Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future.

Background: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor. Methods: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH. Utilizing BMI data from the NCD Risk Factor Collaboration (NCD-RisC) database at both global and regional levels, the prevalence of NAFLD/NASH among adults was estimated from 1975 to 2016, encompassing global, regional, and national perspectives. Additionally, projections were made to forecast the prevalence of adult NAFLD/NASH from 2017 to 2030. Results: In 2016, the global prevalence of NAFLD was 41.12% for males and 37.32% for females, while the global prevalence of NASH was 15.79% for males and 16.48% for females. The prevalence of NAFLD/NASH increased with higher BMI in both genders. Over the period from 1975 to 2016, there has been a gradual increase in the global prevalence of NAFLD/NASH in adults, and this trend is expected to continue between 2017 and 2030. In males, the prevalence of adult NAFLD/NASH was found to be highest in High-income Western countries, while it was highest in Central Asia, Middle East, and North African countries after 1995. Conclusions: The prevalence of adult NAFLD/NASH has been observed to increase annually, with significant variations in burden across different countries and regions.

Neuronal double-stranded DNA accumulation induced by DNase II deficiency drives tau phosphorylation and neurodegeneration.

BACKGROUND: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. METHODS: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. RESULTS: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. CONCLUSIONS: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders.

A new method for scaling inlet flow waveform in hemodynamic analysis of aortic dissection.

Computational fluid dynamics (CFD) simulations have shown great potentials in cardiovascular disease diagnosis and postoperative assessment. Patient-specific and well-tuned boundary conditions are key to obtaining accurate and reliable hemodynamic results. However, CFD simulations are usually performed under non-patient-specific flow conditions due to the absence of in vivo flow and pressure measurements. This study proposes a new method to overcome this challenge by tuning inlet boundary conditions using data extracted from electrocardiogram (ECG). Five patient-specific geometric models of type B aortic dissection were reconstructed from computed tomography (CT) images. Other available data included stoke volume (SV), ECG, and 4D-flow magnetic resonance imaging (MRI). ECG waveforms were processed to extract patient-specific systole to diastole ratio (SDR). Inlet boundary conditions were defined based on a generic aortic flow waveform tuned using (1) SV only, and (2) with ECG and SV (ECG + SV). 4D-flow MRI derived inlet boundary conditions were also used in patient-specific simulations to provide the gold standard for comparison and validation. Simulations using inlet flow waveform tuned with ECG + SV not only successfully reproduced flow distributions in the descending aorta but also provided accurate prediction of time-averaged wall shear stress (TAWSS) in the primary entry tear (PET) and abdominal regions, as well as maximum pressure difference, ∆Pmax, from the aortic root to the distal false lumen. Compared with simulations with inlet waveform tuned with SV alone, using ECG + SV in the tuning method significantly reduced the error in false lumen ejection fraction at the PET (from 149.1% to 6.2%), reduced errors in TAWSS at the PET (from 54.1% to 5.7%) and in the abdominal region (from 61.3% to 11.1%), and improved ∆Pmax prediction (from 283.1% to 18.8%) However, neither of these inlet waveforms could be used for accurate prediction of TAWSS in the ascending aorta. This study demonstrates the importance of SDR in tailoring inlet flow waveforms for patient-specific hemodynamic simulations. A well-tuned flow waveform is essential for ensuring that the simulation results are patient-specific, thereby enhancing the confidence and fidelity of computational tools in future clinical applications.

Data Quality Assessment of Gravity Recovery and Climate Experiment Follow-On Accelerometer.

Accelerometers are mainly used to measure the non-conservative forces at the center of mass of gravity satellites and are the core payloads of gravity satellites. All kinds of disturbances in the satellite platform and the environment will affect the quality of the accelerometer data. This paper focuses on the quality assessment of accelerometer data from the GRACE-FO satellites. Based on the ACC1A data, we focus on the analysis of accelerometer data anomalies caused by various types of disturbances in the satellite platform and environment, including thruster spikes, peaks, twangs, and magnetic torque disturbances. The data characteristics and data accuracy of the accelerometer in different operational states and satellite observation modes are analyzed using accelerometer observation data from different time periods. Finally, the data consistency of the accelerometer is analyzed using the accelerometer transplantation method. The results show that the amplitude spectral density of three-axis linear acceleration is better than the specified accuracy (above 10-1 Hz) in the accelerometer's nominal status. The results are helpful for understanding the characteristics and data accuracy of GRACE-FO accelerometer observations.

