[Zhuyu Pills regulate p53/SLC7A11 signaling pathway-mediated oxidative damage and ferroptosis to treat atherosclerosis].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis(AS) and decipher the underlying mechanism. The mouse model of AS was established by feeding with a high-fat diet for 12 weeks. The 50 successfully modeled mice with the apolipoprotein E knockout(ApoE~(-/-)) were assigned by the random number table method into 5 groups(n=10): model, low-, medium-, and high-dose(130.54, 261.08, 522.16 mg·kg~(-1), respectively) Zhuyu Pills, and atorvastatin calcium(10.40 mg·kg~(-1)). Ten C57BL/6J mice were selected as the blank group. The blank group and model group were administrated with an equal volume of normal saline, and other groups were administrated with corresponding drugs once a day for 12 weeks. At the end of drug intervention, hematoxylin-eosin(HE) staining was employed to observe the pathological changes of fat in the aorta, liver, and epididymis of mice, and the proportion of aortic plaque area, fat area in epididymis, and nonalcoholic fatty liver disease activity score(NAS) were calculated. Lipid and collagen deposition in the aorta was observed by oil red O staining and Masson staining, respectively, and the proportions of lipid and collagen deposition areas were calculated. The serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), and iron ion were measured by colorimetry. The expression of cyclooxygenase 2(COX2), ferritin heavy chain 1(FTH1), cystine/glutamate reverse transporter solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4) in the aorta was detected by the immunofluorescence assay. The level of tumor protein 53(p53) in the aorta was detected by immunohistochemistry. The protein levels of p53 and SLC7A11 in the aorta were determined by Western blot. The mRNA levels of p53, SLC7A11, GPX4, FTH1, prostaglandin G/H synthase 2(PTGS2), and reduced nicotinamide adenine dinucleotide phosphate oxidase 1(NOX1) in mouse aorta were determined by real-time PCR. The results showed that compared with the blank group, the model group showcased enlarged aortic plaque area, increased collagen fiber deposition, liver lipid deposition, and lipid droplets, and enlarged epididymal adipocytes. In addition, the modeling elevated the levels of iron ion and MDA and lowered the levels of SOD and GSH-Px in the serum, promoted the expression of p53 and COX2, down-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and up-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium reduced the aortic plaque area, collagen deposition, liver lipid deposition, lipid droplets, and epididymal adipocyte volume, lowered the levels of iron ion and MDA and elevated the levels of SOD and GSH-Px in the serum, inhibited the expression of p53 and COX2, up-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and down-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. In conclusion, Zhuyu Pills exert definite therapeutic effect on aortic plaque in AS mice by regulating the p53/SLC7A11 signaling pathway to alleviate oxidative damage and inhibit ferroptosis.

Knowledge-based in silico fragmentation and annotation of mass spectra for natural products with MassKG.

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is a potent analytical technique utilized for identifying natural products from complex sources. However, due to the structural diversity, annotating LC-MS/MS data of natural products efficiently remains challenging, hindering the discovery process of novel active structures. Here, we introduce MassKG, an algorithm that combines a knowledge-based fragmentation strategy and a deep learning-based molecule generation model to aid in rapid dereplication and the discovery of novel NP structures. Specifically, MassKG has compiled 407,720 known NP structures and, based on this, generated 266,353 new structures using chemical language models for the discovery of potential novel compounds. Furthermore, MassKG demonstrates exceptional performance in spectra annotation compared to state-of-the-art algorithms. To enhance usability, MassKG has been implemented as a web server for annotating tandem mass spectral data (MS/MS, MS2) with a user-friendly interface, automatic reporting, and fragment tree visualization. Lastly, the interpretive capability of MassKG is comprehensively validated through composition analysis and MS annotation of Panax notoginseng, Ginkgo biloba, Codonopsis pilosula, and Astragalus membranaceus. MassKG is now accessible at https://xomics.com.cn/masskg.

Practical prognostic tools to predict the risk of postoperative delirium in older patients undergoing cardiac surgery: visual and dynamic nomograms.

