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IntroductionAirway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)–autophagy axis in airway epithelial injury in asthma.MethodsWe examined the MTOR–autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related lc3b-/- mice were used for allergic models.ResultsMTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in lc3b-/- mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice.ConclusionCollectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.

Coronavirus disease 2019 (COVID-19) has resulted in more than 8.7 million laboratory-confirmed cases and 0.46 million deaths globally (1). Few therapies, if any, have been shown to rapidly ameliorate the respiratory symptoms and prevent against the disease progression. An important mechanism contributing to dyspnea and disease progression in patients with COVID-19 might be the increased work of breathing because of the heightened airway resistance (2). Inhalation of hydrogen/oxygen mixed gas (H2-O2) might have a role in the treatment of COVID-19 given the decreased resistance compared with room air when passing through the airways.

Red blood cells (RBCs) are exposed to exogenous reactive oxygen species in the circulatory system. To this end, the interactions between the different hemoglobin (Hb) subunits and peroxiredoxin 2, which is a ubiquitous member of the antioxidant enzymes that also controls the cytokine-induced peroxide levels, were assessed. We predicted by the increment of diversity with quadratic discriminant analysis (IDQD) that peroxiredoxin2 (Prx2) could interact with the hemoglobin alpha, beta and gamma subunits but not with the delta subunit. Coimmunoprecipitation (co-IP), electrospray ionization quadrupole time of flight (ESI-Q-TOF) mass spectrometry, Western blotting and X-ray absorption fine structure (XAFS) spectroscopy were performed to verify these predictions. The results showed that Prx2 was a member of the beta-globin immunoprecipitating complex that existed in hemoglobin A, hemolysate-hemoglobin A, hemoglobin A-hemoglobin A2, hemolysate-hemoglobin A-hemoglobin A2 and hemoglobin A2 but not in hemolysate-hemoglobin A2. Adding Prx2 to hemoglobin A altered the second shell of iron embedded in hemoglobin A. Therefore, Prx2 interacts with hemoglobin A (Alpha2Beta2) and hemoglobin F (Alpha2Gamma2) but not with hemoglobin A2 (Alpha2Delta2).

The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) contribute to an increased response rate, compared with chemotherapy, in patients with inhibitor-sensitive EGFR mutations. The present study evaluated the association between the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT), as well as serum carcinoembryonic antigen (CEA) levels and EGFR mutations prior to treatment, in patients with non-small cell lung cancer (NSCLC). Patients with histologically confirmed NSCLC (n=167), who underwent an 18F-FDG PET/CT scan, EGFR mutation analysis and a serum CEA test participated in the present study. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations. Receiver-operating characteristic (ROC) curve analysis was performed to determine the efficient cut-off value. Survival rate analysis was evaluated according to SUVmax and EGFR mutation status. A decreased SUVmax and an increased CEA level was observed in patients with EGFR-mutations, compared with patients with wild-type primary lesions and metastatic lymph nodes. The exon 19 EGFR mutation was associated with increased SUVmax, compared with the exon 21 L858R mutation. The ROC analysis indicated that an 18F-FDG PET/CT uptake SUVmax >11.5 may be a predictor of the wild-type EGFR genotype and increased CEA levels (CEA >9.4 ng/ml) were associated with EGFR mutations. Furthermore, patients with no smoking history, low SUVmax of the primary tumor, metastatic lymph nodes and a high CEA level were significantly associated with EGFR mutation status. The results of the present study indicated that patients with advanced NSCLC, particularly Chinese patients, with decreased SUVmax and increased CEA levels are associated with EGFR mutations, which may serve as predictors for the EGFR-TKI therapeutic response.

We present an innovative and practical scheme of building a miniaturized wavemeter, with the advantages of low cost, high reliability and simple structure. Through a calibration test by a 780 nm external cavity diode laser (ECDL), the results show that our system gets a wavelength resolution of better than 1 pm, measurement accuracy of better than 2 pm (corresponding to a frequency of 1 GHz), and a measurement range of 8.5 nm. Finally, the multi-mode comparison test between our system and a commercial spectrum analyzer further indicates the high-precision, miniaturization and low cost of the proposed system, which shows that it is particularly suitable for ECDL and atom cooling and trapping experiments. The system design, experimental results and conclusions are of definite significance as a fine reference for other ranges of wavelength.

