miRNA-381 regulates renal cancer stem cell properties and sunitinib resistance via targeting SOX4.

Cancer stem cells (CSCs) are crucial in the pathogenesis of human cancers. Existing studies reported that microRNA (miRNA) modulates the stemness of CSCs. We discovered that renal cell CSCs have suppressed miR-381. Suppression of miR-381 promotes renal cell tumorigenesis and CSC-like properties. Furthermore, the forced expression of miR-381 prevents the renal cell tumorigenesis and CSC-like properties. Mechanistically, renal cell CSCs have been found to interact with SOX4 through miR-381 directly. miR-381 inhibits renal cell CSC-like properties and tumorigenesis via downregulating SOX4. Examination of the patient-derived xenografts (PDX) and patient cohorts reveals that miR-381 may be able to forecast the advantages of Sunitinib in RCC patients. Moreover, the introduction of SOX4 could reverse the sensitivity of miR-381 overexpression RCC cells to Sunitinib-induced cell apoptosis. These results indicated that miR-381 is critical in renal cell CSC-like properties and tumorigenesis, making it the ideal therapeutic target for RCC.

The Effect of the Hip Flexion Angle in Osteonecrosis of the Femoral Head Based on China-Japan Friendship Hospital Classification - A Finite Element Study.

OBJECTIVE: The alteration in the mechanical environment of the necrotic area is the primary cause of the collapse observed in osteonecrosis of the femoral head (ONFH). This study aims to evaluate the biomechanical implications of the China-Japan Friendship Hospital (CJFH) classification system and hip flexion angles on the necrotic area in ONFH using finite element analysis (FEA). The goal is to provide valuable guidance for hip preservation treatments and serve as a reference for clinical diagnosis and therapeutic interventions. METHODS: Hip tomography CT scan data from a healthy volunteer was used to create a 3D model of the left hip. The model was preprocessed and imported into Solidworks 2018, based on the CJFH classification. Material parameters and boundary conditions were applied to each fractal model in ANSYS 21.0. Von Mises stresses were calculated, and maximum deformation values were obtained to evaluate the biomechanical effects of the load on the necrotic area and post-necrotic femur, as well as assess each fractal model's collapse risk. RESULTS: (1) At the same hip flexion angle, maximum deformation followed this order: M Type < C Type < L Type. The L3 type necrotic area experienced the most significant deformation at 0, 60, and 110° angles (1.121, 1.7913, and 1.8239 mm respectively). (2) Under the same CJFH classification, maximum deformation values increased with hip flexion angle (0 < 60 < 110°), suggesting a higher risk of collapse at larger angles. (3) Von Mises stress results showed that the maximum stress was not located in the necrotic area but near the inner and outer edge of the femoral neck, indicating decreased stiffness and strength of the subchondral bone after osteonecrosis. CONCLUSION: The study found that femoral head collapse risk was higher when the necrotic area was located in the lateral column under the same stress load and flexion angle. Mechanical properties of the necrotic area changed, resulting in decreased bone strength and stiffness. Large-angle hip flexion is more likely to cause excessive deformation of the necrotic area; thus, ONFH patients should reduce or avoid large-angle hip flexion during weight-bearing training in rehabilitation activities.

Vascular endothelial growth factor protein and gene delivery by novel nanomaterials for promoting liver regeneration after partial hepatectomy.

Partial hepatectomy (PH) can lead to severe complications, including liver failure, due to the low regenerative capacity of the remaining liver, especially after extensive hepatectomy. Liver sinusoidal endothelial cells (LSECs), whose proliferation occurs more slowly and later than hepatocytes after PH, compose the lining of the hepatic sinusoids, which are the smallest blood vessels in the liver. Vascular endothelial growth factor (VEGF), secreted by hepatocytes, promotes LSEC proliferation. Supplementation of exogenous VEGF after hepatectomy also increases the number of LSECs in the remaining liver, thus promoting the reestablishment of the hepatic sinusoids and accelerating liver regeneration. At present, some shortcomings exist in the methods of supplementing exogenous VEGF, such as a low drug concentration in the liver and the reaching of other organs. More-over, VEGF should be administered multiple times and in large doses because of its short half-life. This review summarized the most recent findings on liver regeneration and new strategies for the localized delivery VEGF in the liver.

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer.

BACKGROUND: The development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients. AIM: To investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients. METHODS: The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity (PCA) was determined by fibrin formation and thrombin-antithrombin complex (TAT) assays. Thrombosis in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava (IVC). RESULTS: NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and P-selectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumor-bearing mice compared with control mice. Notably, the combination of deoxyribonuclease I, activated protein C, and sivelestat markedly abolished the PCA of NETs. CONCLUSION: GC-induced NETs strongly increased the risk of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.

