Integration of metabolomics and transcriptomics provides insights into the molecular mechanism of temporomandibular joint osteoarthritis.

The deficiency of clinically specific biomarkers has made it difficult to achieve an accurate diagnosis of temporomandibular joint osteoarthritis (TMJ-OA) and the insufficient comprehension of the pathogenesis of the pathogenesis of TMJ-OA has posed challenges in advancing therapeutic measures. The combined use of metabolomics and transcriptomics technologies presents a highly effective method for identifying vital metabolic pathways and key genes in TMJ-OA patients. In this study, an analysis of synovial fluid untargeted metabolomics of 6 TMJ-OA groups and 6 temporomandibular joint reducible anterior disc displacement (TMJ-DD) groups was conducted using liquid and gas chromatography mass spectrometry (LC/GC-MS). The differential metabolites (DMs) between TMJ-OA and TMJ-DD groups were analyzed through multivariate analysis. Meanwhile, a transcriptomic dataset (GSE205389) was obtained from the GEO database to analyze the differential metabolism-related genes (DE-MTGs) between TMJ-OA and TMJ-DD groups. Finally, an integrated analysis of DMs and DE-MTGs was carried out to investigate the molecular mechanisms associated with TMJ-OA. The analysis revealed significant differences in the levels of 46 DMs between TMJ-OA and TMJ-DD groups, of which 3 metabolites (L-carnitine, taurine, and adenosine) were identified as potential biomarkers for TMJ-OA. Collectively, differential expression analysis identified 20 DE-MTGs. Furthermore, the integration of metabolomics and transcriptomics analysis revealed that the tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, ferroptosis were significantly enriched. This study provides valuable insights into the metabolic abnormalities and associated pathogenic mechanisms, improving our understanding of TMJOA etiopathogenesis and facilitating potential target screening for therapeutic intervention.

Impact of low-level exposure to antibiotics on bile acid homeostasis in adults: Implication for human safety thresholds.

Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis.

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Synchrony or asynchrony: development of facial expression recognition from childhood to adolescence based on large-scale evidence.

The development of facial expression recognition ability in children is crucial for their emotional cognition and social interactions. In this study, 510 children aged between 6 and 15 participated in a two forced-choice task of facial expression recognition. The findings supported that recognition of the six basic facial expressions reached a relatively stable mature level around 8-9 years old. Additionally, model fitting results indicated that children showed the most significant improvement in recognizing expressions of disgust, closely followed by fear. Conversely, recognition of expressions of happiness and sadness showed slower improvement across different age groups. Regarding gender differences, girls exhibited a more pronounced advantage. Further model fitting revealed that boys showed more pronounced improvements in recognizing expressions of disgust, fear, and anger, while girls showed more pronounced improvements in recognizing expressions of surprise, sadness, and happiness. These clear findings suggested the synchronous developmental trajectory of facial expression recognition from childhood to adolescence, likely influenced by socialization processes and interactions related to brain maturation.

Acoustic Metagrating Holograms.

Metasurface holograms represent a common category of metasurface devices that utilize in-plane phase gradients to shape wavefronts, forming holographic images through the application of the generalized Snell's law (GSL). While conventional metasurfaces focus solely on phase gradients, metagratings, which incorporate higher-order wave diffraction, further expand the GSL's generality. Recent advances in certain acoustic metagratings have demonstrated an updated GSL extension capable of reversing anomalous transmission and reflection, whose reversal is characterized by the parity of the number of wave propagation trips through the metagrating. However, the current extension of GSL has remained limited to one-dimensional metagratings, unable to access two-dimensional (2D) holographic images in three-dimensional (3D) spaces. Here, we investigate the GSL extension to 2D metagratings for manipulating waves within 3D spaces. Through our analysis, we experimentally demonstrate a series of acoustic metagrating holograms. These holographic images exhibit the unique ability to switch between transmission and reflection types independently. Our study introduces an additional dimension to modern holography design and metasurface wavefront manipulation. This article is protected by copyright. All rights reserved.

Allogeneic haematopoietic stem cell transplantation might overcome the poor prognosis of adolescents and adult patients with T-lineage acute lymphoblastic leukaemia and CDKN2 deletion.

