Airflow obstruction and small airway dysfunction following pulmonary tuberculosis: a cross-sectional survey.

OBJECTIVES: Pulmonary function impairment and chronic respiratory symptoms after tuberculosis are relatively common in low-income and middle-income countries. We aimed to estimate the impact of post-tuberculosis (post-TB) on pulmonary function. METHODS: This large cross-sectional, population-based study included subjects aged 15 years or older with technically acceptable postbronchodilator spirometry measurements. Post-TB was diagnosed on the basis of radiological evidence and/or medical history. Airflow obstruction was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal of Global Lung Function Initiative (GLI) lung function equations. Small airway dysfunction was diagnosed if at least two of the following indicators were less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50% or FEF 75%. RESULTS: In this population sample (N=8680, mean age: 40.1 years), 610 (7.0% (95% CI 6.5 to 7.6) participants were post-TB. Post-TB subjects had more frequent respiratory symptoms (46.8% vs 28.3%). Among post-TB subjects, 130 (21.3% (95% CI 18.1 to 24.8)) had airflow obstruction; OR of airflow obstruction was significantly associated with post-TB after adjustment for other confounding factors (OR 1.31, 95% CI 1.05 to 1.62). Post-TB was also associated with small airway dysfunction (OR 1.28, 95% CI1.07 to 1.53), which was present in 297 (48.9% (95% CI 33.9 to 53.0)) post-TB subjects. CONCLUSIONS: Our findings support existing knowledge that post-TB is positively associated with pulmonary function impairment and make for frequent respiratory symptoms. Post-TB should be considered as a potentially important cause of airflow obstruction and respiratory symptoms in patients originating from countries with a high burden of tuberculosis.

Combined effect of ozone and household air pollution on COPD in people aged less than 50 years old.

OBJECTIVES: Air pollution has been suggested as an important risk factor for chronic obstructive pulmonary disease (COPD); however, evidence of interactive effects on COPD between different factors was sparse, especially for young adults. We aimed to assess the combined effects of ambient ozone (O3) and household air pollution on COPD in young individuals. METHODS: We conducted a population-based study of residents aged 15-50 years in the low-income and middle-income regions of western China. We used multivariable logistic regression models to examine the associations between long-term ozone exposure and COPD in young individuals. RESULTS: A total of 6537 young cases were identified among the participants, with a COPD prevalence rate of 7.8 (95% CI 7.2% to 8.5%), and most young COPD individuals were asymptomatic. Exposure to household air pollution was associated with COPD in young patients after adjustment for other confounding factors (OR 1.82, 95% CI 1.41 to 2.37). We also found positive associations of COPD with O3 per IQR increase of 20 ppb (OR 1.92, 95% CI 1.59 to 2.32). The individual effects of household air pollution and O3 were 1.68 (95% CI 1.18 to 2.46) and 1.55 (95% CI 0.99 to 2.43), respectively, while their joint effect was 3.28 (95% CI 2.35 to 4.69) with the relative excess risk due to interaction of 1.05 (95% CI 0.33 to 1.78). CONCLUSIONS: This study concludes that exposure to ambient O3 and household air pollution might be important risk factors for COPD among young adults, and simultaneous exposure to high levels of the two pollutants may intensify their individual effects.

The transcription factor GCN4 contributes to maintaining intracellular amino acid contents under nitrogen-limiting conditions in the mushroom Ganoderma lucidum.