Multimetallic CuCoNi Oxide Nanowires In Situ Grown on a Nickel Foam Substrate Catalyze Persulfate Activation via Mediating Electron Transfer.

In situ growth of nanostructures on substrates is a strategy for designing highly efficient catalytic materials. Herein, multimetallic CuCoNi oxide nanowires are synthesized in situ on a three-dimensional nickel foam (NF) substrate (CuCoNi-NF) by a hydrothermal method and applied to peroxydisulfate (PDS) activation as immobilized catalysts. The catalytic performance of CuCoNi-NF is evaluated through the degradation of organic pollutants such as bisphenol A (BPA) and practical wastewater. The results indicate that the NF not only plays an important role as the substrate support but also serves as an internal Ni source for material fabrication. CuCoNi-NF exhibits high activity and stability during PDS activation as it mediates electron transfer from BPA to PDS. CuCoNi-NF first donates electrons to PDS to arrive at an oxidized state and subsequently deprives electrons from BPA to return to the initial state. CuCoNi-NF maintains high catalytic activity in the pH range of 5.2-9.2, adapts to a high ionic strength up to 100 mM, and resists background HCO3- and humic acid. Meanwhile, 76.6% of the total organic carbon can be removed from packaging wastewater by CuCoNi-NF-catalyzed PDS activation. This immobilized catalyst shows promising potential in wastewater treatment, well addressing the separation and recovery of conventional powdered catalysts.

Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis.

Liver fibrosis occurs following inflammation triggered by the integrated actions of activated liver-resident macrophages (Kupffer cells) and hepatic stellate cells (HSCs), and the multiplicity of these mechanisms complicates drug therapy. Here, we demonstrate that the selective bromodomain and extra-terminal (BET) bromodomain inhibitor compound38 can block both the Janus kinase-signal transducer and activator of transcription and mitogen-activated protein kinase signaling pathways in macrophages, which decreased their secretion of proinflammatory cytokines in a dose-dependent manner. The inactivation of macrophages attenuated lipopolysaccharide-induced injurious inflammation concurrent with a reduction in F4/80+ cells, proinflammatory cytokine levels, and neutrophil infiltration. Moreover, compound 38 inhibited the Wnt/ß-catenin and transforming growth factor-beta/SMAD signaling pathways to abolish the activation of HSCs. In vivo, compound 38 significantly decreased the collagen deposition and fibrotic area of a CCl4-induced liver fibrosis model, and restored the deficiency of activated HSCs and the upregulation of liver inflammation. These results highlight the potential role of compound 38 in treating liver fibrosis considering its simultaneous inhibitory effects on liver inflammation and related fibrosis.

Identification of potential autophagy-related genes in steroid-induced osteonecrosis of the femoral head via bioinformatics analysis and experimental verification.

PURPOSE: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopaedic hip joint disease that occurs in young- and middle-aged people. Previous experimental studies have shown that autophagy might be involved in the pathological process of SONFH, but the pathogenesis of autophagy in SONFH remains unclear. We aimed to identify and validate the key potential autophagy-related genes involved in SONFH to further illustrate the mechanism of autophagy in SONFH through bioinformatics analysis. METHODS: The GSE123568 mRNA expression profile dataset, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). The autophagy-related genes involved in SONFH were screened by intersecting the GSE123568 dataset with the set of autophagy genes. The differentially expressed autophagy-related genes involved in SONFH were identified with R software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed autophagy-related genes involved in SONFH were conducted by using R software. Then, the correlations between the expression levels of the differentially expressed autophagy-related genes involved in SONFH were confirmed with R software. Moreover, the protein-protein interaction (PPI) network was analysed by using the Search Tool for the Retrieval of Interacting Genes (STRING), significant gene cluster modules were identified with the MCODE Cytoscape plugin, and hub genes among the differentially expressed autophagy-related genes involved in SONFH were screened by using the CytoHubba Cytoscape plugin. Finally, the expression levels of the hub genes of the differentially expressed autophagy-related genes involved in SONFH were validated in hip articular cartilage specimens from necrotic femur heads (NFHs) by using the GSE74089 dataset and further verification by qRT-PCR. RESULTS: A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 34 differentially expressed autophagy-related genes involved in SONFH were particularly enriched in death domain receptors, the FOXO signalling pathway and apoptosis. Correlation analysis revealed significant correlations among the 34 differentially expressed autophagy-related genes involved in SONFH. The PPI results demonstrated that the 34 differentially expressed autophagy-related genes interacted with each other. Ten hub genes were identified by using the MCC algorithms of CytoHubba. The GSE74089 dataset showed that TNFSF10, PTEN and CFLAR were significantly upregulated while BCL2L1 was significantly downregulated in the hip cartilage specimens, which was consistent with the GSE123568 dataset. TNFSF10, PTEN and BCL2L1 were detected with consistent expression by qRT-PCR. CONCLUSIONS: Thirty-four potential autophagy-related genes involved in SONFH were identified via bioinformatics analysis. TNFSF10, PTEN and BCL2L1 might serve as potential drug targets and biomarkers because they regulate autophagy. These results expand the autophagy-related understanding of SONFH and might be useful in the diagnosis and prognosis of SONFH.

