Bronchial thermoplasty decreases airway remodeling by inhibiting autophagy via the AMPK/mTOR signaling pathway.

Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.

Aurora kinase inhibitor restrains STAT5-activated leukemic cell proliferation by inducing mitochondrial impairment.

Current chemotherapy regimens on acute myeloid leukemia (AML) still have some drawbacks, such as intolerance and drug resistance, which calls need for the development of targeted therapy. Signal transducer and activator of transcription 5 (STAT5) is often overexpressed or abnormally activated in leukemia and involved in cell self-renewal, proliferation, and stress adaptation. Overexpressed Aurora A (AURKA) is associated with poor prognosis in tumors, and inhibitors against AURKA are already in clinical trials. However, it has rarely been reported whether AURKA inhibitors restrain STAT5-activated leukemia cells. In this study, we constructed STAT5 constitutively activated (cS5) cells and found that STAT5 promoted cell proliferation and colony formation. Moreover, cS5 cells showed elevated reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels, which indicated higher mitochondrial metabolism in cS5 cells. A novel AURKA inhibitor AKI604 was synthesized and showed significant inhibitory effects to the proliferation and colony formation in both STAT5 constitutively activated and nonactivated AML cells. AKI604 induced mitochondrial impairment, leading to the disruption of mitochondrial membrane potential and the elevation of ROS as well as cellular calcium (Ca2+ ) levels. AKI604 could also decline basal oxygen consumption rate and ATP biosynthesis, indicating the damage of oxidative phosphorylation. Furthermore, AKI604 exhibited significant antitumor effect in the HL-60 cS5 xenograft model of the BALB/c nude mice without an obvious influence on mice body weight and other healthy indicators. This study suggested that AKI604 was a potential strategy to overcome STAT5-induced leukemic proliferation in AML treatment by inducing mitochondrial impairment.

Synthesis of the impurity F of salbutamol.

First synthesis of the diastereomeric mixture of salbutamol impurity F is described in seven steps by using 4-hydroxyacetophenone as starting material, with 15.2% total yield. The synthesis provides access to multi-gram quantities of impurity F with good purity for reference supplies and further analytical and toxicology investigations. [Formula: see text].

A Myb transcription factor represses conidiation and cephalosporin C production in Acremonium chrysogenum.

Acremonium chrysogenum is the industrial producer of cephalosporin C (CPC). We isolated a mutant (AC554) from a T-DNA inserted mutant library of A. chrysogenum. AC554 exhibited a reduced conidiation and lack of CPC production. In consistent with it, the transcription of cephalosporin biosynthetic genes pcbC and cefEF was significantly decreased in AC554. Thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR) was performed and sequence analysis indicated that a T-DNA was inserted upstream of an open reading frame (ORF) which was designated AcmybA. On the basis of sequence analysis, AcmybA encodes a Myb domain containing transcriptional factor. Observation of red fluorescent protein (RFP) tagged AcMybA showed that AcMybA is naturally located in the nucleus of A. chrysogenum. Transcriptional analysis demonstrated that the AcmybA transcription was increased in AC554. In contrast, the AcmybA deleted mutant (ΔAcmybA) overproduced conidia and CPC. To screen the targets of AcmybA, we sequenced and compared the transcriptome of ΔAcmybA, AC554 and the wild-type strain at different developmental stages. Twelve differentially expressed regulatory genes were identified. Taken together, our results indicate that AcMybA negatively regulates conidiation and CPC production in A. chrysogenum.

Mechanism of KDM5A-mediated H3K4me3 modification in the osteogenic differentiation of mesenchymal stem cells in steroid-induced osteonecrosis of the femoral head.

