Method for GPU-based spectral data cube reconstruction of integral field snapshot imaging spectrometers.

In this paper, the principles of spectral data cube reconstruction based on an integral field snapshot imaging spectrometer and GPU-based acceleration are presented. The primary focus is on improving the reconstruction algorithm using GPU parallel computing technology to enhance the computational efficiency for real-time applications. And the computational tasks of the spectral reconstruction algorithm were transferred to the GPU through program parallelization and memory optimization, resulting in significant performance gains. Experimental results indicate that the average processing time of the GPU-based parallel algorithm is approximately 29.43 ms, showing a substantial acceleration ratio of about 14.27 compared to the traditional CPU serial algorithm with an average processing time of around 420.46 ms. The study aims to refine the GPU parallelization algorithm for continued improvement in computational efficiency and overall performance. The anticipated applications of this research include providing crucial technical support for the perception and monitoring of crop growth traits in agricultural production, contributing to the modernization and advancement of intelligence in the field.

Case Report: A Rare Case of Iodixanol-Induced Anaphylactic Shock in Cerebral Angiography.

Background: Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography. Objective: This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report. Case Summary: A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment. Conclusion: A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.

Improved gene therapy for spinal muscular atrophy in mice using codon-optimized hSMN1 transgene and hSMN1 gene-derived promotor.

Physiological regulation of transgene expression is a major challenge in gene therapy. Onasemnogene abeparvovec (Zolgensma®) is an approved adeno-associated virus (AAV) vector gene therapy for infants with spinal muscular atrophy (SMA), however, adverse events have been observed in both animals and patients following treatment. The construct contains a native human survival motor neuron 1 (hSMN1) transgene driven by a strong, cytomegalovirus enhancer/chicken ß-actin (CMVen/CB) promoter providing high, ubiquitous tissue expression of SMN. We developed a second-generation AAV9 gene therapy expressing a codon-optimized hSMN1 transgene driven by a promoter derived from the native hSMN1 gene. This vector restored SMN expression close to physiological levels in the central nervous system and major systemic organs of a severe SMA mouse model. In a head-to-head comparison between the second-generation vector and a benchmark vector, identical in design to onasemnogene abeparvovec, the 2nd-generation vector showed better safety and improved efficacy in SMA mouse model.

Role of gut microbiota and bacterial metabolites in mucins of colorectal cancer.

Colorectal cancer (CRC) is a major health burden, accounting for approximately 10% of all new cancer cases worldwide. Accumulating evidence suggests that the crosstalk between the host mucins and gut microbiota is associated with the occurrence and development of CRC. Mucins secreted by goblet cells not only protect the intestinal epithelium from microorganisms and invading pathogens but also provide a habitat for commensal bacteria. Conversely, gut dysbiosis results in the dysfunction of mucins, allowing other commensals and their metabolites to pass through the intestinal epithelium, potentially triggering host responses and the subsequent progression of CRC. In this review, we summarize how gut microbiota and bacterial metabolites regulate the function and expression of mucin in CRC and novel treatment strategies for CRC.

A Hybrid Parallel Balanced Phasmatodea Population Evolution Algorithm and Its Application in Workshop Material Scheduling.

The phasmatodea population evolution algorithm (PPE) is a recently proposed meta-heuristic algorithm based on the evolutionary characteristics of the stick insect population. The algorithm simulates the features of convergent evolution, population competition, and population growth in the evolution process of the stick insect population in nature and realizes the above process through the population competition and growth model. Since the algorithm has a slow convergence speed and falls easily into local optimality, in this paper, it is mixed with the equilibrium optimization algorithm to make it easier to avoid the local optimum. Based on the hybrid algorithm, the population is grouped and processed in parallel to accelerate the algorithm's convergence speed and achieve better convergence accuracy. On this basis, we propose the hybrid parallel balanced phasmatodea population evolution algorithm (HP_PPE), and this algorithm is compared and tested on the CEC2017, a novel benchmark function suite. The results show that the performance of HP_PPE is better than that of similar algorithms. Finally, this paper applies HP_PPE to solve the AGV workshop material scheduling problem. Experimental results show that HP_PPE can achieve better scheduling results than other algorithms.

