Air quality and cancer risk in the All of Us Research Program.

INTRODUCTION: The NIH All of Us Research Program has enrolled over 544,000 participants across the US with unprecedented racial/ethnic diversity, offering opportunities to investigate myriad exposures and diseases. This paper aims to investigate the association between PM2.5 exposure and cancer risks. MATERIALS AND METHODS: This work was performed on data from 409,876 All of Us Research Program participants using the All of Us Researcher Workbench. Cancer case ascertainment was performed using data from electronic health records and the self-reported Personal Medical History questionnaire. PM2.5 exposure was retrieved from NASA's Earth Observing System Data and Information Center and assigned using participants' 3-digit zip code prefixes. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Generalized additive models (GAMs) were used to investigate non-linear relationships. RESULTS: A total of 33,387 participants and 46,176 prevalent cancer cases were ascertained from participant EHR data, while 20,297 cases were ascertained from self-reported survey data from 18,133 participants; 9,502 cancer cases were captured in both the EHR and survey data. Average PM2.5 level from 2007 to 2016 was 8.90 µg/m3 (min 2.56, max 15.05). In analysis of cancer cases from EHR, an increased odds for breast cancer (OR 1.17, 95% CI 1.09-1.25), endometrial cancer (OR 1.33, 95% CI 1.09-1.62) and ovarian cancer (OR 1.20, 95% CI 1.01-1.42) in the 4th quartile of exposure compared to the 1st. In GAM, higher PM2.5 concentration was associated with increased odds for blood cancer, bone cancer, brain cancer, breast cancer, colon and rectum cancer, endocrine system cancer, lung cancer, pancreatic cancer, prostate cancer, and thyroid cancer. CONCLUSIONS: We found evidence of an association of PM2.5 with breast, ovarian, and endometrial cancers. There is little to no prior evidence in the literature on the impact of PM2.5 on risk of these cancers, warranting further investigation.

Efficient and scalable synthesis of 3,4-dihydroisoquinolin-1(2H)-ones by benzylic oxidation of tetrahydroisoquinoline derivatives using cerium ammonium nitrate (CAN).

An efficient and scalable method for the synthesis of 3,4-dihydroisoquinolin-1(2H)-ones through benzylic oxidation of tetrahydroisoquinoline derivatives using a catalytic amount of cerium ammonium nitrate (CAN) and a stoichiometric amount of NaBrO3 as oxidants was developed. The reaction is significantly influenced by the substituent groups on the phenyl ring. While electron-withdrawing groups on the phenyl ring can lower the reactivities of the substrates, electron-donating groups on the phenyl ring can dramatically promote the oxidation rate.

Efficient and stable emission of warm-white light from lead-free halide double perovskites.

Lighting accounts for one-fifth of global electricity consumption1. Single materials with efficient and stable white-light emission are ideal for lighting applications, but photon emission covering the entire visible spectrum is difficult to achieve using a single material. Metal halide perovskites have outstanding emission properties2,3; however, the best-performing materials of this type contain lead and have unsatisfactory stability. Here we report a lead-free double perovskite that exhibits efficient and stable white-light emission via self-trapped excitons that originate from the Jahn-Teller distortion of the AgCl6 octahedron in the excited state. By alloying sodium cations into Cs2AgInCl6, we break the dark transition (the inversion-symmetry-induced parity-forbidden transition) by manipulating the parity of the wavefunction of the self-trapped exciton and reduce the electronic dimensionality of the semiconductor4. This leads to an increase in photoluminescence efficiency by three orders of magnitude compared to pure Cs2AgInCl6. The optimally alloyed Cs2(Ag0.60Na0.40)InCl6 with 0.04 per cent bismuth doping emits warm-white light with 86 ± 5 per cent quantum efficiency and works for over 1,000 hours. We anticipate that these results will stimulate research on single-emitter-based white-light-emitting phosphors and diodes for next-generation lighting and display technologies.