OBJECTIVES: Steroid-induced osteonecrosis of the femoral head (SONFH) is characterized by impaired osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study investigates the role of lysine-specific demethylase 5A (KDM5A) in SONFH to identify potential therapeutic targets. METHODS: Human BMSCs were isolated and characterized for cell surface markers and differentiation capacity. A SONFH cell model was established using dexamethasone treatment. BMSCs were transfected with KDM5A overexpression vectors or si-KDM5A, and the expression of KDM5A, miR-107, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) was assessed. Alizarin red staining was used to observe mineralization nodules, while alkaline phosphatase activity and cell viability were measured. The enrichment of KDM5A and histone 3 lysine 4 trimethylation (H3K4me3) on the promoters of RUNX2, OCN, and OPN was analyzed. The binding between miR-107 and KDM5A 3'UTR was validated, and the combined effect of miR-107 overexpression and KDM5A overexpression on BMSC osteogenic differentiation was evaluated. RESULTS: KDM5A was upregulated in BMSCs from SONFH. Inhibition of KDM5A promoted osteogenic differentiation of BMSCs, associated with increased RUNX2, OCN, and OPN promoters. KDM5A bound to the promoters of RUNX2, OCN, and OPN, leading to reduced H3K4me3 levels and downregulation of their expression. Overexpression of miR-107 inhibited KDM5A and enhanced BMSC osteogenic differentiation. CONCLUSION: KDM5A negatively regulates BMSC osteogenic differentiation by modulating H3K4me3 levels on the promoters of key osteogenic genes. miR-107 overexpression counteracts the inhibitory effect of KDM5A on osteogenic differentiation. These findings highlight the potential of targeting the KDM5A/miR-107 axis for SONFH therapy.

Pulpwood holocellulose model transfer based on screening with consistent and stable signals algorithm.

In this study, in order to realize the sharing of the near-infrared analysis model of holocellulose between three spectral instruments of the same type, 84 pulp samples and their content of holocellulose were taken as the research objects. The effects of 10 pre-processing methods, such as 1st derivative (D1st), 2nd derivative (D2nd), multiplicative scatter correction (MSC), standard normal variable transformation (SNV), autoscaling, normalization, mean centering and pairwise combination, on the transfer effect of the stable wavelength selected by screening wavelengths with consistent and stable signals (SWCSS) were discussed. The results showed that the model established by the wavelength selected by the SWCSS algorithm after the autoscaling pre-processing method had the best analysis effect on the two target samples. Root mean square error of prediction (RMSEP) decreased from 2.4769 and 2.3119 before the model transfer to 1.2563 and 1.2384, respectively. Compared with the full-spectrum model, the value of AIC decreased from 3209.83 to 942.82. Therefore, the autoscaling pre-processing method combined with SWCSS algorithm can significantly improve the accuracy and efficiency of model transfer and provide help for the application of SWCSS algorithm in the rapid determination of pulp properties by near-infrared spectroscopy (NIRS).

Functional and structural dissection of glycosyltransferases underlying the glycodiversity of wolfberry-derived bioactive ingredients lycibarbarspermidines.

Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry. Notably, LbUGT3 acts as a distinctive enzyme that catalyzes a tandem sugar transfer to the ortho-dihydroxy group on the caffeoyl moiety to form the unusual ortho-diglucosylated product, while LbUGT1 accurately discriminates caffeoyl and dihydrocaffeoyl groups to catalyze a site-selective sugar transfer. Crystal structure analysis of the complexes of LbUGT1 and LbUGT3 with UDP, combined with molecular dynamics simulations, revealed the structural basis of the difference in glycosylation selectivity between LbUGT1 and LbUGT3. Site-directed mutagenesis illuminates a conserved tyrosine residue (Y389 in LbUGT1 and Y390 in LbUGT3) in PSPG box that plays a crucial role in regulating the regioselectivity of LbUGT1 and LbUGT3. Our study thus sheds light on the enzymatic underpinnings of the chemical diversity of lycibarbarspermidines in wolfberry, and expands the repertoire of glycosyltransferases in nature.

MicroRNA-148a promotes myogenic differentiation by targeting the ROCK1 gene.