Insight into the spatiotemporal distribution of antibiotic resistance genes in estuarine sediments during long-term ecological restoration.

In this study, we aimed to investigate the long-term spatiotemporal changes in hydrodynamics, antibiotics, nine typical subtypes of antibiotic resistance genes (ARGs), class 1 integron gene (intI1), and microbial communities in the sediments of a semi-enclosed estuary during ecological restoration with four treatment stages (influent (#1), effluent of the biological treatment area (#2), oxic area (#3), and plant treatment area (#4)). Ecological restoration of the estuary reduced common pollutants (nitrogen and phosphorus) in the water, whereas variations in ARGs showed noticeable seasonal and spatial features. The absolute abundance of ARGs at sampling site #2 considerably increased in autumn and winter, while it significantly increased at sampling site #3 in spring and summer. The strong intervention of biological treatment (from #1 to #2) and aerators (from #2 to #3) in the estuary substantially affected the distribution of ARGs and dominant antibiotic-resistant bacteria (ARB). The dominant ARB (Thiobacillus) in estuarine sediments may have low abundance but important dissemination roles. Meanwhile, redundancy and network analysis revealed that the microbial communities and intl1 were key factors related to ARG dissemination, which was affected by spatial and seasonal ecological restoration. A positive correlation between low flow velocity and certain ARGs (tetM, tetW, tetA, sul2, and ermC) was observed, implying that flow optimization should also be considered in future ecological restoration to remediate ARGs. Furthermore, the absolute abundance of ARGs can be utilized as an index to evaluate the removal capacity of ARGs by estuarine restoration.

Distribution and drivers of antibiotic resistance genes in brackish water aquaculture sediment.

Brackish water aquaculture has brought numerous economic benefits, whereas anthropogenic activities in aquaculture may cause the dissemination of antibiotic resistance genes (ARGs) in brackish water sediments. The intricate relationships between environmental factors and microbial communities as well as their role in ARGs dissemination in brackish water aquaculture remain unclear. This study applied PCR and 16S sequencing to identify the variations in ARGs, class 1 integron gene (intI1) and microbial communities in brackish water aquaculture sediment. The distribution of ARGs in brackish water aquaculture sediment was similar to that in freshwater aquaculture, and the sulfonamide resistance gene sul1 was the indicator of ARGs. Proteobacteria and Firmicutes were the dominant phyla, and Paenisporosarcina (p_ Firmicutes) was the dominant genus. The results of correlation, network and redundancy analysis indicated that the microbial community in the brackish water aquaculture sediment was function-driven. The neutral model and variation partitioning analysis were used to verify the ecological processes of the bacterial community. The normalized stochasticity ratio showed that pond bacteria community was dominated by determinacy, which was affected by aquaculture activities. The total nitrogen and organic matter influenced the abundance of ARGs, while Proteobacteria and Thiobacillus (p_Proteobacteria) were the key antibiotic-resistant hosts. Our study provides insight into the prevalence of ARGs in brackish water aquaculture sediments, and indicates that brackish water aquaculture is a reservoir of ARGs.

Analysis of lung biopsies using the 2015 WHO criteria and detection of sensitizing mutations--a single-institution experience of 5032 cases.

