Food production is usually a driver of land use change, which has the effect on altering the provisioning services of ecosystems. As one of the main areas of food production in China, the provisioning services of the Songhua River Basin (SHRB) should be taken seriously. In view of this, it is urgent to carry out a study on the assessment of provisioning services in the SHRB to provide data support and scientific reference for the optimization of the spatial pattern of land use in the basin, the sustainable development of agriculture, and the formulation of differentiated protection policies. In this study, based on the equivalent factor method for the unit area value and spatial autocorrelation with the Moran’s I, we assessed the provisioning services values (PSV) of the SHRB every ten years during the period of 2000–2020 under different land use types and analyzed the relationships between different PSV and the production of four different food types, including rice, wheat, corn, and soja. The main conclusions are as follows: (1) From 2000 to 2020, the area of paddy fields in the SHRB increased and then decreased, while the area of dry lands continued to increase. The land use transfer matrix showed a significant expansion of paddy fields (+0.55 × 104 km2), shrinkage of grassland (−0.72 × 104 km2), and loss of water body (−0.43 × 104 km2) in the SHRB from 2000 to 2020; (2) The PSV in the SHRB showed an increasing trend from 2000 to 2020, growing by 16.73 × 1010 RMB, with the growth in 2010–2020 being greater than in 2000–2010. The order of increase in each type of PSV was: water supply > food supply > raw material supply; (3) Spatially, the increase in PSV per unit and total PSV in the SHRB was lesser in the center and greater in the east and west. Meanwhile, the spatial distribution of various PSV showed that the value of unit area food supply was higher in the central and eastern plains, while the raw material supply and water supply were higher in the western and eastern hilly areas. (4) In terms of spatial correlation, the distribution of soja production with the total PSV, food supply, raw materials supply, and water supply services values were positively spatially correlated. However, the production of rice, wheat, and corn with the total PSV, food supply, and raw materials supply services values were negatively spatially correlated. Cluster analysis revealed that changing the crop cultivation structure could protect the ecosystem and increase the value of ecosystem services.

Due to global warming, the overheating risk of residential buildings (especially with no air conditioning) in severe cold and cold regions of China is attracting increasing attention. This phenomenon will seriously affect people’s comfort and even health. Fewer studies and Chinese local building standards, however, are related to overheating in such region, which were not considered overheating in the past. It is not clear whether integrating phase change materials (PCM), which has been considered as a useful method to improve thermal comfort, into building envelopes can effectively alleviate the overheating phenomenon in the severe cold and cold regions. This paper aims to reveal the overheating risk by monitoring four residential buildings, and to verify the effectiveness of using PCM to alleviate the overheating in these regions through simulation. The results indicate a significant overheating risk. During the summertime (May to September), overheating hours were recorded for 395, 618, 857 and 713 h out of total 3672 h (accounted for 25.82%, 40.39%, 56.01% and 46.60%) in the south-facing bedrooms of Yichun, Harbin, Shenyang and Dalian respectively. The study finds that PCM reduces overheating hours in south-facing bedrooms in Yichun, Harbin, Shenyang and Dalian by 19.66%, 17.95%, 15.88% and 10.87%, and saves cooling energy by 25.67%, 15.36%, 14.61%, 15.34% respectively. This paper proposes a standard for evaluation and practical guidance for policy makers on reducing indoor overheating in severe cold and cold regions of China.

The extensive usage of concrete and ordinary Portland cement has generated 5~8% of annual global CO2 emissions, causing serious environmental problems. To reduce such environmental impact, researchers have made significant efforts to develop alternative materials that may partially or entirely replace the ordinary Portland cement, such as limestone calcined clay cement (LC3). LC3 has not been commonly adopted in reality because of uncertain setting times during the transportation and construction processes. Comprehensive investigation and understanding of the setting times of LC3 has great significance to industrial upgrading. As a result, this study is committed to comprehensively reviewing the hydration process and the setting time of LC3 materials.