MicroRNAs are evolutionarily conserved small RNAs that post-transcriptionally regulate gene expression and have emerged as critical regulators of skeletal muscle development. Here, we identified miR-148a as a novel myogenic microRNA that mediated myogenic differentiation. The expression levels of miR-148a increased during C2C12 myoblast differentiation. Overexpression of miR-148a significantly promoted myogenic differentiation of both C2C12 myoblast and primary muscle cells. Blocking the function of miR-148a with a 2'-O-methylated antisense oligonucleotide inhibitor repressed C2C12 myoblast differentiation. Using a bioinformatics approach, we identified Rho-associated coiled-coil containing protein kinase 1 (ROCK1), a known inhibitor of myogenesis, as a target of miR-148a. A dual-luciferase reporter assay was used to demonstrate that miR-148a directly targeted the 3'-UTR of ROCK1. In addition, the overexpression of miR-148a decreased the protein expression of ROCK1 in C2C12 myoblast and primary muscle cells. Furthermore, ROCK1 inhibition with specific siRNA leaded to accelerated myogenic differentiation progression, underscoring a negative regulatory function of ROCK1 in myogenesis. Therefore, our results revealed a novel mechanism in which miR-148a positively regulates myogenic differentiation via ROCK1 down-regulation.

Inhibition of MKK7-JNK by the TOR signaling pathway regulator-like protein contributes to resistance of HCC cells to TRAIL-induced apoptosis.

BACKGROUND & AIMS: The TOR signaling pathway regulator-like (TIPRL) protein, the mammalian ortholog of yeast TIP41, was identified in an expression profiling screen for factors that regulate human liver carcinogenesis. We investigated the role of human TIPRL protein in hepatocellular carcinoma (HCC). METHODS: We measured the level of TIPRL in HCC and adjacent nontumor tissues from patients. We used small interfering RNAs and zebrafish to study the function of TIPRL. We used annexin V propidium iodide staining and immunoblot analyses to measure apoptosis and activation of apoptotic signaling pathways. We used confocal microscopy, coimmunoprecipitation, and glutathione-S transferase pull-down analyses to determine interactions among mitogen-activated protein kinase kinase 7 (MKK7 or MAP2K7), TIPRL, and the protein phosphatase type 2A (PP2Ac). We studied the effects of TIPRL in tumor xenografts in mice. RESULTS: Levels of TIPRL were higher in HCC tissues and cell lines than nontumor tissues and primary hepatocytes. Knockdown of tiprl expression in zebrafish led to large amounts of apoptosis throughout the embryos. Incubation of HCC cells, but not primary human hepatocytes, with small interfering RNA against TIPRL (siTIPRL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) caused prolonged activation (phosphorylation) of MKK7 and c-Jun N-terminal kinase (JNK) and led to apoptosis, indicated by cleavage of procaspase-8,-3 and of poly-(adenosine diphosphate-ribose) polymerase. TIPRL bound to MKK7 and PP2Ac and promoted the interaction between MKK7 and PP2Ac. In mice, injection of HCC xenograft tumors with siTIPRL and TRAIL led to tumor apoptosis and regression. CONCLUSIONS: TIPRL is highly up-regulated in human HCC samples and cell lines, compared with noncancerous liver tissues. TIPRL prevents prolonged activation of MKK7 and JNK and TRAIL-induced apoptosis by mediating the interaction between MKK7 and PP2Ac.

A septation related gene AcsepH in Acremonium chrysogenum is involved in the cellular differentiation and cephalosporin production.

T-DNA inserted mutants of Acremonium chrysogenum were constructed by Agrobacterium tumefaciens-mediated transformation (ATMT). One mutant 1223 which grew slowly was selected. TAIL-PCR and sequence analysis indicated that a putative septation protein encoding gene AcsepH was partially deleted in this mutant. AcsepH contains nine introns, and its deduced protein AcSEPH has a conserved serine/threonine protein kinase catalytic (S_TKc) domain at its N-terminal region. AcSEPH shows high similarity with septation H proteins from other filamentous fungi based on the phylogenetic analysis of S_TKc domains. In sporulation (LPE) medium, the conidia of AcsepH mutant was only about one-seventh of the wild-type, and more than 20% of conidia produced by the mutant contain multiple nuclei which were rare in the wild-type. During fermentation, the AcsepH disruption mutant grew slowly and its cephalosporin production was only about one quarter of the wild-type, and the transcription analysis showed that pcbC expression was delayed and the expressions of cefEF, cefD1 and cefD2 were significantly decreased. The vegetative hyphae of AcsepH mutant swelled abnormally and hardly formed the typical yeast-like cells. The amount of yeast-like cells was about one-tenth of the wild-type after fermentation for 5days. Comparison of hyphal viabilities revealed that the cells of AcsepH mutant died easily than the wild-type at the late stage of fermentation. Fluorescent stains revealed that the absence of AcsepH in A. chrysogenum led to reduction of septation and formation of multinucleate cells. These data indicates that AcsepH is required for the normal cellular septation and differentiation of A. chrysogenum, and its absence may change the cellular physiological status and causes the decline in cephalosporin production.

