Effect of gum-chewing exercise on maintaining and improving oral function in older adults: A pilot randomized controlled trial.

Background/purpose: Gum chewing has been found to improve oral function. Nevertheless, few randomized controlled trials have investigated the effects of gum-chewing exercises on oral function in older adults. This study aimed to examine the effect of gum-chewing exercises on oral function in older adults. Materials and methods: This was a single-blind, randomized controlled trial, conducted from November 2021 to January 2022. A total of 130 participants were divided randomly into the intervention and control groups. The intervention group was told to chew experimental gums for one month, while the control group was instructed to chew experimental tablets for one month. Maximum bite force, occlusal contact areas, oral dryness, tongue pressure, tongue and lip functions (number of times each of the following syllables is pronounced per second:/pa/,/ta/, and/ka/), masticatory function, subjective masticatory function, and gum-chewing time were measured at baseline and one month following intervention to assess outcomes. Results: One month following the intervention, tongue pressure was significantly higher in the intervention group than in the control group (P = 0.027). In the within-group comparisons, maximum bite force (P < 0.001), unstimulated saliva flow (P < 0.001), tongue and lip functions (/pa/: P < 0.001;/ta/: P < 0.001;/ka/: P < 0.001), color scale value (P = 0.019), and ΔE value (P = 0.024) were significantly increased in the intervention group. Conclusion: The results suggest that gum-chewing exercises can improve oral functions in older adults, although additional increases in masticatory load may be necessary to establish a more effective oral function training method using gum-chewing exercises in older adults.

Effects of multiple firings on the translucency, crystalline phase, and mechanical strength of highly translucent zirconia.

This study aimed to clarify the effects of multiple firings on the translucency, crystal structure, and mechanical strength of highly translucent zirconia. Four types of highly translucent zirconia (LAVA Esthetic, LAVA Plus, KATANA Zirconia STML, and KATANA Zirconia HTML) were fired three times at three different temperatures, and the translucency, crystal structure, and flexural strength were evaluated before and after firing. The translucency was statistically compared using repeated-measures analysis of variance; the zirconia phase composition was assessed using X-ray diffraction followed by Rietveld analysis; and the biaxial flexural strength was assessed using Weibull analysis. The translucency of LAVA Esthetic and KATANA Zirconia HTML decreased significantly after firing, and the crystal composition of LAVA Plus and KATANA Zirconia HTML changed after multiple firings, whereas multiple firings did not affect the biaxial flexural strength of any samples. Thus, multiple firings may affect the optical properties of highly translucent zirconia.

Health benefits from the rapid reduction in ambient exposure to air pollutants after China's clean air actions: progress in efficacy and geographic equality.

Clean air actions (CAAs) in China have been linked to considerable benefits in public health. However, whether the beneficial effects of CAAs are equally distributed geographically is unknown. Using high-resolution maps of the distributions of major air pollutants (fine particulate matter [PM2.5] and ozone [O3]) and population, we aimed to track spatiotemporal changes in health impacts from, and geographic inequality embedded in, the reduced exposures to PM2.5 and O3 from 2013 to 2020. We used a method established by the Global Burden of Diseases Study. By analyzing the changes in loss of life expectancy (LLE) attributable to PM2.5 and O3, we calculated the gain of life expectancy (GLE) to quantify the health benefits of the air-quality improvement. Finally, we assessed the geographic inequality embedded in the GLE using the Gini index (GI). Based on risk assessments of PM2.5 and O3, during the first stage of CAAs (2013 to 2017), the mean GLE was 1.87 months. Half of the sum of the GLE was disproportionally distributed in about one quarter of the population exposed (GI 0.44). During the second stage of CAAs (2017 to 2020), the mean GLE increased to 3.94 months and geographic inequality decreased (GI 0.18). According to our assessments, CAAs were enhanced, from the first to second stages, in terms of not only preventing premature mortality but also ameliorating health inequalities. The enhancements were related to increased sensitivity to the health effects of air pollution and synergic control of PM2.5 and O3 levels. Our findings will contribute to optimizing future CAAs.

Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.

