Improving the management of type 2 diabetes in China using a multifaceted digital health intervention in primary health care: the SMARTDiabetes cluster randomised controlled trial.

Background: There is limited evidence, mainly from high-income countries, that digital health interventions improve type 2 diabetes (T2DM) care. Large-scale implementation studies are lacking. Methods: A multifaceted digital health intervention comprising: (1) a self-management application ('app') for patients and lay 'family health promotors' (FHPs); and (2) clinical decision support for primary care doctors was evaluated in an open-label, parallel, cluster randomized controlled trial in 80 communities (serviced by a primary care facility for >1000 residents) in Hebei Province, China. People >40 years with T2DM and a glycated haemoglobin (HbA1c) ≥7% were recruited (∼25/community). After baseline assessment, community clusters were randomly assigned to intervention or control groups (1:1) via a web-based system, stratified by locality (rural/urban). Control arm clusters received usual care without access to the digital health application or family health promoters. The primary outcome was at the participant level defined as the proportion with ≥2 "ABC" risk factor targets achieved (HbA1c < 7.0%, blood pressure < 140/80 mmHg and LDL-cholesterol < 2.6 mmol/L) at 24 months. Findings: A total of 2072 people were recruited from the 80 community clusters (40 urban and 40 rural), with 1872 (90.3%) assessed at 24 months. In the intervention arm, patients used FHPs for support more in rural than urban communities (252 (48.6%) rural vs 92 (21.5%) urban, p < 0.0001). The mean monthly proportion of active app users was 46.4% (SD 7.8%) with no significant difference between urban and rural usage rates. The intervention was associated with improved ABC control rates (339 [35.9%] intervention vs 276 [29.9%] usual care; RR 1.20, 95% CI 1.02-1.40; p = 0.025), with significant heterogeneity by geography (rural 220 [42.6%] vs 158 [31.0%]; urban 119 [27.9%] vs 118 [28.6%]; p = 0.022 for interaction). Risk factor reductions were mainly driven by improved glycaemic control (mean HbA1C difference -0.33%, 95% CI -0.48 to -0.17; p = 0.00025 and mean fasting plasma glucose difference -0.58 mmol, 95% CI -0.89 to -0.27; p = 0.00013). There were no changes in blood pressure and LDL-cholesterol levels. Interpretation: A multifaceted digital health intervention improved T2DM risk factor control rates, particularly in rural communities where there may be stronger relationships between patients and doctors and greater family member support. Funding: National Health and Medical Research CouncilGlobal Alliance for Chronic Diseases (ID 1094712).

Impact of neuromuscular block on myocardial injury after non-cardiac surgery (MINS) incidence in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection: a randomized controlled study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. METHODS: 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. RESULTS: MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg-1·h-1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), µg·kg-1·min-1, P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant. CONCLUSIONS: Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection. TRIAL REGISTRATION: The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323).

Quinoline Derivatives in Discovery and Development of Pesticides.

Finding highly active molecular scaffold structures is always the key research content of new pesticide discovery. In the research and development of new pesticides, the discovery of new agricultural molecular scaffold structures and new targets still faces great challenges. In recent years, quinoline derivatives have developed rapidly in the discovery of new agriculturally active molecules, especially in the discovery of fungicides. The unique quinoline scaffold has many advantages in the discovery of new pesticides and can provide innovative and feasible solutions for the discovery of new pesticides. Therefore, we reviewed the use of quinoline derivatives and their analogues as molecular scaffolds in the discovery of new pesticides since 2000. We systematically summarized the agricultural biological activity of quinoline compounds and discussed the structure-activity relationship (SAR), physiological and biochemical properties, and mechanism of action of the active compounds, hoping to provide ideas and inspiration for the discovery of new pesticides.

Discovery and Mechanism of a Nematicide Candidate (W3): A Novel Amide Compound Containing a Cyclopropyl Moiety.