PURPOSE: Postoperative Delirium (POD) has an incidence of up to 65% in older patients undergoing cardiac surgery. We aimed to develop two dynamic nomograms to predict the risk of POD in older patients undergoing cardiac surgery. METHODS: This was a single-center retrospective cohort study, which included 531 older patients who underwent cardiac surgery from July 2021 to June 2022 at Nanjing First Hospital, China. Univariable and multivariable logistic regression were used to identify the significant predictors used when constructing the models. We evaluated the performances and accuracy, validated, and estimated the clinical utility and net benefit of the models using the receiver operating characteristic (ROC), the 10-fold cross-validation, and decision curve analysis (DCA). RESULTS: A total of 30% of the patients developed POD, the significant predictors in the preoperative model were ASA ( p < 0.001 OR = 3.220), cerebrovascular disease (p < 0.001 OR = 2.326), Alb (p < 0.037 OR = 0.946), and URE (p < 0.001 OR = 1.137), while for the postoperative model they were ASA (p = 0.044, OR = 1.737), preoperative MMSE score (p = 0.005, OR = 0.782), URE (p = 0.017 OR = 1.092), CPB duration (p < 0.001 OR = 1.010) and APACHE II (p < 0.001, OR = 1.353). The preoperative and postoperative models achieved satisfactory predictive performances, with AUC values of 0.731 and 0.799, respectively. The web calculators can be accessed at https://xxh152.shinyapps.io/Pre-POD/ and https://xxh152.shinyapps.io/Post-POD/ . CONCLUSION: We established two nomogram models based on the preoperative and postoperative time points to predict POD risk and guide the flexible implementation of possible interventions at different time points.

Growing-Season Precipitation Is a Key Driver of Plant Leaf Area to Sapwood Area Ratio at the Global Scale.

Leaf area to sapwood area ratio (AL/AS) influences carbon sequestration, community composition, and ecosystem functioning in terrestrial vegetation and is closely related to leaf economics and hydraulics. However, critical predictors of AL/AS are not well understood. We compiled an AL/AS data set with 1612 species-site combinations (1137 species from 285 sites worldwide) from our field experiments and published literature. We found the global mean AL/AS to be 0.63 m2 cm-2, with its variation largely driven by growing-season precipitation (Pgs), which accounted for 18% of the variation in AL/AS. Species in tropical rainforests exhibited the highest AL/AS (0.82 m2 cm-2), whereas desert species showed the lowest AL/AS (0.16 m2 cm-2). Soil factors such as soil nitrogen and soil organic carbon exhibited positive effects on AL/AS, whereas soil pH was negatively correlated with AL/AS. Tree density accounted for 7% of the variation in AL/AS. All biotic and abiotic predictors collectively explained up to 45% of the variation in AL/AS. Additionally, AL/AS was positively correlated to the net primary productivity (NPP) of the ecosystem. Our study provides insights into the driving factors of AL/AS at the global scale and highlights the importance of AL/AS in ecosystem productivity. Given that Pgs is the most critical driver of AL/AS, alterations in global precipitation belts, particularly seasonal precipitation, may induce changes in plant leaf area on the branches.

The causal link between nitrogen structure and physiological processes of Ulva prolifera as the causative species of green tides.

Harmful algal blooms (HABs) increase with eutrophication depending on the nutrient structure (availability and ratios), but an unequivocal causal link between these factors is rarely established. Here, we provide support for the causal link between the nitrogen structure and physiological processes of Ulva prolifera as the causative species of Yellow Sea green tides (YSGTs) using in situ and laboratory experiments. The results showed that the components of nitrogen nutrients in seawater exhibited significant spatiotemporal variation. The concentration of NO3--N showed a notable decreasing trend from south to north. Sufficient dissolved inorganic nitrogen (DIN) induced increases in thalli nitrate reductase (NR) and glutamine synthetase (GS) activities. This could accelerate thalli uptake of nitrogen nutrients. The glutamate dehydrogenase (GDH) activity was significantly upregulated with the increasing proportion of dissolved organic nitrogen (DON) in seawater. The change in nitrogen structure regulated the activity of NR during the long-distance floating migration of the YSGTs. And the activity of NR could modulate the nitric oxide (NO) content in the thalli. NO was used as a signal molecule to enhance the antioxidant defense system of thalli. The efficient antioxidant system in the thalli could reduce oxidative stress and effectively maintain high photosynthetic activity. The findings deepen our understanding of the relationship between nitrogen structures and key biological processes in macroalgae. This study also suggest that NO can enhance key biological processes in U. prolifera under varying nitrogen structures.