The thioredoxin reductase-encoding gene ActrxR1 is involved in the cephalosporin C production of Acremonium chrysogenum in methionine-supplemented medium.

The thioredoxin system including thioredoxin and thioredoxin reductase (TrxR) is used for oxidative stress defenses in fungi. Based on the genomic sequence, a thioredoxin reductase-encoding gene (ActrxR1) was isolated from Acremonium chrysogenum CGMCC3.3795. Like other TrxRs, AcTrxR1 contains FAD binding domain, Redox domain, and NADPH binding domain. Disruption of ActrxR1 in A. chrysogenum led to the formation of smaller colonies and hyphal swelling in Tryptic soy agar (TSA). In chemically defined medium, the spore germination of ActrxR1 disruption mutant was strongly inhibited, which was recovered by the addition of DL-methionine. The disruption mutant grew slowly on TSA compared with the wild-type strain, but it did not show to be more sensitive to exogenous hydrogen peroxide or menadione. In defined medium of fermentation supplemented with DL-methionine, the ActrxR1 disruption mutant grew normally, and its cephalosporin C production increased by about onefold compared with the wild type (73 µg/ml for wild-type strain and 136 µg/ml for the mutant at 5 days of fermentation). Real-time polymerase chain reaction (RT-PCR) showed that the transcriptional levels of pcbC, cefEF, and cefG were obviously enhanced in the ActrxR1 mutant at the early stage of fermentation. These results indicate that ActrxR1 is required for the normal growth of A. chrysogenum and related with cephalosporin C production in methionine-supplemented medium.

Modified Nuss procedure is a safe choice for recurrent pectus excavatum after previous open repair experience of 26 cases.

PURPOSE: This study is aiming to investigate the feasibility and effect of applying modified Nuss procedure on recurrent pectus excavatum following previous open repair. METHODS: By retrospectively reviewing patients of pectus excavatum enrolled in our department from July 2007 to August 2012, we find 27 cases of recurrent PE who received open repair previously. Twenty-six patients received Nuss repair, while one patient refused. Relevant data are collected and processed. A 3-month follow-up after operation is also reviewed. Analysis of data is conducted. RESULTS: Twenty-six recurrent patients underwent modified Nuss procedure safely. Pneumothorax after operation occurred in one case. Pleural effusion occurred for every case, most were mild in quantity except two cases whose pleural effusion were moderate. All patients left hospital within 2 weeks after operation except one patient who died of respiration failure. Mean postoperative Haller Index is significantly different from the preoperative one. Cosmetic effect was excellent for 5 cases, good for 15 cases, moderate for 6 cases. In a 3-month follow-up, no bar displacement or rejection happened and pleural effusion was completely absorbed. CONCLUSION: Although technically challenging, Nuss procedure is feasible and good for recurrent PE after open repair.

Photodynamic therapy for treatment of recurrent hemoptysis secondary to pulmonary endometriosis: a case report.

Pulmonary endometriosis (PEM) is rare, and drug therapy remains the primary treatment. However, patients with PEM frequently experience recurrent hemoptysis that is refractory to pharmacological intervention. We herein describe a patient with PEM who developed recurrent hemoptysis and was successfully treated with photodynamic therapy (PDT) after drug withdrawal. The patient was admitted to our hospital because of recurrent hemoptysis despite repeated drug treatments for more than 1 year. Given that PDT targets specific tissues and destroys vascular endothelial cells through the cytotoxic effect produced by the photodynamic reaction of the photosensitizer, we considered that it may effectively control hemoptysis secondary to vascular morphological changes in PEM. Therefore, we performed PDT in this case, and the patient's recurrent hemoptysis regressed. Approximately 2 years following PDT, the patient had recovered well and reported no discomfort. We recommend consideration of PDT as a treatment option for patients with PEM who develop recurrent hemoptysis after drug withdrawal. Notably, the patient's lung lesions should be superficial and limited, and no contraindications should be present.