BACKGROUND: Edible mushrooms are delicious in flavour and rich in high-quality protein and amino acids required by humans. A transcription factor, general control nonderepressible 4 (GCN4), can regulate the expression of genes involved in amino acid metabolism in yeast and mammals. A previous study revealed that GCN4 plays a pivotal role in nitrogen utilization and growth in Ganoderma lucidum. However, its regulation is nearly unknown in mushrooms. RESULTS: In this study, we found that the amino acid contents reached 120.51 mg per gram of mycelia in the WT strain under 60 mM asparagine (Asn) conditions, but decreased by 62.96% under 3 mM Asn conditions. Second, silencing of gcn4 resulted in a 54.2% decrease in amino acid contents under 60 mM Asn, especially for the essential and monosodium glutamate-like flavour amino acids. However, these effects were more pronounced under 3 mM Asn. Third, silencing of gcn4 markedly inhibited the expression of amino acid biosynthesis and transport genes. In addition, GCN4 enhanced the tricarboxylic acid cycle (TCA) and glycolytic pathway and inhibited the activity of target of rapamycin complex 1 (TORC1), thus being beneficial for maintaining amino acid homeostasis. CONCLUSION: This study confirmed that GCN4 contributes to maintaining the amino acid contents in mushrooms under low concentrations of nitrogen. In conclusion, our study provides a research basis for GCN4 to regulate amino acid synthesis and improve the nutrient contents of edible mushrooms.

Predictors of mortality in COPD exacerbation cases presenting to the respiratory intensive care unit.

BACKGROUND: Studies report high in-hospital mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) especially for those requiring admission to an intensive care unit. Recognizing factors associated with mortality in these patients could reduce health care costs and improve end-of-life care. METHODS: This retrospective study included AECOPD patients admitted to the respiratory intensive care unit of a tertiary hospital in Beijing from Jan 1, 2011 to Dec 31, 2018. Patients demographic characteristics, blood test results and comorbidities were extracted from the electronic medical record system and compared between survivors and non-survivors. RESULTS: We finally enrolled 384 AECOPD patients: 44 (11.5%) patients died in hospital and 340 (88.5%) were discharged. The most common comorbidity was respiratory failure (294 (76.6%)), followed by hypertension (214 (55.7%)), coronary heart disease (115 (29.9%)) and chronic heart failure (76 (19.8%)). Multiple logistic regression analysis revealed that independent risk factors associated with in-hospital mortality included lymphocytopenia, leukopenia, chronic heart failure and requirement for invasive mechanical ventilation. CONCLUSIONS: The in-hospital mortality of patients with acute COPD exacerbation requiring RICU admission is high. Lymphocytes < 0.8 × 109/L, leukopenia, requirement for invasive mechanical ventilation, and chronic heart failure were identified as risk factors associated with increased mortality rates.

Expression, location and biological effects of four and a half LIM domain protein 2 (FHL2) on granulosa cells in ovine.

Previous studies have shown that four and a half LIM domain protein 2 (FHL2) plays an essential role in the regulation of follicular development in mammals. Although the FHL2 genes of human and mouse have been well characterized, the expression and location of FHL2 in ovary and the biological functions of FHL2 on granulosa cells (GCs) of ovine are still not clear. In this study, full-length complementary DNA (cDNA) of FHL2 from ovine follicular GCs was amplified by real-time PCR (RT-PCR). The expression and location of FHL2 in ovary and GCs of ovine were studied by immunohistochemistry and immunofluorescence, and the biological effects of FHL2 on the cell proliferation, cell apoptosis, cell cycles and expression level of related genes of ovine GCs were also explored by overexpression or knockdown of FHL2. The results indicated that FHL2 was expressed in ovine follicular GCs and the sequence of the FHL2 cDNA was consistent with that predicted in GenBank, which did not cause an amino acid change. According to the results, FHL2 was expressed in ovine ovary and mainly located in the cytoplasm and nucleus of GCs. In addition, overexpression of FHL2 significantly reduced the cell viability, promoted the cell apoptosis and decreased the percentage of G0/G1 and S phase cells. RT-PCR showed that overexpression of FHL2 significantly increased the mRNA expression level of Bax and decreased the expression of Bcl-2 and the Bcl-2/Bax mRNA ratio compared with the control group. Besides, the knockdown of FHL2 gene in ovine GCs significantly improved the cell viability, suppressed the cell apoptosis, decreased the mRNA expression level of Caspase-3 gene, increased the Bcl-2/Bax mRNA ratio and increased the percentage of S and G2/M phase cells. Our results suggest that FHL2 may play an important role in the biological functions of GCs in ovine.