BACKGROUND: A specialized classification for small biopsies was added to the 2015 WHO classification of lung tumors. The purpose of this study is to explore and summarize the experience of applying the newly proposed classifications and criteria to clinical practice. METHODS: We used the 2015 WHO criteria to sort out 5032 small lung biopsies from a group of Chinese patients, and demonstrated their clinicopathological features, mutational status and the relationship between these factors. RESULTS: The most common diagnosis was primary lung carcinoma (3130, 62.2%), among which adenocarcinoma (1421, 28.2%) was the most frequent histological type. The mutational assays using ARMS-PCR technology demonstrated that EGFR was positive in 56.1% cases(499/889, from adenocarcinoma and NSCC, favor adenocarcinoma), ALK in 5.7% cases(12/211, from NSCC, which comprised all the primary lung carcinomas except small cell carcinomas), and ROS1 in 0.9% cases(2/211, from NSCC). Another 898 NSCC specimens went through an immunohistochemical (IHC) examination for ALK (D5F3) and 38 of them were positive (4.2%). The overall mutation rate of ALK was 4.5% (50/1119). There was no significant difference between ARMS-PCR and immunohistochemistry in the positive rate of ALK mutation detection (P = 0.359). EGFR mutations (P = 0.02) and ALK mutations (P < 0.001) both decreased with an increasing patient age. Furthermore, the amount of EGFR mutations was higher in adenocarcinoma (64.1% vs 34.1%, P < 0.001) than in NSCC, favor adenocarcinoma. In contrast, ALK mutations were more common in NSCC, favor adenocarcinoma (4.2% vs 8.4%, P = 0.021). CONCLUSIONS: This single-center study exhibited a large subset of small lung biopsies from a Chinese institution and demonstrated that applying the 2015 WHO classification for small lung biopsies can help predict the mutational status of primary lung carcinomas.

biAb Mediated Restoration of the Linkage between Dystroglycan and Laminin-211 as a Therapeutic Approach for α-Dystroglycanopathies.

Patients with α-dystroglycanopathies, a subgroup of rare congenital muscular dystrophies, present with a spectrum of clinical manifestations that includes muscular dystrophy as well as CNS and ocular abnormalities. Although patients with α-dystroglycanopathies are genetically heterogeneous, they share a common defect of aberrant post-translational glycosylation modification of the dystroglycan alpha-subunit, which renders it defective in binding to several extracellular ligands such as laminin-211 in skeletal muscles, agrin in neuromuscular junctions, neurexin in the CNS, and pikachurin in the eye, leading to various symptoms. The genetic heterogeneity associated with the development of α-dystroglycanopathies poses significant challenges to developing a generalized treatment to address the spectrum of genetic defects. Here, we propose the development of a bispecific antibody (biAb) that functions as a surrogate molecular linker to reconnect laminin-211 and the dystroglycan beta-subunit to ameliorate sarcolemmal fragility, a primary pathology in patients with α-dystroglycan-related muscular dystrophies. We show that the treatment of LARGEmyd-3J mice, an α-dystroglycanopathy model, with the biAb improved muscle function and protected muscles from exercise-induced damage. These results demonstrate the viability of a biAb that binds to laminin-211 and dystroglycan simultaneously as a potential treatment for patients with α-dystroglycanopathy.

Rapid discovery and identification of the anti-inflammatory constituents in Zhi-Shi-Zhi-Zi-Chi-Tang.

The anti-inflammatory active ingredients of Zhi-Shi-Zhi-Zi-Chi-Tang (ZSZZCT), a traditional Chinese medicine formula, were predicted and identified using an approach based on activity index, LC-MS, semi-preparative LC and NMR. Firstly, the whole extract of ZSZZCT was analyzed using liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) and liquid chromatography - ion trap mass spectrometry (LC-IT-MS), 79 constituents were detected and 39 constituents were identified unambiguously or tentatively. Subsequently, the whole extract of the formula was separated into multiple components and the activity index method was used to calculate index values of the 79 constituents by integrating the chemical and pharmacological information of multiple components. Four polymethoxyl flavones were predicted as the major active constituents according to the activity index values. Furthermore, three polymethoxyl flavones were prepared using the strategy with semi-preparative LC guided by LC-MS, and their anti-inflammatory activities were validated. The results show that three polymethoxyl flavones with higher positive index values, i.e., 3, 5, 6, 7, 8, 3', 4'-heptamethoxyflavone, 3-hydroxynobiletein and tangeretin had significant anti-inflammatory effects. In conclusion, the predicted results indicated that the activity index method is feasible for the accurate prediction of active constituents in TCM formulae.