In order to improve the nutritional and functional value of the mixed congee products, and to improve its stability, the experiment was carried out to prepare mixed congee powders through pulverisation treatments including general (3000 r/min, 1600 W) and superfine grinding (−20 ℃, 960 r/min, 1100 W). The effects of superfine grinding on the particle size distribution, color parameters, hydration properties, filling properties, fluidity properties，micro structure，antioxidant activity, the dissolutions of flavonoids and total polyphenols were investigated, which would provide reference for the application and promotion of superfine grinding in mixed congee processing industry. The results showed that superfine grinding had a significant effect on the physicochemical and functional properties of mixed congee powder (P

Understanding the role of active sites in electrooxidation reactions is important yet challenging. Here, the authors use operando spectroscopies to monitor the effect of methanol concentration on Ni3B/Ni heterostructures during formate production.

Abstract Background In the present study, we attempted to develop and validate a participatory competency model for medical workers and then evaluate the current status of competency characteristics of Chinese medical workers. Methods The competency model was constructed in a multistage process, including literature review, expert consultation, critical incident and focus group interview. A pilot study was conducted to refine the initial model among 90 participators and the viability and reliability were evaluated by a questionnaire survey among 121 medical workers. Then, the current status of competency characteristics was measured based on the final version of competency model. Results In the pilot study, ten questionnaires were dropped for the poor quality and thus the eligible rate was 92% (138/150). KMO value was 0.785 and Bartlett test showed that the χ2 = 6464.546 (df = 903) and p value

Background: Heart failure (HF) is a cardiovascular disease with high morbidity and mortality. Guanxinning injection (GXNI) is clinically used for the treatment of coronary heart disease, but its therapeutic efficacy and potential mechanism for HF are poorly understood. This study aimed to evaluate the therapeutic potential of GXNI on HF, with a special focus on its role in myocardial remodeling. Methods: 3D cardiac organoids and transverse aortic constriction (TAC) mouse models were established and utilized. Heart function and pathology were evaluated by echocardiography, hemodynamic examination, tail-cuff blood pressure and histopathology. Key targets and pathways regulated by GXNI in HF mouse heart were revealed via RNA-seq and network pharmacology analysis, and were verified by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. Results: GXNI significantly inhibited cardiac hypertrophy and cells death. It protected mitochondrial function in cardiac hypertrophic organoids and markedly improved cardiac function in HF mice. Analysis of GXNI-regulated genes in HF mouse hearts revealed that IL-17A signaling in fibroblasts and the corresponding p38/c-Fos/Mmp1 pathway prominently mediated cardiac. Altered expressions of c-Fos, p38 and Mmp1 by GXNI in heart tissues and in cardiac organoids were validated by RT-PCR, WB, IHC, and IF. H&E and Masson staining confirmed that GXNI substantially ameliorated myocardial hypertrophy and fibrosis in HF mice and in 3D organoids. Conclusion: GXNI inhibited cardiac fibrosis and hypertrophy mainly via down-regulating p38/c-Fos/Mmp1 pathway, thereby ameliorating cardiac remodeling in HF mice. Findings in this study provide a new strategy for the clinical application of GXNI in the treatment of heart failure.

Azadirachtin is regarded as one of the best botanical pesticides due to its broad spectrum of insecticides and low interference with natural enemies. To enhance the effect of azadirachtin and slow down the generation of resistance, the combined activity was studied. Here, we found that Dodonaea viscosa saponin B (DVSB) isolated from the seeds of Dodonaea viscosa has good combined activity with the azadirachtin. The mixture of DVSB and azadirachtin in a volume ratio of 1:4 had the strongest combined effect against Spodoptera litura, with a co-toxicity coefficient (CTC) of 212.87. DVSB exerted its combined activity by affecting the contact angle, surface tension, maximum retention and cell membrane permeability. When mixed with DVSB, the contact angle and surface tension decreased by 30.38% and 23.68%, and the maximum retention increased by 77.15%. DVSB was screened as an effective combined activity botanical compound of azadirachtin upon the control of S. litura and highlights the potential application of botanical compounds as pesticide adjuvants in the pest management.

Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3–8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 ± 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.

