Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.

Hypoxanthine ameliorates diet-induced insulin resistance by improving hepatic lipid metabolism and gluconeogenesis via AMPK/mTOR/PPARα pathway.

AIM: Insulin resistance (IR) is a pivotal metabolic disorder associated with type 2 diabetes and metabolic syndrome. This study investigated the potential of hypoxanthine (Hx), a purine metabolite and uric acid precursor, in ameliorating IR and regulating hepatic glucose and lipid metabolism. METHODS: We utilized both in vitro IR-HepG2 cells and in vivo diet-induced IR mice to investigate the impact of Hx. The HepG2 cells were treated with Hx to evaluate its effects on glucose production and lipid deposition. Activity-based protein profiling (ABPP) was applied to identify Hx-target proteins and the underlying pathways. In vivo studies involved administration of Hx to IR mice, followed by assessments of IR-associated indices, with explores on the potential regulating mechanisms on hepatic glucose and lipid metabolism. KEY FINDINGS: Hx intervention significantly reduced glucose production and lipid deposition in a dose-dependent manner without affecting cell viability in IR-HepG2 cells. ABPP identified key Hx-target proteins engaged in fatty acid and pyruvate metabolism. In vivo, Hx treatment reduced IR severities, as evidenced by decreased HOMA-IR, fasting blood glucose, and serum lipid profiles. Histological assessments confirmed reduced liver lipid deposition. Mechanistic insights revealed that Hx suppresses hepatic gluconeogenesis and fatty acid synthesis, and promotes fatty acid oxidation via the AMPK/mTOR/PPARα pathway. SIGNIFICANCE: This study delineates a novel role of Hx in regulating hepatic metabolism, offering a potential therapeutic strategy for IR and associated metabolic disorders. The findings provide a foundation for further investigation into the role of purine metabolites in metabolic regulation and their clinical implications.

Prevalence of dyslipidemia among teachers in China: a systematic review and meta-analysis.

Objective: To systematically analyze the current situation with dyslipidemia among teachers in China, to provide guidance for lipid management and prevention of ASCVD. Design: A systematic review and meta-analysis of the prevalence of dyslipidemia among teachers in China. Methods: We searched via 9 databases for studies published between June 1, 1996, and July, 25, 2024. The article were evaluated by the Joanna Briggs Institute (JBI) Article Quality Assessment Tool (2016) in Australia. RevMan5.0 and R4.3.1 software were used for statistical analysis to calculate the OR and RR values and the 95% confidence intervals. This systematic review and meta-analysis were reported in line with the PRISMA guidelines. Results: A total of 12 cross-sectional studies from 10 provinces (regions) were included, with the sample of 24,851, including 12,626 males and 12,198 females, the average age of about 40 (1,036 were aged ≤30, 5,872 were aged 30-40, 3,854 were aged 40-50, 4,607 were aged 50-60, and 3,425 were aged ≥60), including 9,114 people with dyslipidemia. The overall prevalence of dyslipidemia among teachers in China was 38% (p < 0.01, 95% CI (1.27-1.95)). The prevalence of hypertriglyceridemia was 21.6% (p < 0.01, 95% CI (1.05-1.50)), that of hypercholesterolemia was 13.3% (p < 0.05, 95% CI (0.98-1.34)), that of hyper-LDL-Cemia was 9.4% (p < 0.01, 95% CI (1.04-1.59)), and that of hypo-HDL-Cemia was 4.3% (p = 0.25, 95% CI (0.61-6.52)). The heterogeneity of dyslipidemia among teachers of the different sexes was I2 = 92% (p < 0.01). The overall prevalence of dyslipidemia, as well as that of high TC, high TG, and high LDL-C levels, was greater in female teachers than in male teachers (df = 10, 95% CI:1.35-1.52, p < 0.01). The heterogeneity of dyslipidemia among teachers of different ages was I2 = 74% (p < 0.01), and the risk was lower for aged <50 years than those aged ≥50 years (df = 7, 95% CI: 0.38-0.44, p = 0.04). The year, region, school type, and these factors showed no effect on the prevalence of dyslipidemia (p = 0.7353). Conclusion: The prevalence of dyslipidemia in the teacher population in China is high and tends to increase with age. We should pay attention to the health management of the teachers, which can be done by appropriately adjusting the educational model settings, increasing the programs on physical activities, promoting the improvement of healthy lifestyles. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42024567785].