Deep convolutional network-based chest radiographs screening model for pneumoconiosis.

Background: Pneumoconiosis is the most important occupational disease all over the world, with high prevalence and mortality. At present, the monitoring of workers exposed to dust and the diagnosis of pneumoconiosis rely on manual interpretation of chest radiographs, which is subjective and low efficiency. With the development of artificial intelligence technology, a more objective and efficient computer aided system for pneumoconiosis diagnosis can be realized. Therefore, the present study reported a novel deep learning (DL) artificial intelligence (AI) system for detecting pneumoconiosis in digital frontal chest radiographs, based on which we aimed to provide references for radiologists. Methods: We annotated 49,872 chest radiographs from patients with pneumoconiosis and workers exposed to dust using a self-developed tool. Next, we used the labeled images to train a convolutional neural network (CNN) algorithm developed for pneumoconiosis screening. Finally, the performance of the trained pneumoconiosis screening model was validated using a validation set containing 495 chest radiographs. Results: Approximately, 51% (25,435/49,872) of the chest radiographs were labeled as normal. Pneumoconiosis was detected in 49% (24,437/49,872) of the labeled radiographs, among which category-1, category-2, and category-3 pneumoconiosis accounted for 53.1% (12,967/24,437), 20.4% (4,987/24,437), and 26.5% (6,483/24,437) of the patients, respectively. The CNN DL algorithm was trained using these data. The validation set of 495 digital radiography chest radiographs included 261 cases of pneumoconiosis and 234 cases of non-pneumoconiosis. As a result, the accuracy of the AI system for pneumoconiosis identification was 95%, the area under the curve was 94.7%, and the sensitivity was 100%. Conclusion: DL algorithm based on CNN helped screen pneumoconiosis in the chest radiographs with high performance; thus, it could be suitable for diagnosing pneumoconiosis automatically and improve the efficiency of radiologists.

Tetrandrine inhibits migration and invasion of BGC-823 and MKN-45 cells by regulating PI3K/AKT/mTOR signaling pathway.

Tetrandrine (Tet), a traditional Chinese herbal medicine extract, exhibits anti-cancer effect on many types of cancer. Nonetheless, the action mechanism of Tet in gastric cancer (GC) is still largely unclear. In the current study, proliferation, invasion, and migration of the BGC-823 and MKN-45 cells were effectively suppressed by Tet treatment in a dose-dependent manner. Moreover, Tet suppressed expression of the proliferation-associated protein PCNA, the interstitial cell phenotype N-cadherin, and the extracellular matrix-associated MMP-2 and MMP-9 in BGC-823 and MKN-45 cells in a dose-dependent manner. PI3K/AKT/mTOR, a cancer promoting signaling, was inactivated by Tet in a dose-dependent manner in BGC-823 and MKN-45 cells. Furthermore, our results demonstrated that the inhibition of Tet to PCNA, N-cadherin, MMP-2, and MMP-9 expression was partly rescuedby AKT inhibitor or mTOR inhibitor. In animal experiments, tumor growth was inhibited by Tet administration in a dose-dependent manner. In conclusion, the current data indicated that Tet had a critical effect on inhibiting BGC-823 and MKN-45 cells proliferation, migration, invasion, and tumor growth via regulating PI3K/AKT/mTOR signaling pathway, suggesting that Tet might be a potential treatment for GC.