Main focus of parents of children with attention deficit hyperactivity disorder and the effectiveness of early clinical screening.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common mental and behavioral disorder among children. AIM: To explore the focus of attention deficit hyperactivity disorder parents and the effectiveness of early clinical screening. METHODS: This study found that the main directions of parents seeking medical help were short attention time for children under 7 years old (16.6%) and poor academic performance for children over 7 years old (12.1%). We employed a two-stage experiment to diagnose ADHD. Among the 5683 children evaluated from 2018 to 2021, 360 met the DSM-5 criteria. Those diagnosed with ADHD underwent assessments for letter, number, and figure attention. Following the exclusion of ADHD-H diagnoses, the detection rate rose to 96.0%, with 310 out of 323 cases identified. RESULTS: This study yielded insights into the primary concerns of parents regarding their children's symptoms and validated the efficacy of a straightforward diagnostic test, offering valuable guidance for directing ADHD treatment, facilitating early detection, and enabling timely intervention. Our research delved into the predominant worries of parents across various age groups. Furthermore, we showcased the precision of the simple exclusion experiment in discerning between ADHD-I and ADHD-C in children. CONCLUSION: Our study will help diagnose and guide future treatment directions for ADHD.

Bioinformatics analysis reveals CCR7 as a potential biomarker for predicting CKD progression.

Chronic kidney disease (CKD) inevitably progresses to end-stage renal disease if intervention does not occur timely. However, there are limitations in predicting the progression of CKD by solely relying on changes in renal function. A biomarker with high sensitivity and specificity that can predict CKD progression early is required. We used the online Gene Expression Omnibus microarray dataset GSE45980 to identify differentially expressed genes (DEGs) in patients with progressive and stable CKD. We then performed functional enrichment and protein-protein interaction network analysis on DEGs and identified key genes. Finally, the expression patterns of key genes were verified using the GSE60860 dataset, and the receiver operating characteristic curve analysis was performed to clarify their predictive ability of progressive CKD. Ultimately, we verified the expression profiles of these hub genes in an in vitro renal interstitial fibrosis model by real-time PCR and western blot analysis. Differential expression analysis identified 50 upregulated genes and 47 downregulated genes. The results of the functional enrichment analysis revealed that upregulated DEGs were mainly enriched in immune response, inflammatory response, and NF-κB signaling pathways, whereas downregulated DEGs were mainly related to angiogenesis and the extracellular environment. Protein-protein interaction network and key gene analysis identified CCR7 as the most important gene. CCR7 mainly plays a role in immune response, and its only receptors, CCL19 and CCL21, have also been identified as DEGs. The receiver operating characteristic curve analysis of CCR7, CCL19, and CCL21 found that CCR7 and CCL19 present good disease prediction ability. CCR7 may be a stable biomarker for predicting CKD progression, and the CCR7-CCL19/CCL21 axis may be a therapeutic target for end-stage renal disease. However, further experiments are needed to explore the relationship between these genes and CKD.

Pre-pubertal sublingual immunotherapy is more effective than immunotherapy during puberty in allergic rhinitis and asthma.

BACKGROUND: To evaluate the clinical efficacy of sublingual-specific immunotherapy (SLIT) and pulmonary function in children with allergic rhinitis and asthma before and after puberty. METHODS: This retrospective analysis included 136 patients aged 4-18 years with allergic asthma and rhinitis who received two years of SLIT treatment. Patients were divided into two groups based on age: the prepubertal group (4-10 years old) and the pubertal group (11-18 years old). After half a year, one year, and two years of SLIT, the total nasal symptom score (TNSS), total rhinitis medication score (TRMS), daytime asthma symptom score (DASS), nighttime asthma symptom score (NASS), total asthma medication score (TAMS), asthma control test (ACT), and peak expiratory flow rate (PEF%) were evaluated and compared with the baseline before treatment. RESULTS: In both groups, TNSS, TRMS, DASS, NASS, TAMS, ACT, and PEF% improved significantly after half a year, one year, and two years of SLIT treatment. After half a year of treatment, prepubertal patients showed better therapy for TNSS, DASS, NASS, and TAMS compared to the pubertal group. The TAMS of the pubertal group was higher than that of the prepubertal group after one year of treatment. Finally, the PEF% showed better therapy compared to the pubertal group. CONCLUSION: SLIT treatment with Dermatophagoides farinae drops can effectively control the symptoms of rhinitis and asthma in children with allergic rhinitis and asthma before and after puberty, reduce the use of symptomatic drugs, significantly improve the pulmonary function of patients, and have better effects on asthma in prepubertal children than in adolescents.

Advancing towards practice: A novel LC-MS/MS method for detecting retinol in dried blood spots.