New sesquiterpenes and viridin derivatives from Penicillium sp. Ameliorates NAFLD by regulating the PINK1/Parkin mitophagy pathway.

Fungi from the plant rhizosphere microbiome are considered an important source of bioactive novel natural compounds. In this study, three new sesquiterpenes, penisterpenoids A-C (1-3), and three new viridin derivatives, peniviridiols A-C (4-6), along with twenty one known compounds (7-27), were isolated from the rhizosphere fungus Penicillium sp. SMU0102 of medicinal plant Bupleurum chinense DC. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1-6 were determined by experimental and calculated ECD spectra, DP4 + probability analysis, modified Mosher's method, and X-ray crystallography. All new compounds were screened for their cytotoxic and lipid-lowering activities in vitro. Among them, compound 1 (20 µM) remarkably alleviated lipid accumulation both in FFA-induced LO2 cells and TAA-induced zebrafish NAFLD models. Furthermore, compound 1 enhanced ATP production and mitochondrial membrane potential (MMP), suppressed reactive oxygen species (ROS) formation, restored mitochondrial structure, and induced autophagosome formation. Moreover, compound 1 significantly upregulated the expression of representative proteins for the mitochondrial homeostasis, including OPA1, DRP1, MFF, and Fis1, as well as mitophagy representative proteins PINK1, Parkin, and P62. Further mechanistic investigations indicated that compound 1 primarily alleviated lipid accumulation through selective activation of the PINK1/Parkin mitophagy signaling pathway.

Sleep restriction promotes brain oxidative stress and inflammation, and aggravates cognitive impairment in insulin-resistant mice.

Sleep deprivation and insulin resistance (IR) are two risk factors for Alzheimer's disease. As the population of people with IR increases and sleep restriction (SR) due to staying up late becomes the "new normal", it is necessary to investigate the effects and molecular pathogenesis of chronic SR on cognitive function in insulin resistance. In this study, 4-week-old mice were fed a high-fat diet (HFD) for 8 weeks to establish IR model, and then the mice were subjected to SR for 21 days, and related indicators were assessed, including cognitive capacity, apoptosis, oxidative stress, glial cell activation, inflammation, blood-brain barrier (BBB) permeability and adiponectin levels, for exploring the potential regulatory mechanisms. Compared with control group, IR mice showed impaired cognitive capacity, meanwhile, SR not only promoted Bax/Bcl2-induced hippocampal neuronal cell apoptosis and Nrf2/HO1- induced oxidative stress, but also increased microglia activation and inflammatory factor levels and BBB permeability, thus aggravating the cognitive impairment in IR mice. Consequently, changing bad living habits and ensuring sufficient sleep are important intervention strategies to moderate the aggravation of IR-induced cognitive impairment.

Discovery, biosynthesis, organic synthesis, and bioactivities of meroterpenoids from Rhododendron species.

Meroterpenoids discovered in Rhododendrons species possess unique chemical structures and biological activities and are expected to become new drug targets for Alzheimer's disease, metabolic disorders, and chronic kidney disease, and these compounds have attracted increasing attention in recent years. In this study, Rhododendron meroterpenoids and their structures, classifications, racemate distribution, biosynthetic pathways, chemical synthesis, and bioactivities are reviewed prior to 2023.

Catalytic and Base-free Suzuki-type α-Arylation of Cyclic 1,3-Dicarbonyls via a Cyclic Iodonium Ylide Strategy.