PURPOSE: Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes. EXPERIMENTAL DESIGN: Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model. RESULTS: PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden. CONCLUSIONS: The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.

Estimating birthweight reduction attributable to maternal ozone exposure in low- and middle-income countries.

The effect of O3 on birthweight in low- and middle-income countries (LMICs) remains unknown. A multicenter epidemiological study was conducted to evaluate the association between maternal peak-season O3 exposure and birthweight, using 697,148 singleton newborns obtained in 54 LMICs between 2003 and 2019. We estimated the birthweight reduction attributable to peak-season O3 exposure in 123 LMICs based on a nonlinear exposure-response function (ERF). With every 10-part per billion increment in O3 concentration, we found a reduction in birthweight of 19.9 g [95% confidence interval (CI): 14.8 to 24.9 g]. The nonlinear ERF had a monotonic decreasing curve, and no safe O3 exposure threshold was identified. The mean reduction in birthweight reduction attributable to O3 across the 123 LMICs was 43.8 g (95% CI: 30.5 to 54.3 g) in 2019. The reduction in O3-related birthweight was greatest in countries in South Asia, the Middle East, and North Africa. Effective O3 pollution control policies have the potential to substantially improve infant health.

Estimating the exposure-response function between long-term ozone exposure and under-5 mortality in 55 low-income and middle-income countries: a retrospective, multicentre, epidemiological study.

BACKGROUND: In 2021, WHO suggested new target concentration limits for long-term exposure to ambient ozone. However, the harmful effects of ozone on vulnerable children have not been sufficiently studied. We aimed to evaluate the association between long-term ozone exposure and mortality in children younger than 5 years (hereafter denoted under-5 mortality) in low-income and middle-income countries (LMICs) and to estimate this mortality burden for 97 LMICs. METHODS: By combining information from 128 Demographic and Health Surveys, we evaluated the association between the survival status of more than 1·2 million children younger than 5 years from 2457 sampling strata in 55 LMICs and the average peak-season ozone concentration during the life course, using a fixed-effects Cox model. A non-linear exposure-response function was developed by integrating the marginal effects of within-strata variation in exposure. We extrapolated the function obtained from the 55 LMICs to estimate the under-5 mortality burden attributable to ozone exposure in 97 LMICs, in which more than 95% of global deaths in this age group occur. FINDINGS: The fixed-effects model showed a robust association between ozone and under-5 mortality. According to the fully adjusted linear model, an increment of 10 ppb in the life-course average peak-season ozone concentration was associated with a 6·4% (95% CI 2·4-10·7) increase in the risk of under-5 mortality. The non-linear exposure-response function showed a sublinear curvature with a threshold, suggesting that the effect of ozone exposure was non-significant at concentrations lower than the first-stage interim target (100 µg/m3) recommended by WHO. Using this function, we estimate that, in 2010, long-term ozone exposure contributed to 153 361 (95% CI 17 077-276 768; 2·3% [0·3-4·1]) deaths of children younger than 5 years in 97 LMICs, which is equivalent to 56·8% of all ozone-related deaths in adults (269 785) in these countries. From 2003 to 2017, the ozone-related under-5 mortality burden decreased in most of the 97 LMICs. INTERPRETATION: Long-term exposure to ozone concentrations higher than the WHO first-stage interim target is a risk factor for under-5 mortality, and ozone exposure contributes substantially to mortality in this age group in LMICs. Increased efforts should be made to control ambient ozone pollution as this will lead to positive health benefits. FUNDING: Ministry of Science and Technology of the People's Republic of China and China National Natural Science Foundation.

Gestational age modifies the association between exposure to fine particles and fetal death: findings from a nationwide epidemiological study in the contiguous United States.

