Unraveling the independent role of METTL3 in m6A modification and tumor progression in esophageal squamous cell carcinoma.

METTL3 and METTL14 are traditionally posited to assemble the m6A methyltransferase complex in a stoichiometric 1:1 ratio, modulating mRNA fate via m6A modifications. Nevertheless, recent investigations reveal inconsistent expression levels and prognostic significance of METTL3 and METTL14 across various tumor types, challenging their consistent functional engagement in neoplastic contexts. A pan-cancer analysis leveraging The Cancer Genome Atlas (TCGA) data has identified pronounced disparities in the expression patterns, functional roles, and correlations with tumor burden between METTL3 and METTL14, particularly in esophageal squamous cell carcinoma (ESCC). Knockdown experiments of METTL3 in EC109 cells markedly suppress cell proliferation both in vitro and in vivo, whereas METTL14 knockdown shows a comparatively muted effect on proliferation and does not significantly alter METTL3 protein levels. mRNA sequencing indicates that METTL3 singularly governs the expression of 1615 genes, with only 776 genes co-regulated with METTL14. Additionally, immunofluorescence co-localization studies suggest discrepancies in cellular localization between METTL3 and METTL14. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analyses demonstrate that METTL3 uniquely associates with the Nop56p-linked pre-rRNA complex and mRNA splicing machinery, independent of METTL14. Preliminary bioinformatics and multi-omics investigations reveal that METTL3's autonomous role in modulating tumor cell proliferation and its involvement in mRNA splicing are potentially pivotal molecular mechanisms. Our study lays both experimental and theoretical groundwork for a deeper understanding of the m6A methyltransferase complex and the development of targeted tumor therapies focusing on METTL3.

Significance and Possible Biological Mechanism for CLDN8 Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.

Background: The clinical role of claudin 8 (CLDN8) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of CLDN8 underlying KIRC were determined. Methods: High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the CLDN8. In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of CLDN8. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of CLDN8. Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC. Results: A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). CLDN8 downregulation was also confirmed at the single-cell level. Knocking out CLDN8 stimulated KIRC cell proliferation. Lower CLDN8 expression was correlated with worse overall survival of KIRC patients (hazard ratio of CLDN8 downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with CLDN8 co-expressed genes were centered on carbon metabolism obstruction, with key hub genes ACADM, ACO2, NDUFS1, PDHB, SDHD, SUCLA2, SUCLG1, and SUCLG2. Conclusions: CLDN8 is downregulated in KIRC and is considered a potential tumor suppressor. CLDN8 deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.

Wutou decoction alleviates arthritis inflammation in CIA mice by regulating Treg cell stability and Treg/Th17 balance via the JAK2/STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wutou Decoction (WTD) is a classic traditional Chinese medicine formula, which has shown clinical efficacy in treating rheumatoid arthritis (RA). The Treg stability and Th17/Treg imbalance is an important immunological mechanism in RA progression. Whether WTD regulates CD4+ T cell subsets has not been thoroughly investigated yet. AIM OF THE STUDY: This study aimed to explore the potential role and mechanisms of WTD in regulating the diminished stability of Treg cells and the imbalance of CD4+ T cell subsets via in vivo and in vitro experiments. MATERIALS AND METHODS: Firstly, the therapeutic effects of WTD on the collagen-induced arthritis (CIA) mouse and its potential regulatory function on CD4+ T cell subsets were evaluated in vivo. Animal specimens were collected after 31 days of treatment with WTD. The anti-arthritic and anti-inflammatory effects of WTD were assessed through arthritis scoring, body weight, spleen index, serum IL-6 levels, and micro-PET/CT imaging. Gene enrichment analysis was performed to evaluate the activation T cell-related signaling pathway. Flow cytometry was used to determine the proportions of CD4+ T cell subsets in vitro and in vitro. Additionally, ELISA was used to assess the secretion of IL-10 and TGF-ß by Treg cells under inflammatory conditions. The suppressive function of Treg cells on cell proliferation under inflammatory conditions was examined using CFSE labeling. Immunofluorescence staining was performed to detect the phosphorylation levels of STAT3 in CD4+ T cells from mouse spleen tissues. Western blotting was used to evaluate the phosphorylation levels of JAK2/STAT3 in Treg cells. RESULTS: WTD significantly alleviated joint inflammation in CIA mice. WTD reduced serum IL-6 levels in CIA mice, improved their body weight and spleen index. WTD treatment inhibited the activation of CD4+ T cell subgroup-related signaling in the joint tissues of CIA mice. In vitro and in vitro experiments showed that WTD increased the proportion of Treg cells and decreased the proportion of Th17 cells in CIA mice spleen. Furthermore, WTD promoted the secretion of IL-10 and TGF-ß by Treg cells and enhanced the inhibitory capacity of Treg cells on cell proliferation under inflammatory conditions. Immunofluorescence detected decreased STAT3 phosphorylation levels in CD4+ T cells from CIA mice spleen, while western blotting revealed a decrease in JAK2/STAT3 phosphorylation levels in Treg cells in vitro. CONCLUSIONS: Inhibiting JAK2/STAT3 phosphorylation is a potential mechanism through which WTD improves Treg cell stability, balances CD4+ T cell subsets, and attenuates RA joint inflammation.