An integrative systems approach identifies novel candidates in Marfan syndrome-related pathophysiology.

Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the FBN1 gene. Although many peripheral tissues are affected, aortic complications, such as dilation, dissection and rupture, are the leading causes of MFS-related mortality. Aberrant TGF-beta signalling plays a major role in the pathophysiology of MFS. However, the contributing mechanisms are still poorly understood. Here, we aimed at identifying novel aorta-specific pathways involved in the pathophysiology of MFS. For this purpose, we employed the Fbn1 under-expressing mgR/mgR mouse model of MFS. We performed RNA-sequencing of aortic tissues of 9-week-old mgR/mgR mice compared with wild-type (WT) mice. With a false discovery rate <5%, our analysis revealed 248 genes to be differentially regulated including 20 genes previously unrelated with MFS-related pathology. Among these, we identified Igfbp2, Ccl8, Spp1, Mylk2, Mfap4, Dsp and H19. We confirmed the expression of regulated genes by quantitative real-time PCR. Pathway classification revealed transcript signatures involved in chemokine signalling, cardiac muscle contraction, dilated and hypertrophic cardiomyopathy. Furthermore, our immunoblot analysis of aortic tissues revealed altered regulation of pSmad2 signalling, Perk1/2, Igfbp2, Mfap4, Ccl8 and Mylk2 protein levels in mgR/mgR vs WT mice. Together, our integrative systems approach identified several novel factors associated with MFS-aortic-specific pathophysiology that might offer potential novel therapeutic targets for MFS.

Inhibiting neutral amino acid transport for the treatment of phenylketonuria.

The neuropathological effects of phenylketonuria (PKU) stem from the inability of the body to metabolize excess phenylalanine (Phe), resulting in accumulation of Phe in the blood and brain. Since the kidney normally reabsorbs circulating amino acids with high efficiency, we hypothesized that preventing the renal uptake of Phe might provide a disposal pathway that could lower systemic Phe levels. SLC6A19 is a neutral amino acid transporter responsible for absorption of the majority of free Phe in the small intestine and reuptake of Phe by renal proximal tubule cells. Transgenic KO mice lacking SLC6A19 have elevated levels of Phe and other amino acids in their urine but are otherwise healthy. Here, we crossed the Pahenu2 mouse model of PKU with the Slc6a19-KO mouse. These mutant/KO mice exhibited abundant excretion of Phe in the urine and an approximately 70% decrease in plasma Phe levels. Importantly, brain Phe levels were decreased by 50%, and the levels of key neurotransmitters were increased in the mutant/KO mice. In addition, a deficit in spatial working memory and markers of neuropathology were corrected. Finally, treatment of Pahenu2 mice with Slc6a19 antisense oligonucleotides lowered Phe levels. The results suggest that inhibition of SLC6A19 may represent a novel approach for the treatment of PKU and related aminoacidopathies.

Hyaluronic Acid Microgels as Intracellular Endosomolysis Reagents.

Hyaluronic acid (HA) microgels were investigated as biocompatible and biodegradable reagents for facilitating endosomolysis in human cells. Employing inverse emulsion templates, HA microgels were prepared by cross-linking aqueous sodium hyaluronate droplets with divinyl sulfone (DVS). Introduction of ether sulfone cross-links was confirmed by infrared (IR) spectroscopy and elemental analysis. The degree of cross-linking of the microgels was estimated using high performance liquid chromatography (HPLC). The size distribution of the water-dispersible HA microgels was studied by laser diffraction analysis, and the gel morphology was investigated using scanning electron microscopy (SEM). Aqueous microgel suspensions were found to be well-tolerated in human cells at concentrations of up to 100 µg/mL. Endosome-rupturing properties of the HA microgels were evaluated in vitro using calcein internalization and Cre protein delivery assays. The results of this study serve as a proof-of-principle for the utility of cross-linked HA microgels as a new class of biocompatible and biodegradable endosomolytic reagents.

