Independent and joint associations of monocyte to high-density lipoprotein-cholesterol ratio and body mass index with cardiorenal syndrome: insights from NHANES 2003-2020.

BACKGROUND: With the development of pathophysiology, cardiorenal syndrome (CRS), a complex and severe disease, has received increasing attention. Monocyte to high-density lipoprotein-cholesterol ratio (MHR) and body mass index (BMI) are independent risk factors for cardiovascular diseases, but their association with CRS remains unexplored. This study aims to explore the independent and joint effects of MHR and BMI on CRS. METHODS: We included 42,178 NHANES participants. The determination of CRS referred to the simultaneous presence of cardiovascular disease (identified through self-report) and chronic kidney disease (eGFR < 60 mL/min per 1.73 m²). We employed multivariate weighted logistic regression to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the independent and joint associations of MHR and BMI with CRS. We also conducted restricted cubic spines to explore nonlinear associations. RESULTS: The prevalence of CRS was 3.45% among all participants. An increase in both MHR and BMI is associated with a higher risk of CRS (MHR: OR = 1.799, 95% CI = 1.520-2.129, P < 0.001, P-trend < 0.001; BMI: OR = 1.037, 95% CI = 1.023-1.051, P < 0.001). Individuals who simultaneously fall into the highest quartile of MHR and have a BMI of 30 or more face the highest risk of CRS compared to those in the lowest MHR quartile with a BMI of less than 25 (OR = 3.45, 95% CI = 2.40-4.98, P < 0.001). However, there is no interactive association between MHR and BMI with CRS. CONCLUSIONS: Higher MHR and BMI are associated with higher odds of CRS. MHR and BMI can serve as tools for early prevention and intervention of CRS, respectively.

Non-dietary exposure to phthalates in primary school children: Risk and correlation with anthropometric indices, cardiovascular and respiratory diseases.

Phthalates are endocrine disruptors of increasing concern for human health; however, previous studies have only assessed the association between internal exposure and human health. We aimed to assess the non-carcinogenic and carcinogenic risks of non-dietary exposure to phthalates in indoor environments among primary school children and their correlations with health indicators. A study involving 54 children was conducted in Jinan, Shandong Province, China. Questionnaires and health examinations were conducted, dust in hard-to-clean corners of students' classrooms and homes was collected, and airborne phthalates in the middle of classrooms and family living rooms were sampled. The gas-phase phthalate concentrations, individual exposure, and non-carcinogenic and carcinogenic risks were calculated. Associations were estimated using linear mixed models. The findings revealed that phthalates posed a non-carcinogenic risk to 7.4 % of the children and a moderate carcinogenic risk to 27.8 % of the children, with higher non-carcinogenic and carcinogenic risks to girls than to boys. Five phthalates were negatively correlated with body mass index, dimethyl phthalate and diethyl phthalate (DEP) were significantly correlated with waist circumference, and di-iso-butyl phthalate (DiBP) was negatively correlated with hip circumference. DiBP, di-n-butyl phthalate, and DEP, were significantly correlated with cardiovascular disease, DEP and di (2-n-butoxyethyl) phthalate were correlated with decreased lung function, and di-n-octyl phthalate influenced airway inflammation. The findings indicated that phthalate exposure may negatively impact children's health, thereby warranting further comprehensive research on the health effects of these chemicals.

Desipramine ameliorates fine particulate matter-induced hepatic insulin resistance by modulating the ceramide metabolism in mice.