Saffron improves the efficacy of immunotherapy for colorectal cancer through the IL-17 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Saffron is one of the traditional medicinal herbs, which contains various active ingredients, such as safranal, crocin, saffron acid, etc. It has anti-inflammatory, antioxidant, and anti-cancer properties, and is widely used in clinical practice. The anti-cancer efficacy of saffron has been previously confirmed, but its anti-cancer mechanism in colorectal cancer remains unclear. OBJECTIVE: We investigated the effect of active compounds of saffron on the efficacy of immunotherapy for colorectal cancer. METHODS: TCMSP and liquid chromatography-mass spectrometry analysis (LC-MS), GeneCards, and DisGeNET databases were used to identify the active compounds of saffron, drug targets and the disease targets of colorectal cancer. They were then subjected to Gene Ontology Enrichment (GO) and Signalling Pathway Enrichment (KEGG) analyses. The core targets and corresponding compounds were selected for molecular docking. The effect of active components of saffron on the proliferation of CT26 and HCT116 cells was investigated using the cell counting kit-8 (CCK-8). In vitro experiments were conducted by subcutaneous injection of CT26 cells to establish a colon cancer model. Enzyme-linked immunosorbent assay (ELISA), western blotting (WB), real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and flow cytometry (FCM) were employed to validate the effects of saffron on colorectal cancer immunotherapy. RESULTS: 1. LC-MS analysis revealed that the main active component of saffron extract was crocin. The active chemicals of saffron intersected with 170 colorectal cancer targets, with 17 predicting targets for saffron treatment. GO and KEGG enrichment analyses revealed that the active components of saffron can prevent colorectal cancer development by enhancing Th17 cell differentiation and the IL-17 signaling pathway. 2. In vitro studies revealed that saffron alcohol extract, crocin, and safranal can suppress the proliferation of CT26 and HCT116 cells. 3. In vivo studies showed that crocin and safranal can increase the body mass and decrease the tumor mass of loaded mice, decrease the serum level of IL-17, and lower the mRNA expression level of IL-17, IL-6, TNF-α, TGF-ß, and PD-L1 and IL-17, PD-L1 protein in tumors. This inhibitory effect was strengthened after combined immunotherapy. In addition, saffron modulated CD4+ and CD8+ T cells and the CD4+/CD8+T ratio in mouse spleens. CONCLUSION: The active components of saffron can reduce the expression of inflammatory factors and ameliorate the immunological microenvironment of tumors via the IL-17 signaling pathway, thereby improving the efficacy of immunotherapy for colorectal cancer. This study provides pharmacological support for the application of saffron in enhancing the efficacy of immunotherapy for colorectal cancer.

[Identification and expression analysis of members of R2R3-MYB transcription factors family in Artemisia argyi].