Navigation accidents and disasters frequently occur when ships sail at sea owing to extreme weather, wind, and wave conditions. The disturbance of wind and waves affects the stability of the ship’s course and makes the ship roll violently. Ships are usually equipped with an autopilot to control the course and a fin stabilizer to reduce rolling during navigation and improve stability and safety. Fin-rudder joint control system considers the coupling effect of the ship’s horizontal plane motion, thereby improving the performance of the rudder and the fin stabilizer. This paper presents an improved linear-quadratic-regulator control algorithm. A rate control law with no static error is proposed based on the traditional linear-quadratic-regulator to eliminate the static error of the state vector and achieve a better control effect. Additionally, a closed-loop state observer is used to estimate the system’s state vector, and a dynamic corrector is designed to reduce rolling and heading angle deviation caused by sea wave interference. The simulation results show that the designed fin-rudder joint controller with the improved linear-quadratic-regulator algorithm can achieve more than 80% roll reduction effect at level 3 and 5 sea states, and has better course keeping ability compared with the rudder control.

Abstract Background The impact of long-term serum uric acid (SUA) exposure and time course of SUA accumulation on diabetes mellitus (DM) is unknown. This study aimed to evaluate the association of cumulative SUA (cumSUA) exposure and its accumulation time course with risk of DM. Methods This prospective study included 46,434 participants without DM and underwent three examinations at 2006, 2008, and 2010. CumSUA from 2006 to 2010 was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Time course of SUA accumulation was categorized as the slope of SUA versus time from 2006 to 2010, or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10). Results During 6.99 years of follow-up, we identified 2971 incident DM cases. In the fully adjusted model, a higher risk of DM was observed in participants with the highest quartile of cumSUA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.17–1.46), cumulative burden >0 (HR, 1.23; 95% CI, 1.08–1.40), and with 6 year of hyperuricemia exposure duration (HR, 1.25; 95% CI, 1.01–1.55). When considering the time course of SUA accumulation, participants with a negative slope (HR, 1.05; 95% CI, 1.01–1.12), or combined with cumSUA ≥ median and a negative slope had elevated risk of DM (HR, 1.58; 95% CI, 1.18–2.11). Conclusions Incident DM risk depends on cumulative exposure of SUA and time course of SUA accumulation. Early SUA accumulation resulted in a greater risk increase compared with later accumulation, emphasizing the importance of optimal SUA control early in life.

Abstract The transient receptor potential vanilloid 2 (TRPV2) channel is a nonselective cation channel that has been implicated in multiple sensory processes in the nervous system. Here, it is shown that TRPV2 in myeloid cells facilitates virus penetration by promoting the tension and mobility of cell membrane through the Ca2+‐LRMDA axis. Knockout of TRPV2 in myeloid cells or inhibition of TRPV2 channel activity suppresses viral infection and protects mice from herpes simplex virus 1 (HSV‐1) and vesicular stomatitis virus (VSV) infection. Reconstitution of TRPV2 but not the Ca2+‐impermeable mutant TRPV2E572Q into LyZ2‐Cre;Trpv2fl/fl bone marrow‐derived dendritic cells (BMDCs) restores viral infection. Mechanistically, knockout of TRPV2 in myeloid cells inhibits the tension and mobility of cell membrane and the penetration of viruses, which is restored by reconstitution of TRPV2 but not TRPV2E572Q. In addition, knockout of TRPV2 leads to downregulation of Lrmda in BMDCs and BMDMs, and knockdown of Lrmda significantly downregulates the mobility and tension of cell membrane and inhibits viral infections in Trpv2fl/fl but not LyZ2‐Cre;Trpv2fl/fl BMDCs. Consistently, complement of LRMDA into LyZ2‐Cre;Trpv2fl/fl BMDCs partially restores the tension and mobility of cell membrane and promotes viral penetration and infection. These findings characterize a previously unknown function of myeloid TRPV2 in facilitating viral infection though the Ca2+‐LRMDA axis.