Recent research has highlighted a correlation between exposure to ambient fine particulate matter (PM2.5) and the development of systemic insulin resistance (IR) along with an elevated risk of diabetes. Ceramide has emerged as one of the pathogenic mechanisms contributing to IR. The inhibition of acid sphingomyelinase (ASMase) activity by desipramine (DES) has been shown to effectively reduce ceramide levels. In the present study, 24 female C57BL/6 N mice were randomized into one of the four groups: the filtered air exposure (FA) group, the concentrated PM2.5 exposure (PM) group, the concentrated PM2.5 treated with low-dose DES (DL) group, and the concentrated PM2.5 treated with high-dose DES (DH) group. The PM, DL and DH groups were exposed to PM2.5 for an 8-week period within a whole-body exposure system. The study encompassed extensive examinations of glucose homeostasis, liver lipid profile, ceramide pathway, and insulin signaling pathway. Our results demonstrated that PM2.5 exposure caused impaired glucose tolerance, elevated ceramide levels, increased phosphorylation PP2A, reduced Akt phosphorylation, and hindered GLUT2 expression. Remarkably, DES administration mitigated PM2.5-induced IR by effectively lowering ceramide levels. In conclusion, the reduction of ceramide levels by DES may be a promising therapeutic strategy for coping PM2.5-induced IR.

Exposure memory and susceptibility to ambient PM2.5: A perspective from hepatic cholesterol and bile acid metabolism.

Both epidemiological and experimental studies increasingly show that exposure to ambient fine particulate matter (PM2.5) is related to the occurrence and development of chronic diseases, such as metabolic diseases. However, whether PM2.5 has "exposure memory" and how these memories affect chronic disease development like hepatic metabolic homeostasis are unknown. Therefore, we aimed to explore the effects of exposure transition on liver cholesterol and bile acids (BAs) metabolism in mice. In this study, C57BL/6 mice were exposed to concentrated ambient PM2.5 or filtered air (FA) in a whole-body exposure facility for an initial period of 10 weeks, followed by another 8 weeks of exposure switch (PM2.5 to FA and FA to PM2.5) comparing to non-switch groups (FA to FA and PM2.5 to PM2.5), which were finally divided into four groups (FF of FA to FA, PP of PM2.5 to PM2.5, PF of PM2.5 to FA, and FP of FA to PM2.5). Our results showed no significant difference in food intake, body composition, glucose homeostasis, and lipid metabolism between FA and PM2.5 groups after the initial exposure before the exposure switch. At the end of the exposure switch, the mice switched from FA to PM2.5 exposure exhibited a high sensitivity to late-onset PM2.5 exposure, as indicated by significantly elevated hepatic cholesterol levels and disturbed BAs metabolism. However, the mice switched from PM2.5 to FA exposure retained a certain memorial effects of previous PM2.5 exposure in hepatic cholesterol levels, cholesterol metabolism, and BAs metabolism. Furthermore, 18-week PM2.5 exposure significantly increased hepatic free BAs levels, which were completely reversed by the FA exposure switch. Finally, the changes in small heterodimeric partner (SHP) and nuclear receptor subfamily 5 group A member 2 (LRH1) in response to exposure switch mechanistically explained the above alterations. Therefore, mice switching from PM2.5 exposure to FA showed only a weak memory of prior PM2.5 exposure. In contrast, the early FA caused mice to be more susceptible to subsequent PM2.5 exposure.

PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Species Diversity of Pectobacterium spp. Causing Potato Aerial Stem Rot in China.

Pectobacterium spp. are the primary causative agents of aerial stem rot in potatoes in China. A nationwide survey revealed the widespread occurrence of aerial stem rot in the northern, southern, and southwestern cultivation regions, with occurrence rates ranging from 1 to 60%. In total, 36 strains were isolated and identified at the species level using multilocus sequence analysis of six housekeeping genes (rpoS, proA, gapA, icdA, gyrA, and mdh). Genome sequencing was conducted on one representative strain for each species, and further confirmation of their identities was achieved through average nucleotide identity and in silico digital DNA-DNA hybridization analysis. Five Pectobacterium species were identified, namely, P. atrosepticum, P. brasiliense, P. carotovorum, P. polaris, and P. punjabense, with P. atrosepticum and P. brasiliense being the most widely distributed. Pathogenicity tests demonstrated that, among the strains isolated in this study and those obtained from other studies, P. atrosepticum and P. brasiliense are also the most virulent species. To the best of our knowledge, this is the first nationwide study describing the diversity and distribution of Pectobacterium spp. affecting potatoes in China. The information gathered will be utilized for disease diagnosis and the development of pathogen-specific integrated pest management strategies to protect potato production.

Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence.

It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-ß1 (TGF-ß1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated ß-galactosidase (SA-ß-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.

Ecological Study on Global Health Effects due to Source-Specific Ambient Fine Particulate Matter Exposure.

Ambient air pollution of fine particulate matter with diameters less than 2.5 µm (PM2.5) is associated with millions of premature deaths per year, recognized as a leading global health concern. The dose-response relation between ambient PM2.5 exposure and mortality risk is the most fundamental information for assessments of the health effects of PM2.5. The existing dose-response relations were generally developed based on the assumption of equal contribution to toxicity from various sources. However, the sources of PM2.5 may significantly influence health effects. In this study, we conducted an ecological study to investigate the global long-term correlation between source-specific PM2.5 exposure and cause-specific mortality risk (SPECM) based on the regional aggregate data of the publically available official health databases from 528 regions worldwide with a total registered population of 3.2 billion. The results provided preliminary epidemiological evidence for differing chronic health effects across various sources. The relative mortality risks of lung cancer and circulatory diseases were closely correlated with the primary emissions from industrial and residential combustion sources. Chronic lower respiratory diseases were mostly associated with the mass concentration of particulate matter.

Heavy metal risk of disposable food containers on human health.

The consumption of disposable materials is booming with the rapid development of urbanization and industrialization, which may inevitably cause the release of toxic and harmful substances during use of them in daily life. This study was to estimate element levels such as Beryllium (Be), Vanadium (V), Zinc (Zn), Manganese (Mn), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Cobalt (Co), Antimony (Sb), Barium (Ba), Lead (Pb), Iron (Fe), Copper (Cu), and Selenium (Se) in leachate and subsequently assess the health risk of exposure to those disposable products such as paper and plastic food containers. We found that a large amount of metals was released from disposable food containers in hot water, and the order of metal concentration is Zn > Ba > Fe > Mn > Ni > Cu > Sb > Cr > Se > Be > Pb > Co > V > Cd. Additionally, the hazard quotient (HQ) of metals in young adults were less than 1, and were decreased in the order of Sb > Fe > Cu > Be > Ni > Cr > Pb > Zn > Se > Cd > Ba > Mn > V > Co. Furthermore, the excess lifetime cancer risk (ELCR) results of Ni and Be indicated that chronic exposure to Ni and Be may have a non-negligible carcinogenic risk. These findings suggest that potential health risk of metals may exist for the individuals to use disposable food containers under high temperature environment.

Hawthorn total flavonoids ameliorate ambient fine particulate matter-induced insulin resistance and metabolic abnormalities of lipids in mice.

Recent studies have shown a strong correlation between ambient fine particulate matter (PM2.5) exposure and diabetes risk, including abnormal lipid accumulation and systemic insulin resistance (IR). Hawthorn total flavonoids (HF) are the main groups of active substances in Hawthorn, which showed anti-hyperlipidemic and anti-hyperglycemic effects. Therefore, we hypothesized that HF may attenuate PM2.5-induced IR and abnormal lipid accumulation. Female C57BL/6 N mice were randomly assigned to the filtered air exposure (FA) group, concentrated PM2.5 exposure (PM) group, PM2.5 exposure maintained on a low-dose HF diet (LHF) group, and PM2.5 exposure maintained on a high-dose HF diet (HHF) group for an 8-week PM2.5 exposure using a whole-body exposure device. Body glucose homeostasis, lipid profiles in the liver and serum, and enzymes responsible for hepatic lipid metabolism were measured. We found that exposure to PM2.5 impaired glucose tolerance and insulin sensitivity. In addition, triacylglycerol (TAG) in serum elevated, whereas hepatic TAG levels were decreased after PM2.5 exposure, accompanied by inhibited fatty acid uptake, lipogenesis, and lipolysis in the liver. HF administration, on the other hand, balanced the hepatic TAG levels by increasing fatty acid uptake and decreasing lipid export, leading to alleviated systemic IR and hyperlipidemia in PM2.5-exposed mice. Therefore, HF administration may be an effective strategy to protect against PM2.5-induced IR and metabolic abnormalities of lipids.

