Association between gut microbiota and influenza: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Previous observational studies have indicated a correlation between the gut microbiota and influenza; however, the exact nature of the bidirectional causal connection remains uncertain. METHOD: A two-way, two-sample Mendelian randomization (MR) study was conducted to evaluate the possible causal connection between the gut microbiota and the two outcomes of influenza (pneumonia without influenza and influenza pneumonia). The statistical analysis of gut microbiota is derived from the information of the most extensive meta-analysis (GWAS) conducted by the MiBioGen Alliance, encompassing a sample size of 18,340.The summary statistical data for influenza (not pneumonia, n = 291,090) and influenza pneumonia (n = 342,499) are from GWAS data published by FinnGen consortium R8.Estimate and summarize Single-nucleotide polymorphisms (SNPs) using Inverse variance weighted (IVW), MR Egger, and Weighted median (WM) in bidirectional MR analysis. To assess the heterogeneity, horizontal pleiotropy, and stability of SNPs, we employed Cochran's Q test, MR Egger intercept test, and sensitivity analysis. RESULT: The IVW analysis indicated that there was a significant association between influenza infection and five bacterial taxa. Additionally, the abundance changes of seven gut microbiota were found to be causally related to influenza infection. In addition, seven bacterial taxa showed a significant association with the occurrence of influenza pneumonia. The findings from the WM analysis largely support the outcomes of IVW, however, the results of MR egger analysis do not align with IVW. Furthermore, there is no proof to substantiate the cause-and-effect relationship between influenza pneumonia and the composition of gut microbiota. CONCLUSION: This analysis demonstrates a possible bidirectional causal connection between the prevalence of particular gut microbiota and the occurrence of influenza infection. The presence of certain gut microbiota may potentially contribute to the development of pneumonia caused by influenza. Additional investigation into the interaction between particular bacterial communities and influenza can enhance efforts in preventing, monitoring, and treating influenza.

Astragaloside IV restores Th17/Treg balance via inhibiting CXCR4 to improve chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has a high fatality rate and poses a great threat to human health. Astragaloside IV (AS-IV) is proven to attenuate cigarette smoke (CS)-induced pulmonary inflammation, based on which this research focuses on the mechanism of AS-IV in COPD. METHODS: To evaluate the effects of AS-IV, CD4+ T cells received different concentrations of AS-IV. CD4+ T cell viability, T helper 17 (Th17)/regulatory T (Treg) markers and CXCR4 expressions in CD4+ T cells or spleen/lung tissues were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction and Western blot. The proportions of Treg and Th17 cells were assessed by flow cytometry. Enzyme-linked immune sorbent assay was employed to determine cytokine contents in serum and lung tissues. RESULTS: AS-IV with concentration exceeding 40 µM inhibited CD4+ T cell viability. In vitro, AS-IV suppressed the expressions of CXCR4, retinoid-related orphan receptor γt (RORγt), and interleukin (IL)-17A as well as Th17 cells but promoted the expressions of forkhead box p3 (Foxp3) and IL-10 as well as Treg cells, while CXCR4 overexpression reversed the effects of AS-IV. In vivo, AS-IV alleviated COPD, and CS-induced Th17/Treg imbalance in mice and reduced CS-induced down-regulation of IL-10 in serum and lung tissues and Foxp3 and up-regulation of IL-1ß, tumor necrosis factor alpha (TNF-α), IL-6, and IL-17A in serum and lung tissues and RORγt. AS-IV mitigated CS-induced CXCR4 up-regulation. Above effects of AS-IV on mice were offset by CXCR4 overexpression. CONCLUSIONS: AS-IV restores Th17/Treg balance via impeding CXCR4 to ameliorate COPD.

QTL Mapping and Transcriptome Analysis Reveal Candidate Genes Regulating Seed Color in Brassica napus.

