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Introduction Cardiovascular disease (CVD) is the world's leading cause of disability and death, responsible for 18.6 million deaths globally in 2019. (1) Over the past four decades, the socioeconomic burdens [...], BACKGROUND: Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain. OBJECTIVES: We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics. METHODS: A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency >50% and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways. RESULTS: Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis. DISCUSSION: It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864

Diabetes osteoporosis is a chronic complication of diabetes mellitus (DM) and is associated with osteoclast formation and enhanced bone resorption. Specnuezhenide (SPN) is an active compound with anti-inflammatory and immunomodulatory properties. However, the roles of SPN in diabetic osteoporosis remain unknown. In this study, primary bone marrow macrophages (BMMs) were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand (RANKL; 50 ng/mL) to induce osteoclastogenesis. The number of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1 (c-Fos/NFATc1), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated by western blot analysis. NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation. The DM model group received a high-glucose, high-fat diet and was then intraperitoneally injected with streptozotocin (STZ). Micro-CT scanning, serum biochemical analysis, histological analysis were used to assess bone loss. We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and c-Fos/NFATc1. SPN inhibited RANKL-induced activation of NF-κB and MAPKs. In vivo experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteoclasts. Furthermore, SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), calcium (Ca) and phosphorus (P). SPN also regulated diabetes-related markers. This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis, and provides an experimental basis for the treatment of diabetic osteoporosis.

Introduction Diabetes mellitus, mainly type 2 diabetes (T2D), is one of the four most prevalent noncommunicable diseases. (1,2) In 2021, 536.6 (10.5%) million adults 20-79 years of age worldwide were [...], Background: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. Objectives: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60- 69 years of age to elucidate the underlying mechanisms using a multi-omics approach. Methods: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. Results: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso- butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3- kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs. Discussion: OPEs are associated with the elevated risk of T2D among older Chinese adults 60-69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. https://doi.org/10.1289/EHP11896

Photoelectrocatalysis has attracted significant attention for water splitting and contaminant degradation. However, the lifetime of photoelectrocatalysis devices is hampered by the severe instability and photocorrosion of the photo‐active nanomaterial on the photoelectrode, which is a key limitation to realizing industrialization. Typically, the conventional protection strategy of photoelectrodes usually suffers from the trade‐off between the photoelectrocatalytic activity and stability. Inspired by biological cell membrane with water channels, here a highly permeable and ultrathin silica coating with ultrasmall straight nanochannels is in situ grown that stabilizes the photoelectrode. These ultrasmall channels boost photoelectrocatalysis by accelerating water transport and reducing the reaction energy within the confined nanochannels. Specifically, the ultrathin coating imparts significant mechanical and structural stability to the photo‐active nanomaterial, thereby preventing its detachment, dissolution, and crystal damage without compromising performance. As a result, the protected photoelectrode exhibits enhanced water splitting activity and excellent stability over 120 h, whereas the photocurrent of the unprotected photoelectrode degrades rapidly. Meanwhile, the coated photoelectrode also exhibits superior photoelectrocatalytic degradation efficiency (>97%), even after the 10th cycle. This strategy is facile and universal and can be extended to construct other stable and high‐performance electrodes for promoting photoelectrocatalysis in practical applications. [ABSTRACT FROM AUTHOR]

Aiming at the problems including complicated procedure, long production cycle, and high energy consumption existing in the current painting process for transmission box of construction machinery, different improvement schemes were proposed. A multifunctional coating with oil-resistant, rust-proof, and decorative properties was selected. Therefore, the comprehensive cost of painting was reduced as shown by simplified process flow, decreased energy consumption, and shortened production cycle. [ABSTRACT FROM AUTHOR]