Maternal exposure to PM2.5 induces cognitive impairment in offspring via cerebellar neuroinflammation and oxidative stress.

Available evidence suggest that exposure to PM2.5 during pregnancy is associated with reduced cognitive function in offspring. This study aimed to investigate the effects of maternal exposure to PM2.5 on offspring cognitive function and to elucidate the underlying mechanisms. In this work, pregnant C57BL/6 female mice were exposed to concentrated ambient PM2.5 or filtered air from day 0.5 (=vaginal plug) to day 15.5 in the Shanghai Meteorological and Environmental Animal Exposure System, and offspring cerebellar tissues were collected on embryonic day 15.5, as well as postnatal days 0, 10 and 42. The mean PM2.5 concentrations exposed to the pregnant mice were 73.06 ± 4.90 µg/m3 and 11.15 ± 2.71 µg/m3 in the concentrated ambient PM2.5 and filtered air chambers, respectively. Maternal concentrated PM2.5 exposure was negatively correlated with offspring spatial memory significantly as assessed by the Morris water maze. Compared with the filtered air group, PM2.5-exposed offspring mice had reduced cerebellar microglia. Both RNA and protein levels of IL-8 and TNF-α were elevated in the concentrated ambient PM2.5 group. PM2.5 exposure increased the level of 8-OHG in miRNA of microglia and Purkinje cells in 6-week-old offspring. The level of prostaglandin F2α (8-iso-PGF2Aα) in the cerebellum was increased at different growing stages of offspring after gestational exposure of PM2.5. These results suggested that maternal air pollution exposure might cause inflammatory damage and oxidative stress to the cerebellum, contributing to reduced cognitive performance in mice offspring.

First Report of Streptomyces niveiscabiei Causing Potato Common Scab in Shanxi and Gansu, China.

