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Abstract Bacterial biofilm infection is a complicated and important global problem. Non-toxic biomass-based Pickering emulsions as an essential oil delivery system are a potentially effective means in biofilm treatment. Herein, the chitosan/gelatin complex nanoparticles (CGNPs) stabilized Pickering (CGP) emulsion loaded with cinnamon essential oil (CEO) was developed to inhibit and remove bacterial biofilms. CGNPs were initially successfully prepared with a particle size of 253.7 nm. Subsequently, CGP emulsions were prepared using CGNPs as the emulsifier and CEO as the oil phase, with the aqueous phase pH value of 5.5 and ionic strength of 50 mM. Amino groups of CGNPs were crosslinked with the aldehyde group of CEO via Schiff base reaction at the oil–water interface to form a denser core–shell structure, thus improving the stability of Pickering emulsion. The CGP emulsions exhibit controlled and long-term sustained release properties in essential oil delivery, with 89.8%, 81.0%, and 62.2% CEO release within 168 h for CGP-0.1, CGP-0.2, and CGP-0.3, respectively. Moreover, CGP emulsions have stronger antioxidant activities (nearly 100%), broad-spectrum antibacterial activities (> 90%), enhanced penetration and removal capabilities against preformed biofilms than single CEO or CGNPs, as well as its better biocompatibility than conventional surfactant-stabilized emulsions. Hence, CEO-delivered CGP emulsion could serve as a potential strategy against biofilm infections and bacterial resistance. Graphical abstract

Abstract Background To explore the pathogenesis of different subtypes of gallstones in high-altitude populations from a molecular perspective. Methods We collected bile samples from 20 cholesterol gallstone disease (CGD) patients and 20 pigment gallstone disease (PGD) patients. Proteomics analysis was performed by LC/MS DIA, while metabolomics analysis was performed by UPLC- Q-TOF/MS. Results We identified 154 up-regulated and 196 down-regulated differentially expressed proteins, which were significantly enriched in neurodegenerative diseases, energy metabolism, amino acid metabolism etc. In metabolomics analysis, 20 up-regulated and 63 down-regulated differentially expressed metabolites were identified, and they were significantly enriched in vitamin B6 metabolism. Three pathways of integrated proteomics and metabolomics were significantly enriched: porphyrin and chlorophyll metabolism, riboflavin metabolism and aminoacyl-tRNA biosynthesis. Remarkably, 7 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. Conclusion The findings of our metabolomics and proteomics analyses help to elucidate the underlying mechanisms of gallstone formation in high-altitude populations.

ABSTRACT Objective This study aimed to evaluate the activity of extraocular muscles (EOMs) in patients with thyroid‐associated ophthalmopathy (TAO) using turbo spin echo imaging. By analyzing tissue heterogeneity, apparent diffusion coefficient (ADC) histogram analysis offers enhanced insights into edema within the EOMs. Methods Eighty‐eight patients with TAO were retrospectively evaluated and allocated into active (n = 24, clinical activity score [CAS] ≥ 3) and inactive (n = 64, CAS 1.26 μm2/s, entropy > 4.03, and standard deviation (SD) > 0.4 of the ADC histogram, were significant predictors of TAO activity, with odds ratios of 2.741 and 6.806, 5.070, 2.652, and 2.197, respectively (all p 1.26 μm²/s, entropy > 4.03, or SD > 0.4 may also predict active TAO.

