De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5' splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

Association of vaccination, international travel, public health and social measures with lineage dynamics of SARS-CoV-2.

Continually emerging SARS-CoV-2 variants of concern that can evade immune defenses are driving recurrent epidemic waves of COVID-19 globally. However, the impact of measures to contain the virus and their effect on lineage diversity dynamics are poorly understood. Here, we jointly analyzed international travel, public health and social measures (PHSM), COVID-19 vaccine rollout, SARS-CoV-2 lineage diversity, and the case growth rate (GR) from March 2020 to September 2022 across 63 countries. We showed that despite worldwide vaccine rollout, PHSM are effective in mitigating epidemic waves and lineage diversity. An increase of 10,000 monthly travelers in a single country-to-country route between endemic countries corresponds to a 5.5% (95% CI: 2.9 to 8.2%) rise in local lineage diversity. After accounting for PHSM, natural immunity from previous infections, and waning immunity, we discovered a negative association between the GR of cases and adjusted vaccine coverage (AVC). We also observed a complex relationship between lineage diversity and vaccine rollout. Specifically, we found a significant negative association between lineage diversity and AVC at both low and high levels but not significant at the medium level. Our study deepens the understanding of population immunity and lineage dynamics for future pandemic preparedness and responsiveness.

Intermediate open state of CD4-bound HIV-1 env heterotrimers in asia CRFs.

The HIV-1 envelope glycoprotein (Env) plays crucial role in viral infection by facilitating viral attachment to host cells and inducing fusion of the virus with the host cell membrane. This fusion allows the HIV-1 viral genome to enter the target cell then triggering various stages of the viral life cycle. The native Env directly interacts with the main receptor CD4 and the co-receptor (CCR5 or CXCR4) in human cell membrane then induces membrane fusion. The elucidation of the structure of Env with CD4 and co-receptors in different HIV-1 subtypes is essential for the understanding of the mechanism of virus entry. Here we report the Cryo-EM structure of the CD4-bound HIV-1 heterotrimeric Env from Asia prevalent CRF07_BC CH119 strain. In this structure, the binding of three CD4 molecules with Env induced extensively conformational changes in gp120, resulting in the transformation of the Env from close state to intermediate open state. Additionally, the conformational shift of V1/V2 loops of the heterotrimeric Env allosterically expose the V3 loop and promoting the further interactions with co-receptor CCR5 or CXCR4. These findings not only illustrate the structural complexity and plasticity of HIV-1 Env but also give new insights how the biological trimeric Env initialize the immune recognition and membrane fusion.

Glutathione-responsive Aggregation-induced Emission Photosensitizers for Enhanced Photodynamic Therapy of Lung Cancer.

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.

A new artificial intelligence system for both stomach and small-bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

Antioxidant Carbon Dots Nanozymes Alleviate Stress-induced Depression by Modulating Gut Microbiota.

Depression is a debilitating mental illness that severely threatens millions of individuals and public health. Because of the multifactorial etiologies, there is currently no cure for depression; thus, it is urgently imperative to find alternative antidepressants and strategies. Growing evidence underscores the prominent role of oxidative stress as key pathological hallmarks of depression, making oxidative stress a potential therapeutic target. In this study, we report a N-doped carbon dot nanozyme (CDzyme) with excellent antioxidant capacity for treating depression by remodeling redox homeostasis and gut microbiota. The CDzymes prepared via microwave-assisted fast polymerization of histidine and glucose exhibit superior biocompatibility. Benefiting from the unique structure, CDzymes can provide abundant electrons, hydrogen atoms, and protons for reducing reactions, as well as catalytic sites to mimic redox enzymes. These mechanisms collaborating endow CDzymes with broad-spectrum antioxidant capacity to scavenge reactive oxygen and nitrogen species (•OH, O2-•, H2O2, ONOO-), and oxygen/nitrogen centered free radicals. A depression animal model was established by chronic unpredictable mild stress (CUMS) to evaluate the therapeutic efficacy of CDzymes from the behavioral, physiological, and biochemical index and intestinal flora assessments. CDzymes can remarkably improve depression-like behaviors and key neurotransmitters produced in hippocampus tissues and restore the gut microbiota compositions and the amino acid metabolic functions, proving the potential in treating depression through the intestinal-brain axis system. This study will facilitate the development of intestinal flora dysbiosis nanomedicines and treatment strategies for depression and other oxidative stress related multifactorial diseases.

Strong and consistent effects of waterbird composition on HPAI H5 occurrences across Europe.