To date, it remains challenging to achieve a general and catalytic α-arylation of cyclic 1,3-dicarbonyls, particularly ubiquitous heteroaromatic ones. In most cases, the preparation of their medically significant arylated derivatives requires multistep synthetic sequences. Herein, we introduce a new, convenient strategy involving the conversion of cyclic 1,3-dicarbonyls to cyclic iodonium ylides (CIYs), followed by rhodium-catalyzed α-arylation with arylboronic reagents via carbene coupling. This approach is mild, operationally simple, base-free, biocompatible, and exhibits broad substrate scope (>100 examples), especially with respect to various heteroaromatic 1,3-dicarbonyls and ortho-substituted or base-sensitive arylboronic acids. Importantly, owing to the excellent compatibility with various arylboronic acids or boronate esters (ArBpin, ArBneop, or ArBF3K), this method allows the late-stage installation of heterocyclic 1,3-dicarbonyl motifs in highly complex settings. The utility of this transformation is further demonstrated through significantly simplifying the synthesis of several bioactive molecules and natural products.

Icaritin with autophagy/mitophagy inhibitors synergistically enhances anticancer efficacy and apoptotic effects through PINK1/Parkin-mediated mitophagy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is among the deadliest malignancies worldwide and still a pressing clinical problem. Icaritin, a natural compound obtained from the Epimedium genus plant, has garnered significant attention as a potential therapeutic drug for HCC therapies. Mitophagy plays a crucial role in mitochondrial quality control through efficiently eliminating damaged mitochondria. However, the specific mechanisms of the interplay between mitophagy and apoptosis in HCC is still unclear. We aimed to explore the cross-talk between icaritin-induced mitophagy and apoptosis in HCC cells and investigate its potential mechanisms. Firstly, we confirmed that icaritin inhibits proliferation and migration while inducing mitochondrial damage and reactive oxygen species (ROS) production in HCC cells. Secondly, based on proteomics analysis, we discovered that icaritin inhibits the growth of tumor cells and disrupts their mitochondrial homeostasis through the regulation of both mitophagy and apoptosis. Thirdly, icaritin causes mitophagy mediated by PINK1-Parkin signaling via regulating feedforward loop. Furthermore, knockdown of PINK1/Parkin leads to inhibition of mitophagy, which promotes cell death induced by icaritin in HCC cells. Finally, autophagy/mitophagy inhibitors remarkably enhance icaritin-induced cell death and anticancer efficacy. Collectively, our findings reveal that icaritin suppresses growth, proliferation and migration of HCC cell through induction of mitophagy and apoptosis, while inhibition of mitophagy significantly increased the anti-cancer and pro-apoptotic effects of icaritin, indicating that targeting autophagy or mitophagy is a novel approach to overcome drug resistance and enhance anticancer therapies.

Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of most common and deadliest malignancies. Celastrol (Cel), a natural product derived from the Tripterygium wilfordii plant, has been extensively researched for its potential effectiveness in fighting cancer. However, its clinical application has been hindered by the unclear mechanism of action. Here, we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and anti-tumor capacity by developing a Cel-based liposomes in HCC. We demonstrated that Cel selectively targets the voltage-dependent anion channel 2 (VDAC2). Cel directly binds to the cysteine residues of VDAC2, and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore (mPTP) function. We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells. Moreover, coencapsulation of Cel into alkyl glucoside-modified liposomes (AGCL) improved its antitumor efficacy and minimized its side effects. AGCL has been shown to effectively suppress the proliferation of tumor cells. In a xenograft nude mice experiment, AGCL significantly inhibited tumor growth and promoted apoptosis. Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death, while the Cel liposomes enhance its targetability and reduces side effects. Overall, Cel shows promise as a therapeutic agent for HCC.

Evaluating the efficiency of primary health care institutions in China: an improved three-stage data envelopment analysis approach.