To find novel nematicides, we screened the nematicidal activity of compounds in our laboratory compound library. Interestingly, the compound N-((1R,2R)-2-(2-fluoro-4-(trifluoromethyl)phenyl)cyclopropyl)-2-(trifluoromethyl)benzamide (W3) showed a broad spectrum and excellent nematicidal activity. The LC50 values of compound W3 against second-stage juveniles of Bursaphelenchus xylophilus (B. xylophilus), Aphelenchoides besseyi, and Ditylenchus destructor are 1.30, 1.63, and 0.72 mg/L, respectively. Nematicidal activities of compound W3 against second-stage juveniles of Meloidogyne incognita were 87.66% at 100 mg/L. Meanwhile, compound W3 can not only observably inhibit the feeding, reproduction, and egg hatching of B. xylophilus but can also effectively promote the oxidative stress adverse reactions of nematodes and cause intestinal damage. Compound W3 can promote the production of MDA and inhibit the activities of defense enzymes SOD and GST in B. xylophilus. Compound W3 can affect the transcription of genes involved in regulating the tricarboxylic acid cycle in nematodes, resulting in weakened nematode respiration and reduced nematode activity and even death. In addition, compound W3 had good inhibitory activity against five pathogenic fungi. Among them, the EC50 of compound W3 against Fusarium graminearum was 8.4 mg/L. In the future, we will devote ourselves to the toxicological and structural optimization research of the candidate nematicide W3.

Design, Synthesis, Nematicidal Activity, and Mechanism of Novel Amide Derivatives Containing an 1,2,4-Oxadiazole Moiety.

To discover new nematicides, a series of novel amide derivatives containing 1,2,4-oxadiazole were designed and synthesized. Several compounds showed excellent nematicidal activity. The LC50 values of compounds A7, A18, and A20-A22 against pine wood nematode (Bursaphelenchus xylophilus), rice stem nematode (Aphelenchoides besseyi), and sweet potato stem nematode (Ditylenchus destructor) were 1.39-3.09 mg/L, which were significantly better than the control nematicide tioxazafen (106, 49.0, and 75.0 mg/L, respectively). Compound A7 had an outstanding inhibitory effect on nematode feeding, reproductive ability, and egg hatching. Compound A7 effectively promoted the oxidative stress of nematodes and caused intestinal damage to nematodes. Compound A7 significantly inhibited the activity of succinate dehydrogenase (SDH) in nematodes, leading to blockage of electron transfer in the respiratory chain and thereby hindering the synthesis of adenosine triphosphate (ATP), which consequently affects the entire oxidative phosphorylation process to finally cause nematode death. Therefore, compound A7 can be used as a potential SDH inhibitor in nematicide applications.

Screening Method and Antibacterial Activity of 1,3,4-Oxadiazole Sulfone Compounds against Citrus Huanglongbing.

Citrus Huanglongbing (HLB) is one of the most destructive diseases in the citrus industry. At present, Candidatus Liberibacter asiaticus (CLas) cannot be cultured in vitro, and there is a lack of rapid methods to test antibacterial activity, which greatly hinders the discovery of new antibacterial agents against HLB. To establish a rapid screening method for antibacterial agents against HLB with simple operation, a short cycle, and a large number of tests, the CLas contents in leaves from different citrus branches, different leaves from the same citrus branch, and two halves of the same citrus leaf were detected. Compared with the leaves on different branches and different leaves on the same branch, the difference in CLas content of the left and right halves of the same leaf was small; the difference was basically between 0.7 and 1.3. A rapid and efficient method for primary screening agents against HLB termed the "half-leaf method" was established through our long-term optimization and improvement. To verify the stability and reliability of the activity data measured using this method, 6-chloropurine riboside, which is highly soluble in water, was used as the test agent, and its antibacterial activity against HLB was tested 45 times. The results of the antibacterial activity test showed little difference in the mean values of each data group, indicating that this method could be used as a rapid method for screening agents against HLB. We used this method to test the antibacterial activity of compounds synthesized by our research group against HLB and found that some of the compounds showed good activity.

Research Progress of Benzothiazole and Benzoxazole Derivatives in the Discovery of Agricultural Chemicals.

