Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus.

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

Co-exposure of bisphenol A and selenium deficiency induces pyroptosis via ROS/NLRP3 pathway in chicken spleen.

Bisphenol A (BPA) is widely applied in plastic products, which will produce immunotoxicity to organisms after spilling in the environment, and become a kind of endocrine disruptor. Selenium (Se) is an essential trace element and plays an important role in maintaining redox homeostasis and immune function. BPA exposure and Se deficiency often occur together in livestock and poultry farming, however, studies on the effects of joint exposure on chicken immunotoxins have not been reported. Therefore, this study established a chicken spleen and MDCC-MSB1 cell model under the combined effects of BPA exposure or/and Se deficiency. Transcriptomic analysis showed that BPA exposure and/or Se deficiency induced differential enrichment of positive regulatory pathways such as NLRP3 inflammatory complex assembly, inflammatory response and cellular oxidative stress response. In the -Se+BPA group, pathological damage was significantly increased, Se content decreased, BPA accumulation, oxidative stress and pyroptosis. Meanwhile, the roles and mechanisms of oxidative stress and pyroptosis in BPA exposure or/and Se deficiency-induced splenic tissue injury were investigated by using IF and qRT-PCR methods. The results showed that joint BPA exposure with Se deficiency resulted in more significant changes in the above outcomes than 1 of them. The oxidative stress inhibitor NAC effectually reduced Se deficiency and BPA-induced oxidative stress and pyroptosis, further suggests that oxidative stress mediated Se deficiency or/and BPA-induced pyroptosis. This study revealed that BPA exposure and Se deficiency induced spleen pyroptosis in chickens via the ROS/NLRP3 pathway. These results provide the theoretical basis for the toxicity of BPA in poultry and enrich the toxicological mechanism of combined exposure of Se deficiency and environmental toxins.

Telemedicine-medical "snack community"-PHS ecosystem: Insights into the double-edged sword role of telemedicine in clinical practice and medical education during the COVID-19 pandemic and beyond.

Telemedicine has gained tremendous development during the COVID-19 pandemic. With deblocking and opening, telemedicine accelerates the evolvution of the medical "snack community" and undermines the perception of medical students and staff, which promotes the incidence of psychosocial-related disorders. Moreover, the inconsistent telemedicine adaptability between medical workers and patients aggravates the doctor-patient conflict due to the aging population and COVID-19 squeal. Telemedicine is colliding with the national healthcare system, whose synchronization with conventional medical service is crucial to coordinate the relationship among medical payment, patient privacy and qualifications of clinicians. This study puts more emphasis on the double-edged sword role of telemedicine in clinical practice and medical education during the COVID-19 pandemic and beyond. Overall, while telemedicine has demonstrated its utility in health care throughout the COVID pandemic, it is pretty critical to continue evaluating the efficacy and limitations of telemedicine in order to maintain equal access to medical service and high-quality medical education. A new concept as telemedicine-medical "snack community"-PHS ecosystem, where the psychological health education system and partners healthcare system with enough bandwidth, especially 5G technology, could optimize the effect of telemedicine on medical practice and education, is proposed.

Ultrasensitive Surface-Enhanced Raman Scattering Platform for Protein Detection via Active Delivery to Nanogaps as a Hotspot.

Surface-enhanced Raman scattering (SERS) is an attractive technique in molecular detection with high sensitivity and label-free characteristics. However, its use in protein detection is limited by the large volume of proteins, hindering its approach to the narrow spaces of hotspots. In this study, we fabricated a Au nanoTriangle plate Array on Gel (AuTAG) as an SERS substrate by attaching a Au nanoTriangle plate (AuNT) arrangement on a thermoresponsive hydrogel surface. The AuTAG acts as an actively tunable plasmonic device, on which the interparticle distance is altered by controlling temperature via changes in hydrogel volume. Further, we designed a Gel Filter Trapping (GFT) method as an active protein delivery strategy based on the characteristics of hydrogels, which can absorb water and separate biopolymers through their three-dimensional (3D) polymer networks. On the AuTAGs, fabricated with AuNTs modified with charged surface ligands to prevent the nonspecific adsorption of analytes to particles, the GFT method helped the delivery of proteins to hotspot areas on the AuNT arrangement. This combination of a AuTAG substrate and the GFT method enables ultrahigh sensitivity for protein detection by SERS up to a single-molecule level as well as a wide quantification concentration range of 6 orders due to their geometric advantages.