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.

Uretero-lumbar artery fistula: A case report.

BACKGROUND: Uretero-arterial fistula (UAF) is a disease that usually involves the aorta, common iliac artery, external iliac artery, hypogastric artery, and lumbar artery. Among them, uretero-lumbar artery fistula (ULAF) is the most unusual type. So, both in China and around the world, the diagnosis and treatment of ULAF is a big challenge. CASE SUMMARY: A 55-year-old female patient with a history of pelvic radiotherapy developed unexplained massive hemorrhage during replacement of the right Resonance metallic ureteral double-J tubes due to a long-standing indwelling ureteral stent for ureteral stricture. Later, we found contrast extravasation from the patient's right L4 artery into the ureter under digital subtraction angiography (DSA) and administered polyvinyl alcohol particle embolic agent and coil embolization; hematuria was controlled. Follow-up investigations at 18 mo showed no sign of recurrence. CONCLUSION: DSA is very important in the diagnosis and treatment of UAF, and DSA should be preferred when UAF is suspected. In addition, the use of softer ureteral stents in patients with primary disease and risk factors for UAF should be considered to avoid increasing the risk of the development of the disease; endovascular treatment should be preferred in patients who have developed UAF.

Protective effect of Pai-Nong-San against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway.

Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4+ and CD8+ T cells, inhibiting the production of HIF-α, IL-6, and TNF-α, and promoting the expression of IL-4 and IFN-γ in colon tissues. Meanwhile, PNS improved the components of gut microbiota, as measured by the adjusted levels of Firmicutes, Bacteroidetes, Proteobacteria, and Lactobacillus. PNS down-regulated the protein expression of p-GSK-3ß, ß-catenin, and c-Myc, while up-regulating the GSK-3ß and p-ß-catenin in colon tissues of CAC mice. In conclusion, our results suggested that PNS exhibits protective effect on AOM/DSS-induced colon injury and alleviates the development of CAC through suppressing inflammation, improving gut microbiota, and inhibiting the Wnt signaling pathway.

Molecular mechanism of Wutou Decoction in the treatment of osteoarthritis: a bioinformatics and molecular docking study.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction and periarticular osteophyte formation. One therapeutic option for this condition, the Wutou Decoction (WTD) Chinese medicine formula, is satisfactory in its efficacy. Here, we used bioinformatic and molecular docking techniques to investigate the mechanism of action of WTD in the treatment of OA. METHODS: The active compounds (and their target proteins) of 5 Chinese herbs in WTD were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The action targets of WTD for OA were obtained by searching the Therapeutic Target Database and by mining the microarray data in the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify key targets for OA treatment with the help of Database for Annotation, Visualization, and Integrated Discovery. Based on the Cytoscape software version 3.6.1, the visual networks of the "TCM drugs-Active Compounds-Targets-Diseases" and protein-protein interaction of the key targets of WTD for the treatment of OA were constructed. The core active compounds and the key targets obtained were molecularly docked and validated. RESULTS: Analyses revealed 140 active compounds in WTD, 123 of which had a total of 163 corresponding targets. In addition, 331 differentially expressed genes and 227 OA-related targets were obtained. The interaction networks among 32 key targets were identified. The biological processes of WTD in treating OA mainly involved regulation of inflammatory factors, transcription of genetic materials, cell cycle, angiogenesis, and endocrine regulation. The signaling pathways involved mainly included TNF signaling pathway, rheumatoid arthritis signaling pathway, cancer-related signals, vascular endothelial growth factor signaling pathway, and osteoclast differentiation signaling pathways. Molecular docking showed that 7 core compounds including quercetin and kaempferol had strong affinities with key target proteins for the WTD treatment of OA. CONCLUSIONS: WTD with multi-component can treats OA through multi-pathway. Its active compounds, including quercetin and kaempferol, can exert their therapeutic effects on OA by acting on TNF, PTGS2, MMP2, IL-6, IL-1ß, and other key targets to regulate inflammation, immunity, autophagy, and endocrine-related signaling pathways.