Benzoxazole and benzothiazole have a broad spectrum of agricultural biological activities, such as antibacterial, antiviral, and herbicidal activities, which are important fused heterocyclic scaffold structures in agrochemical discovery. In recent years, great progress has been made in the research of benzoxazoles and benzothiazoles, especially in the development of herbicides and insecticides. With the widespread use of benzoxazoles and benzothiazoles, there may be more new products containing benzoxazoles and benzothiazoles in the future. We systematically reviewed the application of benzoxazoles and benzothiazoles in discovering new agrochemicals in the past two decades and summarized the antibacterial, fungicidal, antiviral, herbicidal, and insecticidal activities of the active compounds. We also discussed the structural-activity relationship and mechanism of the active compounds. This work aims to provide inspiration and ideas for the discovery of new agrochemicals based on benzoxazole and benzothiazole.

Design, synthesis, antibacterial activity, and mechanism of novel resveratrol derivatives containing an 1,3,4-oxadiazole moiety.

Rice bacterial diseases seriously threaten the development of rice industry in the world, and chemical control is still one of the effective means to control it. To find novel antibacterial agents, 42 resveratrol derivatives were designed and synthesized based on natural product resveratrol as lead structure, and their antibacterial activities were evaluated. Most compounds have excellent antibacterial activities. Among them, the EC50 values of compound B1 against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) were 4.76 and 8.85 mg/L, respectively. The curative activities of compound B1 against bacterial leaf blight and bacterial leaf streak were 45.57 and 38.40%, and the protective activities were 49.41 and 35.93%, respectively. In addition, compound B1 could change bacterial cell surface morphology by inhibiting biofilm formation and exopolysaccharide production, and increasing membrane permeability, thereby affecting the normal growth of bacteria. Furthermore, transcriptome analysis showed that differential expressed genes were mainly enriched in plant-pathogen interaction pathway and MAPK signaling pathway-plant after compound B1 treated susceptible rice. We will further optimize the structure of compound B1 in future work to find more efficient antibacterial agents.

Discovery of quinazoline compound as a novel nematicidal scaffold.

With the aim of discovering novel nematicidal scaffolds, the nematicidal activities of a series of quinazoline compounds were tested, with some compounds showing excellent results. Among them, the LC50 values of compound K11 against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus destructor were 7.33, 6.09, and 10.95 mg/L, respectively. In addition, the nematicidal activity of compound K11 against Meloidogyne incognita was 98.77% at 100 mg/L. Compound K11 not only increased the production of reactive oxygen species and the accumulation of lipofuscin and lipids in nematodes, but it also attenuated nematode pathogenicity by reducing the nematodes' antioxidant capacity. Transcriptomic analysis showed that compound K11 had significant effects on fatty acid degradation, metabolic pathways, and the differentially expressed genes related to redox processes in nematodes. Furthermore, the expression levels of the corresponding differentially expressed genes were verified using real-time quantitative polymerase chain reaction. Quinazoline can be used as a new nematicidal scaffold, and it is expected that more work will be done on the discovery of novel nematicides based on the lead compound K11 in the future.

Characterization of aerosol particles during the most polluted season (winter) in urban Chengdu (China) by single-particle analysis.

Chengdu, the capital city of Sichuan Province, is one of the most polluted cities in China. We used single-particle aerosol mass spectrometer to monitor particulate matter pollution in an urban area of Chengdu from December 9, 2015 to January 4, 2016 to determine the characteristics of air pollution during the winter months. The mass concentrations of particulate matter were high during the whole observation period, with mean values for PM2.5 and PM10 of 101 ± 60 and 162 ± 99 µg m-3, respectively. The particles were clustered into nine distinct particle types: dust (3%), potassium-elemental carbon (KEC) (24%), organic carbon (OC) (12%), combined OC and EC (OCEC) (6%), K-organic nitrogen (KCN) (10%), K-nitrate (KNO3) (12%), K-sulfate (KSO4) (18%), K-sulfate and nitrate (KSN) (12%), and metal (3%) particles. Analysis on different types of day showed that: (1) from "excellent" (days with PM2.5 lower than 35 µg m-3) to "light pollution" (PM2.5 between 75 and 115 µg m-3) days, local/regional combustion was the major contributor, whereas the aggravation of pollution from light pollution to "heavy pollution" (PM2.5 higher than 150 µg m-3) days was mainly determined by the combined effect of local/regional combustion and long-distance transport; (2) as the air quality deteriorated, the mixing of sulfate and nitrate in particles increased sharply, especially sulfate; and (3) the relative aerosols acidity increased from excellent to light pollution days, while decreased significantly from light pollution to heavy pollution days. Backward trajectory analysis showed that there were significant differences in PM2.5 concentrations and particle compositions between clusters of trajectories, which affected the level and evolution of PM2.5 pollution in Chengdu. These results give a deeper understanding of PM2.5 pollution in Chengdu and the Sichuan Basin.