Mucin Production and Hydration Responses to Mucopurulent Materials in Normal versus Cystic Fibrosis Airway Epithelia.

RATIONALE: Cystic fibrosis (CF) airways disease produces a mucoobstructive lung phenotype characterized by airways mucus plugging, epithelial mucous cell metaplasia/hyperplasia, chronic infection, and inflammation. Simultaneous biochemical and functional in vivo studies of mucin synthesis and secretion from CF airways are not available. In vitro translational models may quantitate differential CF versus normal mucin and fluid secretory responses to infectious/inflammatory stimuli. OBJECTIVES: We tested the hypothesis that CF airways exhibit defective epithelial fluid, but not mucin, secretory responses to bacterial/inflammatory host products. METHODS: Well-differentiated primary human bronchial epithelial cultures were exposed to supernatant from mucopurulent material (SMM) from human CF airways as a test of bacterial/inflammatory host product stimulus. Human bronchial epithelia (HBE) with normal CF transmembrane conductance regulator function were compared with ΔF508/ΔF508 CF HBE. MEASUREMENTS AND MAIN RESULTS: Acute (up to 60 min) SMM exposure promoted mucin secretion, but mucins were degraded by the proteolytic enzymes present in SMM. Chronic SMM exposure induced upregulation of mucin synthesis and storage and generated absolute increases in basal and stimulated mucin release in normal and CF cultures. These responses were similar in normal and CF cultures. In contrast, SMM produced a coordinated CF transmembrane conductance regulator-mediated Cl- secretory response in normal HBE, but not in CF HBE. The absence of the fluid secretory response in CF produced quantitatively more dehydrated mucus. CONCLUSIONS: Our study reveals the interplay between regulation of mucin and fluid secretion rates in inflamed versus noninflamed conditions and why a hyperconcentrated mucus is produced in CF airways.

Identification and screening of chemical constituents with hepatoprotective effects from three traditional Chinese medicines for treating jaundice.

The constituents with hepatoprotective activity were investigated in three traditional Chinese medicine formulae for treating jaundice, namely, Zhi-Zi-Da-Huang-Tang, Yin-Chen-Hao-Tang, and Da-Huang-Xiao-Shi-Tang. By using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and liquid chromatography coupled with ion trap mass spectrometry, 79 chemical constituents were identified unambiguously or tentatively in three formulae based on the accurate molecular weight, mass spectrometric fragmentation behavior, and comparison with reference standards. Then the hepatoprotective activities of 27 constituents were evaluated on tert-butylhydroperoxide-injured BRL-3A cells. The results indicated that 11 constituents, including protocatechic acid (19), epijasminoside A (56), rutin (71), tetrahydropalmatine (76), rhaponticin (80), 3,4-dicaffeoylquinic acid (82), 3,5-dicaffeoylquinic acid (85), diosmetin-7-O-glucoside (90), jatrorrhizine (93), berberine (100), and daidzein (101) exerted hepatoprotective activities. Interestingly, most of the crude drugs in three formulae contained hepatoprotective active constituents, and the combinations of constituents from different crude drugs exhibited greater effects. This result provided evidence to the traditional Chinese medicine theory of combining several drugs together to exert synergistic efficacy.