The MYB(v-myb avian myeloblastosis viral oncogene homolog) family of transcription factors is the largest class of genes among higher plant transcription factors, which can be divided into four subfamilies, with the R2R3-MYB being the most common subfamily type. R2R3-MYB transcription factors are widely involved in the regulation of organ development and secondary metabolite biosynthesis in plants. To investigate the role of R2R3-MYB family transcription factors in the synthesis of flavonoids and glandular trichome development in Artemisia argyi, this study screened and identified 92 R2R3-MYB transcription factors based on the whole genome data of A. argyi, and predicted their potential functions based on bioinformatics. The results showed that the amino acid lengths of the 92 transcription factors ranged from 168 to 547 aa, with relative molecular weights ranging from 19. 6 to 60. 5 kDa, all of which were hydrophilic proteins. Subcellular localization analysis showed that 89 AaMYB proteins were located in the nucleus, while three proteins were simultaneously located in the nucleus and cytoplasm. According to the classification of Arabidopsis R2R3-MYB family, the 92 A. argyi R2R3-MYB proteins were divided into 26 subfamilies, with similar gene structures within the same subfamily.Cis-acting element prediction results showed that light-responsive elements, methyl jasmonate elements, and abscisic acid elements were widely distributed in the promoter regions of R2R3-MYB genes. Transcriptome expression analysis results showed that the expression of AaMYB60, AaMYB63, and AaMYB86 in leaves was higher than that in stems and roots, indicating that these three transcription factors mainly function in leaves. Additionally, five candidate R2R3-MYB transcription factors involved in A. argyi flavonoid biosynthesis or glandular trichome development were selected through phylogenetic analysis. This study provides important genetic resources for the breeding of superior varieties and germplasm innovation of A. argyi in the future.

A machine learning model based on CHAT-23 for early screening of autism in Chinese children.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition that significantly impacts the mental, emotional, and social development of children. Early screening for ASD typically involves the use of a series of questionnaires. With answers to these questionnaires, healthcare professionals can identify whether a child is at risk for developing ASD and refer them for further evaluation and diagnosis. CHAT-23 is an effective and widely used screening test in China for the early screening of ASD, which contains 23 different kinds of questions. Methods: We have collected clinical data from Wuxi, China. All the questions of CHAT-23 are regarded as different kinds of features for building machine learning models. We introduce machine learning methods into ASD screening, using the Max-Relevance and Min-Redundancy (mRMR) feature selection method to analyze the most important questions among all 23 from the collected CHAT-23 questionnaires. Seven mainstream supervised machine learning models were built and experiments were conducted. Results: Among the seven supervised machine learning models evaluated, the best-performing model achieved a sensitivity of 0.909 and a specificity of 0.922 when the number of features was reduced to 9. This demonstrates the model's ability to accurately identify children for ASD with high precision, even with a more concise set of features. Discussion: Our study focuses on the health of Chinese children, introducing machine learning methods to provide more accurate and effective early screening tests for autism. This approach not only enhances the early detection of ASD but also helps in refining the CHAT-23 questionnaire by identifying the most relevant questions for the diagnosis process.

Dual-energy computed tomography for predicting cervical lymph node metastasis in laryngeal squamous cell carcinoma.

Rationale and objectives: We constructed a dual-energy computed tomography (DECT)-based model to assess cervical lymph node metastasis (LNM) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods: We retrospectively analysed 164 patients with LSCC who underwent preoperative DECT from May 2019 to May 2023. The patients were randomly divided into training (n = 115) and validation (n = 49) cohorts. Quantitative DECT parameters of the primary tumours and their clinical characteristics were collected. A logistic regression model was used to determine independent predictors of LNM, and a nomogram was constructed along with a corresponding online model. Model performance was assessed using the area under the curve (AUC) and the calibration curve, and the clinical value was evaluated using decision curve analysis (DCA). Results: In total, 64/164 (39.0 %) patients with LSCC had cervical LNM. Independent predictors of LNM included normalized iodine concentration in the arterial phase (odds ratio [OR]: 8.332, 95 % confidence interval [CI]: 2.813-24.678, P < 0.001), normalized effective atomic number in the arterial phase (OR: 5.518, 95 % CI: 1.095-27.818, P = 0.002), clinical T3-4 stage (OR: 5.684, 95 % CI: 1.701-18.989, P = 0.005), and poor histological grade (OR: 5.011, 95 % CI: 1.003-25.026, P = 0.049). These predictors were incorporated into the DECT-based nomogram and the corresponding online model, showing good calibration and favourable performance (training AUC: 0.910, validation AUC: 0.918). The DCA indicated a significant clinical benefit of the nomogram for estimating LNM. Conclusions: DECT parameters may be useful independent predictors of LNM in patients with LSCC, and a DECT-based nomogram may be helpful in clinical decision-making.