Lysosomal biogenesis is an essential adaptive process by which lysosomes exert their function in maintaining cellular homeostasis. Defects in lysosomal enzymes and functions lead to lysosome-related diseases, including lysosomal storage diseases and neurodegenerative disorders. Thus, activation of the autophagy-lysosomal pathway, especially induction of lysosomal biogenesis, might be an effective strategy for the treatment of lysosome-related diseases. In this study, we established a lysosome-based screening system to identify active compounds from natural products that could promote lysosomal biogenesis. The subcellular localizations of master transcriptional regulators of lysosomal genes, TFEB, TFE3 and ZKSCAN3 were examined to reveal the potential mechanisms. More than 200 compounds were screened, and we found that Hdj-23, a triterpene isolated from Walsura cochinchinensis, induced lysosomal biogenesis via activation of TFEB/TFE3. In summary, this study introduced a lysosome-based live cell screening strategy to identify bioactive compounds that promote lysosomal biogenesis, which would provide potential candidate enhancers of lysosomal biogenesis and novel insight for treating lysosome-related diseases.

Coenzyme A (CoA) is a key cellular metabolite which participates in diverse metabolic pathways, regulation of gene expression and the antioxidant defense mechanism. Human NME1 (hNME1), which is a moonlighting protein, was identified as a major CoA-binding protein. Biochemical studies showed that hNME1 is regulated by CoA through both covalent and non-covalent binding, which leads to a decrease in the hNME1 nucleoside diphosphate kinase (NDPK) activity. In this study, we expanded the knowledge on previous findings by focusing on the non-covalent mode of CoA binding to the hNME1. With X-ray crystallography, we solved the CoA bound structure of hNME1 (hNME1-CoA) and determined the stabilization interactions CoA forms within the nucleotide-binding site of hNME1. A hydrophobic patch stabilizing the CoA adenine ring, while salt bridges and hydrogen bonds stabilizing the phosphate groups of CoA were observed. With molecular dynamics studies, we extended our structural analysis by characterizing the hNME1-CoA structure and elucidating possible orientations of the pantetheine tail, which is absent in the X-ray structure due to its flexibility. Crystallographic studies suggested the involvement of arginine 58 and threonine 94 in mediating specific interactions with CoA. Site-directed mutagenesis and CoA-based affinity purifications showed that arginine 58 mutation to glutamate (R58E) and threonine 94 mutation to aspartate (T94D) prevent hNME1 from binding to CoA. Overall, our results reveal a unique mode by which hNME1 binds CoA, which differs significantly from that of ADP binding: the α- and β-phosphates of CoA are oriented away from the nucleotide-binding site, while 3′-phosphate faces catalytic histidine 118 (H118). The interactions formed by the CoA adenine ring and phosphate groups contribute to the specific mode of CoA binding to hNME1.

P53 is a well-known tumour suppressor, however its role in intestinal type 2 immunity is currently unclear. Here authors report that during parasitic infections, p53 triggers tuft cell Ca2+ influx and IL-25 release, and shows a regulatory role for p53 in intestinal type 2 immunity via transcriptional regulation of the Lrmp gene.

ObjectiveThis study aimed to investigate the chronotypes and their relationship with sleep disturbances and mental distress among college students.MethodsStudents from a university in Guangzhou, China, were recruited through a cross-sectional online survey. Data were collected by self-reported questionnaires including socio-demographics, lifestyles and health conditions, sleep patterns on weekdays and weekends, as well as the reduced Morningness-Eveningness Questionnaire (rMEQ), the Insomnia Severity Index, the Epworth Sleepiness Scale, the Beck Depression Inventory-13, and the Zung Self-Rating Anxiety Scale. Multivariate analyses were performed to examine the associations of chronotypes with sleep compensation, sleep disturbances, and mental distress.ResultsA total of 1,607 questionnaires were received, among which 1,569 (97.6%) were valid for further analysis. Among these participants [mean age 19.86 ± 1.16 (15–27) years], morning types (M-types), intermediate types (I-types), and evening types (E-types) accounted for 14.9, 71.5, and 13.6%, respectively. The regression analysis revealed that E-types were positively associated with long sleep compensation on weekends (adjusted OR 2.443, 95%CI 1.740-3.429) compared with I-types, while M-types were the opposite (adjusted OR 0.623, 95%CI 0.392–0.990). E-types were also positively correlated with insomnia symptoms (adjusted OR 2.000, 95%CI 1.428–2.801), depressive symptoms (adjusted OR 2.068, 95%CI 1.496–2.858), and anxiety symptoms (adjusted OR 2.188, 95%CI 1.387–3.451). However, no significant association was found between chronotypes and excessive daytime sleepiness.ConclusionOur study found that E-types were associated with long sleep compensation on weekends and insomnia, depression, and anxiety symptoms. Our findings emphasized the importance of early recognition and intervention of E-types and their accompanied sleep problems and mental distress.