Development of in vitro microfluidic models to study endothelial responses to pulsatility with different mechanical circulatory support devices.

Continuous-flow ventricular assist devices (CFVAD) and counterpulsation devices (CPD) are used to treat heart failure (HF). CFVAD can diminish pulsatility, but pulsatile modes have been implemented to increase vascular pulsatility. The effects of CFVAD in a pulsatile mode and CPD support on the function of endothelial cells (ECs) are yet to be investigated. In this study, two in vitro microfluidic models for culturing ECs are proposed to reproduce blood pressure (BP) and wall shear stress (WSS) on the arterial endothelium while using these medical devices. The layout and parameters of the two microfluidic systems were optimized based on the principle of hemodynamic similarity to efficiently simulate physiological conditions. Moreover, the unique design of the double-pump and double afterload systems could successfully reproduce the working mode of CPDs in an in vitro microfluidic system. The performance of the two systems was verified by numerical simulations and in vitro experiments. BP and WSS under HF, CFVAD in pulsatile modes, and CPD were reproduced accurately in the systems, and these induced signals improved the expression of Ca2+, NO, and reactive oxygen species in ECs, proving that CPD may be effective in normalizing endothelial function and replacing CFVAD to a certain extent to treat non-severe HF. This method offers an important tool for the study of cell mechanobiology and a key experimental basis for exploring the potential value of mechanical circulatory support devices in reducing adverse events and improving outcomes in the treatment of HF in the future.

Local risk factors for one-year dental implant loss and late loss in 287 failed implants caused by peri-implantitis or infection after prosthesis loading: a retrospective study.

The purpose of this paper was to retrospectively assess the local factors that are likely to be associated with the risks for one-year dental implant loss.A retrospective study was designed and implemented. The sample consisted of patients who underwent an implant loss or removal caused by peri-implantitis or infection after prosthesis loading. The chi-squared test and generalised estimating equations (GEE) were used to explore the potential risk factors for one-year implant loss. A total of 279 patients with 287 failed implants were enrolled in this study. Immediate implant placement exhibited a 3.373 (95% CI: 1.652 to 6.886) significantly increased risk to experience one-year implant loss than early and late implant placement (p = 0.001). In addition, implants loaded during a healing period fewer than two months after implant placement were at 18.139 (95% CI: 8.925 to 36.866) significantly higher risk of one-year implant loss when compared with those that loaded within more than two months after implant placement (p < 0.001). Smokers were 1.866 (OR = 1.866,95% CI: 0.993 to 3.510) times as high risk for one-year implant loss as non-smokers, but there were no significant statistical differences (p = 0.053). Immediate implant placement and early implant loading were considered risk factors for one-year implant loss.

