Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Dynamic Near-Infrared Circularly Polarized Luminescence Encoded by Transient Supramolecular Chiral Assemblies.

Circularly polarized luminescence (CPL) is promising for applications in many fields. However, most systems involving CPL are within the visible range; near‒infrared (NIR) CPL‒active materials, especially those that exhibit high glum values and can be controlled spatially and temporally, are rare. Herein, dynamic NIR‒CPL with a glum value of 2.5[[EQUATION]]10‒2 was achieved through supramolecular coassembly and energy transfer strategies. The chiral assemblies formed by the coassembly between adenosine triphosphate (ATP) and a pyrene derivative exhibit a red CPL signal (glum of 10‒3). The further introduction of sulfo‒cyanine5 resulted in a cooperative energy transfer process, which not only aroused the NIR CPL but also increased the glum value to 10‒2. Temporal control of these chiral assemblies was realized by introducing alkaline phosphatase to fabricate a biomimetic enzyme‒catalyzed network, allowing the dynamic NIR CPL signal to be turned on. Based on these enzyme-regulated temporally controllable dynamic CPL-active chiral assemblies, a multilevel information encryption system was further developed. Our work provides a pioneering example for constructing dynamic NIR CPL materials holding the ability to perform temporal control via the supramolecular assembly strategy, which is expected to aid in the design of supramolecular complex systems that more closely resemble natural biological systems.

Critical role of slags in pitting corrosion of additively manufactured stainless steel in simulated seawater.

Pitting corrosion in seawater is one of the most difficult forms of corrosion to identify and control. A workhorse material for marine applications, 316L stainless steel (316L SS) is known to balance resistance to pitting with good mechanical properties. The advent of additive manufacturing (AM), particularly laser powder bed fusion (LPBF), has prompted numerous microstructural and mechanical investigations of LPBF 316L SS; however, the origins of pitting corrosion on as-built surfaces is unknown, despite their utmost importance for certification of LPBF 316L SS prior to fielding. Here, we show that Mn-rich silicate slags are responsible for pitting of the as-built LPBF material in sodium chloride due to their introduction of deleterious defects such as cracks or surface oxide heterogeneities. In addition, we explain how slags are formed in the liquid metal and deposited at the as-built surfaces using high-fidelity melt pool simulations. Our work uncovers how LPBF changes surface oxides due to rapid solidification and high-temperature oxidation, leading to fundamentally different pitting corrosion mechanisms.

Efficacy of prednisone combined with mycophenolate mofetil for immunoglobulin A nephropathy with moderate-to-severe renal dysfunction.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis. Currently, IgAN is one of the main causes of chronic renal failure in China; its prognosis varies greatly between patients, with renal function at the time of diagnosis and prognosis being strongly correlated. Mycophenolate mofetil (MMF) is a drug with a good immunomodulatory effect and is commonly used clinically. However, its effects in IgAN have not yet been clearly demonstrated. Therefore, herein, we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment. AIM: To evaluate the effectiveness and safety of prednisone and MMF in treating IgAN with moderate-to-severe renal dysfunction. METHODS: Between January 2011 and December 2020, 200 patients with moderate-to-severe IgAN were included in this study, all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University. All patients underwent a renal puncture biopsy, which revealed primary IgAN with a glomerular filtration rate (GFR) of 30-60 mL/min. The patients were divided into a glucocorticoid therapy group (GTG) and an immunosuppressive therapy group (ITG) according to the different treatment regimens, with 100 patients in each group. Based on general treatments, such as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers, patients in the GTG were administered prednisone 0.5-0.8 mg/ (kg·d-1) for 4-8 wk, which was reduced by 5 mg every two weeks until the maintenance(30 mg/d) dose was reached and maintained for 12 mo. In the ITG, MMF was administered at 1.0 g/d for 6-12 mo, followed by a maintenance dosage of 0.5 g/d for 12 mo. Age, sex, blood pressure, 24-h urinary egg white measurement, serum creatinine (Scr), blood uric acid, blood albumin, blood potassium (K), hemoglobin, GFR, alanine aminotransferase, total cholesterol (T-CHO), fasting blood glucose, and body mass index were recorded. The 24-h urinary protein, Scr, and GFR levels were recorded 3, 6, 9, and 12 mo after treatment. Follow-up data were also collected. RESULTS: No discernible differences existed between the two groups in terms of age, sex, blood pressure, creatinine, 24-h urinary protein level, GFR, or other biochemical indicators at the time of enrollment. Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function. Nine months after treatment, the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG. By the 12th month of treatment, the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month. In addition, the overall response rate in the ITG was significantly higher than that in the GTG. The occurrence of side effects did not vary significantly between the two regimens; however, endpoint events were significantly more common in the GTG than in the ITG. The follow-up time for the GTG was noticeably lower than that for the ITG. CONCLUSION: Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.