Duration-sensitive association between air pollution exposure and changes in cardiometabolic biomarkers: Evidence from a predominantly African American cohort.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been related to cardiometabolic diseases, but the underlying biological pathways remain unclear at the population level. OBJECTIVE: To investigate the effect of PM2.5 exposure on changes in multiple cardiometabolic biomarkers across different exposure durations. METHOD: Data from a prospective cohort study were analyzed. Ten cardiometabolic biomarkers were measured, including ghrelin, resistin, leptin, C-peptide, creatine kinase myocardial band (CK-MB), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin, and interleukin-6 (IL-6). PM2.5 levels across exposure durations from 1 to 36 months were assessed. Mixed effect model was used to estimate changes in biomarker levels against 1 µg/m3 increase in PM2.5 level across different exposure durations. RESULTS: Totally, 641 participants were included. The average PM2.5 exposure level was 9 µg/m3. PM2.5 exposure was inversely associated with ghrelin, and positively associated with all other biomarkers. The magnitudes of these associations were duration-sensitive and exhibited a U-shaped or inverted-U-shaped trend. For example, the association of resistin were ß = 0.05 (95% CI: 0.00, 0.09) for 1-month duration, strengthened to ß = 0.27 (95% CI: 0.14, 0.41) for 13-month duration, and weakened to ß = 0.12 (95% CI: -0.03, 0.26) for 24-month duration. Similar patterns were observed for other biomarkers except for CK-MB, of which the association direction switched from negative to positive as the duration increased. Resistin, leptin, MCP-1, TNF-alpha, and troponin had a sensitive exposure duration of nearly 12 months. Ghrelin and C-peptide were more sensitive to longer-term exposure (>18 months), while NT-proBNP and IL-6 were more sensitive to shorter-term exposure (<6 months). CONCLUSION: PM2.5 exposure was associated with elevated levels in cardiometabolic biomarkers related to insulin resistance, inflammation, and heart injury. The magnitudes of these associations depended on the exposure duration. The most sensitive exposure durations of different biomarkers varied.

Shift in microorganism and functional gene abundance during completely autotrophic nitrogen removal over nitrite (CANON) process.

Nitrification-denitrification process has failed to meet wastewater treatment standards. The completely autotrophic nitrite removal (CANON) process has a huge advantage in the field of low carbon/nitrogen wastewater nitrogen removal. However, slow start-up and system instability limit its applications. In this study, the time of the start-up CANON process was reduced by using bio-rope as loading materials. The establishing of graded dissolved oxygen improved the stability of the CANON process and enhanced the stratification effect between functional microorganisms. Microbial community structure and the abundance of nitrogen removal functional genes are also analyzed. The results showed that the CANON process was initiated within 75 days in the complete absence of anaerobic ammonium oxidizing bacteria (AnAOB) inoculation. The ammonium and nitrogen removal efficiencies of CANON process reached to 94.45% and 80.76% respectively. The results also showed that the relative abundance of nitrogen removal bacterial in the biofilm gradually increases with the dissolved oxygen content in the solution decreases. In contrast, the relative abundance of ammonia oxidizing bacteria was positively correlated with the dissolved oxygen content in the solution. The relative abundance of g__Candidatus_Brocadia in biofilm was 15.56%, and while g__Nitrosomonas was just 0.6613%. Metagenomic analysis showed that g__Candidatus_Brocadia also contributes 66.37% to the partial-nitrification functional gene Hao (K10535). This study presented a new idea for the cooperation between partial-nitrification and anammox, which improved the nitrogen removal system stability.

Genome-wide identification and characterization of Glutathione S-Transferases (GSTs) and their expression profile under abiotic stresses in tobacco (Nicotiana tabacum L.).

BACKGROUND: Glutathione S-transferases (GSTs) are large and multifunctional proteases that play an important role in detoxification, protection against biotic and abiotic stresses, and secondary metabolite transportation which is essential for plant growth and development. However, there is limited research on the identification and function of NtGSTs. RESULTS: This study uses K326 and other six tobacco varieties (Hongda, HG, GDH11, Va116, VG, and GDH88) as materials to conduct comprehensive genome-wide identification and functional characterization of the GST gene in tobacco. A total of 59 NtGSTs were identified and classified into seven subfamilies via the whole-genome sequence analysis, with the Tau type serving as the major subfamily. The NtGSTs in the same branch of the evolutionary tree had similar exon/intron structure and motif constitution. There were more than 42 collinear blocks between tobacco and pepper, tomato, and potato, indicating high homology conservation between them. Twelve segmental duplicated gene pairs and one tandem duplication may have had a substantial impact on the evolution and expansion of the tobacco GST gene family. The RT-qPCR results showed that the expression patterns of NtGSTs varied significantly among tissues, varieties, and multiple abiotic stresses, suggesting that NtGST genes may widely respond to various abiotic stresses and hormones in tobacco, including NtGSTF4, NtGSTL1, NtGSTZ1, and NtGSTU40. CONCLUSIONS: This study provides a comprehensive analysis of the NtGST gene family, including structures and functions. Many NtGSTs play a critical regulatory role in tobacco growth and development, and responses to abiotic stresses. These findings offer novel and valuable insights for understanding the biological function of NtGSTs and the reference materials for cultivating highly resistant varieties and enhancing the yield and quality of crops.