BACKGROUND: Primary health care (PHC) institutions are key to realizing the main functions of the health care system. Since the new health care reform in 2009, the Chinese government has invested heavily in PHC institutions and launched favorable initiatives to improve the efficiency of such institutions. This study is designed to gauge the efficiency of PHC institutions by using 2012-2020 panel data covering 31 provinces in China. METHODS: This study applied an improved three-stage data envelopment analysis (DEA) model to evaluate the efficiency of PHC institutions in China. Unlike the traditional three-stage DEA model, the input-oriented global super-efficiency slack-based measurement (SBM) DEA model is used to calculate the efficiency in the first and third stages of the improved three-stage DEA model, which not only allows the effects of environmental factors and random noise to be taken into account but also deal with the problem of slack, super-efficiency and the comparability of interperiod efficiency values throughout the efficiency measurement. RESULTS: The results show that the efficiency of PHC institutions has been overestimated due to the impact of external environmental factors and random noise. From 2012 to 2020, the efficiency of PHC institutions displayed a downward trend. Moreover, there are significant differences in the efficiency of PHC institutions between regions, with the lowest efficiency being found in the northeast region. The efficiency of PHC institutions is significantly affected by residents' annual average income, per capita GDP, population density, the percentage of the population aged 0-14, the percentage of the population aged 65 and older, the number of people with a college education and above per 100,000 residents, and the proportion of the urban population. CONCLUSIONS: Substantial investment in PHC institutions has not led to the expected efficiency gains. Therefore, more effective measures should be taken to improve the efficiency of PHC institutions in China based on local conditions. This study provides a new analytical approach to calculating the efficiency of PHC institutions, and this approach can be applied to efficiency evaluation either in other fields or in other countries.

Baicalin inhibits hepatocellular carcinoma cell growth and metastasis by suppressing ROCK1 signaling.

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3ß, and ß-catenin, whereas it up-regulated the expressions of GSK-3ß and p-ß-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3ß/ß-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK-3ß/ß-catenin signaling.

Methamphetamine induces cardiomyopathy through GATA4/NF-κB/SASP axis-mediated cellular senescence.

With the world pandemic of methamphetamine (METH), METH-associated cardiomyopathy (MAC) has become a widespread epidemic and is also recognized as a cause of heart failure in young people. The mechanism of occurrence and development of MAC is not clear. In this study, firstly, the animal model was evaluated by echocardiography and myocardial pathological staining. The results revealed that the animal model exhibited cardiac injury consistent with clinical alterations of MAC, and the mice developed cardiac hypertrophy and fibrosis remodeling, which led to systolic dysfunction and left ventricular ejection fraction (%LVEF) < 40%. The expression of cellular senescence marker proteins (p16 and p21) and senescence-associated secretory phenotype (SASP) was significantly increased in mouse myocardial tissue. Secondly, mRNA sequencing analysis of cardiac tissues revealed the key molecule GATA4, and Western blot, qPCR and immunofluorescence results showed that the expression level of GATA4 was significantly increased after METH exposure. Finally, knockdown of GATA4 expression in H9C2 cells in vitro significantly attenuated METH-induced cardiomyocyte senescence. Consequently, METH causes cardiomyopathy through cellular senescence mediated by the GATA4/NF-κB/SASP axis, which is a feasible target for the treatment of MAC.

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

BACKGROUND: Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown. METHODS: Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo animal studies, we analyzed the liver tissues from untreated and GLY-treated mice. RESULTS: We generated the first scRNA-seq atlas of GLY-exposed mouse liver. GLY induced varied cell composition, shared or cell-type-specific transcriptional alterations, and dysregulated cell-cell communication and thus exerted hepatotoxicity effects. The oxidative stress and inflammatory response were commonly upregulated in several cell types. We also observed activation and upregulated phagocytosis in macrophages, as well as proliferation and extracellular matrix overproduction in hepatic stellate cells. CONCLUSIONS: Our study provides a comprehensive single-cell transcriptional picture of the toxic effect of GLY in the liver, which offers novel insights into the molecular mechanisms of the GLY-associated hepatotoxicity.