Heterophyllin B ameliorates gastric cancer tumor growth through activating ER stress.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Heterophyllin B (HB) has been proved to be a potential drug in cancer treatment. METHODS: In the current study, GC cells were treated with 0, 10, 25, or 50 µM of HB. Cell viability was determined by utilizing MTT assay. Flow cytometry was carried out for cell apoptosis and cell cycle analysis. The expression levels of IRE1, CHOP, GRP78 and Bcl-2 in cells and tumors were measured by Western blot and immunohistochemistry, respectively. RESULTS: Our data uncovered that HB administration significantly suppressed GC cell viability, but facilitated GC cell apoptosis and cell cycle arrest at G0/G1 phase. The effects of HB on GC cell proliferation, apoptosis and cell cycle showed dosage-dependent manner. Furthermore, expression of ER stress-associated proteins like IRE1, CHOP and GRP78 was markedly upregulated, while anti-apoptosis protein Bcl2 expression was inhibited by HB treatment in a dosage-dependent manner. Our data indicated that HB treatment facilitated caspase-3 expression in a dose-dependent manner, but had no effect on caspase-8 expression. Importantly, the inhibition of HB to GC cell apoptosis and cell cycle process and the promotion of HB to GC cell proliferation were partly rescued by inhibition of ER stress utilizing 4-PBA. In animal experiments, HB administration suppressed GC tumor growth, boosted IRE1, CHOP and GRP78 expression and inhibited Bcl-2 expression. CONCLUSION: All in all, HB treatment could effectively suppress GC cells proliferation and tumors growth and facilitate GC cells apoptosis and cell cycle arrest through activating ER stress. Our data indicated that HB may be a potential drug for GC treatment.

A Gene from Ganoderma lucidum with Similarity to nmrA of Filamentous Ascomycetes Contributes to Regulating AreA.

Fungal AreA is a key nitrogen metabolism transcription factor in nitrogen metabolism repression (NMR). Studies have shown that there are different ways to regulate AreA activity in yeast and filamentous ascomycetes, but in Basidiomycota, how AreA is regulated is unknown. Here, a gene from Ganoderma lucidum with similarity to nmrA of filamentous ascomycetes was identified. The NmrA interacted with the C-terminal of AreA according to yeast two-hybrid assay. In order to determine the effect of NmrA on the AreA, 2 nmrA silenced strains of G. lucidum, with silencing efficiencies of 76% and 78%, were constructed using an RNA interference method. Silencing nmrA resulted in a decreased content of AreA. The content of AreA in nmrAi-3 and nmrAi-48 decreased by approximately 68% and 60%, respectively, compared with that in the WT in the ammonium condition. Under the nitrate culture condition, silencing nmrA resulted in a 40% decrease compared with the WT. Silencing nmrA also reduced the stability of the AreA protein. When the mycelia were treated with cycloheximide for 6 h, the AreA protein was almost undetectable in the nmrA silenced strains, while there was still approximately 80% of the AreA protein in the WT strains. In addition, under the nitrate culture, the content of AreA protein in the nuclei of the WT strains was significantly increased compared with that under the ammonium condition. However, when nmrA was silenced, the content of the AreA protein in the nuclei did not change compared with the WT. Compared with the WT, the expression of the glutamine synthetase gene in nmrAi-3 and nmrAi-48 strains increased by approximately 94% and 88%, respectively, under the ammonium condition, while the expression level of the nitrate reductase gene in nmrAi-3 and nmrAi-48 strains increased by approximately 100% and 93%, respectively, under the nitrate condition. Finally, silencing nmrA inhibited mycelial growth and increased ganoderic acid biosynthesis. Our findings are the first to reveal that a gene from G. lucidum with similarity to the nmrA of filamentous ascomycetes contributes to regulating AreA, which provides new insight into how AreA is regulated in Basidiomycota.

Function of a hydrophobin in growth and development, nitrogen regulation, and abiotic stress resistance of Ganoderma lucidum.