We present a low cost radio-frequency (RF) generator suitable for experiments with cold atoms. The RF source achieves a sub-hertz frequency with tunable resolution from 0 MHz to 400 MHz and a maximum output power of 33 dBm. Based on a direct digital synthesizer (DDS) chip, we implement a ramping capability for frequency, amplitude and phase. The system can also operate as an arbitrary waveform generator. By measuring the stability in a duration of 600 s, we find the presented device performs comparably as Agilent33522A in terms of short-term stability. Due to its excellent performance, the RF generator has been already applied to cold atom trapping experiments.

Objective To study the effect of IL -6 on the development of zygotes of mice after controlled ovarian hyperstimulation. Methods The present experiment included three parts: a) Addition of IL-6: 80 female ICR mice were divided into 7 groups by random number table including 6 groups of superovulation (10 each) and a group of natural ovulation cycle (n=20). According to addition of IL-6 in different concentration to culture media, the superovulated ICR mice were divided into superovulation control group (0pg/ml IL -6 group), 1pg/ml IL-6 group, 5pg/ml IL-6 group, 10pg/ml IL -6 group, 25pg/ml IL-6 group, and 50pg/ml IL-6 group, with ICR mice in natural ovulation cycle served as control. b) Addition of IL-6 receptor antibody (RA): 90 female ICR mice were divided into 7 groups according to the random number table, including 5 groups of superovulation (10 each) on the basis of addition of different concentrations IL-6 and IL-6 RA to culture media (0pg/ml IL-6+RA groups, 1pg/ml IL-6+RA group, 5pg/ml IL-6+RA group, 10pg/ml IL-6+RA group, 25pg/ml IL-6+RA group), and 2 groups of normal natural cycle (20 each), including control group and the control group+IL -6 RA (100pg/ml) group. Mice in normal control group conceived naturally while those in superovulation group conceived after superovulation. The zygotes were collected and cultured in vitro for 1 day till the formation of 2-cell embryos, then the rate of 2-cell formation was observed under microscope. Experiments of each group were repeated three times. c) Immunofluorescence identification: 10 female ICR mice were divided into control group and superovulation group (5 each) by random number table method. The expressions of IL -6 in zygotes were determined with confocal immunofluorescence method. Results IL-6 addition experiment: the rate of 2-cell formation was significantly lower (P

We demonstrate a simple and fast way to produce 87Rb Bose–Einstein condensates. A digital optical phase lock loop (OPLL) board is introduced to lock and adjust the frequency of the trap laser, which simplifies the optical design and improves the experimental efficiency. We collect atoms in a magneto-optical trap, then compress the cloud and cut off hot atoms by rf knife in a magnetic quadrupole trap. The atom clouds are then transferred into a spatially mode-matched optical dipole trap by lowering the quadrupole field gradient. Our system reliably produces a condensate with 2×106 atoms every 7.5 s. The compact optical design and rapid preparation speed of our system will open the gate for mobile quantum sensing.

With the continuous drought stress treatment to 12 pot-grown watermelon genotypes originated from different regions, the influence of drought stress on plant height, root length, fresh mass and dry mass was studied, and the physiological responses of these genotypes to drought stress were compared. Drought resistance of these watermelon genotypes was preliminarily determined according to the drought injury, and then confirmed by membership function evaluation method. We found that the watermelon genotypes exhibited great difference in drought tolerance based on the occurrence of drought injury and the degree of injury severity. Drought stress reduced plant height, shoot- and root- fresh mass as well as shoot- and root- dry mass, while increased the root/shoot ratio for most genotypes; but for root length and root dry mass, it had both positive and negative effects depending on the tested genotype. Compared with the control, all drought-treated watermelon genotypes exhibited a decline in leaf relative water content and chlorophyll content, as well as increases in MDA, H以来源于不同地区的12个西瓜基因型为试材,采用盆栽控水的方式进行持续干旱处理,研究干旱胁迫对西瓜幼苗株高、根长、鲜质量及干物质积累等生长状况的影响,比较不同基因型材料对干旱胁迫的生理响应差异,同时依据旱害指数对其抗旱性进行直接评价,并采用隶属函数法进一步验证和综合评价.结果表明: 干旱处理下,12个西瓜基因型对干旱胁迫的耐受能力存在明显差异,各基因型开始出现旱害症状的时间和发生旱害的程度各不相同.干旱胁迫降低了西瓜幼苗的株高、地上、地下鲜质量和地上干物质积累量,普遍提高了根冠比,而对根长和地下干质量存在正向和负向两种不同的影响.干旱处理后,西瓜叶片的相对含水量和叶绿素含量均不同程度降低,丙二醛、过氧化氢和超氧阴离子含量增加,脯氨酸大量积累,而可溶性蛋白含量以及抗氧化酶活性则因基因型的不同而表现出不同的结果.分析认为,3个野生型材料M20、KY-3和Y-2为抗旱性强的西瓜种质,Y34、金美人和04-1-2为敏感种质,而其余基因型为中抗种质.