Application and characterization of digital Sallen-Key filter in nuclear spectrum smoothing.

In the nuclear spectrum analysis processing, spectrum smoothing can remove the statistical fluctuation in the spectrum, which is beneficial for peak detection and peak area calculation. In this work, a spectrum smoothing algorithm is proposed based on digital Sallen-Key filter, which contains four parameters (m, n, k, D). The amplitude-frequency response curve of Sallen-Key filter is deduced and the filtering performance is analyzed. Meanwhile, the effects of the four parameters on the shape of the smoothed spectrum are explored: D affects the counts and peak areas of the spectrum, and the peak area can be corrected by the peak area correction function S'. The parameters of m, n and k affect the peak position after smoothing, making the peak position shift to the right, and the peak position correction function P' can be used to correct the peak position, when n¿2, the spectrum data appear negative after smoothing, when k¿2, the smoothed spectrum broadening degree is greater than 20%. Smoothness (R), noise smoothing factor (NSF), spectrum count ratio before and after smoothing (PER), and comprehensive evaluation factor (Q) are used to evaluate the smoothing effect of the algorithm. The parameters of the algorithm are optimally selected: about the gamma spectrum of 137Cs and 60Co, the optimal parameters are m=1.5 n=2 k=2 D=1, about the characteristic X-ray spectrum of Fe and quasi-geological sample (TiMnFeNiCuZn), the optimal parameters are m=1.1 n=1.1 k=1.3 D=1. Based on Sallen-Key smoothing method, Fourier transform method, Gaussian function method, wavelet transformation method, center of gravity method and least squares method, the gamma spectrum of 137Cs is smoothed and denoised in this paper. The results show that the Sallen-Key method has better spectrum denoising effect (R=0.6056) and comprehensive performance indicators (Q=0.6104), which can be further applied for the smoothing of nuclear spectrum data.

Hemodynamics of ventricular-arterial coupling under enhanced external counterpulsation: An optimized dual-source lumped parameter model.

BACKGROUND AND OBJECTIVE: Enhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. METHODS: A neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. RESULTS: A third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. CONCLUSIONS: The ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.

Study on the hemodynamic effects of different pulsatile working modes of a rotary blood pump using a microfluidic platform that realizes in vitro cell culture effectively.

Rotary blood pumps (RBPs) operating at a constant speed generate non-physiologic blood pressure and flow rate, which can cause endothelial dysfunction, leading to adverse clinical events in peripheral blood vessels and other organs. Notably, pulsatile working modes of the RBP can increase vascular pulsatility to improve arterial endothelial function. However, the laws and related mechanisms of differentially regulating arterial endothelial function under different pulsatile working modes are still unclear. This knowledge gap hinders the optimal selection of the RBP working modes. To address these issues, this study developed a multi-element in vitro endothelial cell culture system (ECCS), which could realize in vitro cell culture effectively and accurately reproduce blood pressure, shear stress, and circumferential strain in the arterial endothelial microenvironment. Performance of this proposed ECCS was validated with numerical simulation and flow experiments. Subsequently, this study investigated the effects of four different pulsation frequency modes that change once every 1-4-fold cardiac cycles (80, 40, 80/3, and 20 cycles per min, respectively) of the RBP on the expression of nitric oxide (NO) and reactive oxygen species (ROS) in endothelial cells. Results indicated that the 2-fold and 3-fold cardiac cycles significantly increased the production of NO and prevented the excessive generation of ROS, potentially minimizing the occurrence of endothelial dysfunction and related adverse events during the RBP support, and were consistent with animal study findings. In general, this study may provide a scientific basis for the optimal selection of the RBP working modes and potential treatment options for heart failure.

Dahuang-Wumei decoction protects against hepatic encephalopathy in mice: Behavioural, biochemical, and molecular evidence.