Mortality burden attributable to temperature variability in China.

BACKGROUND: Several studies have investigated the associations between temperature variability (TV) and death counts. However, evidence of TV-attributable years of life lost (YLL) is scarce. OBJECTIVES: To investigate the associations between TV and YLL rates (/100,000 population), and quantify average life loss per death (LLD) caused by TV in China. METHODS: We calculated daily YLL rates (/100,000 population) of non-accidental causes and cardiorespiratory diseases by using death data from 364 counties of China during 2006-2017, and collected meteorological data during the same period. A distributed lag non-linear model (DLNM) and multivariate meta-analysis were used to estimate the effects of TV at national or regional levels. Then, we calculated the LLD to quantify the mortality burden of TV. RESULTS: U-shaped curves were observed in the associations of YLL rates with TV in China. The minimum YLL TV (MYTV) was 2.5 °C nationwide. An average of 0.89 LLD was attributable to TV in total, most of which was from high TV (0.86, 95% CI: 0.56, 1.16). However, TV caused more LLD in the young (<65 years old) (1.87, 95% CI: 1.03, 2.71) than 65-74 years old (0.85, 95% CI: 0.40-1.31) and ≥75 years old (0.40, 95% CI: 0.21-0.59), cerebrovascular disease (0.74, 95% CI: 0.36, 1.11) than respiratory disease (0.54, 95% CI: 0.21, 0.87), South (1.23, 95% CI: 0.77, 1.68) than North (0.41, 95% CI: -0.7, 1.52) and Central China (0.40, 95% CI: -0.02, 0.81). TV-attributed LLD was modified by annual mean temperature, annual mean relative humidity, altitude, latitude, longitude, and education attainment. SIGNIFICANCE: Our findings indicate that high and low TVs are both associated with increases in premature death, however the majority of LLD was attributable to high TV. TV-related LLD was modified by county level characteristics. TV should be considered in planning adaptation to climate change or variability. IMPACT: (1) We estimated the associations of TV with YLL rates, and quantified the life loss per death (LLD) caused by TV. (2) An average of 0.89 years of LLD were attributable to TV, most of which were from high TVs. (3) TV caused more LLD in the young, cerebrovascular disease, and southern China. (4) The mortality burdens were modified by county level characteristics.

Dissection of cellular and molecular mechanisms of aristolochic acid-induced hepatotoxicity via single-cell transcriptomics.

Background: Aristolochic acids (AAs), a class of carcinogenic and mutagenic natural products from Aristolochia and Asarum plants, are well-known to be responsible for inducing nephrotoxicity and urothelial carcinoma. Recently, accumulating evidence suggests that exposure to AAs could also induce hepatotoxicity and even hepatocellular carcinoma, though the mechanisms are poorly defined. Methods: Here, we aimed to dissect the underlying cellular and molecular mechanisms of aristolochic acid I (AAI)-induced hepatotoxicity by using advanced single-cell RNA sequencing (scRNA-seq) and proteomics techniques. We established the first single-cell atlas of mouse livers in response to AAI. Results: In hepatocytes, our results indicated that AAI activated NF-κB and STAT3 signaling pathways, which may contribute to the inflammatory response and apoptosis. In liver sinusoidal endothelial cells (LSECs), AAI activated multiple oxidative stress and inflammatory associated signaling pathways and induced apoptosis. Importantly, AAI induced infiltration of cytotoxic T cells and activation of proinflammatory macrophage and neutrophil cells in the liver to produce inflammatory cytokines to aggravate inflammation. Conclusions: Collectively, our study provides novel knowledge of AAs-induced molecular characteristics of hepatotoxicity at a single-cell level and suggests future treatment options for AAs associated hepatotoxicity.

Spatiotemporal variation in the blood lead levels of Chinese children with the environmental Kuznets curve trend.