Objectives Lung ischaemia-reperfusion injury is a complex pathophysiological process due to the production of reactive oxygen species and the generation of inflammatory reaction. We investigated the protective effects and the corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on lung injury induced by ischaemia-reperfusion in a mouse model. Methods Adult male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups: sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT. Lung ischaemia-reperfusion injury was induced by thoracotomy followed by clamping of the left hilum for 1 h and subsequent reperfusion for 2 h. Results Histological scoring analysis showed that lung parenchymal damage was ameliorated in the melatonin pretreatment groups when compared with the IR group, with the IR + 20 mg/kg MT group showing the strongest effect among the melatonin pretreatment groups. Wet-to-dry weight ratio, detection of malondialdehyde, protein expressions of inflammatory factors (tumour necrosis factor-α, interleukin-1β, NF-κB and IKK-γ) and apoptotic factors (cleaved caspase-3 and Bax/Bcl-2), as well as TUNEL assay showed changes similar to those of the lung injury scores in all groups. In contrast, the examination of superoxide dismutase showed a pattern contrary to that of the lung injury score in all groups. In addition, immunohistochemistry staining showed that the expressions of the antioxidants glutathione peroxidase and glutathione reductase were increased in the melatonin pretreatment groups. Conclusions This study demonstrated that melatonin pretreatment attenuated lung ischaemia-reperfusion injury via inhibition of oxidative stress, inflammation and apoptosis.

Background Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. Methods Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). Results miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. Conclusions miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

The application of ArcGIS and Maxent modelto analyze the ecological suitability of Gardenia jasminoides.Taking 85 batches of Gardenia as the basis of analysis, the selection of ecological factors for the growth of Gardenia. The results showed that the average precipitation in April, the average precipitation in November and the average precipitation in August were the most important factors affecting the growth of Gardenia. The relative concentration of Gardenia suitable growth region,north to the south of Shaanxi province, south of Henan, central Anhui, south to the north of Hainan province, west to central Sichuan province, east of Zhejiang coastal area, northeast of Taiwan.

The yellow peach moth (YPM), Conogethes punctiferalis (Guenée), is a multivoltine insect pest of crops and fruits. Antennal-expressed receptors are important for insects to detect olfactory cues for host finding, mate attraction and oviposition site selection. However, few olfactory related genes were reported in YPM until now. In the present study, we sequenced and characterized the antennal transcriptomes of male and female YPM. In total, 15 putative odorant binding proteins (OBPs), 46 putative odorant receptors (ORs) and 7 putative ionotropic receptors (IRs) were annotated and identified as olfactory-related genes of C. punctiferalis. Further analysis of RT-qPCR revealed that all these olfactory genes are primarily or uniquely expressed in male and female antennae. Among which, 3 OBPs (OBP4, OBP8 and PBP2) and 4 ORs (OR22, OR26, OR44 and OR46) were specially expressed in male antennae, whereas 4 ORs (OR5, OR16, OR25 and OR42) were primarily expressed in female antennae. The predicted protein sequences were compared with homologs in other lepidopteran species and model insects, which showed high sequence homologies between C. punctiferalis and O. furnacalis. Our work allows for further functional studies of pheromone and general odorant detection genes, which might be meaningful targets for pest management.

For determine the location of the ingestible electronic pill inside the human body ，a new positioning system of the micro medical device inside the human body is designed. CC2430 communication chips combined with ZigBee protocol software are used as radio frequency transceiver of the system. When transmission power is very low, significant error codes will be generated at the receiving terminal. We can locate the electronic pill according to the analysis results of the packet error rate. And we adopt Trilateration to build up a set of nonlinear equations, which is related to the inter-node distance and spatial location variables of the pill. At last, equations are solved with numerical solution. It is found that the method is feasible.