Yellow seeds are desirable in rapeseed breeding because of their higher oil content and better nutritional quality than black seeds. However, the underlying genes and formation mechanism of yellow seeds remain unclear. Here, a novel yellow-seeded rapeseed line (Huangaizao, HAZ) was crossed with a black-seeded rapeseed line (Zhongshuang11, ZS11) to construct a mapping population of 196 F2 individuals, based on which, a high-density genetic linkage map was constructed. This map, comprising 4174 bin markers, was 1618.33 cM in length and had an average distance of 0.39 cM between its adjacent markers. To assess the seed color of the F2 population, three methods (imaging, spectrophotometry, and visual scoring) were used and a common major quantitative trait locus (QTL) on chromosome A09, explaining 10.91-21.83% of the phenotypic variance, was detected. Another minor QTL, accounting for 6.19-6.69% of the phenotypic variance, was detected on chromosome C03, only by means of imaging and spectrophotometry. Furthermore, a dynamic analysis of the differential expressions between the parental lines showed that flavonoid biosynthesis-related genes were down-regulated in the yellow seed coats at 25 and 35 days after flowering. A coexpression network between the differentially expressed genes identified 17 candidate genes for the QTL intervals, including a flavonoid structure gene, novel4557 (BnaC03.TT4), and two transcription factor genes, namely, BnaA09G0616800ZS (BnaA09.NFYA8) and BnaC03G0060200ZS (BnaC03.NAC083), that may regulate flavonoid biosynthesis. Our study lays a foundation for further identifying the genes responsible for and understanding the regulatory mechanism of yellow seed formation in Brassica napus.

Regioselective Hydroalkylation and Arylalkylation of Alkynes by Photoredox/Nickel Dual Catalysis: Application and Mechanism.

Alkynes are an important class of organic molecules due to their utility as versatile building blocks in synthesis. Although efforts have been devoted to the difunctionalization of alkynes, general and practical strategies for the direct hydroalkylation and alkylarylation of terminal alkynes under mild reaction conditions are less explored. Herein, we report a photoredox/nickel dual-catalyzed anti-Markovnikov-type hydroalkylation of terminal alkynes as well as a one-pot arylalkylation of alkynes with alkyl carboxylic acids and aryl bromides via a three-component cross-coupling. The results indicate that the transformations proceed via a new mechanism involving a single-electron transfer with subsequent energy-transfer activation pathways. Moreover, steady-state and time-resolved fluorescence-spectroscopy measurements, density functional theory (DFT) calculations, and wavefunction analysis have been performed to give an insight into the catalytic cycle.

Chemokine (C-X-C motif) ligand 14 contributes to lipopolysaccharide-induced fibrogenesis in mouse L929 fibroblasts via modulating PPM1A.

Herein, we found that serum chemokine ligand 14 (CXCL14) was significantly enhanced in patients with idiopathic pulmonary fibrosis (IPF). In our current study, mouse L929 fibroblasts were stimulated with lipopolysaccharide (LPS) (100 ng/mL). Cell proliferation, the levels of matrix metalloproteinase 2 (MMP2) and MMP9, as well as extracellular matrix (ECM) content were assessed to evaluate the fibrogenesis of L929 cells. Proliferating cell nuclear antigen and cell viability were assessed to evaluate cell proliferation. Hydroxyproline (Hyp), collagen I/III, connective tissue growth factor (CTGF), and phosphorylated Smad2/3 (p-Smad2/3) were assessed to evaluate ECM secretion and deposition. α-Smooth muscle actin (α-SMA) was used to measure the occurrence of differentiation from fibroblast toward myofibroblast. Our data suggested that knockdown of CXCL14 prevented LPS-induced fibrogenesis of L929 cells through inhibiting cell proliferation and decreasing the expression of MMP2/9, Hyp, collagen I/III, CTGF, p-Smad2/3, and α-SMA. Notably, upregulation of protein phosphatase magnesium-dependent 1A (PPM1A) was involved in this process. On the contrary, recombinant CXCL14 protein led to an opposite effect. We first suggested that overexpression of PPM1A ameliorated LPS-induced fibrogenesis. Furthermore, we substantiated that knockdown of CXCL14 exerted an antifibrotic effect in IPF in vitro probably via the upregulation of PPM1A. Besides, evidently enhanced CXCL14, yet reduced PPM1A, was found in bleomycin-induced rat pulmonary fibrosis, confirming the roles of CXCL14 and its potential association with PPM1A in IPF in vivo. In conclusion, CXCL14 could be considered as a therapeutic target for preventing fibrogenesis of mouse L929 fibroblasts.