The environmental Kuznets curve (EKC) is often used to analyze the relationship between environmental pollution health indicators and economic development level in different regions. In developed countries, the blood lead levels (BLLs) of children have been declining fitting the EKC since the 1970s. However, such figures in China have remained at relatively high levels, without any obvious decline, since 2010. We explored spatial variations and graded countermeasures using reported data on BLLs including the lead poisoning rates (LPRs) of children. We found that there were prefectures where either the mean BLLs of the children had reached 100.00 µg/L or the LPRs of more than 40% of the children had reached 100 µg/L. When we reduced the average BLLs to 50 µg/L or lowered the proportion of children with a lead poisoning rate (LPR) above 100 µg/L to 10.00%, the EKC trend decreased, and the linear slope after 2010 became -0.202. If the areas where children's BLLs exceeded 50.00 µg/L or the proportion of children with an LPR above 100 µg/L was more than 10.00% will be controlled, the linear slope of the EKC decrease trend after 2010 will became -0.989, and the national average of children's BLLs would decline by 22.17%. The study concluded that children's BLLs in different regions of China are situated at different EKC stages, and urgent prevention and control strategies must be put in place for undeveloped areas.

Using Structural Equation Modeling to Examine Pathways Between Environmental Characteristics and Perceived Restorativeness on Public Rooftop Gardens in China.

As a kind of informal green space more closely related to the built environment, public rooftop gardens (PRGs) are novel green open space and important salutogenic resource for urban residents. It is one of the most easily accessible method for urban residents to be in contact with outdoor or natural elements from the context of high-altitude living. Given its potential health benefits to city dwellers, existing empirical studies are heavily focused on immediate recovery through visually accessing PRGs (through windows), neglecting the possibility of using PRGs physically as a place of interaction. This paper hypothesizes usage patterns will mediate the associations between the environmental characteristics of PRG and users' restoration. This is done through inputting data from 12 typical samples of PRG in Chengdu, China into structural equation model (SEM). Combining the concept of Perceived Sensory Dimensions (PSD) and Perceived Restorativeness Scales (PRS) with the usage patterns of the above samples, this study aims to examine the correlation of environmental characteristics, usage pattern and restoration, in which identify their relative importance in the context of PRGs. Through serials of numerical tests on the model, the study shows that out of the 20 theoretical pathways constructed by the environmental characteristics (x)-usage patterns (m)-restorative effect (y), only 14 forms a significant correlation. In addition, out of all PSDs, social, serene, refuge, space and nature dimensions are induced into restorative effects through four patterns of use: retreat, nature touch, interpersonal interaction and family-bonding activities. The findings also show that social and family-bonding are the most influential independent and mediating variables respectively in achieving restorative effects in the PRG. This study reveals important findings about how usage patterns mediate the association between the PSD and PRS of users. And it also has generated practical implications on how we can design public rooftop gardens from the perspective of restoration, which could potentially be the key to the future survival and development of PRGs in urban environments.

Uneven development of the lead industry leads to regional differences in blood lead levels of children.

Children's exposure to lead is a global health problem, especially in low- and middle-income countries. However, research on the relationship between children's blood lead levels (BLLs) and the development of the lead industry is still limited. This study examined whether children's BLLs were associated with the development of lead industry in different regions. Using survey data on the BLLs of children living in 250 prefectures in China with corresponding data on their economic factors and lead industries, we explored the regional variation of children's BLLs using statistical methods. The results show that the level of economic development in leaded areas was associated with inequity in children's BLLs and met the environmental Kuznets hypothesis. In areas without lead industries, there was little correlation between the level of economic development and the BLLs of children and thus the environmental Kuznets hypothesis was not supported. Lead mines, lead smelting and chemical companies are major sources of blood lead in children living in leaded areas. This study demonstrated the success of control policies for lead-acid battery manufacturers in promoting the prevention and control of childhood lead poisoning in China. China should consciously support the improvement of children's BLLs in undeveloped areas with lead industries through national financing and policies to avoid the continuous effects of the regional inequality problem of high children's BLLs.