Based on the asymmetry characteristic of 33 coupler output signal, the improved demodulation arithmetic of 3x3 coupler was studied and deduced. To satisfy the requirement of fiber-optic sensor for real time, high accuracy and net work processing, a design method for embedded signal processing based on dual-core microprocessor OMAP is provided. The results of the experiments show that the system can meet the requirements of processing accuracy and real-time property and it has very high practical value.

To study the interactions between hemoglobin (Hb) and other proteins within human erythrocytes by using the electrophoresis release test (ERT) and co-immunoprecipitation.First, the fresh normal adult anti-coagulated whole blood was washed to prepare packed RBCs, which were further prepared to erythrocyte suspension and hemolysate.The erythrocyte suspension and hemolysate were analyzed by the electrophoresis release test (ERT) at the same time, and then the band of HbA of erythrocyte sample (RA) and the corresponding band of hemolysate sample (HA) were cut out from the gel and were enriched by freeze-thaw method. Then, the samples were bound with hemoglobin β antibody (37-8) AC, the complexes were separated through 5%-12% SDS-PAGE followed by Q-TOF.Five bands were found in the gel, each of which was treated by hemoglobin β antibody (37-8) AC, the protein bands of 16,20,22,28 and 50 kD were emerged in RA, HA and RBC lysis.The bands were identified by MS, and the results showed that these bands were hemoglobin, band 3, peroxiredoxin2 (Prx2), band 3 and β-actin, band 3 respectively.HbA may interact with Prx2, Band 3 and β-actin, and then the complexes are formed with each other within erythrocytes.

A multiplex polymerase chain reaction (PCR) was designed for the simultaneous detection of four viruses involved in postweaning multisystemic wasting syndrome (PMWS) in pigs: porcine circovirus type 2 (PCV-2), type 2 porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV) and pseudorabies virus (PRV). Each of the four pairs of primers exclusively amplified the targeted fragment of the specific viruses. The sensitivity of the multiplex PCR, using purified plasmid constructs containing the specific viral target fragments, was 4.0×103, 4.5×103, 3.0×102 and 5.0×102 copies for PCV-2, type 2 PRRSV, PPV, PRV. Among 82 clinical samples, coinfection by PCV-2 and type 2 PRRSV was the most common. When compared with the virus isolation method commonly used to detect viruses, the multiplex PCR assay was found to be more sensitive and rapid and, as such, may prove to be a good alternative method for the detection of and differentiation in PMWS in pigs., Višestruka lančana reakcija polimerazom (PCR) razvijena je za istodobni dokaz četiriju virusa koji se nalaze kod sindroma kržljavosti odbijene prasadi: svinjskog cirkovirusa tip 2, virusa reprodukcijskog i respiratornog sindroma tip 2, parvovirusa i virusa bolesti Aujeszkoga. Svaki od četiri para početnica bio je specifičan isključivo za umnožavanje specifičnog fragmenta određenog virusa. Osjetljivost višestrukog PCR-a upotrebom pročišćenih konstrukata plazmida koji sadrže specifične virusne fragmente bila je na razini 4,0×103 kopija za svinjski cirkovirus tip 2, 4,5×103 kopija za virus reprodukcijskog i respiratornog sindroma, 3,0×102 za svinjski parvovirus i 5,0×102 kopija za virus bolesti Aujeszkoga. Među 82 klinička uzorka često je dokazana koinfekcija svinjskim cirkovirusom tip 2 i virusom respiratornog i reprodukcijskog sindroma. U usporedbi s izolacijom virusa, višestruka lančana reakcija polimerazom pokazala se osjetljivijom i bržom te se kao takva može rabiti kao alternativna metoda za dokaz i razlikovanje uzročnika sindroma kržljavosti prasadi.

In order to elucidate the differences of protein profiles among soybean cultivars, the protein composition of three conventional domestic soybean cultivars and two imported ones including glyphosate-tolerant HS2906 was analyzed by total nitrogen measurement, amino acid analysis and PAGE/densitometry. There were no statistically significant differences in the levels of any amino acid, including aromatic amino acids, between glyphosate-tolerant soybean and the conventional soybean WS82. In the extraction of protein, the SDS/buffer system was more efficient than the defatting/water system. The SDS-PAGE/densitometry analysis showed that there was a similar profile of proteins among cultivars, although the amount of total protein ranged from 380.2 ㎎/g to 423.9 ㎎/g. In addition, there was no discernable difference of protein profile between glyphosate-tolerant soybean (total protein amount, 380.2 ㎎/g) and the conventional soybean WS82 (390.2 ㎎/g), although the amount of β-conglycinin (55 kDa) was lower in glyphosate-tolerant soybean. Meanwhile, the amount of 25 kDa protein was greater in domestic soybean cultivars than imported ones. Thus, normal PAGE/densitometry method would be useful to analyze the difference in protein profiles of soybean proteins, and furthermore evaluate the protein profile of proteins between GMO and conventional soybean.