BACKGROUNDS: The vulnerability of fetuses differs at different developmental stages, in response to environmental stressors such as fine particulate matter (PM2.5), a ubiquitous air pollutant. Whether gestational age (GA) modifies the association between prenatal fine particulate matter (PM2.5) exposure and fetal death remains unclear. METHODS: We selected approximately 47.8 million eligible United States (US) livebirth and fetal death (defined as a termination at a GA of 20-43 weeks) records from 1989 to 2004. For each record, we took the level of prenatal exposure to PM2.5 as the average concentration in the mother's residential county during the entire gestational period, or a specific trimester (i.e., GA-specific exposure), according to well-established estimates of monthly levels across the contiguous US. First, we evaluated the associations between PM2.5 exposure and fetal death at a specific GA (i.e., GA-specific outcome) using five different logit models (unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models). Double robust model was selected as the main model due to its advantages in causal inference. Then, we conducted meta-analyses to pool the estimated GA-specific associations, and explored how the pooled estimates varied with GA. RESULTS: According to the meta-analysis, all models suggested gestational PM2.5 exposure was associated with fetal death. However, there was slight heterogeneity in the estimated effects, as different models revealed a range of 3.6-10.7% increase in the odds of fetal death per 5-µg/m3 increment of PM2.5. Each 5-µg/m3 increase in PM2.5 exposure during the entire gestation period significantly increased the odds of fetal death, by 8.1% (95% confidence interval [CI]: 5.1-11.2%). In terms of GA-specific outcomes, the odds of fetal death at a GA of 20-27, 28-36, or ≥ 37 weeks increased by 11.0% (5.9-16.4%), 5.2% (0.4-10.1%), and 8.3% (2.5-14.5%), respectively. In terms of GA-specific exposure, the odds of fetal death increased by 6.0% (3.9-8.2%), 4.1% (3.9-8.2%), and 4.3% (0.5-8.2%) with 5-µg/m3 increases in PM2.5 exposure during the first, second, and third trimester, respectively. The association had the largest effect size (odds ratio = 1.098, 95% CI: 1.061-1.137) between PM2.5 exposure during early gestation (i.e., first trimester) and early fetal death (i.e., 20-27 weeks). CONCLUSIONS: Prenatal exposure to PM2.5 was significantly associated with an increased risk of fetal death. The association was varied by gestational-age-specific exposures or outcomes, suggesting gestation age as a potential modifier on the effect of PM2.5. The fetus was most vulnerable during the early stage of development to death associated with PM2.5 exposure.

Does speed-sintering affect the optical and mechanical properties of yttria-stabilized zirconia? A systematic review and meta-analysis of in-vitro studies.

Zirconia restorations are increasingly popular in dental treatment. Yttria-stabilized zirconia (YSZ) needs to be sintered for clinical applications and novel speed-sintering protocols are being developed for chairside treatments. Whether the properties of speed-sintered YSZ meet clinical requirements, however, remains unclear. Therefore, we conducted a systematic review and meta-analysis on the influence of speed-sintering on the optical and mechanical properties of dental YSZ according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A literature search was conducted using PubMed, Embase, and Web of Science databases for relevant articles published between January 1, 2010 and February 28, 2022 in English, Chinese, or Japanese. After full-text evaluation and quality assessment, 26 articles were selected. Meta-analysis revealed that speed-sintering does not significantly affect the CIEDE2000-based translucency parameter, contrast ratio, three-point flexural strength, biaxial flexural strength, or fracture toughness of YSZ (p < 0.01) compared to conventional sintering. However, the CIELab-based translucency parameter of conventionally sintered YSZ is higher than that of speed-sintered YSZ. The descriptive analysis indicated that speed-sintering does not affect the hardness of YSZ compared to that of conventionally sintered YSZ. The results indicate that speed-sintering is suitable for preparing YSZ for dental restorations.

Long-term exposure to the components of fine particulate matters and disability after stroke: Findings from the China National Stroke Screening Surveys.