Deep learning radiomics-based preoperative prediction of recurrence in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is characterized by poor prognosis and propensity for recurrence even after surgery. Identification of those CRS patients with high risk of relapse preoperatively will contribute to personalized treatment recommendations. In this paper, we proposed a multi-task deep learning network for sinus segmentation and CRS recurrence prediction simultaneously to develop and validate a deep learning radiomics-based nomogram for preoperatively predicting recurrence in CRS patients who needed surgical treatment. 265 paranasal sinuses computed tomography (CT) images of CRS from two independent medical centers were analyzed to build and test models. The sinus segmentation model achieved good segmentation results. Furthermore, the nomogram combining a deep learning signature and clinical factors also showed excellent recurrence prediction ability for CRS. Our study not only facilitates a technique for sinus segmentation but also provides a noninvasive method for preoperatively predicting recurrence in patients with CRS.

Genome-wide identification and expression profiling of the COBRA-like genes reveal likely roles in stem strength in rapeseed (Brassica napus L.).

The COBRA-like (COBL) genes play key roles in cell anisotropic expansion and the orientation of microfibrils. Mutations in these genes cause the brittle stem and induce pathogen responsive phenotypes in Arabidopsis and several crop plants. In this study, an in silico genome-wide analysis was performed to identify the COBL family members in Brassica. We identified 44, 20 and 23 COBL genes in B. napus and its diploid progenitor species B. rapa and B. oleracea, respectively. All the predicted COBL genes were phylogenetically clustered into two groups: the AtCOB group and the AtCOBL7 group. The conserved chromosome locations of COBLs in Arabidopsis and Brassica, together with clustering, indicated that the expansion of the COBL gene family in B. napus was primarily attributable to whole-genome triplication. Among the BnaCOBLs, 22 contained all the conserved motifs and derived from 9 of 12 subgroups. RNA-seq analysis was used to determine the tissue preferential expression patterns of various subgroups. BnaCOBL9, BnaCOBL35 and BnaCOBL41 were highly expressed in stem with high-breaking resistance, which implies these AtCOB subgroup members may be involved in stem development and stem breaking resistance of rapeseed. Our results of this study may help to elucidate the molecular properties of the COBRA gene family and provide informative clues for high stem-breaking resistance studies.

Concentration, spatial distribution, and health risk assessment of PFASs in serum of teenagers, tap water and soil near a Chinese fluorochemical industrial plant.

Discharges released from fluorochemical industrial plants lead to severe contamination of the environment with per- and polyfluoroalkyl substances (PFASs), which may pose risks to human health. In this study, 187 serum samples from teenagers (age = 14 years), 22 tap water samples and 40 soil samples were collected in areas within 0-11 km of a fluorochemical industrial plant in Huantai County, Shandong Province, and concentrations of 18 PFASs were quantified by UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was found to be predominant, concentrations of which ranged from 40.4 to 845 ng/mL in serum, from 2.88 to 19.3 ng/L in tap water, from 4.40 to 189 ng/g in soil, and accounting for 84.1-98.6%, 15.9-79.8%, and 73.8-96.7% of the total PFASs, respectively. Statistical analysis demonstrated that concentrations of perfluorinated carboxylic acids (PFCAs) in soil (C5-C9) and serum (C8-C10) were associated with the industrial plant. And PFOA concentrations in tap water were not relevant to the industrial plant, which were comparable with the non-contaminated area and lower than the threshold value recommended by U.S. EPA (70 ng/mL), indicating that the contribution to the high concentration of serum PFOA of local teenagers by drinking water was limited. Moreover, PFCAs in soil only made a limited contribution to the serum PFCAs of local residents by direct inhalation and dermal exposure, but the potential health risk by the soil via food chain should be paid attention to. Furthermore, health risk assessment demonstrated that high concentrations of PFOA in serum could pose potential health risk to local teenagers. Therefore, effective measures should be taken to attenuate the health risks caused by the industrial plant to local residents, and further epidemiological studies should be carried out in the future.

Anti-fibrotic effect of melittin on TRIM47 expression in human embryonic lung fibroblast through regulating TRIM47 pathway.