Characteristics and formation mechanisms of autumn haze pollution in Chengdu based on high time-resolved water-soluble ion analysis.

To investigate the characteristics and formation mechanisms of haze pollution in the autumn season in the Sichuan Basin, hourly concentrations of water-soluble inorganic ions in PM2.5 (Na+, K +, NH4+, Mg2+, Ca2+, Cl-, NO3-, and SO42-) and major gaseous precursors (HCl, NH3, SO2, HONO, and HNO3) were measured by a gas and aerosol collector combined with ion chromatography (GAC-IC) from September to November 2017 at an urban site in Chengdu. The average mass concentration of total water-soluble ions was 36.9 ± 29.4 µg m-3, accounting for 62.8% of PM2.5 mass. Nitrate was the most abundant ion, comprising 41.2% of the total ions, followed by sulfate (27.1%) and ammonium (18.1%), indicating the important contribution of motor vehicle emissions to PM2.5 in Chengdu. Secondary formation of inorganic ions and biomass burning emissions played a vital role in the haze pollution processes. The formation of nitrate aerosol was particularly dominant and exhibited the most substantial increase during haze processes. It was likely to be produced primarily through homogeneous reactions, whereas heterogeneous reactions dominated sulfate formation. Additionally, distinct differences in diurnal patterns of secondary inorganic ions between clean days and polluted days were observed, reflecting different formation characteristics under polluted conditions. Due to a large increase of acidic aerosols, most particles collected on polluted days were acidic, and ammonium in most samples existed mainly as NH4HSO4 and NH4NO3. Furthermore, backward-trajectory cluster analysis revealed that air masses originating from the northeast of Chengdu prevailed in the autumn season, and haze pollution was dominated mainly by short-distance transport within the Sichuan Basin.

Water-soluble ions in PM2.5 during spring haze and dust periods in Chengdu, China: Variations, nitrate formation and potential source areas.

Hourly concentrations of water-soluble inorganic ions (Na+, NH4+, K+, Mg2+, Ca2+, Cl-, NO3- and SO42-) in PM2.5 and related reactive gases were measured with a Gas and Aerosol Collector combined with Ion Chromatography (GAC-IC) in urban Chengdu from April 17 to May 27, 2017, during which both haze and dust episodes occurred frequently. Nitrate was the most abundant ion in PM2.5 and substantially increased during haze pollution with the NO3-/SO42- mass ratio increasing from 0.78 during clean period to 1.1 during haze period. Aerosols in Chengdu were generally ammonium-rich, wherein ammonium nitrate was primarily formed through homogeneous gas-phase reactions and limited by the availability of HNO3, indicating that preferentially reducing the emissions of NOx could make for mitigating spring haze pollution in Chengdu. Backward trajectory clustering coupled with measured species and a potential source contribution function (PSCF) for PM2.5, PM10/PM2.5, sulfate, nitrate, ammonium, and Ca2+ indicated that regionally transported pollutants from the southern and southeastern Sichuan Basin strongly contributed to springtime PM2.5 pollution in Chengdu, but long-distance transport from northwestern China also contributed to dust pollution. Moreover, the treatment of urban fugitive dust in southern Sichuan is also important for reducing coarse particles in Chengdu. Therefore, the improvement of air quality in Chengdu, even in the Sichuan Basin, requires the regional joint emission reduction of particles and gaseous precursors across the entire Sichuan Basin, especially for cities located in southeastern Sichuan Basin.