Special AT-rich sequence binding protein 1 promotes multidrug resistance in gastric cancer by regulation of Ezrin to alter subcellular localization of ATP-binding cassette transporters.

Multidrug resistance is a primary factor in the poor response to chemotherapy and subsequent death in gastric cancer patients. However, the molecular mechanisms involved remain unclear. In this study, the high expression of special AT-rich sequence binding protein 1 (SATB1) in gastric cancer was found to be associated with reduced sensitivity to various chemotherapy drugs. Our results demonstrate that SATB1 can promote chemotherapy resistance in gastric cancer in vitro and in vivo. SATB1 exerts its effect by enhancing the activity of multiple ATP-binding cassette (ABC) transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) in gastric cancer cell lines. We also found that SATB1 affects ABC transporters by altering the subcellular localization of the ABC transporter rather than its expression. Subsequently, we confirmed that Ezrin binds to various ABC transporters and affects their subcellular localization. In addition, we found that SATB1 can also bind to the Ezrin promoter and regulate its expression. In the present study, we elucidate the mechanism of SATB1-mediated multidrug resistance in gastric cancer, providing a basis for SATB1 as a potential target for reversal of resistance.

The Impact of Neighborhood Disadvantage on Asthma Prevalence in a Predominantly African-American, Chicago-Based Cohort.

This study aimed to investigate the joint effect of neighborhood disadvantages on asthma prevalence and evaluate whether individual-level variables protect residents against neighborhood disadvantages. Data from the Chicago Multiethnic Prevention and Surveillance Study (from 2013-2020) were analyzed. Eight neighborhood characteristics were measured using the Chicago Health Atlas, including neighborhood unsafety, limited access to healthy food, neighborhood alienation, severe rent burden, vacant housing, single-parent household, neighborhood poverty, and unemployment. A structured questionnaire measured asthma diagnosis (childhood or adulthood) and individual-level variables including sex, age, income, education, and race. Weighted quantile sum (WQS) regression was used to evaluate the impact of neighborhood disadvantages. Stratified analysis was performed by income and education. A total of 6,592 participants (mean age = 53.5 (standard deviation, 11.1) years) were included. Most of the study population were non-Hispanic Black (82.5%) and reported an annual household income less than $15,000 (53%). Asthma prevalence was 23.6%. The WQS index, which represents the overall neighborhood disadvantages, was associated with asthma prevalence (odds ratio = 1.14, 95% confidence interval: 1.07, 1.22) when adjusted for individual-level confounders. Neighborhood poverty contributed 40.8% to the overall impact, followed by vacant housing (23.1%) and neighborhood alienation (22.9%). When stratified by individual-level income or education, no difference was observed for the association between WQS index and asthma prevalence.

High-sensitivity non-cooled near-infrared detector based on lithium niobate surface acoustic wave resonators combined with MXene Ti3C2Tx quantum dot thin films.

In this study, we propose the design of a surface acoustic wave (SAW) near-infrared sensor combined with an MXene quantum dot thin film to improve the infrared absorption efficiency at near-infrared wavelengths. A YZ-cut lithium niobate (LiNbO3) SAW resonator is fabricated as an infrared sensing unit with a resonant frequency shift reflecting the change in infrared radiation. It was observed that the responsivity of the near-infrared sensor (with a base frequency of 460 MHz) increased by approximately 88.89%. Thus, the proposed device exhibits high-performance infrared detection. Owing to the passive wireless capability of the device, it has wide applications.

Vacuum-deposited Rb3CeI6 for deep-blue-light-emitting diodes.