Paratesticular liposarcoma: Two case reports.

BACKGROUND: Paratesticular liposarcoma accounts for approximately 7% of scrotal tumors. They are rare lesions of the reproductive system with approximately 90% of the lesions originating from the spermatic cord. Surgery, with the goal of complete resection, is the mainstay for treatment of this disease. However, treatment consisting of extended resection to decrease local recurrence remains controversial. CASE SUMMARY: We report the cases of two patients with paratesticular liposarcomas who were treated with radical testicular tumor resection without adjuvant therapy. Follow-up investigations at 9 mo showed no sign of recurrence. CONCLUSION: Surgery is the first-line treatment, regardless of whether it is a recurrent or primary tumor. Extended resection carries a higher risk of complications and should not be performed routinely. Preoperative radiotherapy can reduce the local recurrence rate without affecting the overall survival.

Synthesis and evaluation of 1,2,4-oxadiazole derivatives as potential anti-inflammatory agents by inhibiting NF-κB signaling pathway in LPS-stimulated RAW 264.7 cells.

In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1-29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity.

Study on the molecular mechanism of BuShenHuoXue capsule in treatment of steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is the pathological process caused by the death of the active components of the head of the femur due to the high dose of hormones, which has become a common public health problem. BuShenHuoXue capsule (BSHXC) has been clinically proven to be effective against the SONFH, the main pharmacological action of BSHXC is tonifying kidney and promoting blood circulation, but the mechanism remains to be explored. METHODS: We established a rat SONFH model by injecting Methylprednisolone (MPS) into the right gluteus muscle 30 mg/kg/d, 3 days of continuous injection every week, 4 weeks in total. According to the clinical dosage of BSHXC (Herba epimedium 3 g, Eucommia ulmoides 15 g, Salvia miltiorrhizae 30 g, Chuanxiong 15 g, Paeonia lactiflora Pall 15 g, Poria cocos 12 g, Achyranthes bidentata 12 g, antler gum 10 g, Cyperus rotundus L. Nine g and Radix Glycyrrhizae 9 g), it was converted into the equivalent dose of rats, and gavage was performed at the weight of 10 mL/kg, once per day. The BSHXC was subjected to experiments in vivo, SONFH pharmacodynamics, bioinformatics, and network of pharmacology to determine the active ingredients, and its protective role against SONFH, Enrichment analysis was performed to explore the possible mechanism of BSHXC, and cell experiments were undertaken to analyze the impact of BSHXC on the hormones associated with bone marrow mesenchymal stem cells (BMSCs) between osteogenesis and apoptosis. RESULTS: Experiments confirmed that BSHXC could effectively reduce bone loss in SONFH rat models. From bioinformatics and a network constructed from 10 drugs-208 pharmacology-126 targets, the enrichment analysis showed that the core targets were inflammatory reaction, steroid hormones, estrogen receptors, osteoporosis, and adjustment of osteogenesis and osteoclast differentiation, among others. The cell proliferation and staining supported that the mechanism of BSHXC promoted osteogenesis and intervening in apoptosis. CONCLUSIONS: The BSHXC reduced the inflammatory response, changed steroid response, regulated estrogen receptors, delayed osteoporosis, regulated osteoblast and osteoclast differentiation by regulating related targets, and improved the local microenvironment by a multi-component, multi-target, and multi-link process to delay or reverse the progression of SONFH.

[Distribution Characteristics and Ecological Risk Assessment of Organochlorine Pesticides in Sediments of Zhanjiang Bay].

Sixteen surface sediment samples were collected from the estuary of the Suixi river to the mouth of Zhanjiang Bay and then analyzed for organochlorine pesticides (OCPs) by GC-MS to investigate their distribution and ecological risk. The results showed that the concentrations of OCPs in the sediments ranged from nd to 189.52 ng·g-1 (mean 32.17 ng·g-1), including HCHs (mean 5.81 ng·g-1) and DDTs (mean 26.90 ng·g-1). The distribution characteristics showed that the highest OCPs concentrations were found in the estuary and the main shipping lane areas, and the concentration in the nearshore area was higher than that offshore. Source analysis indicated that the HCHs mainly originated from agricultural applications, while no industrial input was observed. Some "hot-spots" areas occurred in harbors and shipping channels, likely as a result of the presence of paint flakes. Additionally, the concentrations of DDTs were found to be higher than the limits of Chinese Marine sediment quality criteria, and p,p'-DDT was the main type of DDT, presenting inevitable adverse biological effects and high ecological risk. Compared with other bays in China, the concentrations of OCPs in this study were in the upper-median pollution level, especially in harbors and boat maintenance facility areas. High OCPs inputs may occur, and thereby represent a certain ecological risk in Zhanjiang Bay.