Multiple species of Streptomyces cause common scab disease in potato (Solanum tuberosum) (Kämpfer et al. 1991). Potato tubers (cv. Jinshu1 #5 and Longshu #6) with severe pitted common scab symptoms were observed from two farms in Chaozhou in Shanxi Province and in Tianzhu in Gansu Province during the national disease survey of bacterial diseases of potatoes in 2021. The disease incidence was around 30% on the 6.7 ha of the Chaozhou farm and 10% on the 0.7 ha on the Tianzhu farm. Three tubers with scab symptoms were surface disinfested with 3% sodium hypochlorite for 1 min. The symptomatic tissue was then ground in sterile water. Serially diluted ground samples were cultured on Streptomyces ISP Medium 5 agar plates (Shirling and Gottlieb 1966) and incubated at 280C for 5 days. Eight pure Streptomyces colonies were obtained and sequenced for identification using the universal 16S rRNA gene primers 27F (5'-AGAGTTTGATCMTGGCTCAG-3') and 1492R (5'-TACGGYTACCTTGTTACGACTT-3') (Monciardini et al. 2002) by colony PCR. Blast results of the sequences against the NCBI GenBank for the eight isolates, ZRIMU1508, ZRIMU1510, ZRIMU1511, ZRIMU1512, ZRIMU1514, ZRIMU1515, ZRIMU1516 and ZRIMU1530 (Accession numbers: OP941573 - OP941580), showed more than 99% sequence identity to S. niveiscabiei NRRLB-24457T type strain. Additionally, 12 housekeeping gene sequences, acnA (OP997624 - OP997625), atpD (OP997622 - OP997623), dnaN (OP997620 - OP997621), gap (OP997618 - OP997619), gyrA (OP997614 - OP997615), gyrB (OP997612 - OP997613), infB (OP997610- OP997611), mdh (OP997608 - OP997609), recA (OP997602 - OP997603), rplB (OP997600 - OP997601), rpoB (OP997598- OP997599), and trpB (OP997594 - OP997595), were extracted from the genome sequences of two strains, ZRIMU1510 and ZRIMU1530, and uploaded to GenBank. Genes for pathogenicity, txtA (OP997593 - OP997594), tomA (OP997596 - OP997597) and Nec1(OP997606 - OP997607), were also identified from the genome sequence and uploaded to GenBank. The housekeeping genes and the pathogenicity genes showed over 98% identity with S. niveiscabiei. Phylogenetic trees were constructed using concatenated housekeeping gene sequences (Kumar et al. 1994) and the cladogram showed that the isolates ZRIMU1510 and ZRIMU1530 grouped with the type strain NRRLB-24457T. Pathogenicity tests were done by drench application of 100 ml spore suspensions (104 CFU/ml) of ZRIMU1530, ZRIMU1510, or phosphate buffer into pots with potato plants (cv. Favorita) grown in potting mix. Five tubers were planted and inoculated with each pathogen or phosphate buffer as the negative control. The plants were then placed in a greenhouse with 12 h of light per day, irrigated regularly, and harvested after 3 months. The newly formed tubers were checked for disease symptoms. Tubers from pots inoculated with ZRIMU1530 and ZRIMU1510 exhibited typical symptoms of common scab with raised corky lesions with deep pits, but the negative controls remained asymptomatic. The pathogens were reisolated from the lesions and confirmed to be identical to the original isolates by 16S rRNA gene sequences, thus completing Koch's postulates. The pot experiment was conducted twice: first in May 2022 and second in February 2023. To our knowledge, this is the first report of S. niveiscabiei causing common scab of potato in Shanxi and Gansu, China. S. niveiscabiei was first reported in Korea (Park et al. 2003) and this report will draw attention to the study and management of scab pathogens in China.

Effects of Coverlys TF150® on the Photosynthetic Characteristics of Grape.

Grape rain-shelter cultivation is a widely employed practice in China. At present, the most commonly used rain shelter film materials are polyvinyl chloride (PVC), polyethylene (PE), ethylene-vinyl acetate copolymer (EVA), and polyolefin (PO). Coverlys TF150® is a woven fabric with an internal antifoggy PE coating that has not yet been popularized as a rain shelter film for grapes in China. To investigate the effects of Coverlys TF150® on grapes, we measured the microdomain environment, leaf development, and photosynthetic characteristics of 'Miguang' (Vitis vinifera × V. labrusca) under rain-shelter cultivation and performed transcriptome analysis. The results showed that Coverlys TF150® significantly reduced (p < 0.05) the light intensity, temperature, and humidity compared with PO film, increased the chlorophyll content and leaf thickness (particularly palisade tissue thickness), and increased stomatal density and stomatal opening from 10:00 to 14:00. Coverlys TF150® was observed to improve the maximum efficiency of photosystem II (Fv/Fm), photochemical quenching (qP), the electron transfer rate (ETR), and the actual photochemical efficiency (ΦPSII) from 10:00 to 14:00. Moreover, the net photosynthetic rate (Pn), intercellular CO2 concentration (Ci), stomatal conductance (Gs), and transpiration rate (Tr) of grape leaves significantly increased (p < 0.05) from 10:00 to 14:00. RNA-Seq analysis of the grape leaves at 8:00, 10:00, and 12:00 revealed 1388, 1562, and 1436 differential genes at these points in time, respectively. KEGG enrichment analysis showed the occurrence of protein processing in the endoplasmic reticulum. Plant hormone signal transduction and plant-pathogen interaction were identified as the metabolic pathways with the highest differential gene expression enrichment. The psbA encoding D1 protein was significantly up-regulated in both CO10vsPO10 and CO12vsPO12, while the sHSPs family genes were significantly down-regulated in all time periods, and thus may play an important role in the maintenance of the photosystem II (PSII) activity in grape leaves under Coverlys TF150®. Compared with PO film, the PSI-related gene psaB was up-regulated, indicating the ability of Coverlys TF150® to better maintain PSI activity. Compared with PO film, the abolic acid receptacle-associated gene PYL1 was down-regulated at all time periods under the Coverlys TF150® treatment, while PP2C47 was significantly up-regulated in CO10vsPO10 and CO12vsPO12, inducing stomatal closure. The results reveal that Coverlys TF150® alleviates the stress of high temperature and strong light compared with PO film, improves the photosynthetic capacity of grape leaves, and reduces the midday depression of photosynthesis.