A practical method was developed for the convenient synthesis of isoxazole-fused tricyclic quinazoline alkaloids. This procedure accesses diverse isoxazole-fused tricyclic quinazoline alkaloids and their derivatives via intramolecular cycloaddition of methyl azaarenes with tert-butyl nitrite (TBN). In this method, TBN acts as the radical initiator and the source of N–O. Moreover, this protocol forms new C–N, C–C, and C–O bonds via sequence nitration and annulation in a one-pot process with broad substrate scope and functionalization of natural products.

Cedryl acetate (CA), also called acetyl cedrene, is approved by the FDA as a flavoring or adjuvant to be added to foods. In this study, we aimed to investigate the preventive benefits of CA on obesity and obesity-related metabolic syndrome caused by a high-fat diet (HFD). Three groups of C57BL/6J mice (ten-week-old) were fed Chow, an HFD, or an HFD with CA supplementation (100 mg/kg) for 19 weeks. We observed that CA supplementation significantly reduced weight gain induced by an HFD, decreased the weight of the visceral fat pads, and prevented adipocyte hypertrophy in mice. Moreover, mice in the CA group showed significant improvements in hepatic lipid accumulation, glucose intolerance, insulin resistance, and gluconeogenesis compared with the mice in the HFD group. Since 16S rRNA analysis revealed that the gut microbiota in the CA and HFD groups were of similar compositions at the phylum and family levels, CA may have limited effects on gut microbiota in HFD-fed mice. The beneficial effects on the metabolic parameters of CA were reflected by CA’s regulation of metabolism-related gene expression in the liver (including Pepck, G6Pase, and Fbp1) and the epididymal white adipose tissues (including PPARγ, C/EBPα, FABP4, FAS, Cytc, PGC-1α, PRDM16, Cidea, and COX4) of the mice. In summary, a potent preventive effect of CA on HFD-induced obesity and related metabolic syndrome was highlighted by our results, and CA could be a promising dietary component for obesity intervention.

Summary: Pyrene is known for the quenched emission of excimers, especially in aqueous solution. Here, we report strong emission of pyrene excimers realized in amphiphile assemblies by controlling the face-to-face distance between the pyrene planes. We find that both the self-assembly behavior and emission properties of a cationic pyrene-containing amphiphile (denoted by PRB) are altered by exchanging the counterions. Upon the addition of sodium mesitylenesulfonate (Na MtS), the excimer emission of pyrene in self-assembled aggregates of PRB is greatly enhanced in aqueous solution. Concomitantly, the disk-like assemblies of PRB are converted to spherical particles, in which the repulsive interactions of the head groups are screened by replacing the counterions of the PRB molecules. The quantum yield of PRB increases from 0.5% to 16.6%, which is attributed to the dense packing of pyrene moieties in the aggregates. This study demonstrates that controlling supramolecular interactions is a feasible avenue to enhance the emission of pyrene excimers in amphiphile assemblies.

Abstract Background MicroRNAs are important gene expression regulators in plants immune system. Aspergillus flavus is the most common causal agents of aflatoxin contamination in peanuts, but information on the function of miRNA in peanut-A. flavus interaction is lacking. In this study, the resistant cultivar (GT-C20) and susceptible cultivar (Tifrunner) were used to investigate regulatory roles of miRNAs in response to A. flavus growth. Results A total of 30 miRNAs, 447 genes and 21 potential miRNA/mRNA pairs were differentially expressed significantly when treated with A. flavus. A total of 62 miRNAs, 451 genes and 44 potential miRNA/mRNA pairs exhibited differential expression profiles between two peanut varieties. Gene Ontology (GO) analysis showed that metabolic-process related GO terms were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses further supported the GO results, in which many enriched pathways were related with biosynthesis and metabolism, such as biosynthesis of secondary metabolites and metabolic pathways. Correlation analysis of small RNA, transcriptome and degradome indicated that miR156/SPL pairs might regulate the accumulation of flavonoids in resistant and susceptible genotypes. The miR482/2118 family might regulate NBS-LRR gene which had the higher expression level in resistant genotype. These results provided useful information for further understanding the roles of miR156/157/SPL and miR482/2118/NBS-LRR pairs. Conclusions Integration analysis of the transcriptome, miRNAome and degradome of resistant and susceptible peanut varieties were performed in this study. The knowledge gained will help to understand the roles of miRNAs of peanut in response to A. flavus.