ABSTRACT The emergence of multidrug-resistant Citrobacter freundii poses a significant threat to public health. C. freundii isolates were collected from clinical patients in a Chinese hospital during 2020–2022. An unusual strain, GMU8049, was not susceptible to any of the antibiotics tested, including the novel β-lactam/β-lactamase inhibitor combination ceftazidime-avibactam. Whole-genome sequencing (WGS) revealed that GMU8049 harbors a circular chromosome belonging to the rare ST257 and an IncX3 resistance plasmid. Genomic analysis revealed the coexistence of two β-lactamase genes, including plasmid-mediated blaNDM-1 and chromosomal blaCMY encoding a novel CMY variant, combined with an outer membrane porin deficiency, which may account for the extreme resistance to β-lactams. Conjugation experiment confirmed that the blaNDM-1 resistance gene located on pGMU8049 could be successfully transferred to Escherichia coli EC600. The novel CMY variant had an amino acid substitution at position 106 (N106S) compared to the closely related CMY-51. Additionally, a GMU8049-specific truncation in an OmpK37 variant that produces a premature stop codon. Moreover, a variety of chromosome-located efflux pump coding genes and virulence-related genes were also identified. Analysis of strain GMU8049 in the context of other C. freundii strains reveals an open pan-genome and the presence of mobile genetic elements that can mediate horizontal gene transfer of antimicrobial resistance and virulence genes. Our work provides comprehensive insights into the genetic mechanisms of highly resistant C. freundii, highlighting the importance of genomic surveillance of this opportunistic pathogen as a high-risk population for emerging resistance and pathogenicity.IMPORTANCEEmerging pathogens exhibiting multi-, extremely, and pan-drug resistance are a major concern for hospitalized patients and the healthcare community due to limited antimicrobial treatment options and the potential for spread. Genomic technologies have enabled clinical surveillance of emerging pathogens and modeling of the evolution and transmission of antimicrobial resistance and virulence. Here, we report the genomic characterization of an extremely drug-resistant ST257 Citrobacter freundii clinical isolate. Genomic analysis of GMU8049 with a rare ST type and unusual phenotypes can provide information on how this extremely resistant clinical isolate has evolved, including the acquisition of blaNDM-1 via the IncX3 plasmid and accumulation through chromosomal mutations leading to a novel CMY variant and deficiency of the outer membrane porin OmpK37. Our work highlights that the emergence of extremely resistant C. freundii poses a significant challenge to the treatment of clinical infections. Therefore, great efforts must be made to specifically monitor this opportunistic pathogen.

Abstract Chronic obstructive pulmonary disease (COPD) is a persistent and progressive disorder characterized by airway or alveolar abnormalities, commonly leading to pulmonary hypertension (PH). This clinical observational study investigates the therapeutic mechanisms of Bufei Huoxue capsules (BHC) in treating PH in patients with COPD‐linked PH (COPD‐PH) using network pharmacology and molecular docking methods, and assesses the therapeutic efficacy and safety of BHCs. The active compounds and their target proteins in BHCs were sourced from the Traditional Chinese Medicine Systems Pharmacology database, with additional target proteins derived from the GeneCards and OMIM databases. An active network was constructed using Cytoscape 3.7.1, and interaction networks were established. Intersecting targets underwent Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Metascape database. Network pharmacology and molecular docking studies demonstrated favorable binding affinities of BHC active ingredients, such as quercetin, bavachalcone, and isobavachin, for key targets including PTGS1, ESR1, and PTGS2. Gene Ontology enrichment analysis highlighted the involvement of these targets in processes such as the positive regulation of locomotion, the transmembrane receptor protein tyrosine kinase signaling pathway, and peptidyl‐tyrosine phosphorylation. KEGG pathway analysis indicated their roles in pathways related to cancer, AGE‐RAGE signaling in diabetic complications, and prostate cancer. BHCs exhibit therapeutic effects on COPD‐PH through multi‐component, multi‐target, and multi‐pathway interactions. This clinical observational study confirms the efficacy and safety of BHCs in improving cardiac and pulmonary functions, enhancing exercise tolerance, and elevating the quality of life in patients with COPD‐PH.

Hot compression tests of a novel dual-phase Mg–Li alloy were performed in temperature range of 200–400 °C and strain rate range of 0.01–10s−1. 2D and 3D processing maps were established using Prasad's and Murty's instability criteria (methods) based on the dynamic materials model. It was found that one instability region obtained based on Prasad's instability criterion exist in the domain of power dissipation efficiency at a strain of 0.7. Prasad's and Murty's instability criteria are difficult to accurately characterize the instability characteristics of the alloy. The accuracy processing map rectified was obtained by means of Murty's and Prasad's instability criteria and microstructural analysis. On the basis of the processing map rectified, the optimum hot working parameters were obtained to be the temperature range of 320–400 °C and strain rate range of 0.01–0.4s−1 with the peak power dissipation efficiency. In this domain, the α phase undergone dynamic recrystallization (DRX) and dynamic recovery (DRV). The β-phase occurred DRX during the hot deformation. The instability regions lie in the temperature range of 200–250 °C with strain rate range of 0.01–1s−1 and the temperature range of 200–312 °C with strain rate range of 1–10s−1. Microstructural observations indicate that characteristics of the flow instabilities were flow localization, deformation twinning, the adiabatic shear bands and macro/micro cracking. The rectified processing map was successfully verified by the hot rolling test. The rectified processing map could accurately characterize workability characteristics of a novel dual-phase Mg–Li alloy and could be used for the optimization of hot working process parameters.