Fungal hydrophobins have many important physiological functions, such as maintaining hydrophobicity and affecting virulence, growth, and development. In Ganoderma lucidum, the molecular regulation mechanisms of hydrophobins in mushroom are unclear. In this study, we investigated a hydrophobin protein 1 (Hyd1) in G. lucidum, which belongs to the fungal Class I hydrophobins. The hyd1 gene was highly expressed during the formation of primordia, and expression was the lowest in fruiting bodies. Through the construction of hyd1 silenced strains, we found that primordia formation was not initiated in these strains. This finding indicated that Hyd1 played an important role in the development of G. lucidum. Second, AreA, a key transcription factor in nitrogen metabolism, negatively regulated the expression of hyd1. In an areA-silenced strain, the expression of hyd1 increased by ∼14-fold compared with that of the wild-type (WT) strain. Electrophoretic mobility shift assays (EMSA) indicated binding of AreA to the promoter of hyd1. Additionally, expression of hyd1 was determined in the presence of different nitrogen sources. Compared with that in the ammonia nitrogen source, the expression of hyd1 in nitrate nitrogen source significantly increased. Finally, we found that hyd1 plays important roles not only in nitrogen regulation but also in the resistance to other abiotic stresses. After silencing of hyd1, the resistance to heat, cell wall, and salt stresses decreased. Our findings reveal the important roles of Hyd1 in the development and resistance to abiotic stresses in G. lucidum and provide insights into the nitrogen regulation mechanism of hydrophobins in higher basidiomycetes.

Comparison of the lower limit of normal to the fixed ratio method for the diagnosis of airflow obstruction at high altitudes: a large cross-sectional survey of subjects living between 3000-4700 m above sea level.

BACKGROUND: There is no general agreement on the preferential use of a fixed ratio (FR) of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 vs. the lower limit of normal (LLN) of FEV1/FVC to define airflow obstruction. Determining the impact of these different cut-off levels in people living at high altitudes has not been studied. We assessed the prevalence of airflow obstruction and its clinical characteristics in residents living at high altitude using a fixed ratio and the LLN of FEV1/FVC according to Global Lung Initiative 2012 (GLI) reference values. METHODS: Using a multistage stratified sampling method, 3702 participants (aged ≥ 15 years) living at an altitude of 3000-4700 m in Tibet were included. RESULTS: 11.4% and 7.7% of participants had airflow obstruction according to GLI-LLN and a fixed FEV1/FVC cut-off value, respectively. The participants in the FR-/LLN+ group were younger, predominantly female, more frequently exposed to household air pollution, and had a higher proportion of chronic obstructive pulmonary disease assessment test scores ≥ 10 than those in the FR-/LLN- group. They also had a significantly lower FEV1 and a higher frequency of small airway dysfunction. Compared with the participants of the FR+/LLN+ group, those in the FR-/LLN+ group showed no significant difference in the risk factors for airflow obstruction and respiratory symptoms, but had a lower prevalence of small airway dysfunction. CONCLUSIONS: Defining airflow obstruction according to LLN, instead of using an FR, identified younger individuals with more frequent clinical symptoms of airflow obstruction and small airway dysfunction.

Ambient particulate matter associates with asthma in high altitude region: A population-based study.

Background: Exposure to particulate matter (PM) has been a major public health threat, but the potentially differential effects on asthma of PM remain largely unknown in high altitude settings. We evaluated the effects of ambient PM on asthma in high altitude settings. Methods: The study recruited a representative sample from high altitude settings using a multistage stratified sampling procedure. Asthma was defined by a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. The annual mean PM2.5 and PM10 concentrations were calculated for each grid cell at 1-km spatial resolution based on the geographical coordinates. Results: We analyzed data for participants (mean age 39.1 years, 51.4% female) and 183 (3.7%, 95% confidence interval (CI): 3.2-4.2) of the participants had asthma. Prevalence was higher in women (4.3%, 95% CI 3.5-5.1) than in men (3.1%, 2.4-3.8) and increasing with higher concentration of PM exposures. For an interquartile range (IQR) difference (8.77 µg/m3) in PM2.5 exposure, the adjusted odds ratio (OR) was 1.64 (95% CI 1.46-1.83, P < 0.001) for risk of asthma. For PM10, there was evidence for an association with risk of asthma (OR 2.34, 95% CI: 1.75-3.15, P < 0.001 per IQR of 43.26 µg/m3). Further analyses showed that household mold or damp exposure may aggravate PM exposure associated risks of asthma. Conclusions: This study identified that PM exposure could be a dominate environmental risk factor for asthma but largely unconsidered in the high-altitude areas. The association between PM exposure and asthma should be of interest for planners of national policies and encourage programs for prevention of asthma in residents living at high altitudes.