AIMS: To investigate the effect and underlying mechanism of melittin and tripartite motif (TRIM) family in human embryonic lung fibroblast (HELF). MATERIALS AND METHODS: Lentiviral RNA interference vector and lentiviral overexpression vector were constructed and packaged by transfecting 293T cells; the proliferation of HELF was examined using Cell Counting Kit 8; Western blot and qRT-PCR were performed to examine protein and mRNA expression; the interaction with protein phosphatase magnesium-dependent 1A (PPM1A) was examined by Co-immunoprecipitation. KEY FINDINGS: Compared with the control group, the mRNA expression of the TRIM6, TRIM8 and TRIM47 in the IPF group significantly increased. Melittin inhibited the mRNA expression and protein expression levels of TRIM47, the HELF proliferation, the hydroxyproline levels, and the phosphorylation of Smad2/3; the interference of TRIM47 inhibited the protein expression of Vimentin, α-SMA, CTGF, the phosphorylation of Smad2/3 and the synthesis of hydroxyproline; TRIM47 overexpression elevated the phosphorylation of Smad2/3, induced ubiquitination of PPM1A and decreased the expression level of PPM1A, while TRIM47 RNA interference reversed this result. SIGNIFICANCE: Melittin has anti-fibrotic effect in HELF by directly reducing the phosphorylation of Smad2/3 or indirectly reducing the phosphorylation of Smad2/3 by decreasing the expression levels of TRIM47 whose overexpression induces ubiquitination of PPM1A.

Dexamethasone combined with berberine is an effective therapy for bleomycin-induced pulmonary fibrosis in rats.

Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)-induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α-smooth muscle actin (α-SMA), MMP2/9 and phosphorylated-Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α-SMA and p-Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.

FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis and lung cancer.

The aim of this study was to investigate the expression of FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) as well as their clinical significance. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to detect FGF2 and FGFR2 expression in LC and adjacent normal tissues of LC patients and lavage fluid of idiopathic pulmonary fibers patients and normal controls (confirmed by bronchoalveolar lavage examination). The expression levels of FGF2 mRNA and protein in the non-small cell LC tissues were significantly higher than those in the adjacent normal tissues (P<0.001). The expression level of FGF2 protein in lavage fluid of patients with IPF was higher than that of the control group (P<0.001). The expression level of FGFR2 mRNA in the non-small cell LC tissues was significantly higher than that in the adjacent normal tissues (P<0.001). The expression level of FGFR2 protein in the non-small cell LC tissues was higher than that in the adjacent normal lung tissues (P<0.001). The expression levels of FGF2 mRNA and FGFR2 mRNA in cancer tissues were not significantly correlated with age, sex and history of smoking (P>0.05), but were significantly correlated with lymph node metastasis, tumor differentiation and TNM staging. FGF2 and FGFR2 proteins were highly expressed in cancer tissues of LC patients and lavage fluid of patients with IPF. The expression of FGF2 mRNA and FGFR2 mRNA was correlated with lymph node metastasis and TNM stage. The high expression levels of FGF2 mRNA and FGFR2 mRNA were associated with tumor metastasis and poor prognosis of LC patients.

Sequential coating upconversion NaYF4:Yb,Tm nanocrystals with SiO2 and ZnO layers for NIR-driven photocatalytic and antibacterial applications.

ZnO is one of the most promising materials for both photocatalytic and antibacterial applications, but its wide bandgap requires the excitation of UV light which limits their applications under visible and NIR bands. Herein, we demonstrate a facile approach to synthesize core-shell-shell hybrid nanoparticles consisting of hexagonal NaYF4:Yb,Tm, amorphous SiO2 and wurtzite ZnO. The upconversion nanocrystals are used as the core seeds and sequentially coated with an insulting shell and a semiconductor layer. Such hybrid nanoparticles can efficiently utilize the NIR light through the upconverting process, and display notable photocatalytic performance and antibacterial activity under NIR irradiation. The developed NaYF4:Yb,Tm@SiO2@ZnO nanoparticles are characterized with TEM, XRD, EDS, XPS and PL spectra, and their working mechanism is also elucidated.

[Clinical and imaging diagnosis of primary hepatic lymphoma].

OBJECTIVE: To investigate the clinical and imaging features of primary hepatic lymphoma (PHL). METHODS: Four PHL cases were analyzed retrospectively for clinical manifestations, transcatheter hepatic arterial angiography and CT features. RESULTS: All the four cases were B-cell non-Hodgkin lymphoma proven by histological and immunohistochemical examination. The main clinical manifestations included pain in the right upper quadrant and B symptoms of the lymphoma (fever, night sweating, and weight loss) in 3 patients. Three cases were complicated by chronic hepatitis or cirrhosis, and the other had renal transplantation two years ago. All these cases exhibited elevated serum lactate dehydrogenase (LDH) level, which was reduced after surgery or chemotherapy. Plain CT scan all identified hypodense lesions which did not display marked enhancement on the arterial phase and portal venous phase scans. On delayed phase scan, the border of the lesions became clear, and slight enhancement was observed in the peripheral and some partitions of the lesions. Angiographic imaging displayed slight tumor staining and arterial displacement in the liver in all the cases with thin tumor-supplying vessels. Global staining or abnormally thickened vessels were not seen. CONCLUSION: A comprehensive evaluation of the clinical manifestations and imaging features can be helpful in the diagnosis of PHL, and serum LDH level may help to assess the therapeutic effect.