Background: Pulmonary fibrosis is common in primary Sjögren's syndrome (pSS)-related interstitial lung disease (ILD). However, research is lacking on the diagnostic immunological examination of pSS-related pulmonary fibrosis. Particularly, the value of detecting anti-Ro52 antibody in pulmonary fibrosis is unclear. Objective: To evaluate the potential diagnostic value of anti-SSA, anti-SSB, and anti-Ro52 autoantibodies as markers of pSS-related pulmonary fibrosis. Methods: One-hundred seventy-nine patients with pSS were analyzed retrospectively at our hospital. They were divided into the fibrosis and non-fibrosis groups. Pulmonary fibrosis was classified as mild, moderate, or severe based on the patients' computed tomography (CT) findings. Laboratory examinations, including anti-SSA, anti-SSB, and anti-Ro52 antibody evaluations, were performed. The influencing factors of pulmonary fibrosis were analyzed using logistic regression. Results: Chest CT revealed pulmonary fibrosis in 45 patients with pSS (25.1%). The positive rates of anti-SSA and anti-Ro52 antibodies in the fibrosis group were lower than in the non-fibrosis group (P=0.04, P=0.001). The frequency of anti-Ro52 antibody showed no significant differences between mild-to-moderate (53.8%) and severe (47.3%) pulmonary fibrosis. The anti-Ro52 antibody was identified as a potentially protective factor against pSS (P=0.041). Conclusions: Patients with pSS and pulmonary fibrosis had a low frequency of anti-SSA and anti-Ro52 antibodies. In patients with pSS and negative anti-Ro52 antibody, a chest CT is recommended to further understand the patients' condition.

Background. Primary liver cancer, dominated by hepatocellular carcinoma (HCC), is one of the most common cancer types and the third leading cause of cancer death in 2020. Previous studies have shown that liquid–liquid phase separation (LLPS) plays an important role in the occurrence and development of cancer including HCC, but its influence on the patient prognosis is still unknown. It is necessary to explore the effect of LLPS genes on prognosis to accurately forecast the prognosis of HCC patients and identify relevant targeted therapeutic sites. Methods. Using The Cancer Genome Atlas dataset and PhaSepDB dataset, we identified LLPS genes linked to the overall survival (OS) of HCC patients. We applied Least Absolute Shrinkage and Selection Operator (LASSO) Cox penalized regression analysis to choose the best genes for the risk score prognostic signature. We then analysed the validation dataset and evaluated the effectiveness of the risk score prognostic signature. Finally, we performed quantitative real-time PCR experiments to validate the genes in the prognostic signature. Results. We identified 43 differentially expressed LLPS genes that were associated with the OS of HCC patients. Five of these genes (BMX, FYN, KPNA2, PFKFB4, and SPP1) were selected to generate a prognostic risk score signature. Patients in the low-risk group were associated with better OS than those in the high-risk group in both the training dataset and the validation dataset. We found that BMX and FYN had lower expression levels in HCC tumour tissues, whereas KPNA2, PFKFB4, and SPP1 had higher expression levels in HCC tumour tissues. The validation demonstrated that the five-LLPS gene risk score signature has the capability of predicting the OS of HCC patients. Conclusion. Our study constructed a five-LLPS gene risk score signature that can be applied as an effective and convenient prognostic tool. These five genes might serve as potential targets for therapy and the treatment of HCC.

ObjectiveTo monitor the radiological courses of symptomatic spontaneous isolated superior mesenteric artery dissection (SISMAD) after conservation, clarify the relationship between its morphological change and initial imaging classification, and identify these factors that affect dissection remodeling.MethodsEighty-nine conservative patients with SISMAD who underwent periodic follow-up of computed tomography angiography (CTA) were enrolled. Initial morphologic classification, imaging features and dissection remodeling were analyzed retrospectively. Logistic regression was used to identify predictors for remodeling. Receiver operating characteristics were performed for cutoff threshold.ResultsZerbib classification was adapted and initial CT appearance divided eighty-nine patients into: type I (15.7%), patent false lumen (FL) with both entry and re-entry; type II (37.1%), “cul-de-sac” shaped FL without re-entry; type III (27.0%), thrombosed FL with ulcer-like-projection (ULP); type IV (18%), intramural hematoma; type V (0%), dissecting aneurysm; and type VI (2.2%), total or partial occlusion of superior mesenteric artery (SMA). Follow-up CTA revealed complete remodeling (33.7%), partial remodeling (16.9%), no change (25.8%), type change (13.5%) and dissection progression (10.1%). There was no dissection-related mortality. Type I (92.9%) sustained patent FL and no angiographic change. Type II showed partial remodeling (42.4%), no change (27.3%) and dissection progression (27.3%), and the length of FL enhancement positively predicted dissection progression with the cutoff of 40.3 millimeters. Type III achieved complete remodeling (58.3%) or evolved into type II (41.7%), and the distance between SMA orifice and ULP negatively predicted type change with the cutoff of 23.5 millimeters. Type IV (87.5%) achieved complete remodeling due to hematoma absorption. One patient underwent stent placement for the evolution of ULP into an enlarged blind-ending FL 2 months after conservation.ConclusionAfter conservation, patent FL with a distal re-entry is no morphological change, FL thrombosis tends to be resolved, and the “cul-de-sac” shaped FL without re-entry is partially shortened, no change or progressively dilated. FL enhancement length ≥ 40.3 millimeters is a predictor for the blinding-end FL enlargement. Thrombosed FL with ULP evolves into a patent “cul-de-sac” shaped FL when the distance between SMA orifice to ULP is less than 23.5 millimeters. A careful follow-up is necessary for the lesions with demonstrated predictors.