Bi-phase CT radiomics nomogram for the preoperative prediction of pylorus lymph node metastasis in non-pyloric gastric cancer patients.

BACKGROUND: The expansion of function-preserving surgery became possible due to a more profound understanding of gastric cancer (GC), and T1N + or T2N + gastric cancer patients might be potential beneficiaries. However, ways to evaluate the possibility of function-preserving pylorus surgery are still unknown. METHODS: A total of 288 patients at Renji Hospital and 58 patients at Huadong Hospital, pathologically diagnosed with gastric cancer staging at T1 and T2 with tumors located in the upper two-thirds of the stomach, were retrospectively enrolled from March 2015 to October 2022. Tumor regions of interest (ROIs) were manually delineated on bi-phase CT images, and a nomogram was built and evaluated. RESULTS: The radiomic features distributed differently between positive and negative pLNm groups. Two radiomic signatures (RS1 and RS2) and one clinical signature were constructed. The radiomic signatures exhibited good performance for discriminating pLNm status in the test set. The three signatures were then combined into an integrated nomogram (IN). The IN showed good discrimination of pLNm in the Renji cohort (AUC 0.918) and the Huadong cohort (AUC 0.649). The verification models showed high values. CONCLUSION: For GC patients with T1 and T2 tumors located in the upper two-thirds of the stomach, a nomogram was successfully built for predicting pylorus lymph node metastasis, which would guide the surgical indication extension of conservative gastrectomies.

Construction of circRNA-mediated ceRNA network and immunoassay for investigating pathogenesis of COPD.

Background: The chronic respiratory condition known as chronic obstructive pulmonary disease (COPD) was one of the main causes of death and disability worldwide. This study aimed to explore and elucidate new targets and molecular mechanisms of COPD by constructing competitive endogenous RNA (ceRNA) networks. Methods: GSE38974 and GSE106986 were used to select DEGs in COPD samples and normal samples. Cytoscape software was used to construct and present protein-protein interaction (PPI) network, mRNA-miRNA co-expression network and ceRNA network. The CIBERSORT algorithm and the Lasso model were used to screen the immune infiltrating cells and hub genes associated with COPD, and the correlation between them was analyzed. COPD cell models were constructed in vitro and the expression level of ceRNA network factors mediated by hub gene was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: In this study, 852 differentially expressed genes were screened in the GSE38974 dataset, including 439 upregulated genes and 413 downregulated genes. Gene clustering analysis of PPI network results was performed using the Minimum Common Tumor Data Element (MCODE) in Cytoscape, and seven hub genes were screened using five algorithms in cytoHubba. CCL20 was verified as an important hub gene based on mRNA-miRNA co-expression network, GSE106986 database validation and the analysis of ROC curve results. Finally, we successfully constructed the circDTL-hsa-miR-330-3p-CCL20 network by Cytoscape. Immune infiltration analysis suggested that CCL20 can co-regulate immune cell migration and infiltration through chemokines CCL7 and CXCL3. In vitro experiments, the expression of circDTL and CCL20 was increased, while the expression of hsa-miR-330-3p was decreased in the COPD cell model. Conclusion: By constructing the circDTL-hsa-miR-330-3p-CCL20 network, this study contributes to a better understanding of the molecular mechanism of COPD development, which also provides important clues for the development of new therapeutic strategies and drug targets.

The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.

Reversible chemoresistance of pancreatic cancer grown as spheroids.

Better in vitro models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.