Since 2014, highly pathogenic avian influenza (HPAI) H5 viruses of clade 2.3.4.4 have been dominating the outbreaks across Europe, causing massive deaths among poultry and wild birds. However, the factors shaping these broad-scale outbreak patterns, especially those related to waterbird community composition, remain unclear. In particular, we do not know whether these risk factors differ from those of other H5 clades. Addressing this knowledge gap is important for predicting and preventing future HPAI outbreaks. Using extensive waterbird survey datasets from about 6883 sites, we here explored the effect of waterbird community composition on HPAI H5Nx (clade 2.3.4.4) spatial patterns in the 2016/2017 and 2020/2021 epidemics in Europe, and compared it with the 2005/2006 HPAI H5N1 (clade 2.2) epidemic. We showed that HPAI H5 occurrences in wild birds in the three epidemics were strongly associated with very similar waterbird community attributes, which suggested that, in nature, similar interspecific transmission processes operate between the HPAI H5 subtypes or clades. Importantly, community phylogenetic diversity consistently showed a negative association with H5 occurrence in all three epidemics, suggesting a dilution effect of phylogenetic diversity. In contrast, waterbird community variables showed much weaker associations with HPAI H5Nx occurrence in poultry. Our results demonstrate that models based on previous epidemics can predict future HPAI H5 patterns in wild birds, implying that it is important to include waterbird community factors in future HPAI studies to predict outbreaks and improve surveillance activities.

Satellite NO2 Retrieval Complicated by Aerosol Composition over Global Urban Agglomerations: Seasonal Variations and Long-Term Trends (2001-2018).

Tropospheric nitrogen dioxide (NO2) poses a serious threat to the environmental quality and public health. Satellite NO2 observations have been continuously used to monitor NO2 variations and improve model performances. However, the accuracy of satellite NO2 retrieval depends on the knowledge of aerosol optical properties, in particular for urban agglomerations accompanied by significant changes in aerosol characteristics. In this study, we investigate the impacts of aerosol composition on tropospheric NO2 retrieval for an 18 year global data set from Global Ozone Monitoring Experiment (GOME)-series satellite sensors. With a focus on cloud-free scenes dominated by the presence of aerosols, individual aerosol composition affects the uncertainties of tropospheric NO2 columns through impacts on the aerosol loading amount, relative vertical distribution of aerosol and NO2, aerosol absorption properties, and surface albedo determination. Among aerosol compositions, secondary inorganic aerosol mostly dominates the NO2 uncertainty by up to 43.5% in urban agglomerations, while organic aerosols contribute significantly to the NO2 uncertainty by -8.9 to 37.3% during biomass burning seasons. The possible contrary influences from different aerosol species highlight the importance and complexity of aerosol correction on tropospheric NO2 retrieval and indicate the need for a full picture of aerosol properties. This is of particular importance for interpreting seasonal variations or long-term trends of tropospheric NO2 columns as well as for mitigating ozone and fine particulate matter pollution.

Large-Area Film Thickness Identification of Transparent Glass by Hyperspectral Imaging.

This study introduces a novel method for detecting and measuring transparent glass sheets using hyperspectral imaging (HSI). The main goal of this study is to create a conversion technique that can accurately display spectral information from collected images, particularly in the visible light spectrum (VIS) and near-infrared (NIR) areas. This technique enables the capture of relevant spectral data when used with images provided by industrial cameras. The next step in this investigation is using principal component analysis to examine the obtained hyperspectral images derived from different treated glass samples. This analytical procedure standardizes the magnitude of light wavelengths that are inherent in the HSI images. The simulated spectral profiles are obtained using the generalized inverse matrix technique on the normalized HSI images. These profiles are then matched with spectroscopic data obtained from microscopic imaging, resulting in the observation of distinct dispersion patterns. The novel use of images coloring methods effectively displays the thickness of the glass processing sheet in a visually noticeable way. Based on empirical research, changes in the thickness of the glass coating in the NIR-HSI range cause significant changes in the transmission of infrared light at different wavelengths within the NIR spectrum. This phenomenon serves as the foundation for the study of film thickness. The root mean square error inside the NIR area is impressively low, calculated to be just 0.02. This highlights the high level of accuracy achieved by the technique stated above. Potential areas of investigation that arise from this study are incorporating the proposed approach into the design of a real-time, wide-scale automated optical inspection system.

Analysis of MRI features and associated factors of the pituitary neuroendocrine tumor streaky sign.