Global research status analysis of the association between aortic aneurysm and inflammation: a bibliometric analysis from 1999 to 2023.

Background: Aortic aneurysm is a chronic arterial disease that can lead to aortic rupture, causing severe complications and life-threatening risks for patients, and it is one of the common causes of death among the elderly. Increasing evidence suggests that inflammation plays an important role in the progression of aortic aneurysm. However, there is a lack of literature-based quantitative analysis in this field. Methods: Up to March 30, 2023, we collected 3,993 articles related to aortic aneurysm and inflammation from the Web of Science Core Collection (WoSCC) database for bibliometric analysis. The collected literature data were subjected to visual analysis of regional distribution, institutions, authors, keywords, and other information using tools such as CiteSpace, VOSviewer, the R package "bibliometric," and online platforms. Results: The number of publications in this research field has been steadily increasing each year, with the United States and China being the main contributing countries. Harvard University in the United States emerged as the most active and influential research institution in this field. Jonathan Golledge and Peter Libby were identified as the authors with the highest publication output and academic impact, respectively. Researchers in this field tend to publish their findings in influential journals such as the Journal of Vascular Surgery and Arteriosclerosis Thrombosis and Vascular Biology. "Abdominal aortic aneurysm," "giant cell arteritis," "arterial stiffness," and "smooth muscle cells" were identified as the hottest topics in the field of aortic aneurysm and inflammation. In terms of keyword co-occurrence analysis, "Clinical relevant studies of AA" (red), "Inflammatory activation" (green), "Inflammatory mechanisms related to pathogenesis" (dark blue), "Cytokines" (yellow), "Risk factors" (purple), and "Pathological changes in vascular wall" (cyan) formed the major research framework in this field. "Inflammation-related pathogenesis" and "inflammation activation" have emerged as recent hot research directions, with "monocytes," "progression," and "proliferation" being the prominent topics. Conclusion: This study provides a comprehensive analysis of the knowledge network framework and research hotspots in the field of aortic aneurysm and inflammation through a literature-based quantitative approach. It offers valuable insights to guide scholars in identifying meaningful research directions in this field.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study.

BACKGROUND: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. METHODS: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. RESULTS: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation. 1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. CONCLUSIONS: The effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

microRNA-130b-3p Attenuates Septic Cardiomyopathy by Regulating the AMPK/mTOR Signaling Pathways and Directly Targeting ACSL4 against Ferroptosis.

Ferroptosis is a newly identified type of programmed cell death that has been shown to contribute to the progression of septic cardiomyopathy. Although the role of miR-130b-3p as an oncogene that accelerates cancer progression by suppressing ferroptosis has been demonstrated, its role in the regulation of ferroptosis and cardiac injury in Lipopolysaccharide (LPS)-induced cardiomyopathy has not been fully clarified. In this study, we demonstrated that miR-130b-3p remarkably improved cardiac function and ameliorated morphological damage to heart tissue in LPS-induced mice. miR-130b-3p also improved cell viability and mitochondrial function and reduced the production of lipid ROS and ferroptosis in LPS-treated H9c2 cells. In addition, miR-130b-3p significantly upregulated GPX4 expression and suppressed ACSL4 activity in LPS-induced mouse heart tissue and H9c2 cells. Mechanistically, we used database analysis to locate miR-130b-3p and confirmed its inhibitory effects on the ferroptosis-related gene ACSL4 and autophagy-related gene PRKAA1 using a dual-luciferase reporter assay. In addition, we found that miR-130b-3p inhibited the activation of autophagy by downregulating the expression of the AMPK/mTOR signaling pathway. Meanwhile, our results show that RAPA (an autophagy activator) reverses the protective effect of miR-130b-3p mimic against LPS-induced ferroptosis, while CQ (an autophagy inhibitor) plays a facilitative role, suggesting that miR-130b-3p plays an important role in the development of ferroptosis by regulating autophagy in vitro. The findings reveal a novel function of miR-130b-3p in attenuating ferroptosis in cardiomyocytes, providing a new therapeutic target for ameliorating septic cardiomyopathy injury.