Innovation is the first driving force for development, and green innovation efficiency (GIE) plays a very important role in regional sustainable development. Data from 31 provinces and cities in China from 2011 to 2020 were used to select the proportion of energy saving and environmental protection costs in GDP as the green financial value, and the proportion of industrial pollution control input in GDP as the environmental regulation index. Green innovation efficiency is measured from two aspects of input and output by DEA method, and carried out for 31 provinces and cities in three regions. Using the DEA-Malmquist index to measure regional green innovation efficiency, the results show that the green innovation efficiency in three regions basically presents an upward trend, but the upward trend of green innovation efficiency is different between the three regions. A Tobit regression model is constructed to explore the impact of green finance and environmental regulations on the green innovation efficiency in these three regions. Research indicates that environmental regulations, the proportion of output value of tertiary industry in GDP, industrial structure, and foreign direct investment have significant impacts on the green innovation efficiency in all regions. Green finance, industrial structure, and power consumption have a significant impact on the green innovation efficiency in eastern China. Industrial structure has a significant impact on green innovation efficiency in central China, while power consumption and industrial structure have a significant impact on green innovation efficiency in western China. Therefore, each region needs to improve the standard of environmental regulation innovation, and introduce and use foreign investment in a scientific and reasonable way so as to promote the improvement of industrial infrastructure. [ABSTRACT FROM AUTHOR]

The authors assessed treatment and control of blood glucose, blood pressure (BP), and blood lipids among patients from Inner Mongolia with diabetes mellitus (DM) and hypertension (HTN) and identified the modifiable factors associated with treatment and achievement of blood glucose, BP, and blood lipid targets. The authors used a multistage stratified cluster sampling method according to geographical location and level of economic development in Inner Mongolia. Among patients with DM and HTN, the crude rates of fasting plasma glucose (FPG) treatment and control was 30.76% and 4.73%, respectively. Crude rates of BP treatment and control were 50.81% and 8.70%, respectively. The authors found that treatment rates of HTN and DM and control rates of BP and FPG showed a gradually increasing trend with increased age. Among patients with DM and HTN, the likelihood of treatment for HTN and DM was significantly increased among participants who were older, non‐Mongolian, male, obese, smokers, and those with previous cardiovascular disease. The authors found that control of BP, FPG, and low‐density lipoprotein cholesterol was far from optimal among study participants. Medical and health departments in Inner Mongolia should take appropriate measures to reduce the burden of DM and HTN in the population, such as by promoting and improving the quality of HTN and DM treatment to achieve control goals and reduce the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

There are currently extensive discussions on the remarkable development of the convention industry and the impact on local economies made by convention visitors, but there is limited research on the human resources expertise which is crucial for sustainable and qualitative development in the field of convention. This study aims to examine differences in core competencies based on the type of job characteristics model of convention project managers. Based on the existing literature, quantitative and qualitative mixed-methods design was used. 12 semi-structured interviews were conducted with professionals to define measurements, especially core competencies. Job characteristics and core competencies were identified with a survey of 392 convention PM. By using a cluster analysis, it investigated the differences in perception of competencies according to the job characteristics model. As a result of the analysis, five job characteristics were verified, and core competencies that were not organized were classified. In addition, it was confirmed through the analysis that there is a difference in perception of core competencies according to job characteristics. Based on the results, this study stresses the importance of the qualitative and sustainable development of the convention industry. Theoretical and practical implications were provided to enhance core competencies according to job characteristics for sustainable growth of convention project managers. [ABSTRACT FROM AUTHOR]

Recent interest in the application of mid-infrared (mid-IR) lasers has made the generation of ~3 µm ultrafast pulses a hot topic. Recently, the generation of femtosecond-scale pulses in Er3+-doped fluoride fiber lasers has been realized by nonlinear polarization rotation (NPR). However, a numerical study on these fiber lasers has not been reported yet. In this work, the output properties of the NPR passively mode-locked Er3+-doped fluoride fiber ring laser in ~3 µm have been numerically investigated based on the coupled Ginzburg–Landu equation. The simulation results indicate that stable uniform solitons (0.75 nJ) with the pulse duration of femtosecond-scale can be generated from this fiber laser. This numerical investigation can provide some reference for developing the high energy femtosecond soliton fiber lasers in the mid-IR. [ABSTRACT FROM AUTHOR]