OBJECTIVES: Observation of pituitary neuroendocrine tumors with streaky sign on MRI, analysis of their features on imaging and further investigation of the relationship between the direction of the streak sign and the direction of optimal tumor expansion. METHODS: The MR images of 237 patients with pituitary neuroendocrine tumors were retrospectively analyzed. The streaky-like high signal with a substantial length of more than 10 mm and obvious enhancement on T1WI was defined as the streaky sign. Finally, 66 patients were included in the study, comprising 33 patients with streaky sign pituitary neuroendocrine tumors and 33 randomly selected patients with non-streaky sign pituitary neuroendocrine tumors. The general condition of these 66 patients, the imaging features of the tumor, and the measurement and analysis of the direction of the streaky sign in relation to the direction of optimal tumor extension were observed and analyzed. RESULTS: On MRI, 85 streaky signs were observed. The average deviation between the direction angle of all the streaky signs and the optimal extension direction angle of the tumor was approximately 11°. The longest streaky sign angle was positively correlated with the optimal extension angle of the tumor, with a correlation coefficient of 0.967. CONCLUSION: The presence of a streaky sign of pituitary neuroendocrine tumors may indicate a dilated sinus or a small blood vessel. Its direction is highly consistent with the optimal extension direction of the tumor, which has a certain supporting effect on the long-distance growth of the tumor.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Camera calibration using the dual double-contact property of circles.

To mitigate the influence of the relative positional relationship between circles on camera calibration, this study explores the double contact of dual circles with dual circular points. We demonstrate that one of the generalized eigenvectors of two dual circles corresponds to the line passing through their respective centers. Moreover, we establish a methodology to identify this line from the three generalized eigenvectors and show that, regardless of the positional arrangement of the three co-planar circles, the image of the circular points can be constructed by calculating the image of this line. Consequently, the applicability of circles as calibration templates is expanded, enabling the development of a novel optimization technique for fitting circular images with enhanced calibration precision.

Occurrence, risk assessment, and in vitro and in vivo toxicity of antibiotics in surface water in China.

Antibiotics have been widely detected in the water environment and thus pose a potential threat to human health. Although antibiotics have health-promoting properties, whether and how they affect health at environmental concentrations remains uncharacterised. We detected antibiotics in surface water and groundwater in China. Sulfonamides (851 ng/L) and tetracyclines (1322 ng/L) showed the highest concentrations in surface water, while the highest concentration of sulfonamides detected in groundwater was 250 ng/L. We analysed the distribution of four classes of antibiotics (sulfonamides, tetracyclines, macrolides, and quinolones) and evaluated the associated health risks in the surface water of seven cities. We found that antibiotic pollution caused health risks to the 0-3-months age group, but not to other age groups. We further demonstrated that simulated long-term exposure to environmental concentrations of antibiotics had concentration-dependent toxic effects on L-02 hepatocytes, affected cell proliferation, and induced oxidative damage and DNA damage. Chronic exposure to mixed sulfonamides affected growth, caused liver damage, and reduced the abundance of intestinal flora in mice. Under exposure to antibiotics, the abundance of Helicobacter pylori in the gut flora significantly increased and posed a health risk to humans. These results indicated that exposure to antibiotics at environmental concentrations can cause oxidative damage and inflammation both in vitro and in vivo. These findings add to the body of basic data on the distribution of antibiotics in the water environment, and provide a scientific basis for the evaluation of antibiotic toxicity.

Enhancing Multi-disease Diagnosis of Chest X-rays with Advanced Deep-learning Networks in Real-world Data.

The current artificial intelligence (AI) models are still insufficient in multi-disease diagnosis for real-world data, which always present a long-tail distribution. To tackle this issue, a long-tail public dataset, "ChestX-ray14," which involved fourteen (14) disease labels, was randomly divided into the train, validation, and test sets with ratios of 0.7, 0.1, and 0.2. Two pretrained state-of-the-art networks, EfficientNet-b5 and CoAtNet-0-rw, were chosen as the backbones. After the fully-connected layer, a final layer of 14 sigmoid activation units was added to output each disease's diagnosis. To achieve better adaptive learning, a novel loss (Lours) was designed, which coalesced reweighting and tail sample focus. For comparison, a pretrained ResNet50 network with weighted binary cross-entropy loss (LWBCE) was used as a baseline, which showed the best performance in a previous study. The overall and individual areas under the receiver operating curve (AUROC) for each disease label were evaluated and compared among different models. Group-score-weighted class activation mapping (Group-CAM) is applied for visual interpretations. As a result, the pretrained CoAtNet-0-rw + Lours showed the best overall AUROC of 0.842, significantly higher than ResNet50 + LWBCE (AUROC: 0.811, p = 0.037). Group-CAM presented that the model could pay the proper attention to lesions for most disease labels (e.g., atelectasis, edema, effusion) but wrong attention for the other labels, such as pneumothorax; meanwhile, mislabeling of the dataset was found. Overall, this study presented an advanced AI diagnostic model achieving a significant improvement in the multi-disease diagnosis of chest X-rays, particularly in real-world data with challenging long-tail distributions.