BACKGROUND: Disturbance of the blood‒brain barrier (BBB) and associated inflammatory responses are observed in patients with hepatic encephalopathy (HE) and can cause long-term complications. Dahuang-Wumei decoction (DWD) is a renowned traditional Chinese herbal medicine with a long history of clinical use and has been widely employed as an effective treatment for hepatic encephalopathy (HE). Despite its established efficacy, the precise mechanisms underlying the therapeutic effects of DWD have not been fully elucidated. PURPOSE: The present study aimed to comprehensively explore the potential effects and underlying molecular mechanisms of DWD on HE through an integrated investigation that included both in vivo and in vitro experiments. METHODS: In the present study, carbon tetrachloride (CCl4) and thioacetamide (TAA) were used to establish an HE model in mice. The therapeutic effects of DWD on liver injury, fibrosis, brain injury, behaviour, and consciousness disorders were evaluated in vivo. C8-D1A and bEnd.3 cells were used to construct a BBB model in vitro. The effects of DWD on proinflammatory factor expression, BBB damage and the Wnt/ß-catenin pathway were detected in vivo and in vitro. RESULTS: Our results showed that DWD can improve liver injury and fibrosis and brain damage and inhibit neurofunctional and behavioural disorders in mice with HE. Afterwards, we found that DWD decreased the levels of proinflammatory factors and suppressed BBB disruption by increasing the levels of junction proteins in vivo and vitro. Further studies verified that the Wnt/ß-catenin pathway may play a pivotal role in mediating the inhibitory effect of DWD on HE. CONCLUSION: These results demonstrated that DWD can treat HE by preventing BBB disruption, and the underlying mechanisms involved were associated with the activation of the Wnt/ß-catenin pathway and the inhibition of inflammatory responses.

Abnormal thermally-stimulated dynamic organic phosphorescence.

Dynamic luminescence behavior by external stimuli, such as light, thermal field, electricity, mechanical force, etc., endows the materials with great promise in optoelectronic applications. Upon thermal stimulus, the emission is inevitably quenched due to intensive non-radiative transition, especially for phosphorescence at high temperature. Herein, we report an abnormal thermally-stimulated phosphorescence behavior in a series of organic phosphors. As temperature changes from 198 to 343 K, the phosphorescence at around 479 nm gradually enhances for the model phosphor, of which the phosphorescent colors are tuned from yellow to cyan-blue. Furthermore, we demonstrate the potential applications of such dynamic emission for smart dyes and colorful afterglow displays. Our results would initiate the exploration of dynamic high-temperature phosphorescence for applications in smart optoelectronics. This finding not only contributes to an in-depth understanding of the thermally-stimulated phosphorescence, but also paves the way toward the development of smart materials for applications in optoelectronics.

Association between perceived neighborhood environment and depression among residents living in mega-communities in Guiyang, China: a cross-sectional study.

BACKGROUND: Little was known about the relationship between perceived neighborhood environment and depression among residents living in mega-communities. Furthermore, the mediating effects of physical activity (PA) and anxiety in this relationship have not been investigated. Thus, this study aimed to comprehensively examine the association between perceived neighborhood environment and depression among residents living in mega-communities, and test whether PA and anxiety mediated the association. METHODS: A cross-sectional study on perceived neighborhood environment and depression was conducted among individuals who lived in mega-communities (n = 665) in Guiyang, China from July to August 2022. Perceived neighborhood environment was assessed from the following six aspects: traffic, building quality, accessibility, neighborhood, indoor, and pollution. Depression was measured by the Patients Health Questionnaire-9. Structural equation model was used to evaluate the association between perceived neighborhood environment and depression, and test the mediating effect of PA and anxiety in this association. RESULTS: We found that neighborhood (ß = -0.144, p = 0.002) and PA (ß = -0.074, p < 0.001) were both negatively associated with depression, while anxiety was positively associated with depression (ß = 0.447, p < 0.001). Married residents were less likely to experience depression than residents of other marital status. PA played a mediator role in the relationship between accessibility and depression (ß = 0.014, p = 0.033). PA mediated the relationship between neighborhood and depression (ß = -0.032, p = 0.015). The mediating effect of anxiety in the relationship between perceived neighborhood environment and depression was not significant. CONCLUSIONS: This study demonstrated that neighborhood, which was assessed by satisfaction with safety, hygiene, parking, greening, lighting, and building shape, was negatively associated with depression, and PA mediated the relationship.