Global trends in research of acute type a aortic dissection: A bibliometric analysis from 2002 to 2022.

Background: Acute type A aortic dissection (ATAAD) is life-threatening and needs urgent and highly invasive surgery. So far, there is no comprehensive review of the status quo of ATAAD studies. Therefore, this study aimed to quantify and identify the global trends of ATAAD research over the past two decades through bibliometric analysis and to provide reference for clinical practice, research funding allocation, and decision-making. Methods: The original research articles and reviews related to ATAAD research were downloaded from the Web of Science Core Collection on March 19, 2023. CiteSpace (6.2.1) and VOSviewer (1.6.18) were used for bibliometric analysis of the number of publications by each country, institution, and authors and the establishment of knowledge maps. The raw data collected were examined using the Online Analysis Platform of Bibliometric to assess the collaboration of countries in the field. Results: The number of documents on ATAAD research increased continuously. A total of 1,943 publications published from 2002 to 2022 from 66 countries/regions were identified: 637 (32.78%) were conducted in China and 360 (18.53%) in the United States; 152 (cited frequency 941) were conducted by Capital Medical University and 107 (cited frequency 370) by Fujian Medical University. The Journal of Cardiac Surgery was the most frequently published journal (143 publications, cited frequency 695). The highest citation and co-cited journal was the Annals of Thoracic Surgery (cited frequency 3,888, co-cited frequency 6,224). We identified 8,050 authors among which Lizhong Sun (61 publications, cited frequency 721) had the largest number of publications, and Nienaber Christoph A (cited frequency 1,536, co-cited frequency 392) was co-cited most often. Meanwhile, the most common keywords were acute type A aortic dissection (occurrences, 1,211), surgery (occurrences, 657), repair (occurrences, 404), and management (occurrences, 386). The earliest and latest used keywords were "axillary artery" (average publication year: 2011.23) and "inflammation" (average publication year: 2019.09), respectively. The keyword "surgical treatment" (strength 12.31) and the co-cited reference "Evangelista A, 2018, Circulation" (strength 28.55) had the highest citation bursts. The keywords "impact" and "acute kidney injury" remained high citation bursts. The co-cited references with the largest and smallest size clusters were "cerebral protection" (#0, size = 126) and "pregnancy" (#12, size = 11). The reference "Hagan PG, 2000, JAMA" (cited frequency, 350) had the highest co-citations. Conclusions: The bibliometric and visualized analysis generated objective evidence for a comprehensive understanding and evaluation of ATAAD research.

A prognostic gene signature for gastric cancer and the immune infiltration-associated mechanism underlying the signature gene, PLG.