Naringenin counteracts LPS-induced inflammation and immune deficits in chicken thymus by alleviating mtROS/ferroptosis levels.

Naringenin is a flavonoid with significant anti-inflammatory and antioxidant properties. Mitochondrial dynamics, the mitochondrial respiratory chain, and mtROS are closely related to each other and regulate various biological processes. Ferroptosis is closely related to inflammatory responses and immune function in multiple tissues and organs. However, whether naringenin can alleviate LPS-induced inflammation and immune disorders in the chicken thymus via mtROS/ferroptosis has not been reported. Therefore, in this study, we constructed chicken thymus and MSB-1 cell models of LPS and naringenin based on screening for naringenin concentrations that have positive effects on inflammation and immune function to further investigate the anti-inflammatory, antiferroptosis, and maintenance of the immune function of naringenin. The results showed that 40 mg/kg naringenin alleviated LPS-induced tissue damage, elevated serum inflammatory factors, and decreased serum immune factors. The mechanism by which naringenin attenuates mtROS release by alleviating the imbalance of mitochondrial dynamics and the blockage of the respiratory chain. The effect of naringenin on alleviating LPS-induced lipid peroxidation, disruption of the GSH/GSSG system, iron overload, and GPx4 inactivation, thereby attenuating ferroptosis in thymus tissue, was inhibited by the addition of mtROS activators. In conclusion, naringenin alleviates LPS-induced ferroptosis in chicken thymus by attenuating mtROS release.

SLC25A48 controls mitochondrial choline import and metabolism.

Choline is an essential nutrient for the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism with a critical step being its import into mitochondria. However, the underlying mechanisms and biological significance remain poorly understood. Here, we report that SLC25A48, a previously uncharacterized mitochondrial inner-membrane carrier protein, controls mitochondrial choline transport and the synthesis of choline-derived methyl donors. We found that SLC25A48 was required for brown fat thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. Choline uptake into the mitochondrial matrix via SLC25A48 facilitated the synthesis of betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased production of mitochondrial reactive oxygen species and imbalanced mitochondrial lipids. Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 gene and cancer cells lacking SLC25A48 exhibited decreased mitochondrial choline import, increased oxidative stress, and impaired cell proliferation. Together, this study demonstrates that SLC25A48 regulates mitochondrial choline catabolism, bioenergetics, and cell survival.

The application of laparoscopic ultrasound-guided intervention in renal hybrid surgery: case report.

Background: Conventional vascular interventions and hybrid surgery relied on digital subtraction angiography (DSA). Previously our center explored hybrid partial nephrectomy with DSA guidance, which demonstrates the superiority of omitting the dissection of renal hilum. However, this approach is limited to scarce hybrid operating rooms, involves radiation exposure, and poses compatibility issues with robotic surgery platforms. Laparoscopic ultrasound (LUS) can assist in robotic surgery. This study explored the application of LUS-guided occlusion of renal artery blood supply with a Fogarty balloon catheter, particularly in hybrid partial nephrectomy for renal tumor treatment. Case Description: The LUS-guided renal artery balloon catheter occluded hybrid partial nephrectomy (UBo-HPN) involved several steps: trans-femoral artery cannulation, placement of the balloon catheter into the renal artery via the femoral vascular sheath, occlusion of the renal blood supply by inflating the balloon catheter, completion of zero-ischemia partial nephrectomy with arterial flow occluded, withdrawal of the balloon catheter after deflation. For all three patients, the balloon catheter was successfully and accurately placed into the selected renal artery under LUS guidance. Intraoperative occlusion of the renal blood supply was confirmed to be complete and reversible. No complications were observed during follow-up. Conclusions: LUS guidance presents a safe alternative to DSA guidance for assisting in hybrid surgery. LUS-guided hybrid partial nephrectomy is safe and feasible.

Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Building a translational cancer dependency map for The Cancer Genome Atlas.

Cancer dependency maps have accelerated the discovery of tumor vulnerabilities that can be exploited as drug targets when translatable to patients. The Cancer Genome Atlas (TCGA) is a compendium of 'maps' detailing the genetic, epigenetic and molecular changes that occur during the pathogenesis of cancer, yet it lacks a dependency map to translate gene essentiality in patient tumors. Here, we used machine learning to build translational dependency maps for patient tumors, which identified tumor vulnerabilities that predict drug responses and disease outcomes. A similar approach was used to map gene tolerability in healthy tissues to prioritize tumor vulnerabilities with the best therapeutic windows. A subset of patient-translatable synthetic lethalities were experimentally tested, including PAPSS1/PAPSS12 and CNOT7/CNOT78, which were validated in vitro and in vivo. Notably, PAPSS1 synthetic lethality was driven by collateral deletion of PAPSS2 with PTEN and was correlated with patient survival. Finally, the translational dependency map is provided as a web-based application for exploring tumor vulnerabilities.

BPA exposure and Se deficiency caused spleen damage in chickens by nitrification stress-TNF-α.

With the increasing production and demand of plastic products in life, inescapable bisphenol A (BPA) exposure results in a threat to the health of organisms. Selenium (Se) is an essential trace element for living organisms. The insufficient Se intake can cause multi-tissue organ damage. In the process of production and life, the exposure of BPA is usually accompanied by Se deficiency. In this study, the models of chicken with BPA exposure and/or Se deficiency was duplicated, the status of nitrification stress, apoptosis, necroptosis, and changes in TNF-α/FADD signaling pathways in chicken spleen were examined. At the same time, nitrification stress inhibitor and TNF-α inhibitor were introduced into MSB-1 cell model tests in vitro, indicating that BPA exposure and Se deficiency up-regulated TNF-α/FADD signaling pathway through nitrification stress, inducing necroptosis and apoptosis, and heat shock protein was also involved in this process. This study provides a new control idea for healthy poultry breeding based on Se, and also provides a new reference for toxicity control of environmental pollutants.

Neighborhood Resources and Health Outcomes Among Stroke Survivors in a Population-Based Cohort.

BACKGROUND: Stroke survivors believe neighborhood resources such as community centers are beneficial; however, little is known about the influence of these resources on stroke outcomes. We evaluated whether residing in neighborhoods with greater resource density is associated with favorable post-stroke outcomes. METHODS AND RESULTS: We included Mexican American and non-Hispanic White stroke survivors from the Brain Attack Surveillance in Corpus Christi project (2009-2019). The exposure was density of neighborhood resources (eg, community centers, restaurants, stores) within a residential census tract at stroke onset. Outcomes included time to death and recurrence, and at 3 months following stroke: disability (activities of daily living/instrumental activities of daily living), cognition (Modified Mini-Mental State Exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life scale). We fit multivariable Cox regression and mixed linear models. We considered interactions with stroke severity, ethnicity, and sex. Among 1786 stroke survivors, median age was 64 years (interquartile range, 56-73), 55% men, and 62% Mexican American. Resource density was not associated with death, recurrence, or depression. Greater resource density (75th versus 25th percentile) was associated with more favorable cognition (Modified Mini-Mental State Exam mean difference=0.838, 95% CI=0.092, 1.584) and among moderate-severe stroke survivors, with more favorable functioning (activities of daily living/instrumental activities of daily living=-0.156 [95% CI, -0.284 to 0.027]) and quality of life (abbreviated Stroke-Specific Quality of Life scale=0.194 [95% CI, 0.029-0.359]). CONCLUSIONS: We observed associations between greater resource density and cognition overall and with functioning and quality of life among moderate-severe stroke survivors. Further research is needed to confirm these findings and determine if neighborhood resources may be a tool for recovery.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

Meta-analysis of the accuracy for RASSF1A methylation in bronchial aspirates for the diagnosis of lung cancer.