This study delves into the clinical implications of cyclin-dependent kinase inhibitor 2 (CDKN2) deletion in adult T-lineage acute lymphoblastic leukemia (T-ALL). Among 241 patients included in this study, 57 had CDKN2 deletion and 184 had CDKN2 wild-type (WT), and 165 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 76 did not undergo allo-HSCT. CDKN2 deletion correlated with higher white blood cell count, more high-risk diseases, and complex karyotype. The 5-year overall survival (OS) was 36.8% and 58.2% (P < 0.001), 5-year disease-free survival (DFS) was 47.1% and 59.3% (P = 0.018), and 5-year cumulative incidence of relapse (CIR) was 33.7% and 22.3% (P = 0.019) in patients with CDKN2 deletion and WT, respectively. Multivariate analysis identified CDKN2 deletion as an independent adverse prognostic factor for OS (HR 2.11, P = 0.003). In the CDKN2 deletion subgroup, landmark analysis showed that the 5-year OS was 56.7% and 19% (P = 0.002) for patients who underwent allo-HSCT and those who did not, respectively. And multivariate analysis confirmed the beneficial role of allo-HSCT in OS (HR 0.23, P < 0.001). In conclusion, CDKN2 deletion was associated with a poor prognosis in adult T-ALL, and allo-HSCT might be beneficial for this population.

Genome-wide identification and expression analysis of the Eriobotrya japonica TIFY gene family reveals its functional diversity under abiotic stress conditions.

BACKGROUND: Plant-specific TIFY proteins are widely found in terrestrial plants and play important roles in plant adversity responses. Although the genome of loquat at the chromosome level has been published, studies on the TIFY family in loquat are lacking. Therefore, the EjTIFY gene family was bioinformatically analyzed by constructing a phylogenetic tree, chromosomal localization, gene structure, and adversity expression profiling in this study. RESULTS: Twenty-six EjTIFY genes were identified and categorized into four subfamilies (ZML, JAZ, PPD, and TIFY) based on their structural domains. Twenty-four EjTIFY genes were irregularly distributed on 11 of the 17 chromosomes, and the remaining two genes were distributed in fragments. We identified 15 covariate TIFY gene pairs in the loquat genome, 13 of which were involved in large-scale interchromosomal segmental duplication events, and two of which were involved in tandem duplication events. Many abiotic stress cis-elements were widely present in the promoter region. Analysis of the Ka/Ks ratio showed that the paralogous homologs of the EjTIFY family were mainly subjected to purifying selection. Analysis of the RNA-seq data revealed that a total of five differentially expressed genes (DEGs) were expressed in the shoots under gibberellin treatment, whereas only one gene was significantly differentially expressed in the leaves; under both low-temperature and high-temperature stresses, there were significantly differentially expressed genes, and the EjJAZ15 gene was significantly upregulated under both low- and high-temperature stress. RNA-seq and qRT-PCR expression analysis under salt stress conditions revealed that EjJAZ2, EjJAZ4, and EjJAZ9 responded to salt stress in loquat plants, which promoted resistance to salt stress through the JA pathway. The response model of the TIFY genes in the jasmonic acid pathway under salt stress in loquat was systematically summarized. CONCLUSIONS: These results provide a theoretical basis for exploring the characteristics and functions of additional EjTIFY genes in the future. This study also provides a theoretical basis for further research on breeding for salt stress resistance in loquat. RT-qPCR analysis revealed that the expression of one of the three EjTIFY genes increased and the expression of two decreased under salt stress conditions, suggesting that EjTIFY exhibited different expression patterns under salt stress conditions.

Bacterial community drives soil organic carbon transformation in vanadium titanium magnetite tailings through remediation using Pongamia pinnata.