BACKGROUND: Globally, gastric cancer (GC) is a common and lethal solid malignant tumor. Identifying the molecular signature and its functions can provide mechanistic insights into GC development and new methods for targeted therapy. METHODS: Differentially expressed genes (DEGs) and prognostic genes (from univariate Cox regression analysis) were overlapped to obtain prognostic DEGs. Subsequently, molecular modules and the functions of these prognostic DEGs were identified by Metascape and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/Gene Set Enrichment Analysis (GSEA) enrichment analyses, respectively. Protein-protein interaction (PPI) networks of up- and down-regulated prognostic DEGs in GC were analyzed using the MCC algorithm of the Cytohubba plug-in in Cytoscape. The prognostic gene signature was defined on hub genes of the PPI networks by least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Furthermore, the expressional level of PLG in our clinical GC samples was validated by quantitative PCR (qPCR), western blotting, and immunohistochemistry (IHC). Subsequently, the PLG expression-correlation analysis was performed to assess the role of PLG in GC progression. Immune infiltration analysis was performed by single-sample gene set enrichment analysis (ssGSEA) to assess the inhibitory effect of PLG on immune infiltration. RESULTS: Firstly, Up- and down-regulated prognostic DEGs and hub genes in protein-protein interaction (PPI) networks in GC were identified. A prognostic five-gene signature (i.e., PLG, SPARC, FGB, SERPINE1, and KLHL41) was identified. Among the five genes, the relationship between plasminogen (PLG) and GC remains largely unclear. Moreover, the functions of PLG-correlated genes in GC, like 'fibrinolysis', 'hemostasis', 'ion channel complex', and 'transporter complex' were identified. In addition, PLG expression correlated negatively with the infiltration of almost all immune cell types. Interestingly, the expression of PLG was significantly and highly correlated with that of CD160, an immune checkpoint inhibitor. CONCLUSION: Our findings defined a new five-gene signature for predicting GC prognosis, but more validation is required to assess the effects and mechanism of the five genes, especially PLG, for the development of new GC therapies.

Effect of Hydrophobic Chain Length in Amphiphilic Chitosan Conjugates on Intracellular Drug Delivery and Smart Drug Release of Redox-Responsive Micelle.

Three redox-sensitive nanocarriers were rationally designed based on amphiphilic low molecular weight chitosan-cystamine-octylamine/dodecylamin/cetylamine (LC-Cys-OA, LC-Cys-DA, LC-Cys-CA) conjugates containing disulfide linkage for maximizing therapeutic effect by regulating hydrophobic interaction. The resultant spherical micelles had the characteristics of low CMC, suitable size, excellent biosafety and desired stability. The drug-loaded micelles were fabricated by embedding doxorubicin (Dox) into the hydrophobic cores. The effect of hydrophobic chain lengths of amphiphilic conjugates on encapsulation capacity, redox sensitivity, trigger-release behavior, cellular uptake efficacy, antitumor effect and antimigratory activity of Dox-loaded micelles was systematically investigated. Studies found that Dox-loaded LC-Cys-CA micelle had superior loading capacity and enhanced redox sensitivity compared with the other two micelles. Release assay indicated that the three Dox-loaded micelles maintained sufficiently stability in normal blood circulation but rapidly disintegrated in tumor cells. More importantly, the LC-Cys-CA micelle with a longer hydrophobic chain length exhibited a higher accumulative Dox release percentage than the other two micelles. Additionally, an increase in hydrophobic chain lengths of amphiphilic conjugates improved cellular uptake efficiency, antitumor effect and antimigration activity of Dox-loaded micelles, which could be explained by enhanced loading ability and redox sensitivity. Our research was expected to provide a viable platform for achieving a desired therapeutic efficacy via the alteration of hydrophobic interaction.

Clinical performance evaluation of O-Ring Halcyon Linac: A real-world study.

BACKGROUND: Radiation therapy, especially the development of linear accelerators, plays a key role in cancer management. The fast-rotating coplanar O-ring Halcyon Linac has demonstrated many advantages. The previous literature has mainly focused on the machine parameters and plan quality of Halcyon, with a lack of relevant research on its clinical application. AIM: To evaluate the clinical performance of the O-ring Halcyon treatment system in a real-world application setting. METHODS: Data from sixty-one patients who were treated with the Halcyon system throughout the entire radiotherapy process in Peking Union Medical College Hospital between August 2019 and September 2020 were retrospectively reviewed. We evaluated the target tumour response to radiotherapy and irradiation toxicity from 1 to 3 mo after treatment. Dosimetric verification of Halcyon plans was performed using a quality assurance procedure, including portal dosimetry, ArcCHECK and point dose measurements for verification of the system delivery accuracy. RESULTS: Of the 61 patients in the five groups, 16, 12, 7 and 26 patients had complete response, partial response, progressive disease and stable disease, respectively. No increase in the irradiated target tumour volume was observed when separately evaluating the local response. Regarding irradiation toxicity, no radiation-induced deaths were observed. Thirty-eight percent (23/61 patients) had no radiation toxicity after radiotherapy, 56% (34/61 patients) experienced radiation toxicity that resolved after treatment, and 6% (4/61 patients) had irreversible adverse reactions. The average gamma passing rates with a 2% dose difference and 2-mm distance to agreement for IMRT/VMAT/SRT plans were ArcCHECK at 96.4% and portal dosimetry at 96.7%, respectively. All of the validated clinical plans were within 3% for point dose measurements, and Halcyon's ArcCHECK demonstrated a high pass rate of 99.1% ± 1.1% for clinical gamma passing criteria of 3%/3 mm. CONCLUSION: The O-ring Halcyon Linac could achieve a better therapeutic effect on the target volume by providing accurate treatment delivery plans with tolerable irradiation toxicity.