Enhanced Therapeutic Potential of Liposome-Coated Bushen Jianpi Recipe for Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) poses a major healthcare burden globally. Traditional Chinese medicine formula Bushen Jianpi (BSJP) recipe shows inhibitory effects on HCC but suffers from low bioavailability. This study aims to develop a BSJP-loaded liposome (BSJP@Lip) for targeted HCC treatment. METHODS: BSJP@Lip was prepared using a microfluidic device. Particle characterization included size, morphology, drug loading, encapsulation efficiency, and release kinetics analysis. In vitro cytotoxicity, cellular uptake, apoptosis, and protein expression were evaluated in hepG2, Smmc-7721, and hepa 1-6 hepatic cancer cell lines treated with BSJP@Lip. RESULTS: BSJP@Lip nanoparticles showed a uniform spherical shape with an average size of 50 nm and zeta potential at around -2.24 mV. They significantly inhibited cell viability and induced apoptosis in a dose-dependent manner compared with traditional decoction formulations. Enhanced cellular uptake of BSJP@Lip increased the expression of proinflammatory factors IL-18 and NLRP3. CONCLUSION: BSJP@Lip nanoparticles were found to be efficiently internalized by hepatic cancer cell lines, resulting in a dose-dependent inhibition of cell viability and induction of apoptosis. This effect was accompanied by the upregulation of IL-18 and NLRP3.

Interleukin-9 promotes EMT-mediated PM2.5-induced pulmonary fibrosis by activating the STAT3 pathway.

This study investigated the impact of PM2.5 on promoting EMT in PM2.5-induced pulmonary fibrosis (PF) development and explored molecular mechanisms of the IL-9/STAT3/Snail/TWIST1 signaling pathway in PF owing to PM2.5. Four groups of male SD rats were formed: control (0 mg/kg.bw), low (1 mg/kg.bw), medium (5 mg/kg.bw), and high-dose (25 mg/kg.bw) PM2.5 groups. Experimental rats were subjected to PM2.5 exposure via intratracheal instillation, given once weekly for 16 weeks. 24 h after the final exposure, blood, BALF, and lung tissues were collected. Pulmonary epithelial cells underwent cultivation and exposure to varying PM2.5 concentrations with/without inhibitors for 24 h, after which total protein was extracted for relevant protein assays. The findings demonstrated that PM2.5 damaged lung tissue to different degrees and led to PF in rats. Rats subjected to PM2.5 exposure exhibited elevated concentrations of IL-9 protein in both serum and BALF, and elevated levels of IL-9 and its receptor, IL-9R, in lung tissues, compared to control counterparts. Furthermore, PM2.5-exposed groups demonstrated significantly augmented protein levels of p-STAT3, Snail, TWIST1, Vimentin, COL-I, and α-SMA, while displaying notably diminished levels of E-Cadherin compared to control group. The same findings were observed in PM2.5-treated cells. In BEAS-2B cells co-treated with Stattic (STAT3 inhibitor) and PM2.5, the opposite results occurred. Similar results were obtained for cells co-treated with IL-9-neutralizing antibody and PM2.5. Our findings suggest PM2.5 mediates PF development by promoting IL-9 expression, leading to STAT3 phosphorylation and upregulation of Snail and TWIST1 expression, triggering EMT occurrence and progression in lung epithelial cells.

Bimetal loaded graphitic carbon nitride with synergistic enhanced peroxidase-like activity for colorimetric detection of p-phenylenediamine.

In recent years, great progress has been made on the study of nanozymes with enzyme-like properties. Here, bimetallic Fe and Ni nanoclusters were anchored on the nanosheets of nitrogen-rich layered graphitic carbon nitride by one-step pyrolysis at high temperature (Fe/Ni-CN). The loading content of Fe and Ni on Fe/Ni-CN is as high as 8.0%, and Fe/Ni-CN has a high specific surface area of 121.86 m2 g-1. The Fe/Ni-CN can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and exhibits efficient peroxidase-like activity, leading to a 17.2-fold increase compared to pure graphitic carbon nitride (CN). Similar to the natural horseradish peroxidase (HRP), the Fe/Ni-CN nanozyme follows catalytic kinetics. The Michaelis-Menten constant (Km) value of the Fe/Ni-CN nanozyme for TMB is about 8.3-fold lower than that for HRP, which means that the Fe/Ni-CN nanozyme has better affinity for TMB. In addition, the catalytic mechanism was investigated by combination of free radical quenching experiments and density-functional theory (DFT) calculations. The results show that the high peroxidase-like activity is due to the easy adsorption of H2O2 after bimetal loading, which is conducive to the production of hydroxyl radicals. Based on the extraordinary peroxidase-like activity, the colorimetric detection of p-phenylenediamine (PPD) was constructed with a wide linear range of 0.2-30 µM and a low detection limit of 0.02 µM. The sensor system has been successfully applied to the detection of residual PPD in real dyed hair samples. The results show that the colorimetric method is sensitive, highly selective and accurate. This study provides a new idea for the efficient enhancement of nanozyme activity and effective detection of PPD by a bimetallic synergistic strategy.