BACKGROUND: Long-term exposure to ambient fine particulate matter (PM2.5) has been linked to an increased risk of stroke. However, the effect of long-term exposure to PM2.5 and its major components on the functional disability of stroke patients remains unclear. METHODS: Based on China National Stroke Screening Survey data obtained from 2013 to 2019, we conducted a national multicenter longitudinal study of the associations of long-term exposure to PM2.5 and its components with the risk of disability after stroke in China. Post-stroke disability was assessed using the modified Rankin scale (mRS), which ranges from 0 to 5, with higher scores indicating greater disability. Long-term exposure to PM2.5 and its five components [sulfate (SO42-), nitrate (NO3-), ammonium salt (NH4+), organic matter (OM), and black carbon (BC)] was determined based on average concentrations during the 3 years preceding mRS administration according to the geographic coordinates of residential communities, using state-of-the-art estimates from multiple sources. We used a fixed-effect model to evaluate the associations between mRS scores and PM2.5 exposure, with adjustment for multiple covariates. RESULTS: Every 10 µg/m3 increase in PM2.5 was associated with a 0.019 (95% confidence interval, 0.003, 0.036) increase in mRS score, but the effect was not significant after adjusting for all covariates [0.016 (95% CI, -0.003, 0.032)]. For PM2.5 components, each IQR (7.92 µg/m3) increment in OM exposure was associated significantly with 0.062 (95% CI, 0.013, 0.111) increment in the mRS score. A significant association was observed between SO42- exposure and the mRS score [0.057 (95% CI, 0.003, 0.112), per IQR: 6.28 µg/m3]. However, no significant association was found with BC, NO3-, or NH4+ exposure. Furthermore, the nonlinear curves were observed for the exposure-response relationship between PM2.5 exposure and the mRS score. CONCLUSION: Greater PM2.5 exposure increased the mRS score and was associated with post-stroke functional disability among stroke patients. However, different chemical components showed unequal neurotoxic effects, and long-term exposure to OM and SO42- may play a more important role. SYNOPSIS: This study reports fine particulate matter at higher concentrations damages the functional ability among specific stroke patients, and PM2.5 components have different neurotoxicities.

Air pollution attenuated the benefits of physical activity on blood pressure: Evidence from a nationwide cross-sectional study.

INTRODUCTION: Although physical activity (PA) has multiple health benefits, the inhaled dose of fine particulate matter (PM2.5) during PA may increase. The trade-off between harmful effects of PM2.5 exposure and protective effects of PA remain unclear. Our study aims to examine the joint effects of PA and PM2.5 exposure on blood pressure (BP) in Chinese adults. METHODS: A total of 203,108 adults aged ≥ 18 years from the China Hypertension Survey study (2012-2015) were included. Individual-level PA was assessed as minutes of metabolic equivalent tasks per week (MET-min/week). The average weekly PM2.5 exposures were estimated by using a spatial resolution of 10 km, integrating multiple data sources, including monitoring values, satellite measurements and model simulations. BP was measured with a professional portable BP monitor. Generalized linear regressions were used to estimate joint associations and to further explore two-dimensional nonlinear associations. RESULTS: The median PA and 4-week PM2.5 average exposures were 3213.0 MET-min/week and 47.8 µg/m3, respectively. PA was negatively associated with BP, while PM2.5 exposure was positively with BP. The associations between PA and systolic BP were significantly modified by PM2.5 exposure (Pinteraction < 0.001). Compared with inactive participants under low PM2.5 exposure, those with highest level of PA under low PM2.5 exposure had a 0.90 (95 % CI: 0.53, 1.26) mmHg decrease in systolic BP, whereas they had a 0.48 (95 % CI: 0.07, 0.89) mmHg increase under high PM2.5 exposure. When PM2.5 exposure was approximately > 25 µg/m3, the joint exposure to total PA and PM2.5 was associated with an increase in systolic BP. CONCLUSIONS: The benefits of PA on BP were counteracted by high PM2.5 levels.

Associations between hemoglobin levels and source-specific exposure to ambient fine particles among children aged <5 years in low- and middle-income countries.