Background: Cultivated peanut (Arachis hypogaea. L) represents one of the most important oil crops in the world. Although much effort has been expended to characterize microsatellites or Simple Sequence Repeats (SSRs) in peanut, the quantity and quality of the markers in breeding applications remain limited. Here, genome-wide SSR characterization and marker development were performed using the recently assembled genome of the cultivar Tifrunner. Results: In total, 512,900 microsatellites were identified from 2556.9-Mb genomic sequences. Based on the flanking sequences of the identified microsatellites, 7757 primer pairs (markers) were designed, and further evaluated in the assembled genomic sequences of the tetraploid Arachis cultivars, Tifrunner and Shitouqi, and the diploid ancestral species, A. duranensis and A. ipaensis. In silico PCR analysis showed that the SSR markers had high amplification efficiency and polymorphism in four Arachis genotypes. Notably, nearly 60% of these markers were single-locus SSRs in tetraploid Arachis species, indicating they are more specific in distinguishing the alleles of the A and B sub-genomes of peanut. In addition, two markers closely related with purple testa color and 27 markers near to FAD2 genes were identified, which could be used for breeding varieties with purple testa and high-oleic acid content, respectively. Moreover, the potential application of these SSR markers in tracking introgressions from Arachis wild relatives was discussed. Conclusions: This study reported the development of genomic SSRs from assembled genomic sequences of the tetraploid Arachis Tifrunner, which will be useful for diversity analysis, genetic mapping and functional genomics studies in peanut. Keywords: Arachis hypogaea. L, Crops, Genome sequence, Microsatellites, Molecular markers, Peanut breeding program, Peanut, Polymorphic microsatellite, Polymorphism, SSR

Dodonaea viscosa is a medicinal plant which has been used to treat various diseases in humans. However, the anti-insect activity of extracts from D. viscosa has not been evaluated. Here, we found that the total saponins from D. viscosa (TSDV) had strong antifeedant and growth inhibition activities against 4th-instar larvae of Spodoptera litura. The median antifeeding concentration (AFC50) value of TSDV on larvae was 1621.81 μg/mL. TSDV affected the detoxification enzyme system of the larvae and also exerted antifeedant activity possibly through targeting the γ-aminobutyric acid (GABA) system. The AFC50 concentration, the carboxylesterase activity, glutathione S-transferases activity, and cytochrome P450 content increased to 258%, 205%, and 215%, respectively, and likewise the glutamate decarboxylase activity and GABA content to 195% and 230%, respectively, in larvae which fed on TSDV. However, D. viscosa saponin A (DVSA) showed better antifeedant activity and growth inhibition activity in larvae, compared to TSDV. DVSA also exerted their antifeedant activity possibly through targeting the GABA system and subsequently affected the detoxification enzyme system. Further, DVSA directly affected the medial sensillum and the lateral sensillum of the 4th-instar larvae. Stimulation of Spodoptera litura. with DVSA elicited clear, consistent, and robust excitatory responses in a single taste cell.

Investigation on the pore-fracture features and crack propagation behavior of coal is necessary to prevent coal mine disasters. The pore structure features of coal samples taken from high gas seam were obtained by mercury injection porosimetry (MIP) and gas adsorption methods. The process of deformation and failure for coal samples under three-point bending conditions were obtained. The results demonstrate that the adsorption pores with diameter less than 100 nm are the most developed and their surfaces are the roughest (the average surface fractal dimension Ds is 2.933). The surface of micro-cracks is smoother (Ds is 2.481), which is conducive to gas seepage. It may be the explanation for that 14-3# coal seam is a high gas seam, while there was almost no gas outburst accident so far. At the initial stage of crack propagation, the main crack on the coal sample expanded along the direction of the natural cracks. In the process of crack propagation, the surface fractal dimension of the main crack increased, suggesting that the bending degree of the main crack enhanced. The brittle characteristics of coal samples can be reflected by the ratio of the dissipated energy to the accumulated energy.