A hierarchical opportunistic screening model for osteoporosis using machine learning applied to clinical data and CT images.

BACKGROUND: Osteoporosis is a common metabolic skeletal disease and usually lacks obvious symptoms. Many individuals are not diagnosed until osteoporotic fractures occur. Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis detection. However, only a limited percentage of people with osteoporosis risks undergo the DXA test. As a result, it is vital to develop methods to identify individuals at-risk based on methods other than DXA. RESULTS: We proposed a hierarchical model with three layers to detect osteoporosis using clinical data (including demographic characteristics and routine laboratory tests data) and CT images covering lumbar vertebral bodies rather than DXA data via machine learning. 2210 individuals over age 40 were collected retrospectively, among which 246 individuals' clinical data and CT images are both available. Irrelevant and redundant features were removed via statistical analysis. Consequently, 28 features, including 16 clinical data and 12 texture features demonstrated statistically significant differences (p < 0.05) between osteoporosis and normal groups. Six machine learning algorithms including logistic regression (LR), support vector machine with radial-basis function kernel, artificial neural network, random forests, eXtreme Gradient Boosting and Stacking that combined the above five classifiers were employed as classifiers to assess the performances of the model. Furthermore, to diminish the influence of data partitioning, the dataset was randomly split into training and test set with stratified sampling repeated five times. The results demonstrated that the hierarchical model based on LR showed better performances with an area under the receiver operating characteristic curve of 0.818, 0.838, and 0.962 for three layers, respectively in distinguishing individuals with osteoporosis and normal BMD. CONCLUSIONS: The proposed model showed great potential in opportunistic screening for osteoporosis without additional expense. It is hoped that this model could serve to detect osteoporosis as early as possible and thereby prevent serious complications of osteoporosis, such as osteoporosis fractures.

Human papillomavirus 16 E6/E7 contributes to immune escape and progression of cervical cancer by regulating miR-142-5p/PD-L1 axis.

Persistent infection of human papillomavirus (HPV) and immune escape are the main causes of cervical cancer. E6/E7 encoded by HPV16 may be closely related to carcinogenesis. HPV infection may upregulate PD-L1 expression, resulting in immune escape and cervical cancerigenesis. Evidence indicates that miRNAs may mediate the regulation of E6/E7 on PD-L1. Therefore, we aimed to screen the miRNA, and further verify its expression and functions. Bioinformatics approaches were used to screen the miRNAs that mediate the regulation of E6/E7 on PD-L1. The expression of the miRNA and PD-L1 in HPV+ and HPV- cervical cancer cells were compared, and the effect of E6E7 on them was evaluated. Then, the effect of the miRNA on PD-L1 was assessed by the Gain- and Loss-of-function test. Finally, in vivo experiments were conducted to verify the effects of the miRNA on tumor growth and survival of tumor-bearing mice. Six miRNAs were screened, of which miR-142-5p was identified. MiR-142-5p was downregulated and PD-L1 was upregulated in HPV- cells after transfection of E6, E7, or E6/E7. The rescue test showed that the upregulation of miR-142-5p attenuated the effect of E6/E7 on PD-L1. The reverse relationship between PD-L1 and miR-142-5p was confirmed. In vivo experiments suggest that miR-142-5p upregulation inhibits the growth of the transplanted tumors by targeting PD-L1. MiR-142-5p acts as a tumor suppressor in cervical cancer. HPV16 E6E7 may promote the immune escape of cervical cancer cells by regulating the miR-142-5p/PD-L1 axis. Using miR-142-5p in tumor immunotherapy as a new strategy is proposed.