Deciphering functional groups of rumen microbiome and their underlying potentially causal relationships in shaping host traits.

Over the years, microbiome research has achieved tremendous advancements driven by culture-independent meta-omics approaches. Despite extensive research, our understanding of the functional roles and causal effects of the microbiome on phenotypes remains limited. In this study, we focused on the rumen metaproteome, combining it with metatranscriptome and metabolome data to accurately identify the active functional distributions of rumen microorganisms and specific functional groups that influence feed efficiency. By integrating host genetics data, we established the potentially causal relationships between microbes-proteins/metabolites-phenotype, and identified specific patterns in which functional groups of rumen microorganisms influence host feed efficiency. We found a causal link between Selenomonas bovis and rumen carbohydrate metabolism, potentially mediated by bacterial chemotaxis and a two-component regulatory system, impacting feed utilization efficiency of dairy cows. Our study on the nutrient utilization functional groups in the rumen of high-feed-efficiency dairy cows, along with the identification of key microbiota functional proteins and their potentially causal relationships, will help move from correlation to causation in rumen microbiome research. This will ultimately enable precise regulation of the rumen microbiota for optimized ruminant production.

Scalable, Controlled Bimodal Pore-Structured Polymer Coating for Efficient Passive Daytime Radiative Cooling.

Outdoor thermal irritation poses a serious threat to public health, with the frequent occurrence of increasingly intense heat waves. With the global goal of carbon peaking and carbon neutrality, there is an urgent need for a strategy that is efficient and can provide localized outdoor cooling without an intensive energy input. This paper demonstrated a rapidly formable polyurethane-based coating with controlled bimodal spherical micropores. Nano-Al2O3 particles (300 nm) embedded in the polymer were used for targeted enhancement of reflectance at 0.38-0.5 wavelengths. The enhanced film reflected 93% solar irradiance and selectively transmitted 95% thermal radiation (8-13 µm), enabling rapid cooling and the creation of a comfortable thermal microclimate to avoid overheating of 6-11 °C during daytime conditions. The ultrawide material compatibility and excellent adaptive mechanical strength of polyurethane-based coatings are expected to benefit the sustainable development of society in a wide range of fields, from health to economics.

Comparative Genomics Revealing the Genomic Characteristics of Klebsiella variicola Clinical Isolates in China.

Klebsiella variicola is an opportunistic pathogen often misidentified as Klebsiella pneumoniae, leading to misdiagnoses and inappropriate treatment in clinical settings. The genetic and molecular characteristics of clinically isolated K. variicola remain largely unexplored. We aim to fill this knowledge gap by examining the genomic properties of and evolutionary relationships between clinical isolates of K. variicola. The genomic data of 70 K. variicola strains were analyzed using whole-genome sequencing. A phylogenetic tree was generated based on the gene sequences from these K. variicola strains and public databases. Among the K. variicola strains, the drug resistance genes with the highest carrying rates were beta-lactamase and aminoglycoside. Locally isolated strains had a higher detection rate for virulence genes than those in public databases, with yersiniabactin genes being the most prevalent. The K locus types and MLST subtypes of the strains exhibited a dispersed distribution, with O3/O3a being the predominant subtype within the O category. In total, 28 isolates carried both IncFIB(K)_Kpn3 and IncFII_pKP91 replicons. This study underscores the importance of developing more effective diagnostic tools and therapeutic strategies for K. variicola infections. The continued surveillance and monitoring of K. variicola strains is essential for understanding the epidemiology of infections and informing public health strategies.