Recently, perovskite light-emitting diodes (PeLEDs) have exhibited outstanding performance in next-generation high-definition display applications. However, compared with green and red PeLEDs, the development of efficient and stable blue PeLEDs to meet the requirement for a wide color gamut has been a challenge. Herein, we vacuum thermally deposited a film of the lead-free rare earth halide Rb3CeI6, which shows deep blue emission with peaks at 427 nm and 468 nm. Due to the parity-allowed 5d-4f transition of Ce(III), the excited-state lifetime is as short as 22.3 ns (427 nm) and 25 ns (468 nm), respectively. The photoluminescence quantum yield (PLQY) is optimized to 51% by regulating the nucleation and growth of Rb3CeI6 grains. In a prototype rare earth light-emitting diode (ReLED) device, a thin insulating Al2O3 layer (5 nm) is inserted between the electron transport layer (ETL) and the emitting layer (EML, Rb3CeI6) to balance the carriers and reduce the dark current. The device shows a maximum luminance and EQE of 98 cd m-2 and 0.67%, respectively, and the electroluminescence (EL) spectrum maintains stability with changes in the operating voltage. In addition, the corresponding CIE coordinate is (0.15, 0.06), which closely matches the Rec. 2020 standard (0.131, 0.046).

A metabolome-wide case-control study of african american breast cancer patients.

BACKGROUND: Breast cancer survivors face long-term sequelae compared to the general population, suggesting altered metabolic profiles after breast cancer. We used metabolomics approaches to investigate the metabolic differences between breast cancer patients and women in the general population, aiming to elaborate metabolic changes among breast cancer patients and identify potential targets for clinical interventions to mitigate long-term sequelae. METHODS: Serum samples were retrieved from 125 breast cancer cases recruited from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), and 125 healthy controls selected from Chicago Multiethnic Prevention and Surveillance Study (COMPASS). We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) combined with fold change to select metabolic features associated with breast cancer. Pathway analyses were conducted using Mummichog to identify differentially enriched metabolic pathways among cancer patients. As potential confounders we included age, marital status, tobacco smoking, alcohol drinking, type 2 diabetes, and area deprivation index in our model. Random effects of residence for intercept was also included in the model. We further conducted subgroup analysis by treatment timing (chemotherapy/radiotherapy/surgery), lymph node status, and cancer stages. RESULTS: The entire study participants were African American. The average ages were 57.1 for cases and 58.0 for controls. We extracted 15,829 features in total, among which 507 features were eventually selected by our criteria. Pathway enrichment analysis of these 507 features identified three differentially enriched metabolic pathways related to prostaglandin, leukotriene, and glycerophospholipid. The three pathways demonstrated inconsistent patterns. Metabolic features in the prostaglandin and leukotriene pathways exhibited increased abundances among cancer patients. In contrast, metabolic intensity in the glycerolphospholipid pathway was deregulated among cancer patients. Subgroup analysis yielded consistent results. However, changes in these pathways were strengthened when only using cases with positive lymph nodes, and attenuated when only using cases with stage I disease. CONCLUSION: Breast cancer in African American women is associated with increase in serum metabolites involved in prostaglandin and leukotriene pathways, but with decrease in serum metabolites in glycerolphospholipid pathway. Positive lymph nodes and advanced cancer stage may strengthen changes in these pathways.

Pharmacological evaluation of a novel skeleton compound isobavachin (4',7-dihydroxy-8-prenylflavanone) as a hypouricemic agent: Dual actions of URAT1/GLUT9 and xanthine oxidase inhibitory activity.