The Males Absent on the First (MOF) Mediated Acetylation Alters the Protein Stability and Transcriptional Activity of YY1 in HCT116 Cells.

Yin Yang 1 (YY1) is a well-known transcription factor that controls the expression of many genes and plays an important role in the occurrence and development of various cancers. We previously found that the human males absent on the first (MOF)-containing histone acetyltransferase (HAT) complex may be involved in regulating YY1 transcriptional activity; however, the precise interaction between MOF-HAT and YY1, as well as whether the acetylation activity of MOF impacts the function of YY1, has not been reported. Here, we present evidence that the MOF-containing male-specific lethal (MSL) HAT complex regulates YY1 stability and transcriptional activity in an acetylation-dependent manner. First, the MOF/MSL HAT complex was bound to and acetylated YY1, and this acetylation further promoted the ubiquitin-proteasome degradation pathway of YY1. The MOF-mediated degradation of YY1 was mainly related to the 146-270 amino acid residues of YY1. Further research clarified that acetylation-mediated ubiquitin degradation of YY1 mainly occurred through lysine 183. A mutation at the YY1K183 site was sufficient to alter the expression level of p53-mediated downstream target genes, such as CDKN1A (encoding p21), and it also suppressed the transactivation of YY1 on CDC6. Furthermore, a YY1K183R mutant and MOF remarkably antagonized the clone-forming ability of HCT116 and SW480 cells facilitated by YY1, suggesting that the acetylation-ubiquitin mode of YY1 plays an important role in tumor cell proliferation. These data may provide new strategies for the development of therapeutic drugs for tumors with high expression of YY1.

Involvement of m6A regulatory factor IGF2BP1 in malignant transformation of human bronchial epithelial Beas-2B cells induced by tobacco carcinogen NNK.

Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a Group 1 human carcinogen, as classified by the International Agency for Research of Cancer (IARC), and plays a significant role in lung carcinogenesis. However, its carcinogenic mechanism has not yet been fully elucidated. In this study, we performed colony formation assays, soft-agar assays, and tumor growth in nude mice to show that 100 mg/L NNK facilitates the malignant transformation of human bronchial epithelial Beas-2B cells. Transcriptome sequencing showed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a post-transcriptional regulator, was differentially expressed in NNK-induced malignant transformed Beas-2B cells (2B-NNK cells). Small interfering RNA (SiRNA) was used to downregulate the expression of the IGF2BP1 gene. The reduction in protein expression, cell proliferation rate, and colony-forming ability and the increase in the apoptosis rate of Beas-2B cells transfected with the SiRNA indicated a role for IGF2BP1 in NNK-induced malignant transformation. IGF2BP1 is an N6-methyladenosine (m6A) regulatory factor, but it is not known whether its association with m6A mediates the malignant transformation of cells. Therefore, we measured the overall levels of m6A in Beas-2B cells. We found that the overall m6A level was lower in 2B-NNK cells, and knocking down IGF2BP1, the overall level of m6A was restored. Hence, we concluded that IGF2BP1 is involved in the NNK-induced malignant transformation of Beas-2B cells, possibly via m6A modification. This study therefore contributes novel insights into the environmental pathogenesis of lung cancer and the gene regulatory mechanisms of chemical carcinogenesis.

Oxidative Stress, Endocrine Disturbance, and Immune Interference in Humans Showed Relationships to Serum Bisphenol Concentrations in a Dense Industrial Area.