Surface water and groundwater interaction variations in time and space are crucial for effective water management, especially in low-precipitation regions. To comprehensively determine the hydrochemical characteristics and interaction processes of surface water and groundwater and to investigate the decreasing causes of water resources in semi-arid mountainous watersheds under changing environments, intensive field surveys were conducted in the Daqing River watershed, a tributary of the Haihe River basin in northern China, during two different times of the year: after the rainy season (September 2018) and before the rainy season (July 2019). Sixty surface water and groundwater samples were collected along the mountainous watershed. Using a combination method of hydrogen and oxygen stable isotope tracing and hydrochemical analysis, the hydrogen and oxygen isotopes and hydrochemical characteristics of surface water and groundwater in the mountainous watershed of the Daqing River were analyzed. Furthermore, the effect of elevation (altitude) on isotopes was discussed, and the correlation between hydrogen and oxygen isotope composition and hydrochemical characteristics was obtained. The results were processed using endmember mixing analysis to determine the amount of contribution of the surface water and groundwater interaction processes. The results show that the hydrochemical characteristics are relatively stable in the mountainous watersheds of the Daqing River, and the surface water and groundwater are mainly of the HCO3-Ca type. The slope of the local meteoric water line is smaller than the slope of the global meteoric water line, and the δD and δ18O in surface water and groundwater show a good linear relationship both before and after the rainy season. There is a decreasing trend of the value of δ18O in surface water samples with decreasing altitude, but a decreasing trend of the value of δ18O in groundwater samples is not obvious. The evaporation intensity of surface water is stronger after the rainy season than before the rainy season, and the connection between the surface water and the groundwater is stronger before the rainy season. Influenced by topographic conditions and other factors, the exchange of surface water and groundwater is frequent, and there is a large difference in the exchange ratio before and after the rainy season. The exchange ratio can be more than 50% after the rainy season. Thus, the reasons for decreasing water resources in the mountains can be implied to be due to the increasing hydraulic gradient between the mountains and the piedmont plains, and the water resources are discharged more in the form of groundwater to the downstream. The conclusions help to enhance the understanding of the water cycle in the mountainous watershed and can provide some theoretical basis for the sustainable development and utilization of water resources in the Haihe River basin and the regional water ecology of the Xiong’an New Area.

Despite the declining hunger in Central Asia, food insecurity remains an important issue due to the dry climate. Taking Kazakhstan, Uzbekistan, Kyrgyzstan, Turkmenistan, and Tajikistan as examples, this study assesses their land-water resources carrying capacity in 1999, 2009, and 2018, on the premise that agricultural water and farmland are spatially matched based on the “buckets effect”, using the ecological footprint and water footprint methods. Results show the following: (1) the total farmland area in Central Asia is sufficient to achieve food self-sufficiency; the available farmland area is 2.45 times that of the farmland required for self-sufficiency in 1999, which decreased to 1.71 times in 2009, but slightly increased to 1.92 times in 2018. Specifically, Kazakhstan maintains a surplus of more than 15 × 106 ha in farmland, while the other 4 countries could not achieve self-sufficiency. (2) The water resources pressure rises; the available agricultural water resource (AAWR) in Central Asia is 3.07 times that of the water demand for agricultural irrigation (WDAI), and 3.06 times that of the water demand for irrigation and environmental purification (WDIEP) in 1999, which decreased to 1.69 times of WDAI and to 1.60 times of WDIEP in 2018. Tajikistan has the highest level of water surplus, followed by Kyrgyzstan and Kazakhstan. Turkmenistan and Uzbekistan do not have enough water to sustain agricultural production. (3) The trend of land-water resources carrying capacity declines in Central Asia. In 1999, 2009, and 2018, the land-water resources could support the population’s food demand in this region when only considering farmland matched with WDAI. However, the population carrying capacity deficit would emerge if we considered the matching farmland with WDIEP.