BACKGROUND: To date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards. METHODS: We incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis. RESULTS: By comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %. CONCLUSIONS: We realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients' vitamin A status by using DBS samples in the future.

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis.

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.

Laminarin-modulated osmium nanozymes with high substrate-affinity and selective peroxidase-like behavior engineered colorimetric assay for hydroxyl radical scavenging capacity estimation.

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3',5,5'-tetramethylbenzidine (TMB) (KM = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01-0.075 mM, glutathione 1-15 µg/mL, tannic acid 0.5-5 µM, and monoammonium glycyrrhizinate cysteine 1.06-10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond.

Four-dimensional analysis of aortic root motion in normal population using retrospective multiphase computed tomography.

Aims: Aortic root motion is suspected to contribute to proximal aortic dissection. While motion of the aorta in four dimensions can be traced with real-time imaging, displacement and rotation in quantitative terms remain unknown. The hypothesis was to show feasibility of quantification of three-dimensional aortic root motion from dynamic CT imaging. Methods and results: Dynamic CT images of 40 patients for coronary assessment were acquired using a dynamic protocol. Scans were ECG-triggered and segmented in 10 time-stepped phases (0-90%) per cardiac cycle. With identification of the sinotubular junction (STJ), a patient-specific co-ordinate system was created with the z-axis (out-of-plane) parallel to longitudinal direction. The left and right coronary ostia were traced at each time-step to quantify downward motion in reference to the STJ plane, motion within the STJ plane (in-plane), and the degree of rotation. Enrolled individuals had an age of 65 ± 12, and 14 were male (35%). The out-of-plane motion was recorded with the largest displacement of 10.26 ± 2.20 and 8.67 ± 1.69 mm referenced by left and right coronary ostia, respectively. The mean downward movement of aortic root was 9.13 ± 1.86 mm. The largest in-plane motion was recorded at 9.17 ± 2.33 mm and 6.51 ± 1.75 mm referenced by left and right coronary ostia, respectively. The largest STJ in-plane motion was 7.37 ± 1.96 mm, and rotation of the aortic root was 11.8 ± 4.60°. Conclusion: In vivo spatial and temporal displacement of the aortic root can be identified and quantified from multiphase ECG-gated contrast-enhanced CT images. Knowledge of normal 4D motion of the aortic root may help understand its biomechanical impact in patients with aortopathy and pre- and post-surgical or transcatheter aortic valve replacement.

Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy.

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

Gain-of-function variants in GSDME cause pyroptosis and apoptosis associated with post-lingual hearing loss.

Gasdermin E (GSDME), a member of the gasdermin protein family, is associated with post-lingual hearing loss. All GSDME pathogenic mutations lead to skipping exon 8; however, the molecular mechanisms underlying hearing loss caused by GSDME mutants remain unclear. GSDME was recently identified as one of the mediators of programmed cell death, including apoptosis and pyroptosis. Therefore, in this study, we injected mice with GSDME mutant (MT) and examined the expression levels to assess its effect on hearing impairment. We observed loss of hair cells in the organ of Corti and spiral ganglion neurons. Further, the N-terminal release from the GSDME mutant in HEI-OC1 cells caused pyroptosis, characterized by cell swelling and rupture of the plasma membrane, releasing lactate dehydrogenase and cytokines such as interleukin-1ß. We also observed that the N-terminal release from GSDME mutants could permeabilize the mitochondrial membrane, releasing cytochromes and activating the mitochondrial apoptotic pathway, thereby generating possible positive feedback on the cleavage of GSDME. Furthermore, we found that treatment with disulfiram or dimethyl fumarate might inhibit pyroptosis and apoptosis by inhibiting the release of GSDME-N from GSDME mutants. In conclusion, this study elucidated the molecular mechanism associated with hearing loss caused by GSDME gene mutations, offering novel insights for potential treatment strategies.

Oxysophoridine inhibits oxidative stress and inflammation in hepatic fibrosis via regulating Nrf2 and NF-κB pathways.