Abstract Background Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear. Methods This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed. Results After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5‐year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM patients. To date, most prognostic models for predicting survival in GBM were constructed based on bulk RNA‐seq dataset, which failed to accurately reflect the difference between tumor cores and peripheral regions, and thus show low predictive capability. An effective prognostic model is desperately needed in clinical practice. Methods We studied single‐cell RNA‐seq dataset and The Cancer Genome Atlas‐glioblastoma multiforme (TCGA‐GBM) dataset to identify differentially expressed genes (DEGs) that impact the OS of GBM patients. We then applied the least absolute shrinkage and selection operator (LASSO) Cox penalized regression analysis to determine the optimal genes to be included in our risk score prognostic model. Then, we used another dataset to test the accuracy of our risk score prognostic model. Results We identified 2128 DEGs from the single‐cell RNA‐seq dataset and 6461 DEGs from the bulk RNA‐seq dataset. In addition, 896 DEGs associated with the OS of GBM patients were obtained. Five of these genes (LITAF, MTHFD2, NRXN3, OSMR, and RUFY2) were selected to generate a risk score prognostic model. Using training and validation datasets, we found that patients in the low‐risk group showed better OS than those in the high‐risk group. We validated our risk score model with the training and validating datasets and demonstrated that it can effectively predict the OS of GBM patients. Conclusion We constructed a novel prognostic model to predict survival in GBM patients by integrating a scRNA‐seq dataset and a bulk RNA‐seq dataset. Our findings may advance the development of new therapeutic targets and improve clinical outcomes for GBM patients.

Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3′UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.

New Findings What is the central question of this study? In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment‐induced chronic obstructive pulmonary disease (COPD) models in mice. What is the main finding and its importance? Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis. Abstract Although it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.

Abstract Background Long-term excess exposure to environmental manganese (Mn) can lead to multi-system damage, especially in occupational populations. Therefore, we established a manganese-exposed workers healthy cohort (MEWHC), focusing on the systemic health effects related to Mn exposure. Here, we aimed to describe the follow-up activity for the MEWHC study and establish a standardized biological sample bank for the scientific management of high-quality biospecimens and the attached data from 2011 to 2017. Methods Baseline examinations for onsite workers were conducted, and the biobank for the MEWHC was first established in 2011; follow-up examinations occurred four times between July 2012 and November 2017. All questionnaires, clinical data and biological samples were routinely collected during each follow-up activity. Additional workers were recruited in 2016, which further enriched the resources of the biobank. Results A total of 2359 onsite workers and 612 retired workers at a ferromanganese refinery were enrolled in the prospective cohort, and their biological samples were obtained in the preliminary baseline survey and the follow-up investigation, including 2971 blood and urine samples from the cohort. In addition, 1524 hair samples, 1404 nail (toe and finger nails) and 1226 fecal samples were also collected. All specimens were preserved in the biobank, and the data were scientifically managed using a computer system. Conclusions The MEWHC study in China provides an effective way to obtain biological samples such as plasma, DNA, hair and urine for storage in a biobank for further study. The standardized management of various samples is crucial for accessing high-quality biospecimens.

Abstract Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.