Impact of Heavy PM2.5 Pollution Events on Mortality in 250 Chinese Counties.

We explored the impact of heavy PM2.5 pollution events on the health of residents in 250 counties in China. A time-series approach involving a two-stage analysis was applied to estimate the association between heavy PM2.5 pollution events and mortality from 2013 to 2018. The associations between heavy (PM2.5 ≥75 µg/m3 and <150 µg/m3) and extremely heavy (PM2.5 ≥150 µg/m3) PM2.5 pollution days with mortality were explored. The added effects of the heavy PM2.5 pollution events were evaluated by controlling PM2.5 concentration in the model. From 2013 to 2018, there were 57,279 county days of heavy PM2.5 pollution and 21,248 county days of extremely heavy PM2.5 pollution. The risks of mortality during this period of heavy PM2.5 pollution events increased by 1.22% (95% CI: 0.82-1.63%), 1.14% (95% CI: 0.74-1.53%), 1.09% (95% CI: 0.58-1.60%), and 1.30% (95% CI: 0.40-2.20%), for all-cause, nonaccidental, circulatory, and respiratory mortality, respectively. We also observed that heavy PM2.5 pollution events had an added effect on mortality risk associated with all-cause, nonaccidental, circulatory, and respiratory mortality, evident from an observed increase by 0.77% (95% CI: 0.29-1.24%), 0.73% (95% CI: 0.27-1.19%), 0.96% (95% CI: 0.37-1.55%), and 0.55% (95% CI: -0.52-1.63%), respectively. Heavy PM2.5 pollution events increased mortality risks and caused an independent added effect. The findings serve as a foundation for policymakers in developing early warning systems and policy interventions.

Associations between Individual Exposure to Fine Particulate Matter Elemental Constituent Mixtures and Blood Lipid Profiles: A Panel Study in Chinese People Aged 60-69 Years.

Dyslipidemia may be a potential mechanism linking fine particulate matter (PM2.5) to adverse cardiovascular outcomes. However, inconsistent associations between PM2.5 and blood lipids have resulted from the existing research, and the joint effect of PM2.5 elemental constituents on blood lipid profiles remains unclear. We aimed to explore the overall associations between PM2.5 elemental constituents and blood lipid profiles and to identify the significant PM2.5 elemental constituents in this association. Sixty-nine elderly people were recruited between September 2018 and January 2019. Each participant completed a survey questionnaire, 3 days of individual exposure monitoring, health examination, and biological sample collection at each follow-up visit. Bayesian kernel machine regression (BKMR) models were used to identify the joint effects of the 17 elemental constituents on blood lipid profiles. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly increased in older adults when exposed to the mixture of PM2.5 elemental constituents. Copper and titanium had higher posterior inclusion probabilities than other constituents, ranging from 0.76 to 0.90 (Cu) and 0.74 to 0.94 (Ti). Copper and titanium in the PM2.5 elemental constituent mixture played an essential role in changes to blood lipid levels. This study highlights the importance of identifying critical hazardous PM2.5 constituents that may cause adverse cardiovascular outcomes in the future.

Associations of Fine Particulate Matter Constituents with Metabolic Syndrome and the Mediating Role of Apolipoprotein B: A Multicenter Study in Middle-Aged and Elderly Chinese Adults.