BACKGROUND: Hepatic fibrosis (HF) runs through multiple stages of liver diseases and promotes these diseases progression. Oxysophoridine (OSR), derived from Sophora alopecuroides l., is a bioactive alkaloid that has been reported to antagonize alcoholic hepatic injury. However, whether OSR suppresses HF and the mechanisms involved in Nrf2 remain unknown. PURPOSE: Since the dysregulation of inflammation and oxidative stress is responsible for the excessive accumulation of extracellular matrix (ECM) and fibrosis in the liver. We hypothesized that OSR may attenuate HF by inhibiting inflammation and oxidative stress through activating Nrf2 signaling. METHODS: In this study, we employed LPS-stimulated HSC-T6 cells, RAW264.7 cells, and a CCl4-induced C57BL/6 mouse fibrotic model to evaluate its suppressing inflammation and oxidative stress, as well as fibrosis. RESULTS: The result showed that OSR significantly reduced α-SMA and TGF-ß1 at a low dose of 10 µM in vitro and at a dose of 50 mg/kg in vivo, which is comparable to Silymarin, the only Chinese herbal active ingredient that has been marketed for anti-liver fibrosis. Moreover, OSR effectively suppressed the expression of iNOS at a dose of 10 µM and COX-2 at a dose of 40 µM, respectively. Furthermore, OSR demonstrated inhibitory effects on the IL-1ß, IL-6, and TNF-α in vitro and almost extinguished cytokine storm in vivo. OSR exhibited antioxidative effects by reducing MDA and increasing GSH, thereby protecting the cell membrane against oxidative damage and reducing LDH release. Moreover, OSR effectively upregulated the protein levels of Nrf2, HO-1, and p62, but decreased p-NF-κB p65, p-IκBα, and Keap1. Alternatively, mechanisms involved in Nrf2 were verified by siNrf2 interference, siNrf2 interference revealed that the anti-fibrotic effect of OSR was attributed to its activation of Nrf2. CONCLUSION: The present study provided an effective candidate for HF involved in both activation of Nrf2 and blockage of NF-κB, which has not been reported in the published work. The present study provides new insights for the identification of novel drug development for HF.

[Spatio-temporal Evolution and Coordinated Development of Compactness with Carbon Emission Intensity in the Chengdu-Chongqing Urban Agglomeration].

Studies on the spatio-temporal variation and coordinated development level of compactness with carbon emission intensity in the Chengdu-Chongqing urban agglomeration is of great significance to achieve green, low-carbon, and high-quality development of society. The spatial-temporal differentiation, coupling coordination, and driving factors of the compactness and carbon emission intensity of the Chengdu-Chongqing urban agglomeration from 2010 to 2020 were analyzed by using the methods of comprehensive evaluation, carbon emission identical equality, coupling coordination, and the Geo-detector model. The results showed that:① The compactness of the Chengdu-Chongqing urban agglomeration continued to rise from 0.18 in 2010 to 0.22 in 2020, with an overall increase of 22.22 %, in which the contribution rate of economic compactness to urban compactness increased yearly. There were significant regional differences in the compactness of cities. The high-value areas were concentrated in Chengdu, Deyang, and Mianyang in the northwest and Zigong, Neijiang, and Luzhou in the southwest, whereas the low-value areas were distributed in the middle. Ya'an was always the area with the lowest compactness of urban agglomeration. ② The carbon emission intensity of the Chengdu-Chongqing urban agglomeration was decreasing yearly, with a decrease rate of 39.57 % during the study period. The carbon emission intensity in the southern part of the urban agglomeration was higher than that in other regions as a whole, whereas Chengdu and Chongqing were low-value areas all the year round, and the regional differences of carbon emission intensity were gradually narrowing. ③ The coupling degree between urban compactness and carbon emission intensity changed from the antagonistic stage to the running-in stage; the coupling coordination degree increased notably, from 0.21 in 2010 to 0.69 in 2020; and the two systems gradually moved towards benign and coordinated development. The coupling coordination between the northwest of the urban agglomeration (Chengdu, Deyang, and Mianyang) and the south of Sichuan (Zigong and Luzhou) was generally high. Industrial structure, scientific and technological innovation, urbanization level, government intervention, and environmental livability all had significant effects on the coupling and coordination of the two systems. ④ Optimizing industrial structure, strengthening scientific and technological support, improving the quality of urbanization development, implementing active policy guidance, and building green barriers were effective ways to promote the coordinated development of compactness and low carbon in the Chengdu-Chongqing urban agglomeration.

Lidar AOD inversion and aerosol extinction profile correction method based on GA-BP neural network.

Lidar is an effective remote sensing method to obtain the vertical distribution of aerosols, and how to select the aerosol extinction-backscattering ratio (AE-BR) during the inversion process is a key step to guarantee the accuracy of the lidar inversion of aerosol optical thickness (AOD) and aerosol extinction coefficient profile (AECP). In this paper, an inversion algorithm for AOD and AECP based on a genetic BP (GA-BP) neural network is proposed. Simultaneous measurements are carried out using CE318 sun photometer and lidar, and the mapping relationship between the lidar echo signal and AOD is established based on the genetic BP (GA-BP) neural network method, which achieves the accurate inversion of AOD with an absolute error mean value of 0.0156. Based on the AOD output from the GA-BP neural network, the real-time best AE- BR to improve the inversion accuracy of AECP. Finally, practical tests show that the method achieves accurate inversion of AOD, determines the range of AE-BR from 20-50sr, realizes real-time dynamic correction of AECP, and has strong generalization ability and applicability in practical situations.