Airway remodeling is one of the characteristics for chronic obstructive pulmonary disease (COPD). The mechanism underlying airway remodeling is associated with epithelial-mesenchymal transition (EMT) in the small airways of smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to reduce oxidative stress, and to modulate EMT. Here, we investigated the effects and mechanisms of hydrogen sulfide (H2S) on pulmonary EMT in vitro and in vivo. We found that H2S donor NaHS inhibited cigarette smoke (CS)-induced airway remodeling, EMT and collagen deposition in mouse lungs. In human bronchial epithelial 16HBE cells, NaHS treatment also reduced CS extract (CSE)-induced EMT, collagen deposition and oxidative stress. Mechanistically, NaHS upregulated SIRT1 expression, but inhibited activation of TGF-β1/Smad3 signaling in vivo and in vitro. SIRT1 inhibition by a specific inhibitor EX527 significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress. SIRT1 inhibition also abolished the protection of NaHS against CSE-induced EMT. Moreover, SIRT1 activation attenuated CSE-induced EMT by modifying TGF-β1-mediated Smad3 transactivation. In conclusion, H2S prevented CS-induced airway remodeling in mice by reversing oxidative stress and EMT, which was partially ameliorated by SIRT1 activation. These findings suggest that H2S may have therapeutic potential for the prevention and treatment of COPD. Keywords: Hydrogen sulfide, COPD, Airway remodeling, Oxidative stress, Epithelial-mesenchymal transition, Sirtuin 1

Backgrounds: Bone morphogenetic protein receptor type 2 (BMPR2) signaling is anti-inflammatory. Decreased BMPR2 expression was seen in lung tissue from chronic obstructive pulmonary disease (COPD) patients. Methods: The selected single nucleotide polymorphisms (SNPs) in BMPR2 were genotyped with polymerase chain reaction (PCR) ligase detection reaction. The effects of SNPs on gene expression were analyzed with luciferase assays. The mRNA and protein expression levels of BMPR2 in peripheral blood mononuclear cells (PBMCs) from COPD patients were determined by quantitative PCR and western blotting, respectively. Findings: Two SNPs, rs6435156C>T and rs1048829G>T in the 3′-untranslated region (3′UTR) of BMPR2 were selected and genotyped in COPD case and healthy control subjects from southern Chinese population. Both of them were found associated with significantly increased COPD risk (adjusted odds ratio [OR] = 1.58 with 95% confidence interval [CI] = 1.14–2.15, P = 0.0056 for rs6435156C>T; adjusted OR = 1.47 and 95% CI = 1.10–1.97, P = 0.0092 for rs1048829G>T). Older age, cigarette smoking, family history of cancer and COPD were all factors that interacted with rs6435156C>T and rs1048829G>T causing increased COPD risk. Cigarette smokers with rs6435156 (CT + TT) or rs1048829 (GT + TT) were more susceptible to COPD than that with the rs6435156CC or rs1048829GG genotypes. In A549 human alveolar epithelial cells, luciferase reporter assays revealed that introduction of 3′UTR of BMPR2 plasmids carrying rs6435156T allele but not rs1048829T led to lower luciferase activity than the wild-type C or G alleles. Comparing to rs6435156CC, treatment with hsa-miR-20a mimics deceased whereas hsa-miR-20a inhibitor restored the luciferase reporter activity in cells transfected with constructs carrying rs6435156TT. BMPR2 mRNA and protein expressions were significantly lower in PBMCs from COPD smokers than that in non-smokers. COPD patients carrying rs6435156T allele had less BMPR2 expression in PBMCs. Interpretation: This study demonstrated that both rs6435156C>T and rs1048829G>T variants in BMPR2 contributed to increased susceptibility to COPD. The T variants of rs6435156 increased COPD risk likely by binding with hsa-miR-20a, thus leading to downregulated BMPR2 expression in lung epithelial and immune cells.

Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.

To explore the protective effects of a black bean-whey double protein (B-W double protein, B-W DP) diet on intestinal barrier injury induced by lipopolysaccharides (LPS) in rats. Sprague-Dawley rats were fed low, medium, and high doses of B-W DP for 28 d, and then, LPS was used to induce intestinal barrier injury. The intestinal morphology of the rats was observed using hematoxylin and eosin staining. The expression of tight junction proteins was quantified using immunohistochemistry, and the TLR4 and MyD88 expression levels were determined using real-time fluorescence quantitative polymerase chain reaction. Results showed that compared with low- and high-dose B-W DP, intermediate-dose B-W DP significantly (P

Strawberry 'Kaorino' is one of the perfect early- maturing strawberry varieties with high quality and high yield due to its anthracnose resistance, early maturity and good quality. The variety has become more and more popular with the promotion over the last few years, but there are great differences from other varieties in cultivation. Based on its varietal characteristics and cultivation performance in production over the last few years, we summarized the seedling cultivation techniques, planting management techniques, main disease control techniques and harvesting and storage techniques, aiming to provide reference for better promotion and application of (Kaorino). [ABSTRACT FROM AUTHOR]