Comprehensive analysis of gene-expression profile in chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD) patients and explore the possible therapeutic targets. METHODS: The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus. After data preprocessing with the Affy package, Student's t-test was employed to identify the differentially expressed genes (DEGs). The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA. Furthermore, we constructed a protein-protein interaction (PPI) network for DEGs. The surfactant protein D (SP-D) serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction, respectively. RESULTS: A total of 39 up- and 15 downregulated DEGs were screened. Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process. Moreover, we also found that HLA-A has the highest degree in the PPI network. The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P<0.05). CONCLUSION: Our results may help further the understanding of the mechanisms of COPD. The identified DEGs, especially HLA-A, may serve as diagnosis markers for COPD.

[18F-FDG positron emission tomography for mediastinal staging of lung cancer].

OBJECTIVE: To evaluate the diagnostic value of (18)F-FDG positron emission tomography (PET) in mediastinal staging of lung cancer. METHOD: A retrospective analysis of mediastinal staging was carried out in 41 cases of lung cancer by comparing the preoperative mediastinal FDG PET and CT findings with the pathological results. RESULTS: According to the pathological results, 18 patients had mediastinal metastasis, 17 of whom were correctly identified by FDG PET, and 10 by CT. Of the other 23 patients without mediastinal metastasis pathologically, 22 were correctly diagnosed by FDG PET and 20 by CT. The sensitivity and accuracy for diagnosis of regional mediastinal lymph node metastasis with FDG PET were 94.4% and 95.1%, obviously higher than those of CT (55.6% and 73.2%, P<0.05). CONCLUSION: FDG PET is a better alternative for mediastinal staging of lung cancer, specially for identification of small lymph node metastasis escaping detection by CT, to provide important evidence for clinical staging and treatment planning of lung cancer.

[18F-Fluorodeoxyglucose uptake in hepatocellular carcinoma on positron emission tomography correlates with alpha-fetoprotein].

OBJECTIVE: To investigate whether (18)F-fluorodexyglucose (FDG) uptake in the primary hepatocellular carcinoma (HCC) correlates with serum alpha-fetoprotein (AFP). METHODS: Forty-five patients with histologically confirmed HCC underwent whole-body (18)F-FDG PET examination. Standardized uptake value (SUV) and tumor-to-nontumor ratio of the SUV (SUVratio) were calculated, and the relationship between serum AFP and glucose metabolism in HCC was analyzed. RESULTS: Of the 45 cases, the primary tumor and metastatic lymph nodes were clearly displayed on PET images in 43 cases and the well-differentiated tumors were shown negative in the other 2 cases. A linear correlation of the AFP with SUV (r=0.426, P<0.05) and SUVratio (r=0.532, P<0.001) was noted. CONCLUSION: Serum AFP correlates significantly with both SUV and SUN ratio, indicating that AFP is involved in glucose metabolism and cell proliferation in HCC.

[Application of 16-slice spiral CT angiography in aortic dissection].

OBJECTIVE: To explore the value of 16-slice spiral CT angiography in the diagnosis of aortic dissection (AD). METHODS: Twenty patients with AD underwent 16-slice spiral CT angiography with multi-planar reformation (MPR), curved planar reformation (CPR), maximum intensity projection (MIP), volume rendering (VR) and CT virtual endoscopy (CTVE). All the original and reconstructed images were studied. RESULTS: The original transverse axial images most reliably preserved the fundamental information. The reconstructed images gave better performance in displaying the spatial relation between the blood vessels and the lesions. Images obtained by different reconstruction methods had different characteristics, and combining different display modes allowed clear representation of the features of aortic dissection such as the extension of the lesion, true and false cavity, disrepair of the intimal flap, aortal branch involvement, thrombi and outcome of endoluminal stenting. CONCLUSION: Multislice spiral CT angiography can fully display the details of aortic dissection and is therefore of important value for the diagnosis and preoperative and postoperative evaluations.