[Effect of Straw Residues in Combination with Reduced Fertilization Rate on Greenhouse Gas Emissions from a Vegetable Field].

Greenhouse gases mainly come from farmland soils. Re-spreading chaff (straw returning) is an effective ecological management in China. Quantitative analysis of straw residues together with reduced fertilization rates can provide a scientific basis for reducing greenhouse gas emissions. A field experiment with six different fertilizer amounts combined with straw residues was carried out in a vegetable field (lettuce-cabbage-chili rotation), including the control (CK), conventional fertilizing (F), straw returning with 100% conventional fertilizing (100FS), straw returning with 70% conventional fertilizing (70FS), straw returning with 60% conventional fertilizing (60FS),and straw returning with 50% conventional fertilizing (50FS). The dynamic characteristics and emission factors of CO2, CH4 and N2O in the soil were analyzed using an in-situ, closed chamber, gas chromatography-based system, from November 2016 to September 2017. The results showed that the emission of CO2, CH4 and N2O has seasonal variation characteristics. The peak value mainly occurred in April to August, and the gas emission peak would appear after fertilizing and irrigating. Compared with F treatment, straw returning with fertilizing treatments reduced the N2O emission fluxes, cumulative emission and emission factor, especially in the 100FS treatment. The N2O cumulative emission and emission factor was 60.76 kg·hm-2, 0.138 kg·kg-1 (N2O-N/N) respectively in 100FS treatment during planting chili was more than that during planting lettuce and cabbage. Moreover, straw returning with reducing conventional fertilizing could reduce the N2O emission factor compared with 100FS treatment. The CO2 emission fluxes 55.28-1831.62[mg·(m2·h)-1] and cumulative emission (7502.13-25988.55 kg·hm-2) in 70FS treatment were lower than that in CK and F treatments, while other treatments increased the CO2 emission fluxes and cumulative emission, especially in 60FS and 50FS treatments. During planting lettuce and cabbage, the CH4 cumulative emission mainly showed negative values in treatments except for CK, indicating that soil could adsorb CH4. Moreover, straw returning with 30%-50% conventional fertilizing treatment could reduce CH4 emission fluxes and cumulative emission during planting chili, but increased in 100FS. Compared with CK and F treatment, generally, straw retuning with conventional fertilizing could significantly increase the global warming potential (GWP) in the study, except for 70FS treatment. 70FS could reduce the CO2, CH4 emission and the GWP of greenhouse gases, but could not significantly affect N2O emission reduction.

Next-generation sequencing for identifying genetic mutations in adults with bronchiectasis.

BACKGROUND: Defective airway host-defense (e.g., altered mucus properties, ciliary defects) contributes to the pathogenesis of bronchiectasis. This study aims to determine whether genetic mutations associated with defective airway host-defense are implicated in the pathogenesis of bronchiectasis. METHODS: Based on the systematic screening of 32 frequently reported bronchiectasis-associated genes, we performed next-generation sequencing (NGS) on peripheral blood samples from 192 bronchiectasis patients and 100 healthy subjects. The variant distribution frequency and pathogenicity of mutations were analyzed. RESULTS: We identified 162 rare variants in 192 bronchiectasis patients, and 85 rare variants among 100 healthy subjects. Among bronchiectasis patients, 25 (15.4%), 117 (72.2%) and 18 (11.1%) rare variants were associated with cystic fibrosis transmembrane receptor (CFTR), epithelial sodium channel, and primary ciliary dyskinesia genes, respectively. Biallelic CFTR variants were detected in four bronchiectasis patients but none of the healthy subjects. Carriers of homozygous p.M470 plus at least one CFTR rare variant were detected in 6.3% of bronchiectasis patients (n=12) and in 1.0% of healthy subjects (n=1, P=0.039). Twenty-six patients (16 with idiopathic and 6 with post-infectious bronchiectasis) harbored biallelic variants. Bronchiectasis patients with biallelic DNAH5 variants, or biallelic CFTR variants plus an epithelial sodium channel variant, tended to have greater disease severity. CONCLUSIONS: Genetic mutations leading to impaired host-defense might have implicated in the pathogenesis of bronchiectasis. Genetic screening may be a useful tool for unraveling the underlying causes of bronchiectasis, and offers molecular information which is complementary to conventional etiologic assessment for bronchiectasis.