We develop a simple and practical scheme to apply sideband cooling to a cloud of rubidium atoms. A sample containing 4 × 10 Rb is trapped in a far red detuned optical lattice. Through optimizing the relevant parameters, i.e., laser detuning, magnetic field, polarization, and duration time, a temperature around 1.5 μK and phase space density close to 1/500 are achieved. Compared with polarization gradient cooling, the temperature decreases by around one order of magnitude. This technique could be used in high precision measurement such as atomic clocks and atom interferometer. It could also serve as a precooling means before evaporation cooling in a dipole trap, and may be a promising method of achieving quantum degeneracy with purely optical means.

To evaluate the effect of impressions made by agar/alginate compared with silicon rubber material.Five moulds of bi-root canal molar, with different root canal angles of 0°, 10°, 20°, 30° and 40° were made. Twenty impressions were made for each mould with either silicon rubber or agar/alginate. The effects of two methods were evaluated and the influence of angles between root canals on the impression methods was analyzed. The data was analyzed with SPSS16.0 software package.Significant difference of integrality rate (IR) of impression was not found in silicon rubber group among different angle groups (P0.05). IR of 40° group (60%) was significantly lower than that of 0°(95%) and general IR (83%) when using agar (P0.05). IR of agar (60%) was statistically lower than silicon rubber (90%) in 40° group (P0.05).The success rate of agar method was significantly lower than silicon rubber method in 40° group. The general IR of agar (83%) was significantly lower than that of silicon rubber (95%) (P0.05). A significant negative correlation was observed between root canal angles and IR (r=-0.901,P=0.037).Silicon rubber impression materials are suggested for impression taking when root canal angles are over 30° in molars, while agar/alginate impression method is qualified for smaller angles. The general IR of silicon rubber material is better than that of agar when taking the impression of post and core in molar.

Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling. A family-wide structural library of human DUSPs was constructed based on experimental structure determination supplemented with homology modelling. The catalytic domain of each individual DUSP has characteristic features in the active site and in surface-charge distribution, indicating substrate-interaction specificity. The active-site loop-to-strand switch occurs in a subtype-specific manner, indicating that the switch process is necessary for characteristic substrate interactions in the corresponding DUSPs. A comprehensive analysis of the activity–inhibition profile and active-site geometry of DUSPs revealed a novel role of the active-pocket structure in the substrate specificity of DUSPs. A structure-based analysis of redox responses indicated that the additional cysteine residues are important for the protection of enzyme activity. The family-wide structures of DUSPs form a basis for the understanding of phosphorylation-mediated signal transduction and the development of therapeutics.

To evaluate the therapeutic effect of Chaipo Granule (CPG) combined with routine treatment on refractory asthma.Sixty patient with refractory asthma were assigned equally in a double-blind, randomized way to the treatment group and the control group. Routine treatment (including regular inhalation of salmeterol and fluticasone propionate 50/250 microg, and if necessary, inhalation of salbutamol + ipratropium bromide) were given to all patients. CPG (3 pouches every time, twice a day) were administered to the treatment group in addition, while to the control group, placebo with similar appearance in equal volume was given. The therapeutic course for all was 24 weeks. Asthma control test (ACT) scoring and lung function tests (FEV1 and PEF) were performed before treatment and at the end of the 4th, 12th and 24th week; daily records of asthma, dose of hormone used, withdrawal reaction and adverse reaction occurred were monitored, and serum levels of cortisol, total IgE and cytokines (IL-4, IL-5, IL-13 and IFN-gamma) were measured before treatment and at terminating the 24-week treatment.Symptoms and lung function were significantly improved after treatment in both groups, but the improvements were better in the treatment group than the control group at all time points, the difference between groups was statistically significant (P0.05). Levels of IL-5, IL-13, total IgE decreased, IFN-gamma and Cor increased in all patients after 24-week treatment, but the improvements in the treatment group was more significant, with statistical difference between groups (P0.05); the mean hormone withdrawal time in the treatment group was (14.6 +/- 5.1) days, with the incidence of systemic withdrawal reactions of 20%, while those in the control group was (22.1 +/- 6.8) days and 36.7% correspondingly, the difference between groups was statistically significant (P0.05). However, one patient in the treatment group quit the trial due to a severe seizure of asthma. No obvious treatment-related side effects appeared in the treatment group, except that 3 patients suffered from slight abdominal pain.CPG could improve the clinical symptoms and lung function, facilitate to Th1/Th2 balance and enhance the secretion of adrenal cortex. It is an effective and safe Chinese herbal remedy for treatment of refractory asthma.