Trend Analysis of the Mortality Rates of the Top Three Causes of Death Among Chinese Residents from 2003 to 2019.

Objective: To delineate the mortality trends of malignant tumors, heart disease and cerebrovascular disease in China. Methods: The crude mortality from 2003 to 2019 was derived from the China Health Statistical Yearbook, and the mortality rates were analyzed through joinpoint regression supplemented by descriptive statistics and χ2 tests. Results: The fitting model of age-standardized mortality due to malignant tumors showed three joinpoints. The APCs from 2003 to 2005, 2005-2008, 2008-2012 and 2012-2019 were -11.00%, 9.63%, -4.67% and -1.40%, respectively, and the AAPC was -1.54%. The mortality rate of cerebrovascular disease consistently decreased (APC = AAPC = -0.98%). In the subgroup analyses, significant differences were observed between sexes and regions. The mortality rate of heart disease among rural females exhibited an upward trend (APC = AAPC = 2.33%). Older adults aged over 75 years had the highest mortality rates and the most drastic change. Conclusion: The three diseases had variable change trends. The government should focus more on policies that promote the equalization of basic public health services. Continuous education on heart disease, which includes not only beneficial behaviors but also knowledge of first aid, should be strengthened for rural females.

A Computational Platform Integrating a Mechanistic Model of Crohn's Disease for Predicting Temporal Progression of Mucosal Damage and Healing.

INTRODUCTION: Physicians are often required to make treatment decisions for patients with Crohn's disease on the basis of limited objective information about the state of the patient's gastrointestinal tissue while aiming to achieve mucosal healing. Tools to predict changes in mucosal health with treatment are needed. We evaluated a computational approach integrating a mechanistic model of Crohn's disease with a responder classifier to predict temporal changes in mucosal health. METHODS: A hybrid mechanistic-statistical platform was developed to predict biomarker and tissue health time courses in patients with Crohn's disease. Eligible patients from the VERSIFY study (n = 69) were classified into archetypical response cohorts using a decision tree based on early treatment data and baseline characteristics. A virtual patient matching algorithm assigned a digital twin to each patient from their corresponding response cohort. The digital twin was used to forecast response to treatment using the mechanistic model. RESULTS: The responder classifier predicted endoscopic remission and mucosal healing for treatment with vedolizumab over 26 weeks, with overall sensitivities of 80% and 75% and overall specificities of 69% and 70%, respectively. Predictions for changes in tissue damage over time in the validation set (n = 31), a measure of the overall performance of the platform, were considered good (at least 70% of data points matched), fair (at least 50%), and poor (less than 50%) for 71%, 23%, and 6% of patients, respectively. CONCLUSION: Hybrid computational tools including mechanistic components represent a promising form of decision support that can predict outcomes and patient progress in Crohn's disease.

Fine and ultrafine airborne PM influence inflammation response of young adults and toxicological responses in vitro.