The dried rattan stem of Tinospora sinensis (Lour.) Merr. is valued for its efficacy of clearing heat and removing toxicity, calming and soothing the nerves. It is widely used in Tibetan medicine for the treatment of rheumatic and aging diseases. Studies have confirmed its anti-inflammatory and ameliorating effects on Alzheimer's disease; however, the anti-neuroinflammation efficacy and mechanism remain unclear. This study aimed to explore the anti-neuroinflammation efficacy, major effective ingredients, and potential mechanism of extract of Tinosporae sinenisis (TIS). UPLC-Q-TOF/MS was used to identify the compounds of TIS and the plasma components of rats after gastric administration of TIS. C57BL/6 J mice were continuously intraperitoneally injected with lipopolysaccharide (LPS) (250 μg/kg) for 14 d to establish a neuroinflammation model. The effects of TIS (4.5 g/kg, 9 g/kg) on the learning and memory abilities in mice with neuroinflammation was evaluated using spontaneous activity, novel object recognition, and Morris water maze tests. Pathological changes in the hippocampus were observed using hematoxylin and eosin staining. Gene and protein levels of inflammatory factors in the brain were detected using qRT-PCR and ELISA kits. Iba-1 levels in the brain were detected using immunofluorescence to assess the degree of microglial activation. Network pharmacology, based on the components absorbed into plasma of TIS, was used to predict potential targets and pathways. Proteomics was used to study the differentially expressed proteins and related pathways in the brain tissue of mice with neuroinflammation. Finally, correlation analysis was performed on the results of network pharmacology and proteomics, and proteins related the anti-neuroinflammatory effect of TIS were detected by western blot. A total of 39 compounds were identified in TIS: genipingentiobioside, isocorydin, reticuline, (−)-argemonine, tinosineside A, tinosinenside A, and costunolide were absorbed into the plasma. After continuous intraperitoneal injection of LPS into C57BL/6 J mice, microglia in the brain tissue were activated and the gene and protein levels of IL-1β, TNF-α, IL-6, and iNOS were increased in the brain tissue, suggesting that the neuroinflammation model was successfully established. TIS reduced Iba-1 levels and gene expression and protein levels of inflammatory factors in the brain of mice with neuroinflammation. Furthermore, TIS improved the pathological changes in the hippocampus and learning and memory abilities caused by neuroinflammation. Network pharmacology has predicted that TNF, IL-1β, and IκBKB are closely related to neuroinflammation. Proteomics identified key differentially expressed proteins, including TNF, NF-κB2, NF-κBIA, and TLR4. Toll-like receptor (TLR), NF-κB, and NOD-like receptor (NLR) signaling pathways are involved in neuroinflammation-related pathways. Correlation analysis revealed TLR, TNF and NLR signaling pathways were closely related to the anti-neuroinflammatory effects of TIS. We observed that TIS alleviated neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 pathway. Thirty-nine compounds were identified from TIS, among which seven were absorbed into the plasma as prototype components. TIS alleviated LPS-induced neuroinflammation in mice, and its mechanism was related to inhibition of TLR4/NF-κB/NLRP3 signaling pathway. [Display omitted] • Seven components of Extract of Tinospora sinensis (TIS) were absorbed into plasma after administration. • The mechanism of TIS was studied by plasma component network pharmacology combined with proteomics. • TIS alleviates neuroinflammation in LPS-induced mice by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO 4 H/CPs-SO 4 H-OH), 14 chlorinated benzene sulfates (CBs-SO 4 H), and 19 CP sulfite esters (CPs-SO 3 /CPs-S 2 O 6 ), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph 4 PCl), respectively, were performed to determine the ionization forms ([M + Cl] - or [M - H] - ) of CPs-S. The presence of fragment ions (SO 4 H - , SO 3 - , SO 2 Cl - , and HSO 3 - ) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