Previously we discovered a novel natural scaffold compound, isobavachin (4', 7-dihydroxy-8-prenylflavanone), as a potent URAT1 inhibitor by shape and structure based on a virtue screening approach. In this study, further urate-lowering mechanism, pharmacokinetics and toxicities of isobavachin were conducted. Isobavachin inhibited URAT1 with an IC50 value of 0.24 ± 0.06 µM, and residues S35, F365, I481 and R477 of URAT1 contributed to high affinity for isobavachin. Isobavachin also inhibited glucose transporter 9 (GLUT9), another pivotal urate reabsorption transporter, with an IC50 value of 1.12 ± 0.26 µM. Molecular docking and MMGBSA results indicated that isobavachin might compete residues R171, L75 and N333 with uric acid, which leads to inhibition of uric acid transport of GLUT9. Isobavachin weakly inhibited urate secretion transporters OAT1 with an IC50 value of 4.38 ± 1.27 µM, OAT3 with an IC50 of 3.64 ± 0.62 µM, and ABCG2 with an IC50 of 10.45 ± 2.17 µM. Isobavachin also inhibited xanthine oxidase (XOD) activity in vitro with an IC50 value of 14.43 ± 3.56 µM, and inhibited the hepatic XOD activities at 5-20 mg/kg in vivo. Docking and MMGBSA analysis indicated that isobavachin might bind to the Mo-Pt catalyze center of XOD, which leads to inhibition of uric acid production. In vivo, isobavachin exhibited powerful urate-lowering and uricosuric effects at 5-20 mg/kg compared with the positive drugs morin (20 mg/kg) and RDEA3170 (10 mg/kg). Safety assessments revealed that isobavachin was safe and had no obvious toxicities. Isobavachin has little cell toxicity in HK2 cells as indicated by the MTT assay. In vivo, after treatment with 50 mg/kg isobavachin for 14 days, isobavachin had little renal toxicity, as revealed by serum CR/BUN levels, and no hepatotoxicity as revealed by ALT/AST levels. Further HE examination also suggests that isobavachin has no obvious kidney/liver damage. A pharmacokinetic study in SD rats indicated isobavachin had lower bioavailability (12.84 ± 5.13 %) but long half-time (7.04 ± 2.68 h) to maintain a continuous plasma concentration. Collectively, these results indicate that isobavachin deserves further investigation as a candidate anti-hyperuricemic drug with a novel mechanism of action: selective urate reabsorption inhibitor (URAT1/GLUT9) with a moderate inhibitory effect on XOD.

Per- and polyfluoroalkyl substances and sleep health in U.S. adults, NHANES 2005-2014.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that induce oxidative inflammatory responses and disrupt the endocrine and central nervous systems, all of which can influence sleep. OBJECTIVE: To investigate the association between PFAS exposure and sleep health measures in U.S. adults. METHODS: We analyzed serum concentration data of four PFAS [perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] reported for 8913 adults in NHANES 2005-2014. Sleep outcomes, including trouble sleeping, having a diagnosis of sleep disorder, and recent daily sleep duration classified as insufficient or excessive sleep (<6 or >9 h/day) were examined. Weighted logistic regression was used to estimate the association between the sleep outcomes and each PFAS modeled continuously (log2) or in exposure tertiles. We applied quantile g-computation to estimate the effect of the four PFAS as a mixture on the sleep outcomes. We conducted a quantitative bias analysis to assess the potential influence of self-selection and uncontrolled confounding. RESULTS: We observed some inverse associations between serum PFAS and trouble sleeping or sleep disorder, which were more consistent for PFOS (e.g., per log2-PFOS (ng/ml) and trouble sleeping OR = 0.93, 95%CI: 0.89, 0.98; sleep disorder OR = 0.89, 95%CI: 0.83, 0.95). Per quartile increase of the PFAS mixture was inversely associated with trouble sleeping and sleep disorder. No consistent associations were found for sleep duration across analyses. Our bias analysis suggests that the finding on sleep disorder could be explained by a moderate level of self-selection and negative confounding effects. CONCLUSIONS: We found no evidence to suggest exposure to four legacy PFAS worsened self-reported sleep health among U.S. adults. While some inverse associations between specific PFAS and sleep disorder were observed, self-selection and uncontrolled confounding biases may play a role in these findings.

Carbonene Fibers: Toward Next-Generation Fiber Materials.

The development of human society has set unprecedented demands for advanced fiber materials, such as lightweight and high-performance fibers for reinforcement of composite materials in frontier fields and functional and intelligent fibers in wearable electronics. Carbonene materials composed of sp2-hybridized carbon atoms have been demonstrated to be ideal building blocks for advanced fiber materials, which are referred to as carbonene fibers. Carbonene fibers that generally include pristine carbonene fibers, composite carbonene fibers, and carbonene-modified fibers hold great promise in transferring the extraordinary properties of nanoscale carbonene materials to macroscopic applications. Herein, we give a comprehensive discussion on the conception, classification, and design strategies of carbonene fibers and then summarize recent progress regarding the preparations and applications of carbonene fibers. Finally, we provide insights into developing lightweight, high-performance, functional, and intelligent carbonene fibers for next-generation fiber materials in the near future.