Little evidence is available regarding the impact of different sizes of inhaled particulate matter (PM) on inflammatory responses in healthy young adults in connection with toxicological responses. We conducted a five-time repeated measurement panel study on 88 healthy young college students in Guangzhou, China from December 2017 to January 2018. Blood samples were collected from each participant and tested for tumor necrosis factor alpha (TNF-α) levels every week for 5 consecutive weeks. Mass concentrations of ambient PM2.5, PM1, PM0.5 and number concentrations of ambient PM0.1 were measured. RAW 264.7 macrophages were exposed to PM (PM10-2.5, PM2.5-1, PM1-0.2, PM0.2) collected at the same time as the panel study. Cytotoxicity, oxidation and inflammatory parameters, cell cycle and genotoxicity were tested. Particles were characterized for their chemical composition. The trends of associations between PM2.5, PM1, PM0.5 and TNF-α level were consistent in lag 0 and 3 days, and the relative risk decreased as the particle size decreased. All the ambient air pollutants had the similar change trends in lag 1, 4 and 5 days. Similar results in RAW 264.7 macrophages were found; PM10-2.5 induced the greatest TNF-α and macrophage inflammatory protein 2 (MIP-2) productions and oxidative damage. PM1-0.2 and PM0.2 induced more significant dose-dependent increases of cell cycle and genotoxic response. In the component concentrations of PM samples, metal elements were PM10-2.5 > PM2.5-1 > PM0.2 ≥ PM1-0.2; ions and polycyclic aromatic hydrocarbons (PAHs) were PM0.2 > PM1-0.2 > PM2.5-1 > PM10-2.5. Our results suggested that exposure to all particle sizes was significantly associated with inflammation among healthy young adults and toxicological responses in RAW 264.7 macrophages. Different human and toxicological reactions caused by PM samples indicated the importance of investigating various particle sizes.

The E3 Ubiquitin Ligase Gene Sl1 Is Critical for Cadmium Tolerance in Solanum lycopersicum L.

Heavy metal cadmium (Cd) at high concentrations severely disturbs plant growth and development. The E3 ubiquitin ligase involved in protein degradation is critical for plant tolerance to abiotic stress, but the role of E3 ubiquitin ligases in Cd tolerance is largely unknown in tomato. Here, we characterized an E3 ubiquitin ligase gene Sl1, which was highly expressed in roots under Cd stress in our previous study. The subcellular localization of Sl1 revealed that it was located in plasma membranes. In vitro ubiquitination assays confirmed that Sl1 had E3 ubiquitin ligase activity. Knockout of the Sl1 gene by CRISPR/Cas9 genome editing technology reduced while its overexpression increased Cd tolerance as reflected by the changes in the actual quantum efficiency of PSII photochemistry (ΦPSII) and hydrogen peroxide (H2O2) accumulation. Cd-induced increased activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) were compromised in sl1 mutants but were enhanced in Sl1 overexpressing lines. Furthermore, the content of Cd in both shoots and roots increased in sl1 mutants while reduced in Sl1 overexpressing plants. Gene expression assays revealed that Sl1 regulated the transcript levels of heavy metal transport-related genes to inhibit Cd accumulation. These findings demonstrate that Sl1 plays a critical role in regulating Cd tolerance by relieving oxidative stress and resisting heavy metal transportation in tomato. The study provides a new understanding of the mechanism of plant tolerance to heavy metal stress.

Scalable Gas Diffusion Electrode Fabrication for Electrochemical CO2 Reduction Using Physical Vapor Deposition Methods.

Electrochemical CO2 reduction (ECR) promises the replacement of fossil fuels as the source of feedstock chemicals and seasonal storage of renewable energy. While much progress has been made in catalyst development and electrochemical reactor design, few studies have addressed the effect of catalyst integration on device performance. Using a microfluidic gas diffusion electrolyzer, we systematically studied the effect of thickness and the morphology of electron beam (EB) and magnetron-sputtered (MS) Cu catalyst coatings on ECR performance. We observed that EB-Cu outperforms MS-Cu in current density, selectivity, and energy efficiency, with 400 nm thick catalyst coatings performing the best. The superior performance of EB-Cu catalysts is assigned to their faceted surface morphology and sharper Cu/gas diffusion layer interface, which increases their hydrophobicity. Tests in a large-scale zero-gap electrolyzer yielded similar product selectivity distributions with an ethylene Faradaic efficiency of 39% at 200 mA/cm2, demonstrating the scalability for industrial ECR applications.

Exposure to second-hand smoke during early life and subsequent sleep problems in children: a population-based cross-sectional study.

BACKGROUND: Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children. METHODS: In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems. RESULTS: We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (ß = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses. CONCLUSIONS: Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6-18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life.