Parkin is an E3 ubiquitin ligase involved in Parkinson’s disease. Parkin has also been linked to cancer suppression but the mechanisms are unclear. Here the authors show that Parkin regulates HIF-1α through ubiquitin-dependent degradation, thus inhibiting metastasis of breast cancer cells.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.

Personalized medicine: Mutated tumors respond to therapy Mutations in the p53 tumor suppressor gene could offer a predictive biomarker of response to certain drugs in triple-negative breast cancer. Jill Bargonetti from Hunter College in New York, USA, and colleagues showed that mutant p53, which is expressed in more than 80% of patients with triple-negative breast cancer, interacts with and regulates hundreds of proteins, including those found in a complex needed for DNA replication. Members of this complex, called the minichromosome maintenance protein complex, interact with mutant p53—but less with wild-type p53. Bargonetti’s team targeted this pathway in mutated breast cancer cells with the PARP inhibitor talazoparib and the chemotherapeutic agent temozolomide. They observed synergistic cell killing with the two drugs, but only when the minichromosome maintenance protein complex was working and when p53 was mutated. These findings point toward a new strategy for personalizing therapy.

A new type of path-following method has been developed to steer marine surface vehicles along desired paths. Path-following is achieved by a new hyperbolic guidance law for straight-line paths and a backstepping control law for curved paths. An optimal controller has been improved for heading control, based on linear quadratic regulator (LQR) theory with nonlinear feedback control techniques. The control algorithm performance is validated by simulation and comparison against the requirements of International Standard IEC62065. Deviations are within the allowable range of the standard. In addition, the experimental results show that the proposed method has higher control accuracy.

Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice. Further, P72 mice have a delayed development of aging-associated phenotypes compared with R72 mice. Mechanistically, P72 mice can better retain the self-renewal function of stem/progenitor cells compared with R72 mice during aging. This study provides direct genetic evidence demonstrating that p53 codon 72 SNP directly impacts aging and longevity, which supports a role of p53 in regulation of longevity.

Apigenin-7-O-glucoside is an active phenolic compound in Asteraceae flowers and possesses remarkable therapeutic applications. However, its high price and low abundance in plants limit its use, meanwhile it would hydrolyze in the purification process. In this study, apigenin-7-O-glucoside extracted with ultrasound and purified with preparative HPLC from Chrysanthemum morifolium ‘Huangju’ was investigated, as well as its hydrolysis behavior and bioactivities. The optimized extraction conditions were: solid/liquid ratio: 1:20, extraction time: 35 min, temperature: 50 °C, and ultrasound power: 350 W. The content of apigenin-7-O-glucoside was up to 16.04 mg/g. Apigenin-7-O-glucoside was then purified with preparative HPLC from the extract, and confirmed by Q-TOF/MS. Apigenin-7-O-glucoside was partially hydrolyzed in acidic condition, and the hydrolysis rate depended on the pH value and temperature. The antioxidant activity increased as a result of the hydrolysis process. This study provided a green and effective way to obtain apigenin-7-O-glucoside and would be beneficial for further investigations into nutritional and functional aspects apigenin-7-O-glucoside and other glycosides.

Glutaminase (GLS) isoenzymes GLS1 and GLS2 are key enzymes for glutamine metabolism. Interestingly, GLS1 and GLS2 display contrasting functions in tumorigenesis with elusive mechanism; GLS1 promotes tumorigenesis, whereas GLS2 exhibits a tumor-suppressive function. In this study, we found that GLS2 but not GLS1 binds to small GTPase Rac1 and inhibits its interaction with Rac1 activators guanine-nucleotide exchange factors, which in turn inhibits Rac1 to suppress cancer metastasis. This function of GLS2 is independent of GLS2 glutaminase activity. Furthermore, decreased GLS2 expression is associated with enhanced metastasis in human cancer. As a p53 target, GLS2 mediates p53’s function in metastasis suppression through inhibiting Rac1. In summary, our results reveal that GLS2 is a novel negative regulator of Rac1, and uncover a novel function and mechanism whereby GLS2 suppresses metastasis. Our results also elucidate a novel mechanism that contributes to the contrasting functions of GLS1 and GLS2 in tumorigenesis.