Solid Fuel Exposure and Chronic Obstructive Pulmonary Disease in Never-Smokers.

Background: Chronic obstructive pulmonary disease (COPD) is a public health challenge globally. The burden of COPD is high in never-smokers but little is known about its causes. We aimed to find the prevalence and correlates of COPD in never-smokers, with a special focus on solid fuel exposure. Methods: We conducted a cross-sectional study in Western China. COPD was defined by FEV1/FVC < lower limits of normal (LLN). Descriptive statistics and multivariable logistic regression were used for analyses. Results: Six thousand two hundred and seventy one patients were enrolled between June 2015 and August 2016. The prevalence of COPD in never-smokers was 15.0% (95% confidence interval 14.1-15.9). The common independent predictors of COPD in never-smokers included age ≥60 years, exposure to solid fuel, living in a rural area and a history of tuberculosis. Participants with solid fuel exposure were 69% more likely to have COPD (adjusted odds ratio 1.69, 95% CI 1.41-2.04) than those without such exposure. In addition, we found a positive association between small airway dysfunction and solid fuel exposure (OR 1.35, 95% CI 1.18-1.53). Conclusions: This study confirmed the substantial burden of COPD among never-smokers and also defined the risk factors for COPD in never-smokers. Furthermore, we found a positive association between solid fuel exposure and COPD or small airway dysfunction.

Complete genome of a unicellular parasite (Antonospora locustae) and transcriptional interactions with its host locust.

Microsporidia are a large group of unicellular parasites that infect insects and mammals. The simpler life cycle of microsporidia in insects provides a model system for understanding their evolution and molecular interactions with their hosts. However, no complete genome is available for insect-parasitic microsporidian species. The complete genome of Antonospora locustae, a microsporidian parasite that obligately infects insects, is reported here. The genome size of A. locustae is 3 170 203 nucleotides, composed of 17 chromosomes onto which a total of 1857 annotated genes have been mapped and detailed. A unique feature of the A. locustae genome is the presence of an ultra-low GC region of approximately 25 kb on 16 of the 17 chromosomes, in which the average GC content is only 20 %. Transcription profiling indicated that the ultra-low GC region of the parasite could be associated with differential regulation of host defences in the fat body to promote the parasite's survival and propagation. Phylogenetic gene analysis showed that A. locustae, and the microsporidian family in general, is likely at an evolutionarily transitional position between prokaryotes and eukaryotes, and that it evolved independently. Transcriptomic analysis showed that A. locustae can systematically inhibit the locust phenoloxidase PPO, TCA and glyoxylate cycles, and PPAR pathways to escape melanization, and can activate host energy transfer pathways to support its reproduction in the fat body, which is an insect energy-producing organ. Our study provides a platform and model for studies of the molecular mechanisms of microsporidium-host interactions in an energy-producing organ and for understanding the evolution of microsporidia.

Prevalence and Risk Factors for COPD at High Altitude: A Large Cross-Sectional Survey of Subjects Living Between 2,100-4,700 m Above Sea Level.