OBJECTIVE: We investigated associations between source-specific fine particulate matter (PM2.5) exposure and hemoglobin levels among children in low- and middle-income countries (LMICs). METHOD: 36,675 children aged < 5 years were collected in 11 LMICs during 2017. We associated child hemoglobin with 20 source-specific PM2.5, and calculated changes in hemoglobin that could be attributed to different PM2.5-mixture scenarios, established using real-world data from 88 Asian and African LMICs (AA-LMICs). RESULTS: Multiple-source analysis revealed PM2.5 produced by solvents (change in hemoglobin for 1-µg/m3 increment in PM2.5: -10.34 g/L, 95% CI -14.88 to -5.91), industrial coal combustion (-0.51 g/L, 95% CI -9.25 to -0.08), road transportation (-0.50 g/L, 95% CI -6.96 to -0.29), or waste handling and disposal (-0.34 g/L, 95% CI -4.38 to -0.23) was significantly associated with a decrease in hemoglobin level. Decreases in hemoglobin attributable to the PM2.5 mixtures were co-determined by the concentrations and their source profiles. The largest PM2.5-related change in hemoglobin was -10.25 g/L (95% CI -15.54 to -5.27) for a mean exposure of 61.01 µg/m3 in India. CONCLUSION: Association between PM2.5 and a decrease in hemoglobin was affected by variations in PM2.5 source profiles. Source-oriented interventions are warranted to protect children in LMICs from air pollution.

Integrated genome-centric metagenomic and metaproteomic analyses unravel the responses of the microbial community to ammonia stress.

Ammonia is a major inhibitor in anaerobic digestion of nitrogen-rich organic wastes. In this study, integrated genome-centric metagenomic and metaproteomic analyses were used to identify the key microorganisms and metabolic links causing instability by characterizing the process performance, microbial community, and metabolic responses of key microorganisms during endogenous ammonia accumulation. The identification of 89 metagenome-assembled genomes and analysis of their abundance profile in different operational phases permitted the identification of key taxa (Firmicutes and Proteobacteria) causing poor performance. Metabolic reconstruction indicated that the key taxa had the genetic potential to participate in the metabolism of C2C5 volatile fatty acids (VFAs). Further investigation suggested that during Phase I, the total ammonia nitrogen (TAN) level was maintained below 2000 mg N/L, and the reactor showed a high methane yield (478.30 ± 33.35 mL/g VS) and low VFAs concentration. When the TAN accumulated to > 2000 mg N/L, acid accumulation, mainly of acetate, began to occur, and the methane yield gradually decreased to 330.44 mL/g VS (Phase II). During this phase, the VFA degradation functions of the community were mainly mediated by Firmicutes. Approximately 61.54% of significant differentially expressed proteins (DEPs) related to acetate metabolism in Firmicutes were down-regulated, which led to an increase in acetate concentration to 4897.91 ± 1558.96 mg/L. However, the reactor performance showed spontaneous recovery without any interference (Phase III), during which Firmicutes gradually adapted to the high ammonia conditions. Approximately 75% of the significant DEPs related to acetate metabolism of Proteobacteria were also up-regulated in Phase III compared with Phase II; thus, VFA-related metabolic functions of the community were enhanced, which resulted in a decrease in the total VFA concentration to 195.39 mg/L. When the TAN increased above 4000 mg N/L, the system gradually showed acid accumulation dominated by propionate, accompanied by a second decrease in methane yield (Phase IV). During this phase, the number of up-regulated and down-regulated proteins related to acetate metabolism of Firmicutes and butyrate/valerate metabolism of Proteobacteria was comparable with that of Phase III, indicating that the metabolic functions related to acetate, butyrate, and valerate of the microbial community were not significantly affected. However, for propionate metabolism, the expression activity of fumarate hydratase from Firmicutes and Proteobacteria was severely inhibited by ammonia, as shown by down-regulation ratios of 63.64% and 85.71%, respectively. No protein with the same function that was not inhibited by ammonia could be detected, and the fumarate degradation function of the microbial community was severely damaged, leading to blocked propionate metabolism and irreversible deterioration of reactor performance. This study has provided a new perspective on the microecological mechanisms of ammonia inhibition.

Ambient fine particulate matter and allergic symptoms in the middle-aged and elderly population: results from the PIFCOPD study.

BACKGROUND: The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. METHODS: Participants (n = 10,142; age = 40-75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0-7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. RESULTS: A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0-7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. CONCLUSIONS: Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. TRIAL REGISTRATION: Clinical trial ID: NCT03532893 (29 Mar 2018).