With continuous mine exploitation, regional ecosystems have been damaged, resulting in a decline in the carbon sink capacity of mining areas. There is a global shortage of effective soil ecological restoration techniques for mining areas, especially for vanadium (V) and titanium (Ti) magnetite tailings, and the impact of phytoremediation techniques on the soil carbon cycle remains unclear. Therefore, this study aimed to explore the effects of long-term Pongamia pinnata remediation on soil organic carbon transformation of V-Ti magnetite tailing to reveal the bacterial community driving mechanism. In this study, it was found that four soil active organic carbon components (ROC, POC, DOC, and MBC) and three carbon transformation related enzymes (S-CL, S-SC, and S-PPO) in vanadium titanium magnetite tailings significantly (P < 0.05) increased with P. pinnata remediation. The abundance of carbon transformation functional genes such as carbon degradation, carbon fixation, and methane oxidation were also significantly (P < 0.05) enriched. The network nodes, links, and modularity of the microbial community, carbon components, and carbon transformation genes were enhanced, indicating stronger connections among the soil microbes, carbon components, and carbon transformation functional genes. Structural equation model (SEM) analysis revealed that the bacterial communities indirectly affected the soil organic carbon fraction and enzyme activity to regulate the soil total organic carbon after P. pinnata remediation. The soil active organic carbon fraction and free light fraction carbon also directly regulated the soil carbon and nitrogen ratio by directly affecting the soil total organic carbon content. These results provide a theoretical reference for the use of phytoremediation to drive soil carbon transformation for carbon sequestration enhancement through the remediation of degraded ecosystems in mining areas.

Electrical impedance tomography as a bedside assessment tool for COPD treatment during hospitalization.

For patients with chronic obstructive pulmonary disease (COPD), the assessment of the treatment efficacy during hospitalization is of importance to the optimization of clinical treatments. Conventional spirometry might not be sensitive enough to capture the regional lung function development. The study aimed to evaluate the feasibility of using electrical impedance tomography (EIT) as an objective bedside evaluation tool for the treatment of acute exacerbation of COPD (AECOPD). Consecutive patients who required hospitalization due to AECOPD were included prospectively. EIT measurements were conducted at the time of admission and before the discharge simultaneously when a forced vital capacity maneuver was conducted. EIT-based heterogeneity measures of regional lung function were calculated based on the impedance changes over time. Surveys for attending doctors and patients were designed to evaluate the ease of use, feasibility, and overall satisfaction level to understand the acceptability of EIT measurements. Patient-reported outcome assessments were conducted. User's acceptance of EIT technology was investigated with a five-dimension survey. A total of 32 patients were included, and 8 patients were excluded due to the FVC maneuver not meeting the ATS criteria. Spirometry-based lung function was improved during hospitalization but not significantly different (FEV1 %pred.: 35.8% ± 6.7% vs. 45.3% ± 8.8% at admission vs. discharge; p = 0.11. FVC %pred.: 67.8% ± 0.4% vs. 82.6% ± 5.0%; p = 0.15. FEV1/FVC: 0.41 ± 0.09 vs. 0.42 ± 0.07, p = 0.71). The symptoms of COPD were significantly improved, but the correlations between the improvement of symptoms and spirometry FEV1 and FEV1/FVC were low (R = 0.1 and -0.01, respectively). The differences in blood gasses and blood tests were insignificant. All but one EIT-based regional lung function parameter were significantly improved after hospitalization. The results highly correlated with the patient-reported outcome assessment (R > 0.6, p < 0.001). The overall acceptability score of EIT measurement for both attending physicians and patients was high (4.1 ± 0.8 for physicians, 4.5 ± 0.5 for patients out of 5). These results demonstrated that it was feasible and acceptable to use EIT as an objective bedside evaluation tool for COPD treatment efficacy.

Enhancing Efficiency and Stability in Carbon-Based Perovskite Solar Cells by Double Passivation with Ultralow-Cost Coal-Derived Graphene and Its Derivatives.

Coal-derived carbon nanomaterials possess numerous superior features compared to other classic carbon, such as readily accessible surfaces, tunable pore structure, and facile and precise surface functionalization. Therefore, the controllable preparation of coal-derived carbon nanomaterials is anticipated to be of great significance for the performance improvement and commercialization process of carbon-based perovskite solar cells (C-PSCs). In this study, we successfully synthesized highly stable and commercially valuable graphene oxide (GO) and reduced graphene oxide (rGO) utilizing coal. Compared to traditional methods and commercial graphene, the chemical oxidation and pyrolysis process used in this study is mild and simple, offering the advantages of controlled composition and the absence of other impurities. GO or rGO was incorporated into the top of the SnO2 electron transport layer (ETL) of C-PSCs. Under optimized conditions and ultraviolet-ozone (UVO) irradiation, the ultimate power conversion efficiency (PCE) increased from the unmodified 12.4 to 14.04% (based on rGO) and 15.18% (based on GO), representing improvements of 22 and 31%, respectively. The improved photovoltaic performance is mainly owing to enhanced charge transport capabilities, denser interfacial contacts, improved carrier separation properties, increased conductivity, and abundance of hydrophilic functional groups in GO, which can form more stable hydrogen bonds with SnO2. After being stored at room temperature and ambient humidity for 30 days, the modified, unpacked devices retained 87% of the highest power conversion efficiency (PCE). This study introduces a practical and manageable method to enhance the performance of C-PSCs by using functional carbon nanomaterials derived from coal.