Elucidating contributions of volatile organic compounds to ozone formation using random forest during COVID-19 pandemic: A case study in China.

Ozone has been reported to increase despite nitrogen oxides reductions during the COVID-19 pandemic, and ozone formation needs to be revisited using volatile organic compounds (VOCs), which are rarely measured during the pandemic. Here, a total of 98 VOCs species were monitored in an economy-active city in China from January 2021 to August 2022 to assess contributions to ozone formation during the pandemic. Total VOCs concentrations were 35.55 ± 21.47 ppb during the entire period, among which alkanes account for the largest fraction (13.78 ppb, 38.0%), followed by aromatics (6.16 ppb, 16.8%) and oxygenated VOCs (OVOCs, 5.69 ppb, 15.7%). Most VOCs groups (e.g., alkenes, OVOCs) and individual species (e.g., isoprene, methyl vinyl ketone) display obvious seasonal and diurnal variations, which are related to their sources and reactivities. No weekend effects of VOCs suggest limited influences from traffic emissions during pandemic. Aromatics and alkenes are the major contributors (39% and 33%) to ozone formation potential, largely driven by o/m/p-xylene (21%), ethylene (15%), toluene (9%). Secondary organic aerosol formation potential is dominated by toluene (>50%) despite its low proportion (5%). Further inclusion of VOCs and meteorology in the Random Forest model shows good ozone prediction performance (R2 = 0.77-0.86, RMSE = 11.95-19.91 µg/m3, MAE = 8.89-14.58 µg/m3). VOCs and NO2 contribute >50% of total importance with the largest difference in importance ratio of VOCs/NO2 in the summer and winter, implying ozone formation regime may vary. No seasonal variations in importance of meteorology are observed, while importance of other variables (e.g., PM2.5) is highest in the summer. This work identifies critical VOCs groups and species for ozone formation during the pandemic, and demonstrates the feasibility of machine learning algorithms in elucidation of ozone formation mechanisms.

Short-term and Long-term Outcomes of Robotic Enucleation of Tumors Located in the Pancreatic Head and Uncinate Process.

OBJECTIVE: To assess short-term and long-term outcomes following robotic enucleation (REn) of tumors in the proximal pancreas. BACKGROUND: Despite the advantages of preserving function via pancreatic enucleation, controversies persist, since this can be associated with severe complications, such as clinically relevant postoperative pancreatic fistula, especially when performed near the main pancreatic duct. The safety and efficacy of REn in this context remain largely unknown. METHODS: A retrospective analysis was performed of all patients who underwent REn for benign and low-grade malignant neoplasms in the pancreatic head and uncinate process between January 2005 and December 2021. Clinicopathologic, perioperative, and long-term outcomes were compared with a similar open enucleation (OEn) group. RESULTS: Of 146 patients, 92 underwent REn with a zero conversion-to-open rate. REn was superior to OEn in terms of shorter operative time (90.0 minutes vs 120.0 minutes, P<0.001), decreased blood loss (20.0 mL vs 100.0 min, P=0.001), and lower clinically relevant postoperative pancreatic fistula rate (43.5% vs 61.1%, P=0.040). Bile leakage rate, major morbidity, 90-day mortality, and length of hospital stay were comparable between groups. No post-REn grade C POPF or grade IV/V complication was identified. Subgroup analyses for uncinate process tumors and proximity to the main pancreatic duct did not demonstrate inferior postoperative outcomes. In a median follow-up period of 50 months, REn outcomes were comparable to OEn regarding recurrence rate and pancreatic endocrine or exocrine function. CONCLUSIONS: REn for pancreatic head and uncinate process tumors improved clinically relevant outcomes without increased major complications compared to OEn, while demonstrating comparable long-term oncological and functional outcomes.