Layer characteristics in strength-gradient multilayered yttria-stabilized zirconia.

OBJECTIVES: To investigate crystallography, translucency, phase content, microstructure and flexural strength of two commercial strength-gradient multilayered dental zirconia grades. METHODS: Two zirconia grades, i.e., KATANA Zirconia YML (Kuraray Noritake; referred to as "YML"; composed of four layers: enamel, body 1-3) and IPS e.max ZirCAD Prime (Ivoclar Vivadent; referred to as "Prime"; composed of three layers: enamel, transition, body) were investigated. Fully sintered square-shaped zirconia specimens from each layer were prepared. Microstructure, chemical composition, translucency parameter and zirconia-phase composition of each layer were characterized. Four-point and biaxial flexural strength of each layer was measured using fully sintered bar- and square-shaped specimens. Square-shaped samples were used to measure strength across the layers. RESULTS: For both multilayer zirconia grades, the 'enamel' layer contains a higher amount of c-ZrO2, which resulted in higher translucency but lower flexural strength than the 'body' layers. The characteristic 4-point flexural strength of the YML 'body 2' (923 MPa) and 'body 3' (911 MPa) layers, and of the Prime 'body' (989 MPa) layer were comparable and higher than for the YML 'enamel' (634 MPa), Prime 'transition' (693 MPa) and 'enamel' (535 MPa) layers. The biaxial strength of specimens sectioned across the layers was in-between that of the 'enamel' and 'body' layers for both YML and Prime, implying the interfaces did not form a weak link. SIGNIFICANCE: The difference in yttria content affects the phase composition and mechanical properties of each layer of the multi-layer zirconia. The strength-gradient approach allowed to integrate monoliths with irreconcilable properties.

Health Impacts of Long-Term NO2 Exposure and Inequalities among the Chinese Population from 2013 to 2020.

Nitrogen dioxide (NO2) is associated with mortality and many other adverse health outcomes. In 2021, the World Health Organization established a new NO2 air quality guideline (AQG) (annual average <10 µg/m3). However, the burden of diseases attributable to long-term NO2 exposure above the AQG is unknown in China. Nitrogen oxide is a major air pollutant in populous cities, which are disproportionately impacted by NO2; this represents a form of environmental inequality. We conducted a nationwide risk assessment of premature deaths attributable to long-term NO2 exposure from 2013 to 2020 based on the exposure-response relationship, high-resolution annual NO2 concentrations, and gridded population data (considering sex, age, and residence [urban vs rural]). We calculated health metrics including attributable deaths, years of life lost (YLL), and loss of life expectancy (LLE). Inequality in the distribution of attributable deaths and YLLs was evaluated by the Lorenz curve and Gini index. According to the health impact assessments, in 2013, long-term NO2 exposure contributed to 315,847 (95% confidence interval [CI]: 306,709-319,269) premature deaths, 7.90 (7.68-7.99) million YLLs, and an LLE of 0.51 (0.50-0.52) years. The high-risk subgroup (top 20%) accounted for 85.7% of all NO2-related deaths and 85.2% of YLLs, resulting in Gini index values of 0.81 and 0.67, respectively. From 2013 to 2020, the estimated health impact from NO2 exposure was significantly reduced, but inequality displayed a slightly increasing trend. Our study revealed a considerable burden of NO2-related deaths in China, which were disproportionally frequent in a small high-risk subgroup. Future clean air initiatives should focus not only on reducing the average level of NO2 exposure but also minimizing inequality.

Source sectors underlying PM2.5-related deaths among children under 5 years of age in 17 low- and middle-income countries.