Multi-omics analysis provides new insights into the changes of important nutrients and fructose metabolism in loquat bud sport mutant.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

Mechanistic Study of Novel Dipeptidyl Peptidase IV Inhibitory Peptides from Goat's Milk Based on Peptidomics and In Silico Analysis.

Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (<23 AA) were successfully identified by LC-MS/MS from goat milk hydrolysates (hydrolyzed by papaian plus proteinase K). Then, 105 potential DPP-IV inhibitory peptides were screened using PeptideRanker, the ToxinPred tool, Libdock, iDPPIV-SCM, and sequence characteristics. After ADME, physicochemical property evaluation, and a literature search, 12 candidates were efficiently selected and synthesized in vitro for functional validation. Two peptides (YPF and LLLP) were found to exert relatively high in vitro chemical system (IC50 = 368.54 ± 12.97 µM and 213.99 ± 0.64 µM) and in situ (IC50 = 159.46 ± 17.40 µM and 154.96 ± 8.41 µM) DPP-IV inhibitory capacities, and their inhibitory mechanisms were further explored by molecular docking. Our study showed that the formation of strong non-bonding interactions with the core residues from the pocket of DPP-IV (such as ARG358, PHE357, GLU205, TYR662, TYR547, and TYR666) might primarily account for the DPP-IV inhibitory activity of two identified peptides. Overall, the two novel DPP-IV inhibitory peptides rapidly identified in this study can be used as functional food ingredients for the control of diabetes.

Association of ambient ozone exposure and greenness exposure with hemorrhagic stroke mortality at different times: A cohort study in Shandong Province, China.

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01-1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.

Distribution, seasonal variation and ecological risk assessment of phthalates in the Yitong River, a typical urban watercourse located in Northeast China.

Phthalates (PAEs) are a typical class of endocrine disruptors (EEDs). As one of the most commonly used plasticizers, they have received widespread attention due to their wide application in various countries and high detection rates in various environmental media. To be able to clarify the contamination status of PAEs pollutants in a typical northern cold-temperate urban river, 30 water samples from Yitong River in Changchun City, northern China were collected, during the 2023 dry season (March), normal season (May) and wet season (July). Using these samples, a total of 16 target PAEs are investigated. The resulting total PAEs concentrations are: dry season 408 to 1494 ng/L, wet season 491 to 1299 ng/L, and normal season 341 to 780 ng/L. The average concentration of the 16 PAEs over the three seasons is 773 ng/L. Di-2-ethylhexyl phthalate (DEHP) and Dibutyl phthalate (DBP) have the highest concentrations, ranging from 12 to 403 ng/L and 28-680 ng/L respectively. The ecological risks within the Yitong River Basin are evaluated based on the degree of PAEs contamination. DBP and DEHP pose higher risk assessment levels for algae, crustaceans and fish than the other target PAEs. The accurate determination of PAEs provided baseline data on PAEs for the management of the Yitong River, which is of great significance for the prediction of ecological risk assessment and the development of corresponding control measures, supported further research on PAEs in the cold-temperate zone aquatic environments, and shed light on the seasonal variations of PAEs in the Northeast region in the future. Moreover, considering the bioaccumulation and persistence of PAEs, it is necessary to continue to pay attention to the pollution status of cold-temperate zones rivers and the changes in ecological risks in the future.

Research progress on the origin, fate, impacts and harm of microplastics and antibiotic resistance genes in wastewater treatment plants.