Co-benefits of nonpharmaceutical intervention against COVID-19 on infectious diseases in China: A large population-based observational study.

Background: Nonpharmaceutical interventions (NPIs) are public health measures that aim to suppress the transmission of infectious diseases, including border restrictions, quarantine and isolation, community management, social distancing, face mask usage, and personal hygiene. This research aimed to assess the co-benefits of NPIs against COVID-19 on notifiable infectious diseases (NIDs) in Guangdong Province, China. Methods: Based on NID data from the Notifiable Infectious Diseases Surveillance System in Guangdong, we first compared the incidence of NIDs during the emergency response period (weeks 4-53 of 2020) with those in the same period of 2015-2019 and then compared that with the expected incidence during the synchronous period of 2020 for each city by using a Bayesian structural time series model. Findings: A total of 514,341 cases of 39 types of NIDs were reported in Guangdong during the emergency response period in 2020, which decreased by 50·7% compared with the synchronous period during 2015-2019. It was estimated that the number of 39 NIDs during the emergency response in 2020 was 65·6% (95% credible interval [CI]: 64·0% - 68·2%) lower than expected, which means that 982,356 (95% CI: 913,443 - 1,105,170) cases were averted. The largest reduction (82·1%) was found for children aged 0-14 years. For different categories of NIDs, natural focal diseases and insect-borne infectious diseases had the greatest reduction (89·4%), followed by respiratory infectious diseases (87·4%), intestinal infectious diseases (59·4%), and blood-borne and sexually transmitted infections (18·2%). Dengue, influenza, and hand-foot-and-mouth disease were reduced by 99·3%, 95·1%, and 76·2%, respectively. Larger reductions were found in the regions with developed economies and a higher number of COVID-19 cases. Interpretation: NPIs against COVID-19 may have a large co-benefit on the prevention of other infectious diseases in Guangdong, China, and the effects have heterogeneity in populations, diseases, time and space. Funding: Key-Area Research and Development Program of Guangdong Province.

Reduction of air pollutants and associated mortality during and after the COVID-19 lockdown in China: Impacts and implications.

Although strict lockdown measurements implemented during the COVID-19 pandemic have dramatically reduced the anthropogenic-based emissions, changes in air quality and its health impacts remain unclear in China. We comprehensively described air pollution during and after the lockdown periods in 2020 compared with 2018-2019, and estimated the mortality burden indicated by the number of deaths and years of life lost (YLL) related to the air pollution changes. The mean air quality index (AQI), PM10, PM2.5, NO2, SO2 and CO concentrations during the lockdown across China declined by 18.2 (21.2%), 27.0 µg/m3 (28.9%), 10.5 µg/m3 (18.3%), 8.4 µg/m3 (44.2%), 13.1 µg/m3 (38.8%), and 0.3 mg/m3 (27.3%) respectively, when compared to the same periods during 2018-2019. We observed an increase in O3 concentration during the lockdown by 5.5 µg/m3 (10.4%), and a slight decrease after the lockdown by 3.4 µg/m3 (4.4%). As a result, there were 51.3 (95%CI: 32.2, 70.1) thousand fewer premature deaths (16.2 thousand during and 35.1 thousand after the lockdown), and 1066.8 (95%CI: 668.7, 1456.8) thousand fewer YLLs (343.3 thousand during and 723.5 thousand after the lockdown) than these in 2018-2019. Our findings suggest that the COVID-19 lockdown has caused substantial decreases in air pollutants except for O3, and that substantial human health benefits can be achieved when strict control measures for air pollution are taken to reduce emissions from vehicles and industries. Stricter tailored policy solutions of air pollution are urgently needed in China and other countries, especially in well-developed industrial regions, such as upgrading industry structure and promoting green transportation.