Mechanisms of NLRP3 inflammasome in rheumatoid arthritis and osteoarthritis and the effects of traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: It has been widely reported that various anti-rheumatic traditional Chinese medicines (TCMs) ameliorate rheumatoid arthritis (RA) and osteoarthritis (OA) through regulating the abnormal production, assembly, and activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome. These TCMs include monomers isolated from Chinese herbs, extracts of Chinese herbs, and Chinese medical formulae with a lengthy application history. AIM OF THE STUDY: This review aimed to summarize and analyze the published articles about the NLRP3 inflammasome and its role in the pathogenesis of RA and OA. We also reviewed existing knowledge on the therapeutic mechanism of TCMs in RA and OA via the regulation of the NLRP3 inflammasome. MATERIALS AND METHODS: We searched for relevant articles with the keywords "NLRP3 inflammasome", "traditional Chinese medicine," "Chinese herbal drugs," "rheumatoid arthritis," and "osteoarthritis." The information retrieval was conducted in medical Chinese and English databases from the date of construction to April 19, 2023, including PubMed, MEDLINE, Web of Science, Scopus, Ovid, China National Knowledge Infrastructure (CNKI), Chinese Biomedicine Literature Database (CBM), Chinese Science and Technology Periodicals Database (VIP), and China Online Journals (COJ). RESULTS: According to retrieval results, 35 TCMs have been demonstrated to relieve RA by targeting the NLRP3 inflammasome, including six traditional Chinese prescriptions, seven extracts of Chinese herbs, and 22 monomers extracted from traditional Chinese herbs and formulae. Additionally, 23 TCMs have shown anti-OA effects with abilities to modulate the NLRP3 inflammasome, including five traditional Chinese prescriptions, one extract of Chinese herbs, and 17 monomers from Chinese herbs. CONCLUSIONS: We summarized mechanism research about the pivotal roles of the NLRP3 inflammasome in the pathogenesis of RA and OA. Moreover, a review of TCMs with targets of the NLRP3 inflammasome in RA and OA treatment was also conducted. Our work is conducive to a better application of TCMs in complementary and alternative therapies in RA and OA.

Effects of meteorological conditions on the mixing height of Nitrogen dioxide in China using new-generation geostationary satellite measurements and machine learning.

Nitrogen dioxide (NO2) plays a critical role in terms of air quality, human health, ecosystems, and its impact on climate change. While the crucial roles of the vertical structure of NO2 have been acknowledged for some time, there is currently limited knowledge about this aspect in China. The Geostationary Environment Monitoring Spectrometer (GEMS) is the world's first geostationary satellite instrument capable of measuring the hourly columnar amount of NO2. The study presented here introduces the use of mixing height for NO2 in the atmosphere. A thorough examination of spatiotemporal variations in the mixing height of NO2 was conducted using data from both the GEMS and ground-based air quality monitoring networks. A random forest model based on machine learning techniques was utilized to examine how meteorological parameters affect the mixing height of NO2. The results of our study reveal a notable seasonal fluctuation in the mixing height of NO2, with the highest values observed during the summer and the lowest values during the winter. Additionally, there was an increasing diurnal trend from early morning to mid-afternoon. Moreover, the study discovered elevated NO2 mixing heights in the dry regions of northern China. The results also indicated a positive correlation between the mixing height of NO2 and temperature and wind speed, while negative associations were found with relative humidity and air pressure. The machine learning model's predicted NO2 mixing heights were in good agreement with the measurement-based outcomes, as evidenced by a coefficient of determination (R2) value of 0.96 (0.84 for the 10-fold cross-validation). These findings emphasize the noteworthy influence of meteorological variables on the vertical distribution of NO2 in the atmosphere and enhance our comprehension of the three-dimensional variations in NO2.