OBJECTIVE: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis. METHODS: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias. RESULTS: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance. CONCLUSIONS: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer.

Circulating Metabolite Biomarkers of Glycemic Control in Youth-Onset Type 2 Diabetes.

OBJECTIVE: We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10-17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0-36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS: Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of ß-cell function. CONCLUSIONS: Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.

The photoactivated antifungal activity and possible mode of action of sodium pheophorbide a on Diaporthe mahothocarpus causing leaf spot blight in Camellia oleifera.

Introduction: Sodium pheophorbide a (SPA) is a natural plant-derived photosensitizer, with high photoactivated antifungal activity against some phytopathogenic fungi. However, its fungicidal effect on Diaporthe mahothocarpus, a novel pathogen that causes Camellia oleifera leaf spot blight, is unclear. Methods: In the present study, we explored its inhibitory effects on spore germination and mycelial growth of D. mahothocarpus. Then we determined its effects on the cell membrane, mycelial morphology, redox homeostasis, and cell death through bioassay. Finally, RNA-seq was used further to elucidate its mode of action at the transcriptional level. Results: We found that SPA effectively inhibited the growth of D. mahothocarpus, with half-maximal effective concentrations to inhibit mycelial growth and spore germination of 1.059 and 2.287 mg/mL, respectively. After 1.0 mg/mL SPA treatment, the conductivity and malondialdehyde content of D. mahothocarpus were significantly increased. Scanning electron microscopy and transmission electron microscopy indicated that SPA significantly affected the morphology and ultrastructure of D. mahothocarpus hyphae, revealing that SPA can destroy the mycelial morphology and cell structure, especially the cell membrane of D. mahothocarpus. Furthermore, transcriptome analysis revealed that SPA significantly suppressed the expression of genes involved in morphology, cell membrane permeability, and oxidative stress. Then, we also found that SPA significantly promoted the accumulation of reactive oxygen species (ROS) in of D. mahothocarpus, while it decreased the content of reduced glutathione, inhibited the enzyme activities of superoxide dismutase and catalase, and exacerbated DNA damage. Annexin V-FITC/PI staining also confirmed that 1.0 mg/mL SPA could significantly induce apoptosis and necrosis. Discussion: Generally, SPA can induce ROS-mediated oxidative stress and cell death, thus destroying the cell membrane and hyphal morphology, and ultimately inhibiting mycelial growth, which indicates that SPA has multiple modes of action, providing a scientific basis for the use of SPA as an alternative plant-derived photoactivated fungicide against C. oleifera leaf spot blight.

TIR8 protects against nonalcoholic steatohepatitis by antagonizing lipotoxicity-induced PPARα downregulation and reducing the sensitivity of hepatocytes to LPS.