Rapid weaning from mechanical ventilation and bronchial thermoplasty for near-fatal asthma: A case report.

Background: The action mechanism of bronchial thermoplasty (BT) is poorly understood. Generally, patients with severe asthma who are in desperate need of treatment have relatively low baseline values. In this paper, we describe the case of an asthmatic patient who was saved by a combination of therapy and bronchial thermoplasty. Case information: A patient with near-fatal asthma was initially treated in our hospital with conventional medication, but his condition did not improve. The patient was next subjected to invasive mechanical ventilation, which did not provide significant relief. Additionally, he was treated with BT in conjunction with mechanical ventilation, which promptly reversed his status asthmaticus and stabilized his condition. Conclusion: Patients with near-fatal asthma who do not react effectively to aggressive therapy may benefit from BT.

Research on the effectiveness and safety of bronchial thermoplasty in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To investigate the clinical efficacy and safety of bronchial thermoplasty (BT) in treating patients with chronic obstructive pulmonary disease (COPD). METHODS: Clinical data of 57 COPD patients were randomized into the control (n = 29, conventional inhalation therapy) or intervention group (n = 28, conventional inhalation therapy plus BT). Primary outcomes were differences in clinical symptom changes, pulmonary function-related indicators, modified Medical Research Council (mMRC), 6-min walk test (6MWT), COPD assessment test (CAT) score and acute exacerbation incidence from baseline to an average of 3 and 12 months. Safety was assessed by adverse events. RESULTS: FEV1, FEV1(%, predicted) and FVC in both groups improved to varying degrees post-treatment compared with those pre-treatment (P < 0.05). The Intervention group showed greater improving amplitudes of FEV1 (Ftime × between groups = 21.713, P < 0.001) and FEV1(%, predicted) (Ftime × between groups = 31.216, P < 0.001) than the control group, and there was no significant difference in FVC variation trend (Ftime × between groups = 1.705, P = 0.193). mMRC, 6MWT and CAT scores of both groups post-treatment improved to varying degrees (Ps < 0.05), but the improving amplitudes of mMRC (Ftime × between groups = 3.947, P = 0.025), 6MWT (Ftime × between groups = 16.988, P < 0.001) and CAT score (Ftime × between groups = 16.741, P < 0.001) in the intervention group were greater than the control group. According to risk assessment of COPD acute exacerbation, the proportion of high-risk COPD patients with acute exacerbation in the control and intervention groups at 1 year post-treatment (100% vs 65%, 100% vs 28.6%), inpatient proportion (100% vs 62.1%; 100% vs 28.6%), COPD acute exacerbations [3.0 (2.50, 5.0) vs 1.0 (1.0, 2.50); 3.0(3.0, 4.0) vs 0 (0, 1.0)] and hospitalizations [2.0 (2.0, 3.0) vs 1.0 (0, 2.0); 2.0 (2.0, 3.0) vs 0 (0, 1.0)] were significantly lower than those pre-treatment (P < 0.05). Besides, data of the intervention group were significantly lower than the control group at each timepoint after treatment (P < 0.05). CONCLUSIONS: Combined BT therapy is superior to conventional medical treatment in improving lung function and quality of life of COPD patients, and it also significantly reduces the COPD exacerbation risk without causing serious adverse events.

Oxidative aromatization mechanism of ligustilide.

The aromatization mechanisms of ligustilide (1), a versatile monomeric phthalide, were investigated. DFT calculations combined with control experiments prove that the aromatization could result from direct oxidation by triplet oxygen in mild conditions with no catalyst, which is generally thought to be difficult. Moreover, it is predicted that the aromatization could rapidly clear away the harmful-to-organism singlet oxygen, which may be relevant to the general antioxidation activity of phthalides, providing a new point of view to understand the bioactivity from chemical reaction.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.