Towards Optical Information Recording: A Robust Visible-Light-Driven Molecular Photoswitch with the Ring-Closure Reaction Yield Exceeding 96.3 .

Diarylethene molecular photoswitches hold great fascination as optical information materials due to their unique bistability and exceptional reversible photoswitching properties. Conventional diarylethenes, however, rely on UV light for ring-closure reactions, typically with modest yields. For practical application, diarylethenes driven by visible lights are preferred but achieving high ring-closure reaction yield remains a significant challenge. Herein, we synthesized a novel all-visible-light-driven photoswitch, TPAP-DTE, by facilely endcapping the dithienylethene (DTE) core with triphenylamine phenyl (TPAP) groups. Owing to the electron-donating conjugation effect of TPAP, the open-form TPAP-DTE responds strongly to short-wavelength visible lights with considerable photocyclization quantum yields and molar absorption coefficient. Upon 405 nm visible-light irradiation, TPAP-DTE achieves a ring-closure reaction yield exceeding 96.3 % (confirmed by both nuclear magnetic resonance spectroscopy and high-performance liquid chromatography). Its ring-opening reaction yield is 100 % upon irradiation with long-wavelength visible light. TPAP-DTE could be regarded as a bidirectional "quasi"-quantitative conversion molecular switch. Furthermore, TPAP-DTE exhibits robust fatigue resistance over 100 full photoswitching cycles and great anti-aging property under 85 °C and 85 % humidity for at least 1000 h. Consequently, its rewritable QR-code, multilevel data storage, and anti-counterfeiting/encryption applications are successfully demonstrated exclusively using visible lights, positioning TPAP-DTE as a highly promising medium for information recording.

Comprehensive analysis of m6A modification patterns and m6A-related lncRNAs as potential biomarkers in lung adenocarcinoma.

BACKGROUND: N6-methyladenosine (m6A) methylation is considered to induce tumor cell proliferation, migration, and apoptosis. Understanding the mechanism of m6A-related lncRNAs in the development of lung adenocarcinoma (LUAD) may help predict prognosis. METHODS: m6A-related lncRNAs related to lung cancer were identified and combined with the MeRIP-Seq dataset. The consensus clustering method was utilized to divide LUAD patients, and prognostic model was constructed using the Lasso Cox algorithm. The cluster profiler package was used for gene ontology and KEGG enrichment. The proportion of immune infiltration was estimated using the CIBERSORT algorithm. The decision tree was constructed by the rpart package, and nomograms were built by the rms package. The Connectivity Map database was analyzed for the therapeutic effects of small molecule drugs for LUAD. In addition, qPCR, colony formation and transwell assays were performed to validate functions of m6A-associated lncRNAs. RESULTS: Nineteen m6A-modified lncRNAs in LUAD were identified. LUAD patients were divided into two categories based on the expression of 19 m6A-related lncRNAs. Cluster 2 patients had better antigen production and expression, while naive B cells, plasma cells, and activated NK cells were lower in cluster 1. Nine m6A-related lncRNAs were selected to establish a risk model for evaluating the prognosis of LUAD patients. The high-risk group had higher tumor mutational burden and lower TIDE scores with more gamma delta T cells and neutrophils. Nomograms showed that the prognostic model had predominant predictive ability for LUAD patients based on the risk score analyzed by the decision tree model. Benzo(a)pyrene and neurodazine might improve the prognosis of LUAD patients. The qRT-PCR results confirmed the reliability of the analytical results. CONCLUSION: The establishment of a prognostic model of m6A-related lncRNAs can independently predict overall survival in LUAD and may help to develop personalized immunotherapy strategies.

TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma.