Development of a Nomogram Model for Treatment of Elderly Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

(1) Purpose: This study aims to explore risk-adapted treatment for elderly patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) according to their pretreatment risk stratification and the degree of comorbidity. (2) Methods: A total of 583 elderly LA-NPC patients diagnosed from January 2011 to January 2018 are retrospectively studied. A nomogram for disease-free survival (DFS) is constructed based on multivariate Cox regression analysis. The performance of the model is evaluated by using the area under the curve (AUC) of the receiver operating characteristic curve and Harrell concordance index (C-index). Then, the entire cohort is divided into different risk groups according to the nomogram cutoff value determined by X-tile analysis. The degree of comorbidities is assessed by the Charlson Comorbidity Index (CCI). Finally, survival rates are estimated and compared by the Kaplan-Meier method and the log-rank test. (3) Results: A nomogram for DFS is constructed with T/N classification, Epstein-Barr virus DNA and albumin. The nomogram shows well prognostic performance and significantly outperformed the tumor-node-metastasis staging system for estimating DFS (AUC, 0.710 vs. 0.607; C-index, 0.668 vs. 0.585; both p < 0.001). The high-risk group generated by nomogram has significantly poorer survival compared with the low-risk group (3-year DFS, 76.7% vs. 44.6%, p < 0.001). For high-risk patients with fewer comorbidities (CCI = 2), chemotherapy combined with radiotherapy is associated with significantly better survival (p < 0.05) than radiotherapy alone. (4) Conclusion: A prognostic nomogram for DFS is constructed with generating two risk groups. Combining risk stratification and the degree of comorbidities can guide risk-adapted treatment for elderly LA-NPC patients.

lncRNA LINC00355 Acts as a Novel Biomarker and Promotes Glioma Biological Activities via the Regulation of miR-1225/FNDC3B.

BACKGROUND: Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in glioma progression. Here, we aimed to explore the potential roles of a novel lncRNA, LINC00355, in glioma and to clarify the underlying mechanisms. METHODS: RT-PCR was used to examine the relative expressions of LINC00355 in glioma cell lines and specimen samples. The clinicopathological and prognostic significances of LINC00355 in glioma patients were statistically analyzed. To determine cell activities, CCK-8, clonogenic assays, flow cytometry, migration, and invasion assays were performed. Moreover, the potential mechanisms of LINC00355 were investigated by bioinformatics assays and luciferase reporter assays. RESULTS: LINC00355 expression was increased in glioma cell lines and specimens, and higher LINC00355 expression predicted advanced clinical progress and reduced overall survival and disease-free survival in glioma patients. Functionally, LINC00355 depletion promoted cell proliferation, invasion, and migration in glioma cells and induced apoptosis of glioma cells, whereas LINC00355 upregulation resulted in the opposite effects in vitro. Mechanistic assays revealed that LINC00355 as a sponge for miR-1225 repressed fibronectin type III domain-containing 3B (FNDC3B) expressions. CONCLUSION: Our findings revealed the tumor-promotive roles of LINC00355 in the progression of glioma, indicating that LINC00355 exhibited ceRNA functions via modulating miR-1225/FNDC3B axis.

E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-ß1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene.

The differentiation of cardiac fibroblast to myofibroblast is the key process of cardiac fibrosis. In the study, we aimed to determine the function of E2F Transcription Factor 1 (E2F1) in human cardiac fibroblasts (HCFs) differentiation, search for its downstream genes and elucidate the function of them in HCFs differentiation. As a result, we found that E2F1 was up-regulated in TGF-ß1-induced HCFs differentiation. Silencing the expression of E2F1 by siRNA in HCFs, we found that the expression of differentiation-related genes (Collagen-1, α-Smooth muscle actin, and Fibronectin-1) was significantly suppressed, combining with proliferation and migration assay, we determined that HCFs differentiation was decreased. Luciferase report assay and immunoprecipitation proved that the oncogene CCNE2 was a direct target gene of E2F1, overexpression of CCNE2 was found in differentiated HCFs, silencing the expression of CCNE2 by siRNA decreased HCFs differentiation. Our research suggested that E2F1 and its downstream target gene CCNE2 play a vital role in TGF-ß1-induced HCFs differentiation, thus E2F1 and CCNE2 may be a potential therapeutic target for cardiac fibrosis.