Aim of Study: Four hundred million people live at high altitude worldwide. Prevalence and risk factors for COPD in these populations are poorly documented. We examined the prevalence and risk factors for COPD in residents living at an altitude of 2,100-4,700 m. Methods: We performed a cross-sectional survey in Xinjiang and Tibet autonomous region. A multistage stratified sampling procedure was used to select a representative population aged 15 years or older from eight high altitude regions. All participants underwent pre- and post-bronchodilator measurement of forced expiratory volumes. COPD was diagnosed according to 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Results: Between June, 2015 and August 2016, 4,967 subjects were included. Median age was 38.0 years (range: 15-91 years; inter-quartile range: 28-49 years); 51.4% participants were female. Overall prevalence of spirometry-defined COPD was 8.2% (95% CI 7.4-8.9%): 9.3% in male (95% CI 8.2-10.4%), and 7.1% in female (95% CI 6.1-8.2%). By multivariable logistic regression analysis, COPD was significantly associated with being aged ≥40 years (odds ratio: 2.25 [95% CI 1.72-2.95], P < 0.0001), exposure to household air pollution (OR: 1.34 [95% CI 1.01-1.79], P = 0.043), and a history of tuberculosis (OR: 1.79 [95% CI 1.23-2.61], P = 0.030), while living at a higher altitude (OR: 0.45 [95% CI 0.33-0.61], P < 0.0001) and having a higher educational level (OR: 0.64 [95% CI 0.43-0.95], P = 0.025) were associated with a lower prevalence of COPD. Conclusions: Our results show that the spirometry-defined COPD is a considerable health problem for residents living at high altitudes and COPD prevalence was inversely correlated with altitude. Preventing exposure to household air pollution and reducing the incidence of tuberculosis should be public health priorities for high altitude residents.

Epitope-directed antibody selection by site-specific photocrosslinking.

Currently, there are no methods available offering solutions to select and identify antibodies binding to a specific conformational epitope of an antigen. Here, we developed a method to allow epitope-directed antibody selection from a phage display library by photocrosslinking bound antibodies to a site that specifically incorporates a noncanonical amino acid, p-benzoyl-l-phenylalanine (pBpa), on the target antigen epitope. By one or two rounds of panning against antibody phage display libraries, those hits that covalently bind to the proximity site of pBpa on specific epitopes of target antigens after ultraviolet irradiation are enriched and selected. This method was applied to specific epitopes on human interleukin-1ß and complement 5a. In both cases, more than one-third of hits identified bind to the target epitopes, demonstrating the feasibility and versatility of this method.

Association between the level of circulating adiponectin and prediabetes: A meta-analysis.

AIMS/INTRODUCTION: Adiponectin has been proposed to have an essential role in the regulation of insulin sensitivity and metabolism, but previous studies on levels of adiponectin in prediabetes remain inconsistent. The present study aimed to assess the differences of adiponectin levels between prediabetes patients and healthy controls by carrying out a meta-analysis. MATERIALS AND METHODS: We carried out a systematic literature search of PubMed, EMBASE, and other databases for case-control studies and cohort studies measuring adiponectin levels in serum or plasma from prediabetes patients and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between adiponectin levels and prediabetes. RESULTS: Three cohort studies and 15 case-control studies with a total of 41,841 participants were included in the meta-analysis. The results showed that circulating adiponectin levels in prediabetes patients were significantly lower than that of healthy controls (WMD -1.694 µg/mL; 95% CI -2.151, -1.237; P < 0.001). Subgroup analysis showed more significant differences between prediabetes patients and healthy controls when the ratio of the homeostatic model assessment of insulin resistance was >2.12 (WMD -2.95 µg/mL; 95% CI -4.103, -1.806; P < 0.001) and average age was >60 years (WMD -2.20 µg/mL; 95% CI -3.207, -1.201; P < 0.001). Additionally, WMD in adiponectin showed a trend of direct correlation in subgroups of homeostatic model assessment of insulin resistance ratio, body mass index and age. CONCLUSIONS: The present meta-analysis supports adiponectin levels in prediabetes patients being lower than that of healthy controls,indicating that the level of circulating adiponectin decreases before the onset of diabetes.