In up to one-third of nonalcoholic fatty liver disease (NAFLD) patients, simple steatosis progresses to its more severe form, nonalcoholic steatohepatitis (NASH), but the precise mechanisms underlying this transition are not fully understood. Toll/interleukin-1 receptor 8 (TIR8), a conventional innate immune regulator highly expressed in hepatic tissue, has shown potential for ameliorating various inflammation-related disorders. However, its role in NASH pathogenesis, especially its regulatory effects on lipid metabolism and inflammatory responses, is still unclear. Here, using a TIR8 knockout (TIR8KO) mouse model and mass spectrometry analyses, we found that TIR8KO mice displayed aggravated hepatic steatosis and inflammation, whereas TIR8 overexpression attenuated these adverse effects. Ectopic TIR8 expression counteracts free fatty acid (FFA)-induced PPARα inhibition and downstream signaling. A decrease in TIR8 levels in hepatocytes heightened lipopolysaccharide (LPS) sensitivity. Notably, FFA stimulation led to a direct interaction between TIR8 and proteasome subunit alpha type 4 (PSMA4), facilitating TIR8 degradation. These results revealed that TIR8 safeguards PPARα-regulated lipid metabolism and mitigates inflammation induced by external factors during NASH progression. Our study highlights TIR8 as a promising target for NASH therapy, indicating the potential of TIR8 agonists in treatment strategies.

Obscured Contribution of Oxygenated Intermediate-Volatility Organic Compounds to Secondary Organic Aerosol Formation from Gasoline Vehicle Emissions.

Secondary organic aerosol (SOA) formation from gasoline vehicles spanning a wide range of emission types was investigated using an oxidation flow reactor (OFR) by conducting chassis dynamometer tests. Aided by advanced mass spectrometric techniques, SOA precursors, including volatile organic compounds (VOCs) and intermediate/semivolatile organic compounds (I/SVOCs), were comprehensively characterized. The reconstructed SOA produced from the speciated VOCs and I/SVOCs can explain 69% of the SOA measured downstream of an OFR upon 0.5-3 days' OH exposure. While VOCs can only explain 10% of total SOA production, the contribution from I/SVOCs is 59%, with oxygenated I/SVOCs (O-I/SVOCs) taking up 20% of that contribution. O-I/SVOCs (e.g., benzylic or aliphatic aldehydes and ketones), as an obscured source, account for 16% of total nonmethane organic gas (NMOG) emission. More importantly, with the improvement in emission standards, the NMOG is effectively mitigated by 35% from China 4 to China 6, which is predominantly attributed to the decrease of VOCs. Real-time measurements of different NMOG components as well as SOA production further reveal that the current emission control measures, such as advances in engine and three-way catalytic converter (TWC) techniques, are effective in reducing the "light" SOA precursors (i.e., single-ring aromatics) but not for the I/SVOC emissions. Our results also highlight greater effects of O-I/SVOCs to SOA formation than previously observed and the urgent need for further investigation into their origins, i.e., incomplete combustion, lubricating oil, etc., which requires improvements in real-time molecular-level characterization of I/SVOC molecules and in turn will benefit the future design of control measures.

Metal-containing nanoparticles in road dust from a Chinese megacity over the last decade: Spatiotemporal variation and driving factors.

As a crucial sink of metal-containing nanoparticles (MNPs), road dust can record their spatiotemporal variations in urban environments. In this study, taking Shanghai as a representative megacity in China, a total of 272 dust samples were collected in the winter and summer of 2013 and 2021/2022 to understand the spatiotemporal variations and driving factors of MNPs. The number concentrations of Fe-, Ti-, and Zn-containing NPs were 3.8 × 106 - 8.4 × 108, 2.3 × 106-1.4 × 108, and 6.0 × 105-2.3 × 108 particles/mg, respectively, according to single particle (sp)ICP-MS analysis. These MNPs showed significantly higher number concentrations in summer than in winter. Hotspots of Fe-containing NPs were more concentrated in industrial and traffic areas, Zn-containing NPs were mainly distributed in the central urban areas, while Ti-containing NPs were abundant in areas receiving high rainfall. The structural equation model results indicates that substantial rainfall in summer can help remove MNPs from atmospheric PM2.5 into dust, while in winter industrial and traffic activities were the primary contributors for MNPs. Moreover, the contribution of traffic emissions to MNPs has surpassed industrial one over the last decade, highlighting the urgency to control traffic-sourced MNPs, especially those from non-exhaust emissions by electric vehicles.

Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.