BACKGROUND: Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC. METHODS: We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021. The genomic alterations of PDAC were analyzed, and the association of TP53 mutation subtypes and other core gene pathway alterations with patients' clinical characteristics were evaluated by Chi-squared test, Kaplan-Meier method and Cox regression model. RESULTS: TP53 missense mutation was significantly associated with poor differentiation in KRASmut PDAC (50.7% vs. 36.1%, P = 0.001). In small-sized (≤ 2 cm) KRASmut tumors, significantly higher LNs involvement (54.8% vs. 23.5%, P = 0.010) and distal metastic rate (20.5% vs. 2.9%, P = 0.030) were observed in those with TP53 missense mutation instead of truncating mutation. Compared with TP53 truncating mutation, missense mutation was significantly associated with reduced DFS (6.6 [5.6-7.6] vs. 9.2 [5.2-13.3] months, HR 0.368 [0.200-0.677], P = 0.005) and OS (9.6 [8.0-11.1] vs. 18.3 [6.7-30.0] months, HR 0.457 [0.248-0.842], P = 0.012) in patients who failed to receive chemotherapy, while higher OS (24.2 [20.8-27.7] vs. 23.8 [19.0-28.5] months, HR 1.461 [1.005-2.124], P = 0.047) was observed in TP53missense cases after chemotherapy. CONCLUSIONS: TP53 missense mutation was associated with poor tumor differentiation, and revealed gain-of-function properties in small-sized KRAS transformed PDAC. Nonetheless, it was not associated with insensitivity to chemotherapy, highlighting the neoadjuvant therapy before surgery as the potential optimized strategy for the treatment of a subset of patients.

[Spatial and Temporal Variations in PM1 Concentration and its Correlation with AOD in China from 2014 to 2017].

Based on the PM1 mass concentration data from all the air quality monitoring stations in China from 2014 to 2017, the temporal and spatial distribution characteristics of PM1 concentration were studied using the time series statistical and spatial hierarchical clustering methods, and the PM1 spatiotemporal evolution characteristics were revealed. Combined with AOD data of the MODIS remote-sensing satellite, the temporal and spatial variation in PM1-AOD correlation was analyzed on a fine scale. The results showed that, from 2014 to 2017, the annual average PM1 concentration in China decreased yearly, the seasonal PM1 concentration showed the characteristics of "high in winter and low in summer," and the monthly average PM1 concentration showed a "U"-shaped variation. An "M"-shaped PM1 variation pattern was presented before and after the holidays. Weekly variation showed that high PM1 values occurred on Mondays and Fridays, and low ones occurred on Sundays. Based on the spatial clustering method, the national average annual PM1 concentration in China was divided into seven categories, and the overall spatial distribution pattern was "high in the east and low in the west and high in the north and low in the south." The highest and the lowest values of average PM1 concentration occurred in central China(54.59 µg·m-3) and in Xinjiang-Qinghai-Xizang(11.37 µg·m-3), respectively. The PM1-AOD relationship was positively correlated as a whole, the highest correlation coefficient was 0.55 in central China, and the lowest value was 0.36 in central and southern China.

Microfluidic characterization of single-cell biophysical properties and the applications in cancer diagnosis.

Single-cell biophysical properties play a crucial role in regulating cellular physiological states and functions, demonstrating significant potential in the fields of life sciences and clinical diagnostics. Therefore, over the last few decades, researchers have developed various detection tools to explore the relationship between the biophysical changes of biological cells and human diseases. With the rapid advancement of modern microfabrication technology, microfluidic devices have quickly emerged as a promising platform for single-cell analysis offering advantages including high-throughput, exceptional precision, and ease of manipulation. Consequently, this paper provides an overview of the recent advances in microfluidic analysis and detection systems for single-cell biophysical properties and their applications in the field of cancer. The working principles and latest research progress of single-cell biophysical property detection are first analyzed, highlighting the significance of electrical and mechanical properties. The development of data acquisition and processing methods for real-time, high-throughput, and practical applications are then discussed. Furthermore, the differences in biophysical properties between tumor and normal cells are outlined, illustrating the potential for utilizing single-cell biophysical properties for tumor cell identification, classification, and drug response assessment. Lastly, we summarize the limitations of existing microfluidic analysis and detection systems in single-cell biophysical properties, while also pointing out the prospects and future directions of their applications in cancer diagnosis and treatment.