Bisphenol A (BPA) analogues, used in a range of products due to health concerns regarding BPA, have emerged as ubiquitous environmental contaminants worldwide. This study aims to evaluate the levels of nine bisphenols (BPs) and eight biomarkers (malondialdehyde, MDA; 8-hydroxy-2'-deoxyguanosine, 8-OHdG; estradiol, E2; follicle-stimulating hormone, FSH; luteinizing hormone, LH; complement compound 3, C3; immunoglobulin M, IgM and c-reaction protein, CRP) in human serum (n = 353) to explore their potential relationships. The detection rates (DRs) of eight BPs in serum samples taken from people working in a dense industrial area of Shenzhen (Guangdong Province, China) were over 72% except for bisphenol B (BPB) (DR = 27.5%). The mean concentrations of BPA, bisphenol P (BPP), BPB, bisphenol F (BPF), bisphenol FL (BPFL), 4,4'-dihydroxy-benzophenone (DHBP), bisphenol AF (BPAF), 4,4'-thiodiphenol (TDP) and bisphenol S (BPS) were 42.062, 2.083, 0.765, 0.578, 0.423, 0.402, 0.191, 0.120, and 0.071 ng/mL, respectively. BPA and BPFL were significantly correlated with the level of oxidative stress indices MDA and 8-OHdG; BPAF, BPB, and DHBP were strongly correlated with the level of endocrine disturbance indices E2, FSH, and LH; and BPF, DHBP, and BPAF were apparently related to the level of immune interference indices C3 and IgM. This study also suggests multiple impacts (oxidative stress, endocrine disturbance, and immune interference) mediated by BPs contaminants in vivo. To our knowledge, this is the first study to report the correlations among these nine serum BPs and oxidative stress and endocrine and immune system indices in human serum samples collected from dense industrial areas.

Global Significant Changes in Formaldehyde (HCHO) Columns Observed From Space at the Early Stage of the COVID-19 Pandemic.

Satellite HCHO data are widely used as a reliable proxy of non-methane volatile organic compounds (NMVOCs) to constrain underlying emissions and chemistry. Here, we examine global significant changes in HCHO columns at the early stage of the COVID-19 pandemic (January-April 2020) compared with the same period in 2019 with observations from the TROPOspheric Monitoring Instrument (TROPOMI). HCHO columns decline (11.0%) in the Northern China Plain (NCP) because of a combination of meteorological impacts, lower HCHO yields as NO x emission plunges (by 36.0%), and reduced NMVOC emissions (by 15.0%) resulting from the lockdown. HCHO columns change near Beijing (+8.4%) due mainly to elevated hydroxyl radical as NO x emission decreases in a NO x -saturated regime. HCHO columns change in Australia (+17.5%), Northeastern Myanmar of Southeast Asia (+14.9%), Central Africa (+7.8%), and Central America (+18.9%), consistent with fire activities. Our work also points to other changes related to temperature and meteorological variations.

Effect of CRRT combined with low-flow ECMO on canines with ARDS and hypercapnia.

To observe the effect of continuous renal replacement therapy (CRRT) combined with low-flow extracorporeal membrane oxygenation (ECMO) of V-V mode on anti-inflammation, improving oxygenation and reducing PaCO2 in canines with acute respiratory distress syndrome (ARDS) and hypercapnia. A total of 30 healthy adult canines were randomly divided into sham group (n = 10), ECMO (EC) group (n = 10) and CRRT + ECMO (CR + EC) group (n = 10). Sham group was only treated with invasive mechanical ventilation. EC group was also treated with ECMO. CR + EC group was treated with CRRT combined with low-flow ECMO of V-V mode besides invasive mechanical ventilation. The results showed that hazard ratio was lower in the CR + EC group. Inflammatory factors, OI values, and PaCO2 levels were lower in the CR + EC group. There was no significant difference in the levels of MAP, CO and T among the three groups. No significant complications or death was developed in the three groups. Compared with ECMO group at T3, T6 and T9, IL-6 [(276.13 ± 8.32, 262.04 ± 7.15, 259.33 ± 7.31)ng/L VS (352.67 ± 19.24, 360.24 ± 23.58, 362.21 ± 25.24)ng/L] and TNF-α [(50.14 ± 1.75, 50.45 ± 1.81, 48.03 ± 1.24) ng/L VS (70.25 ± 3.02, 72.45 ± 3.25, 76.69 ± 2.18)ng/L] in CR + EC group were decreased (P < 0.0001). Compared with sham group, IL-6 [(343.76 ± 21.97, 345.91 ± 19.89, 340.34 ± 22.17)ng/L]and TNF-α [(68.10 ± 2.96, 67.31 ± 3.01, 70.34 ± 3.35)ng/L] of T3, T6 and T9 in CR + EC group were lower (P < 0.0001). These findings indicated that CRRT combined with low-flow ECMO of V-V mode had a positive effect on anti-inflammation, oxygenation improvement and surplus blood CO2 removal in canines with ARDS and hypercapnia. These results provide a promising treatment regimen for ARDS.