BACKGROUND: Fine particulate matter (PM2.5) from different source sectors might differ in toxicity. However, data from large-scale studies on vulnerable children in low- and middle-income countries (LMICs) are insufficient. OBJECTIVE: To analyze the association of under-five death (U5D) with long-term exposure to PM2.5 from different sources. METHOD: We evaluated demographic and health survey data for 79,995 babies born in 2017 in 16 Asian and African LMICs (AA-LMICs) and a Latin America low-income country (i.e., Haiti). Long-term exposure to PM2.5 was assessed by a well-established product that attributed the annual concentration to 20 source sectors in 2017. The associations of survival during < 5-year periods with each source-specific concentration of PM2.5 were analyzed by Cox regression with multiple adjustments. We derived a multiple-pollutant ridge regression model to estimate the joint exposure-response function (JERF) between U5D and PM2.5 mixtures. To evaluate how sources affected PM2.5 toxicity, we evaluated the number of U5Ds attributable to PM2.5 based on the source profiles for 88 AA-LMICs. RESULTS: According to the single-pollutant model, the risk of U5D increased by 7% (95% confidence interval [CI]: 5%, 9%) for each 10 µg/m3 increment in total PM2.5 concentration. The model performance was lower than that of the multiple-pollutant ridge regression model. For each 10 µg/m3 increment in PM2.5, the excess risk of U5D ranged from 6% (95% CI: 4%, 9%) in Nepal to 10% (95% CI: 6%, 14%) in Mauritania. Based on the JERF, PM2.5 contributed to 817,647 (95% CI: 585,729, 1,050,439), i.e., 28.0% (95% CI: 20.1%, 35.8%), of all U5Ds across the 88 AA-LMICs. The PM2.5-related U5Ds were mostly attributable to PM2.5 produced by desert dust, followed by solid biofuel combustion and open fires. CONCLUSION: The average toxicity of PM2.5 varied by source profile, which should be taken into consideration when planning public health interventions. For some AA LMICs, natural sources of PM2.5 had the most significant health effects, and should not be ignored to ensure the protection of child health.

Development and characterization of new patient-derived xenograft (PDX) models of osteosarcoma with distinct metastatic capacities.

Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology, especially for highly aggressive cancers with a propensity for metastatic spread. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, a large panel of models is needed to fully elucidate key aspects of disease biology and to recapitulate clinically-relevant phenotypes. We describe the development and characterization of osteosarcoma patient-derived xenografts (PDXs) and a panel of PDX-derived cell lines. Matched patient samples, PDXs, and PDX-derived cell lines were comprehensively evaluated using whole genome sequencing and RNA sequencing. PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication (WGD) in a subset of cell lines. These cell line models were heterogeneous in their metastatic capacity and their tissue tropism as observed in both intravenous and orthotopic models. As proof-of-concept study, we used one of these models to test the preclinical effectiveness of a CDK inhibitor on the growth of metastatic tumors in an orthotopic amputation model. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden in this model.

Short-term effect of PM2.5 on stroke in susceptible populations: A case-crossover study.

BACKGROUND: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia. METHODS: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities. RESULTS: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF (n = 15,430), hypertension (n = 138,220), diabetes (n = 43,737), or hyperlipidemia (n = 16,855) were assessed separately. A 10 µg/m3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively. CONCLUSION: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

IAnimal: a cross-species omics knowledgebase for animals.

With the exponential growth of multi-omics data, its integration and utilization have brought unprecedented opportunities for the interpretation of gene regulation mechanisms and the comprehensive analyses of biological systems. IAnimal (https://ianimal.pro/), a cross-species, multi-omics knowledgebase, was developed to improve the utilization of massive public data and simplify the integration of multi-omics information to mine the genetic mechanisms of objective traits. Currently, IAnimal provides 61 191 individual omics data of genome (WGS), transcriptome (RNA-Seq), epigenome (ChIP-Seq, ATAC-Seq) and genome annotation information for 21 species, such as mice, pigs, cattle, chickens, and macaques. The scale of its total clean data has reached 846.46 TB. To better understand the biological significance of omics information, a deep learning model for IAnimal was built based on BioBERT and AutoNER to mine 'gene' and 'trait' entities from 2 794 237 abstracts, which has practical significance for comprehending how each omics layer regulates genes to affect traits. By means of user-friendly web interfaces, flexible data application programming interfaces, and abundant functional modules, IAnimal enables users to easily query, mine, and visualize characteristics in various omics, and to infer how genes play biological roles under the influence of various omics layers.