Introduction: Metagenomic next-generation sequencing (mNGS) has emerged as a powerful tool for rapid pathogen identification in clinical practice. However, the parameters used to interpret mNGS data, such as read count, genus rank, and coverage, lack explicit performance evaluation. In this study, the developed indicators as well as novel parameters were assessed for their performance in bacterium detection. Methods: We developed several relevant parameters, including 10M normalized reads, double-discard reads, Genus Rank Ratio, King Genus Rank Ratio, Genus Rank Ratio*Genus Rank, and King Genus Rank Ratio*Genus Rank. These parameters, together with frequently used read indicators including raw reads, reads per million mapped reads (RPM), transcript per kilobase per million mapped reads (TPM), Genus Rank, and coverage were analyzed for their diagnostic efficiency in bronchoalveolar lavage fluid (BALF), a common source for detecting eight bacterium pathogens: Acinetobacter baumannii , Klebsiella pneumoniae , Streptococcus pneumoniae , Staphylococcus aureus , Hemophilus influenzae , Stenotrophomonas maltophilia , Pseudomonas aeruginosa , and Aspergillus fumigatus. Results: The results demonstrated that these indicators exhibited good diagnostic efficacy for the eight pathogens. The AUC values of all indicators were almost greater than 0.9, and the corresponding sensitivity and specificity values were almost greater than 0.8, excepted coverage. The negative predictive value of all indicators was greater than 0.9. The results showed that the use of double-discarded reads, Genus Rank Ratio*Genus Rank, and King Genus Rank Ratio*Genus Rank exhibited better diagnostic efficiency than that of raw reads, RPM, TPM, and in Genus Rank. These parameters can serve as a reference for interpreting mNGS data of BALF. Moreover, precision filters integrating our novel parameters were built to detect the eight bacterium pathogens in BALF samples through machine learning. Summary: In this study, we developed a set of novel parameters for pathogen identification in clinical mNGS based on reads and ranking. These parameters were found to be more effective in diagnosing pathogens than traditional approaches. The findings provide valuable insights for improving the interpretation of mNGS reports in clinical settings, specifically in BALF analysis., Competing Interests: Authors ZL, WQ, HuH, WY, and YL were employed by Guangzhou Darui Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Yan, Huang, Ai, Yu, Zhong, Chen, Liang, Qiu, Huang, Yan, Liang, Chen and Wang.)

We performed a retrospective chart review of 245 patients with papillary thyroid microcarcinoma (PTMC) to define factors linked to central lymph node metastasis and thus prognosis. Univariate and multivariate analyses showed that being male ( p < 0.001), age <45 years at diagnosis ( p = 0.045), maximum tumor size > 5 mm ( p = 0.030), multifocal tumor ( p = 0.040) and tumor envelope invasion ( p < 0.001) were all independent risk factors for central compartment lymph node metastasis. Unifocal lesions at the thyroid gland's upper pole, middle and lower pole, had lymph node metastasis rates of 22.7%, 14.0% and 35.0%, respectively ( p = 0.048). The rate of central lymph node metastasis was much higher when there was bilateral thyroid involvement than with multifocal unilateral lesions (58.6% vs 37.5%; p = 0.040). These results suggest that for patients at low risk of central lymph node metastasis, unilateral thyroid lobe and isthmus resection is sufficient. However, for patients at high risk of central lymph node metastasis, central lymph node dissection increases the likelihood of complete tumor excision., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Calcification of octacalcium phosphate [Ca8H2(PO4)6 x 5H2O, OCP] on differently packaged "Ultem" and "Surefold" intraocular implant lens surfaces has been studied in vitro in solutions supersaturated with respect to OCP at pH = 7.10 and 37 degrees C. No mineral deposition was observed on the lenses packaged in Ultem vials even after treatment with behenic acid, one of the fatty acids identified on explanted lenses. Following treatment with behenic acid, nucleation of OCP occurred on the lenses from Surefold vials, which incorporate silicone gaskets; induction periods preceding calcification were about 6 h. No mineralization was found on the lenses in vials with other gasket materials, including polytetrafluoroethylene, fluorocarbon elastomer, and polypropylene. The results of this study indicate that both silicone and fatty acids such as behenic acid play important roles in inducing the in vivo calcification of OCP on IOL lenses; all of the lens treatment steps were necessary for nucleation induction.