Previous studies reported microplastics (MPs), antibiotics, and antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs). There is still a lack of research progress on the origin, fate, impact and hazards of MPs and ARGs in WWTPs. This paper fills a gap in this regard. In our search, we used "microplastics", "antibiotic resistance genes", and "wastewater treatment plant" as topic terms in Web of Science, checking the returned results for relevance by examining paper titles and abstracts. This study mainly explores the following points: (1) the origins and fate of MPs, antibiotics and ARGs in WWTPs; (2) the mechanisms of action of MPs, antibiotics and ARGs in sludge biochemical pools; (3) the impacts of MPs in WWTPs and the spread of ARGs; (4) and the harm inflicted by MPs and ARGs on the environment and human body. Contaminants in sewage sludge such as MPs, ARGs, and antibiotic-resistant bacteria enter the soil and water. Contaminants can travel through the food chain and thus reach humans, leading to increased illness, hospitalization, and even mortality. This study will enhance our understanding of the mechanisms of action among MPs, antibiotics, ARGs, and the harm they inflict on the human body.

Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier.

BACKGROUND: The specific pathogenesis of UC is still unclear, but it has been clear that defects in intestinal barrier function play an important role in it. There is a temporary lack of specific drugs for clinical treatment. Astragaloside IV (AS-IV) is one of the main active ingredients extracted from Astragalus root and is a common Chinese herbal medicine for the treatment of gastrointestinal diseases. This study aimed to determine whether AS-IV has therapeutic value for DSS or LPS-induced intestinal epithelial barrier dysfunction in vivo and in vitro and its potential molecular mechanisms. METHODS: The intestinal tissues from UC patients and colitis mice were collected, intestinal inflammation was observed by colonoscopy, and mucosal barrier function was measured by immunofluorescence staining. PI3K/AKT signaling pathway activator YS-49 and inhibitor LY-29 were administered to colitic mice to uncover the effect of this pathway on gut mucosal barrier modulation. Then, network pharmacology was used to screen Astragaloside IV (AS-IV), a core active component of the traditional Chinese medicine Astragalus membranaceus. The potential of AS-IV for intestinal barrier function repairment and UC treatment through blockade of the PI3K/AKT pathway was further confirmed by histopathological staining, FITC-dextran, transmission electron microscopy, ELISA, immunofluorescence, qRT-PCR, and western blotting. Finally, 16 S rRNA sequencing was performed to uncover whether AS-IV can ameliorate UC by regulating gut microbiota homeostasis. RESULTS: Mucosal barrier function was significantly damaged in UC patients and murine colitis, and the activated PI3K/AKT signaling pathway was extensively involved. Both in vivo and vitro showed that the AS-IV-treated group significantly relieved inflammation and improved intestinal epithelial permeability by inhibiting the activation of the PI3K/AKT signaling pathway. In addition, microbiome data found that gut microbiota participates in AS-IV-mediated intestinal barrier recovery as well. CONCLUSIONS: Our study highlights that AS-IV exerts a protective effect on the integrality of the mucosal barrier in UC based on the PI3K/AKT pathway, and AS-IV may serve as a novel AKT inhibitor to provide a potential therapy for UC.

Structure-guided design of novel biphenyl-quinazoline derivatives as potent non-nucleoside reverse transcriptase inhibitors featuring improved anti-resistance, selectivity, and solubility.

In pursuit of enhancing the anti-resistance efficacy and solubility of our previously identified NNRTI 1, a series of biphenyl-quinazoline derivatives were synthesized employing a structure-based drug design strategy. Noteworthy advancements in anti-resistance efficacy were discerned among some of these analogs, prominently exemplified by compound 7ag, which exhibited a remarkable 1.37 to 602.41-fold increase in potency against mutant strains (Y181C, L100I, Y188L, F227L + V106A, and K103N + Y181C) in comparison to compound 1. Compound 7ag also demonstrated comparable anti-HIV activity against both WT HIV and K103N, albeit with a marginal reduction in activity against E138K. Of significance, this analog showed augmented selectivity index (SI > 5368) relative to compound 1 (SI > 37764), Nevirapine (SI > 158), Efavirenz (SI > 269), and Etravirine (SI > 1519). Moreover, it displayed a significant enhancement in water solubility, surpassing that of compound 1, Etravirine, and Rilpivirine. To elucidate the underlying molecular mechanisms, molecular docking studies were undertaken to probe the critical interactions between 7ag and both WT and mutant strains of HIV-1 RT. These findings furnish invaluable insights driving further advancements in the development of DAPYs for HIV therapy.

Occurrence, removal, and risk assessment of polycyclic aromatic hydrocarbons and their derivatives in typical wastewater treatment plants.