Study of MXene Ti3C2Tx quantum dot thin film on quartz bulk acoustic wave uncooled infrared sensors.

The infrared absorption efficiency is essential for an infrared sensor. We propose a quartz bulk acoustic wave (BAW) uncooled infrared sensor coated with MXene quantum dot film. The infrared detection is realized by measuring the resonant frequency of a Y-cut quartz BAW sensitive unit. An infrared sensor is fabricated by MEMS process, then the MXene quantum dot film is coated through the spin coating technology. The mechanism of infrared absorption enhancement is analyzed. Test results show that after coating the film, the responsivity (R) of the sensor increased by nearly 41% at a wavelength of 830nm, from 10.88MHz/W to 15.28 MHz/W. The quartz BAW infrared sensor combined with MXene quantum dots film has the potential of high-performance infrared detection.

Alpha-Lipoic Acid Promotes Intestinal Epithelial Injury Repair by Regulating MAPK Signaling Pathways.

Intestinal epithelial cells are an essential barrier in human gastrointestinal tract, and healing of epithelial wound is a key process in many intestinal diseases. α-Lipoic acid (ALA) was shown to have antioxidative and anti-inflammatory effects, which could be helpful in intestinal epithelial injury repair. The effects of ALA in human colonic epithelial cells NCM460 and human colorectal adenocarcinoma cells Caco-2 were studied. ALA significantly promoted NCM460 and Caco-2 migration, increased mucosal tight junction factors ZO-1 and OCLN expression, and ALA accelerated cell injury repair of both cells in wound healing assay. Western blot analysis indicated that ALA inhibited a variety of mitogen-activated protein kinase (MAPK) signaling pathways in the epithelial cells. In conclusion, ALA was beneficial to repair of intestinal epithelial injury by regulating MAPK signaling pathways.

Gestational PM2.5 exposure may increase the risk of small for gestational age through maternal blood pressure and hemoglobin: A mediation analysis based on a prospective cohort in China, 2014-2018.

BACKGROUND: Maternal gestational PM2.5 exposure was associated with small for gestational age (SGA). Identifying potential mediating factors may help design preventive strategies to reduce this risk. OBJECTIVE: This study aimed to explore the roles of maternal blood pressure and hemoglobin may play in the PM2.5 exposure and SGA relationship among 117,162 births in 16 counties across China during 2014-2018. METHODS: Daily PM2.5 concentration was collected from China National Environmental Monitoring Center. According to maternal residency during pregnancy, the PM2.5 exposure for each trimester and the whole pregnancy was assessed using an inverse-distance weighting approach. Repeated measurements of maternal blood pressure and hemoglobin during pregnancy were collected for each woman. We estimated the total effect of gestational PM2.5 exposure on SGA, and further tested the mediation effects of maternal blood pressure and hemoglobin concentration during pregnancy. RESULTS: Of 117,162 included mother-infant pairs, 11,361 (9.7 %) were SGA. The odds ratios of SGA associated with PM2.5 exposure (per 10 µg/m3 increase) in the second trimester and the whole pregnancy were 1.023 (95 % CI: 1.009, 1.037) and 1.024 (1.001, 1.048), respectively. We identified the independent mediating effect of blood pressure and hemoglobin in the second and third trimesters, with the proportion of mediation ranging from 1.64 % to 5.78 % and 2.40 % to 8.70 %, respectively. When considering the mediators jointly, we found a stronger mediating effect with a proportion of mediation ranging from 3.93 % to 13.69 %. DISCUSSION: Increases in maternal blood pressure and hemoglobin in the second and third trimesters can independently and jointly mediate the effects of gestational PM2.5 exposure on SGA. Monitoring and managing maternal blood pressure and hemoglobin during prenatal care may constitute a promising avenue to reducing SGA risk associated with gestational PM2.5 exposure.

Pressure-Driven Reverse Intersystem Crossing: New Path toward Bright Deep-Blue Emission of Lead-Free Halide Double Perovskites.