Chromatographic separation of soluble proteins from rice (Oryza sativa L.) yielded a major albumin protein (16 kDa), with the DHHQVYSPGEQ sequence in the N terminus, showing antioxidant action. The rice albumin was more potent than other rice proteins in preventing Cu2+-induced low-density lipoprotein (LDL) oxidation. Additionally, it also exhibited a remarkable suppression of HOCl oxidation. In a further study, albumin inhibited Cu2+-induced oxidation of LDL in a stoichiometric manner with an EC50 value of 4.3 microM, close to that of serum albumins. Moreover, after digestion with trypsin or chymotrypsin, it maintained its antioxidant action. In an experiment to see the involvement of the N terminus in antioxidant action, a synthetic tetrapeptide, equivalent to the N terminus DHHQ, was found to inhibit Cu2+-induced LDL oxidation or degradation of apolipoprotein B, similar to that of rice albumin. In mechanistic analyses, the action of rice albumin or tetrapeptide is primarily due to the removal of Cu2+, as suggested from its inhibitory effect on Cu2+/diphenylcarbohydrazide (DPCH) complex formation. However, despite its similar inhibitory effect on Cu2+-induced oxidation of LDL, rice albumin was less effective than serum albumin in inhibiting Cu2+/DPCH complex formation, suggesting that the number of Cu2+-binding sites in rice albumin may be less than that in serum albumins. Taken together, rice albumin exerts a potent preventive action against Cu2+-induced oxidations, which is due to the Cu2+ binding by DHHQ in the N-terminal sequence. Such a role as a Cu2+ chelator would add up to the application of rice albumin protein.

Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma.This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy.In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment.Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P.001). The improvement was slightly but significantly greater in the prednisone group (P.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P.001) and were lower in the prednisone-treated group (P.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P.001) but significantly increased in the ASHMI group (P.001). No severe side effects were observed in either group.Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.

Homophilic interaction of the L1 family of cell adhesion molecules plays a pivotal role in regulating neurite outgrowth and neural cell networking in vivo. Functional defects in L1 family members are associated with neurological disorders such as X-linked mental retardation, multiple sclerosis, low-IQ syndrome, developmental delay, and schizophrenia. Various human tumors with poor prognosis also implicate the role of L1, a representative member of the L1 family of cell adhesion molecules, and ectopic expression of L1 in fibroblastic cells induces metastasis-associated gene expression. Previous studies on L1 homologs indicated that four N-terminal immunoglobulin-like domains form a horseshoe-like structure that mediates homophilic interactions. Various models including the zipper, domain-swap, and symmetry-related models are proposed to be involved in structural mechanism of homophilic interaction of the L1 family members. Recently, cryo-electron tomography of L1 and crystal structure studies of neurofascin, an L1 family protein, have been performed. This review focuses on recent discoveries of different models and describes the possible structural mechanisms of homophilic interactions of L1 family members. Understanding structural mechanisms of homophilic interactions in various cell adhesion proteins should aid the development of therapeutic strategies for L1 family cell adhesion molecule-associated diseases.

The L1CAM antibody A10-A3 efficiently reduces tumor growth in a nude mouse model. Here, we describe the crystal structure of the Fab fragment of A10-A3 determined at 2.0 angstrom resolution. The A10-A3 antibody H3 loop reveals a characteristic arrangement of exposed aromatic residues that may play an important role in antigen binding. A structure model of the complex between L1CAM Ig1-4 and A10-A3 Fab indicates that the Fab binds to three small loops outside Ig1 and a residue between Ig1 and Ig2, consistent with an epitope mapping result. The data presented here should contribute to the design of high-affinity antibody for therapeutic purposes as well as to the understanding of neural cell remodeling and cancer progression mechanism mediated by L1CAM.