Fine particulate matter (PM2.5) was reported to be associated with metabolic syndrome (MetS), but how PM2.5 constituents affect MetS and the underlying mediators remains unclear. We aimed to investigate the associations of long-term exposure to 24 kinds of PM2.5 constituents with MetS (defined by five indicators) in middle-aged and elderly adults and to further explore the potential mediating role of apolipoprotein B (ApoB). A multicenter study was conducted by recruiting subjects (n = 2045) in the Beijing-Tianjin-Hebei region from the cohort of Sub-Clinical Outcomes of Polluted Air in China (SCOPA-China Cohort). Relationships among PM2.5 constituents, serum ApoB levels, and MetS were estimated by multiple logistic/linear regression models. Mediation analysis quantified the role of ApoB in "PM2.5 constituents-MetS" associations. Results indicated PM2.5 was significantly related to elevated MetS prevalence. The MetS odds increased after exposure to sulfate (SO42-), calcium ion (Ca2+), magnesium ion (Mg2+), Si, Zn, Ca, Mn, Ba, Cu, As, Cr, Ni, or Se (odds ratios ranged from 1.103 to 3.025 per interquartile range increase in each constituent). PM2.5 and some constituents (SO42-, Ca2+, Mg2+, Ca, and As) were positively related to serum ApoB levels. ApoB mediated 22.10% of the association between PM2.5 and MetS. Besides, ApoB mediated 24.59%, 50.17%, 12.70%, and 9.63% of the associations of SO42-, Ca2+, Ca, and As with MetS, respectively. Our findings suggest that ApoB partially mediates relationships between PM2.5 constituents and MetS risk in China.

Linking the Fasting Blood Glucose Level to Short-Term-Exposed Particulate Constituents and Pollution Sources: Results from a Multicenter Cross-Sectional Study in China.

Ambient PM2.5 (fine particulate matter with aerodynamic diameters ≤ 2.5 µm) is thought to be associated with the development of diabetes, but few studies traced the effects of PM2.5 components and pollution sources on the change in the fasting blood glucose (FBG). In the present study, we assessed the associations of PM2.5 constituents and their sources with the FBG in a general Chinese population aged over 40 years. Exposure to PM2.5 was positively associated with the FBG level, and each interquartile range (IQR) increase in a lag period of 30 days (18.4 µg/m3) showed the strongest association with an elevated FBG of 0.16 mmol/L (95% confidence interval: 0.04, 0.28). Among various constituents, increases in exposed elemental carbon, organic matter, arsenic, and heavy metals such as silver, cadmium, lead, and zinc were associated with higher FBG, whereas barium and chromium were associated with lower FBG levels. The elevated FBG level was closely associated with the PM2.5 from coal combustion, industrial sources, and vehicle emissions, while the association with secondary sources was statistically insignificant. Improving air quality by tracing back to the pollution sources would help to develop well-directed policies to protect human health.

Using an Exposome-Wide Approach to Explore the Impact of Urban Environments on Blood Pressure among Adults in Beijing-Tianjin-Hebei and Surrounding Areas of China.

Existing studies mostly explored the association between urban environmental exposures and blood pressure (BP) in isolation, ignoring correlations across exposures. This study aimed to systematically evaluate the impact of a wide range of urban exposures on BP using an exposome-wide approach. A multicenter cross-sectional study was conducted in ten cities of China. For each enrolled participant, we estimated their urban exposures, including air pollution, built environment, surrounding natural space, and road traffic indicator. On the whole, this study comprised three statistical analysis steps, that is, single exposure analysis, multiple exposure analysis and a cluster analysis. We also used deletion-substitution-addition algorithm to conduct variable selection. After considering multiple exposures, for hypertension risk, most significant associations in single exposure model disappeared, with only neighborhood walkability remaining negatively statistically significant. Besides, it was observed that SBP (systolic BP) raised gradually with the increase in PM2.5, but such rising pattern slowed down when PM2.5 concentration reached a relatively high level. For surrounding natural spaces, significant protective associations between green and blue spaces with BP were found. This study also found that high population density and public transport accessibility have beneficially significant association with BP. Additionally, with the increase in the distance to the nearest major road, DBP (diastolic BP) decreased rapidly. When the distance was beyond around 200 m, however, there was no obvious change to DBP anymore. By cluster analysis, six clusters of urban exposures were identified. These findings reinforce the importance of improving urban design, which help promote healthy urban environments to optimize human BP health.