Maximizing the regeneration of singlet excitons remains a considerable challenge in deep-blue emission systems to obtain low-cost, high-efficiency fluorescent materials. However, the formation of the long-lifetime triplet excitons generally dominates the radiative process, making it greatly difficult to harvest deep-blue emission with high color purity because of the depression of singlet excitons. Here, a very bright deep-blue emission in double perovskite Cs2Na0.4Ag0.6InCl6 alloyed with Bi doping (CNAICB) was successfully achieved by pressure-driven reverse intersystem crossing (RISC), an abnormal photophysical process of energy transfer from the excited triplet state back to the singlet. Therein, the inherently broad emission of CNAICB was associated with the self-trapped excitons (STEs) at excited triplet states, whereas the radiative recombination of STEs populated in excited singlet states was responsible for the observed deep-blue emission. Moreover, the deep-blue emission corresponds to Commission Internationale de L'Eclairage (CIE) coordinates (0.16, 0.06) at 5.01 GPa, which meets the requirement of Rec. 2020 display standards. Likewise, pressure was introduced as an efficient tool to rule out the possibility of the recombination of free excitons and clarify the long-standing conventional dispute over the origin of the low-wavelength emission of Cs2AgInCl6. Our study not only demonstrates that pressure can be a robust means to boost the deep-blue emission but also provides deep insights into the structure-property relationship of lead-free CNAICB double perovskites.

Novel natural scaffold as hURAT1 inhibitor identified by 3D-shape-based, docking-based virtual screening approach and biological evaluation.

As a promising therapeutic target for gout, hURAT1 has attracted increasing attention. In this work, we identified a novel scaffold of hURAT1 inhibitors from a personal natural product database of verified herb-treated gout. First, we constructed more than 800 natural compounds from Chinese medicine that were verified to treat gout. Following the application of both shape-based and docking-based virtual screening (VS) methods, taking into account the shape similarity and flexibility of the target, we identified isopentenyl dihydroflavones that might inhibit hURAT1. Specifically, 9 compounds with commercial availability were tested with biochemical assays for the inhibition of 14C-uric acid uptake in high-expression hURAT1 cells (HEK293-hURAT1), and their structure-activity relationship was evaluated. As a result, 8-isopentenyl dihydroflavone was identified as a novel scaffold of hURAT1 inhibitors since isobavachin (DHF3) inhibited hURAT1 with an IC50 value of 0.39 ± 0.17 µM, which was comparable to verinurad with an IC50 value of 0.32 ± 0.23 µM. Remarkably, isobavachin also displayed an eminent effect in the decline of serum uric acid in vivo experiments. Taken together, isobavachin is a promising candidate for the treatment of hyperuricemia and gout.

The Role of Heart Rate, Body Temperature, and Respiratory Rate in Predicting Anastomotic Leakage following Surgery for Rectal Cancer.

OBJECTIVE: To explore the value of the heart rate, body temperature, and respiratory rate in the early prediction of anastomotic leakage after rectal cancer surgery. METHODS: Clinical data from patients with rectal cancer who underwent anterior rectal resection in the Department of Gastroenterology, Renmin Hospital of Wuhan University, from January 2017 to December 2019 were collected and analyzed retrospectively. Based on the occurrence of anastomotic leakage after surgery, the patients were divided into two groups: those with and without anastomotic leakage. The quantitative values of the heart rate, body temperature, and respiration rate at day 7 postsurgery were compared between the two groups. The ROC curve was used to analyze their role in the early prediction of anastomotic leakage. RESULTS: Among 441 patients with rectal cancer, 30 (6.81%) had clinical anastomotic leakage and were diagnosed at 7 ± 3 days postsurgery. Within 7 days postsurgery, the heart rate, body temperature, and respiratory rate in the anastomotic leakage group were higher than those in the nonanastomotic leakage group. The differences in heart rate (1-5 d), body temperature (2-7 d), and respiratory rate (1-7 d) were statistically significant (P < 0.05). The three ROC curves were drawn, respectively. The predictive value of the heart rate is greatest at days 2-3 postsurgery. The predictive value of the body temperature is greatest at days 4-6 postsurgery. The predictive value of the respiratory rate is best at days 1-4 postsurgery. CONCLUSION: The changes of vital signs (heart rate, body temperature, and respiratory rate) have a certain value in the early prediction of anastomotic leakage after rectal cancer surgery. Observation of postoperative vital signs at 7 days postsurgery is helpful for the early diagnosis of anastomotic leakage.