Three new flavonoids from the roots of Sophora tonkinensis.

Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

The impact of microplastics polystyrene on the microscopic structure of mouse intestine, tight junction genes and gut microbiota.

Microplastics, which are tiny plastic particles less than 5 mm in diameter, are widely present in the environment, have become a serious threat to aquatic life and human health, potentially causing ecosystem disorders and health problems. The present study aimed to investigate the effects of microplastics, specifically microplastics-polystyrene (MPs-PS), on the structural integrity, gene expression related to tight junctions, and gut microbiota in mice. A total of 24 Kunming mice aged 30 days were randomly assigned into four groups: control male (CM), control female (CF), PS-exposed male (PSM), and PS-exposed female (PSF)(n = 6). There were significant differences in villus height, width, intestinal surface area, and villus height to crypt depth ratio (V/C) between the PS group and the control group(C) (p <0.05). Gene expression analysis demonstrated the downregulation of Claudin-1, Claudin-2, Claudin-15, and Occludin, in both duodenum and jejunum of the PS group (p < 0.05). Analysis of microbial species using 16S rRNA sequencing indicated decreased diversity in the PSF group, as well as reduced diversity in the PSM group at various taxonomic levels. Beta diversity analysis showed a significant difference in gut microbiota distribution between the PS-exposed and C groups (R2 = 0.113, p<0.01), with this difference being more pronounced among females exposed to MPs-PS. KEGG analysis revealed enrichment of differential microbiota mainly involved in seven signaling pathways, such as nucleotide metabolism(p<0.05). The relative abundance ratio of transcriptional pathways was significantly increased for the PSF group (p<0.01), while excretory system pathways were for PSM group(p<0.05). Overall findings suggest that MPs-PS exhibit a notable sex-dependent impact on mouse gut microbiota, with a stronger effect observed among females; reduced expression of tight junction genes may be associated with dysbiosis, particularly elevated levels of Prevotellaceae.

Toenail and blood selenium mediated regulation of thyroid dysfunction through immune cells: a mediation Mendelian randomization analysis.

Purpose: Specific nutrients found in food, such as minerals, antioxidants, and macronutrients, have a significant impact on immune function and human health. However, there is currently limited research exploring the relationship between specific nutrients, immune system function, and thyroid dysfunction commonly observed in autoimmune thyroid diseases, which manifest predominantly as hyperthyroidism or hypothyroidism. Therefore, the objective of this study was to investigate the connections between dietary traits and thyroid dysfunction, as well as the potential mediating role of immune cells, using Mendelian randomization (MR) analysis. Methods: The two-step MR analysis used single-nucleotide polymorphisms as instruments, with a threshold of p < 5e-08 for nutrients and thyroid dysfunction, and p < 5e-06 for immune cells. Data from different GWAS databases and UK Biobank were combined to analyze 8 antioxidants and 7 minerals, while the data for 4 macronutrients came from a cohort of 235,000 individuals of European. The outcome data (hypothyroidism, N = 3340; hyperthyroidism, N = 1840; free thyroxin [FT4], N = 49,269; thyroid-stimulating hormone [TSH], N = 54,288) were source from the ThyroidOmics consortium. Immune trait data, including 731 immune phenotypes, were collected from the GWAS catalog. Results: The results revealed that nutrient changes, such as lycopene, toenail and blood selenium, and α-tocopherol, impacted the immune system. Immune cells also affected thyroid function, with cDC cells promoting hypothyroidism and median fluorescence intensity (MFI) phenotypes correlating strongly with FT4 levels. Toenail and blood selenium reduce the relative cell counts (RCC) phenotypes of immune cells (CD62L- plasmacytoid DC %DC and transitional B cells %Lymphocyte), thereby diminishing its promoting effect on hypothyroidis. Furthermore, toenail and blood selenium mainly impacted phenotypes in three types of T cells (CD25 + ⁣ + CD8br, CD3 on CD45RA- CD4+, and CD45RA on Terminally Differentiated CD8br), reinforcing the negative regulation of FT4 levels. Conclusion: The role of immune cells as mediators in the relationship between nutrients and thyroid dysfunction highlights their potential as diagnostic or therapeutic markers. Toenail and blood selenium levels can indirectly impact hypothyroidism by influencing the RCC levels of two types of immune cells, and can indirectly affect FT4 levels by influencing three types of T cells.