Wastewater treatment plants (WWTPs) have a certain removal capacity for polycyclic aromatic hydrocarbons (PAHs) and their derivatives, but some of them are discharged with effluent into the environment, which can affect the environment. Therefore, to understand the presence, sources, and potential risks of PAHs and their derivatives in WWTPs. Sixteen PAHs, three chlorinated polycyclic aromatic hydrocarbons (ClPAHs), three oxidized polycyclic aromatic hydrocarbons (OPAHs), and three methylated polycyclic aromatic hydrocarbons (MPAHs) were detected in the influent and effluent water of three WWTPs in China. The average concentrations of their influent ∑PAHs, ∑ClPAHs, ∑OPAHs, and ∑MPAHs ranged from 2682.50 to 2774.53 ng/L, 553.26-906.28 ng/L, 415.40-731.56 ng/L, and 534.04-969.83 ng/L, respectively, and the effluent concentrations ranged from 823.28 to 993.37 ng/L, 269.43-489.94 ng/L, 285.93-463.55 ng/L, and 376.25-512.34 ng/L, respectively. The growth of heat transport and industrial energy consumption in the region has a significant impact on the level of PAHs in WWTPs. According to the calculated removal efficiencies of PAHs and their derivatives in the three WWTPs (A, B, and C), the removal rates of PAHs and their derivatives were 69-72%, 62-71%, and 68-73%, respectively, and for the substituted polycyclic aromatic hydrocarbons (SPAHs), the removal rates were 41-49%, 31-40%, and 33-39%, respectively; moreover, the removal rates of PAHs were greater than those of SPAHs in the WWTPs. The results obtained via the ratio method indicated that the main sources of PAHs in the influent of WWTPs were the combustion of coal and biomass, and petroleum contamination was the secondary source. In risk evaluation, there were 5 compounds for which the risk quotient was considered high ecological risk. During chronic disease evaluation, there were 11 compounds with a risk quotient considered to indicate high risk. PAHs and SPAHs with high relative molecular masses in the effluent of WWTPs pose more serious environmental hazards than their PAHs counterparts.

[Simultaneous Immobilization of Cadmium and Arsenic in Paddy Soils with Novel Fe-Mn Combined Graphene Oxide].

Novel Fe-Mn combined graphene oxide （GO-FM） material was produced and tested for its efficacy in remediating agricultural soil co-contaminated by Cd and As. In a 60-day soil incubation experiment， the remediation mechanism and immobilization effects of GO and GO-FM at different addition ratios （0.1%， 0.2%， and 0.3%） were investigated in Shangyu and Foshan soils， which had varying physicochemical properties and contamination degrees. The dynamic changes in pH， DOC concentration， bioavailable Cd and As content， and morphology of Cd and As were explored to determine the remediation efficacy of the materials. The results demonstrated that compared with that in the blank control， GO-FM increased the pH in Shangyu soil but decreased the pH in Foshan soil. After culture， both GO and GO-FM increased the soil DOC content. GO-FM decreased the soluble Cd concentration by 5.08%-19.19% and the bioavailability of Cd by 36.57%-42.8% in Foshan soil， and the main immobilization mechanism was electrostatic adsorption， complexation， and hydroxylated metal ion formation. The immobilization ability of GO-FM on Cd was lower than that of Foshan soil due to the influence of electrostatic repulsion in Shangyu acidic soil. However， with the increase in the amount of GO-FM， the trend of increasing the bioavailability of Cd by graphene oxide was inhibited. The addition of 0.2% and 0.3% GO-FM decreased the bioavailability of Cd by 6.45%-13.56% in Shangyu soil. Additionally， GO-FM decreased the bioavailability of As in Shangyu soil and Foshan soil by 4.34%-9.15% and 0.87%-5.71%， respectively. This was due to the immobilization mechanism of oxidation of As by manganese oxides and inner surface chelate between As and the surface hydroxyl group of iron oxides. In summary， the immobilization effect of GO-FM on Cd in Foshan soil was better than that in Shangyu soil， and the immobilization effect of GO-FM on As in Shangyu soil was better than that in Foshan soil， which can provide a theoretical basis and reference for the prevention and control of Cd and As co-contamination in different types of soil.

Factors affecting the compliance of hepatocellular carcinoma screening among high-risk populations: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.