Fecal miR-29a and miR-224 as the noninvasive biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related death around the world. MicroRNAs (miRNAs) are small non-coding RNAs that often are abnormally expressed in tumors. Detection and quantitation of miRNAs may provide information for the screening and early diagnosis of CRC. OBJECTIVES: The objective of our study was to determine whether fecal microRNAs (miR-29a, miR-145, miR-223, miR-224) could be used as biomarkers for the screening and early diagnosis of colorectal cancer. METHODS: We carried out a retrospective analysis of the miRNAs in fecal samples from 80 CRC patients and 51 normal controls. The levels of 4 miRNAs (miR-29a, miR-145, miR-223, and miR-224) were quantitated using the SYBR Green miScript PCR system and 2( - Δ Δ Ct) method. RESULTS: Our data indicated that the expression levels of miR-29a (p< 0.001), miR-223 (p< 0.001) and miR-224 (p< 0.001) are significantly lower in feces from CRC patients than these from normal volunteers, whereas their miR-145 levels are not significantly different (p= 0.59). Interestingly, the level of miR-29a (p< 0.001) in feces from individuals with rectum cancer is also significantly higher than that from patients with colon cancer. CONCLUSION: There are reduced expression of miR-29a, miR-223, and miR-224 in the feces from the CRC patients, which could be an informative biomarker for screening and early diagnosis of CRC.

Identification of chemical constituents in two traditional Chinese medicine formulae by liquid chromatography-mass spectrometry and off-line nuclear magnetic resonance.

There have been increasing works on identification of the chemical constituents in traditional Chinese medicines (TCMs) by liquid chromatography-mass spectrometry (LC-MS). However, isomers cannot be distinguished generally only by MS data, and the structures of unknown compounds cannot be confirmed. In this study, semi-preparative LC guided by LC-MS was used to prepare the isomers in microscale followed by off-line NMR analysis to confirm their structures. This approach was applied to identifying the constituents in two TCM formulae, Zhi-Zi-Gan-Cao-Chi-Tang (ZZGCCT) and Zhi-Zi-Bai-Pi-Tang (ZZBPT). A total number of 119 constituents were identified tentatively or unambiguously by LC-IT-MS, LC-Q-TOF-MS, and NMR. Among them, 20 constituents were characterized unambiguously by comparing with the reference substances. In addition, 21 constituents without reference substances were prepared for the following 1D-NMR and/or 2D-NMR analysis, and their structures were unambiguously identified by MS, 1D-NMR, and 2D-NMR. Two triterpenoid glycosides (compounds 134 and 140) and one flavonoid glycoside (compound 62a or 62b) were showed to be novel compounds. Compounds 125 and 129, as well as 62a,b, were epimers.

SNAP23 is selectively expressed in airway secretory cells and mediates baseline and stimulated mucin secretion.

Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type (WT) mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated.

Baseline Goblet Cell Mucin Secretion in the Airways Exceeds Stimulated Secretion over Extended Time Periods, and Is Sensitive to Shear Stress and Intracellular Mucin Stores.

Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5-2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin secretion.

[Identification of constituents in Suanzaoren tang by LC-Q-TOF-MS and LC-IT-MS].

LC-Q-TOF-MS and LC-IT-MS in positive and negative ion mode were applied to simultaneously characterize the constituents in Suanzaoren tang. Analysis was performed on an Agilent Zorbax SB-C18, Rapid Resolution HT column(4.6 mmx 50 mm, 1. 8 micro m) with gradient elution of acetonitrile(A) -aqueous solution containing 0. 05% formic acid(B) at a flow rate of 0. 6 mL min(-1) and the column temperature was 30 degreesC. By comparing MS fragmentation, accurate molecular weight, literature date and standard compounds information, a total of48 compounds were successfully identified or speculated. The origins of these compounds were assigned to the corresponding Chinese medicine. Thirty-one compounds were reported in Suanzaoren tang for the first time. LC-Q-TOF-MS combined with LC-IT-MS is a simple and rapid tool for the identification of constituents of Suanzaoren tang, and the results could provide evidence for the research on quality combined and effective constituents of Suanzaoren tang.