Disruption of a glutathione reductase encoding gene in Acremonium chrysogenum leads to reduction of its growth, cephalosporin production and antioxidative ability which is recovered by exogenous methionine.

Glutathione is a ubiquitous thiol in eukaryotic cells, and its high intracellular ratio of reduced form (GSH) to oxidized form (GSSG) is largely maintained by glutathione reductase (GR) using NADPH as electron donor. glrA, a glutathione reductase encoding gene, was found and cloned from Acremonium chrysogenum by searching its genomic sequence based on similarity. Its deduced protein exhibits high similarity to GRs of other eukaryotic organisms. Disruption of glrA resulted in lack of GR activity and accumulation of a high level of GSSG in A. chrysogenum. Overexpression of glrA dramatically enhanced GR activity and the ratio of GSH/GSSG in this fungus. The spore germination and hyphal growth of glrA disruption mutant was strongly reduced in chemical defined medium. Meanwhile, the mutant was more sensitive to hydrogen peroxide than the wild-type strain. We found that the glrA mutant recovered normal germination and growth by adding exogenous methionine (Met). Exogenous Met also enhanced the antioxidative ability of both the mutant and wild-type strain. GSH determination indicated that the total GSH and ratio of GSH/GSSG in the mutant or wild-type strain were significantly increased when addition of Met into the medium. The glrA mutant grew poorly and could not produce detectable cephalosporin in the fermentation medium without Met. However, its growth and cephalosporin production was restored with addition of exogenous Met. These results indicate that glrA is required for the normal growth and protection against oxidative damage in A. chrysogenum, and its absence can be complemented by exogenous Met.

[Characteristics and Dfferences of Dissolved Oxygen Stratification in Different Tributaries of Three Gorges Reservoir During Impoundment Period].

Taking the Xiaojiang and Xiangxi Rivers, two typical tributaries of the Three Gorges Reservoir, as examples, this study analyzed and compared the hydrodynamic, thermal stratification, and temporal and spatial differences in dissolved oxygen (DO) and their responses to the water storage process in the two tributaries through field monitoring at different stages of the 2020 impoundment period. The results showed that:① at the initial stage of water storage, the DO in the surface layer of the Xiaojiang River was higher (7.00-13.00 mg·L-1) due to atmospheric reoxygenation and phytoplankton photosynthesis, and the oxycline appeared in the water depth of 3-5 m. A large area of anoxia (DO<2.00 mg·L-1) or even an anaerobic sublayer occurred in the water below 5 m. The DO in the Xiangxi River could be divided into three layers vertically:oxygen-rich surface water (8.00-12.00 mg·L-1), middle water (6.00-8.00 mg·L-1), and low-oxygen bottom water (4.00-6.00 mg·L-1). ② Thermal stratification provided a stable physical environment, whereas the upstream inflow and vegetation decomposition in the water-level fluctuation zone increased the content of organic matter, which likely increased the oxygen consumption which was conducive to the formation of an anaerobic bottom layer. In the Xiangxi River, the risk of hypoxia in the bottom water body was low because of the oxygen replenishment from the long-term downslope-bottom density current.③ Continuous monitoring also showed that the storage of the reservoir played a significant role in the replenishment of DO in tributaries, which effectively and rapidly improved the anaerobic phenomenon in the Xiaojiang River. In the Three Gorges Reservoir, it is feasible to ameliorate the water ecological problems such as anoxia and anaerobic conditions in the tributaries via reservoir operation. This study aids understanding of the characteristics and differences of DO stratification in different tributaries of the Three Gorges Reservoir, which can provide theoretical and technical support for reservoir ecological operation.

Correlation of Activation Site and Number with the Clinical Response to Bronchial Thermoplasty.

Objective: To investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients. Methods: This work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response. Results: ACQ score (3.19±1.14 vs 1.26±0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53±21.66 vs 66.19±22.50), FEV1 (1.53±0.74 vs 1.93±0.82), and forced vital capacity (FVC) (2.49±0.86 vs 2.92±0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions. Conclusion: Main bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.