Protein Profiles and Novel Molecular Biomarkers of Schizophrenia Based on 4D-DIA Proteomics.

Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Identification of three potential novel biomarkers for early diagnosis of acute ischemic stroke via plasma lipidomics.

INTRODUCTION: Acute ischemic stroke (AIS) accounts for the majority of all stroke, globally the second leading cause of death. Due to its rapid development after onset, its early diagnosis is crucial. OBJECTIVES: We aim to identify potential highly reliable blood-based biomarkers for early diagnosis of AIS using quantitative plasma lipid profiling via a machine learning approach. METHODS: Lipidomics was used for quantitative plasma lipid profiling, based on ultra-performance liquid chromatography tandem mass spectrometry. Our samples were divided into a discovery and a validation set, each containing 30 AIS patients and 30 health controls (HC). Differentially expressed lipid metabolites were screened based on the criteria VIP > 1, p < 0.05, and fold change > 1.5 or < 0.67. The least absolute shrinkage and selection operator (LASSO) and random forest algorithms in machine learning were used to select differential lipid metabolites as potential biomarkers. RESULTS: Three key differential lipid metabolites, CarnitineC10:1, CarnitineC10:1-OH and Cer(d18:0/16:0), were identified as potential biomarkers for early diagnosis of AIS. The former two, associated with thermogenesis, were down-regulated, whereas the latter, associated with necroptosis and sphingolipd metabolism, was upregulated. Univariate and multivariate logistic regressions showed that these three lipid metabolites and the resulting diagnostic model exhibited a strong ability in discriminating between AIS patients and HCs in both the discovery and validation sets, with an area under the curve above 0.9. CONCLUSIONS: Our work provides valuable information on the pathophysiology of AIS and constitutes an important step toward clinical application of blood-based biomarkers for diagnosing AIS.

Serum sCD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics.

Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR-TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR-TB, a mass spectrometry strategy of data-independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR-TB group and the drug-sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR-TB. Our study has paved the way for a novel method to diagnose MDR-TB and may contribute to elucidate the mechanisms underlying MDR-TB.

Screening and identification of potential protein biomarkers for evaluating the efficacy of intensive therapy in pulmonary tuberculosis.

This research aimed to discover potential biomarkers for evaluating the therapeutic efficacy of intensive therapy in pulmonary tuberculosis (TB). Protein profiles in 2-months intensively treated TB patients, untreated TB patients, and healthy controls were investigated with iTRAQ-2DLC-MS/MS technique. 71 differential proteins were identified in 2-months intensively treated TB patients. Significant differences in complement component C7 (CO7), apolipoprotein A-IV (APOA4), apolipoprotein C-II (APOC2), and angiotensinogen (ANGT) were found by ELISA validation. CO7 and ANGT were also found significantly different in sputum negative patients, compared with sputum positive patients after intensive treatment. Clinical analysis showed that after 2-months intensive treatment several indicators were significantly changed, and the one-year cure rate of sputum negative patients were significantly higher than sputum positive patients. Diagnostic models consisting of APOC2, CO7 and APOA4 were established to distinguish intensively treated TB patients from untreated TB patients and healthy controls with the AUC value of 0.910 and 0.935. Meanwhile, ANGT and CO7 were combined to identify sputum negative and sputum positive TB patients after intensive treatment with 89.36% sensitivity, 71.43% specificity, and the AUC value of 0.853. The results showed that APOC2, CO7, APOA4, and ANGT may be potential biomarkers for evaluating the efficacy of intensive anti-TB therapy.

Anti-Aging Effect of Chitosan Oligosaccharide on d-Galactose-Induced Subacute Aging in Mice.

Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate the possible anti-aging effect of COS on the aging model mouse induced by d-galactose (d-gal) and explore the underlying mechanism. In the experiment, 48 male Kunming mice (KM mice) were randomly divided into the normal group, model group, positive group, and low-medium-high dose polysaccharide groups (300, 600, 1200 mg/kg/day). The results showed that COS, by intragastric gavage after subcutaneous injection of d-gal (250 mg/kg/day) into the neck of mice consecutively for eight weeks, gradually recovered the body weight, the activity of daily living, and organ indices of mice, as well as effectively ameliorated the histological deterioration of the liver and kidney in mice triggered by d-gal. To be specific, COS obviously improved the activities of antioxidant enzymes in liver and kidney of KM mice, including catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as decreased malondialdehyde (MDA) levels when compared with those in model group mice. Furthermore, COS not only elevated the diminished levels of serum immunoglobulin G (IgG) and IgM induced by d-gal, but also significantly inhibited the d-gal-caused upregulation of serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) and creatinine (CREA) levels as compared with those of mice in the model group. These results demonstrate that COS has an obvious anti-aging activity in d-gal-induced subacute aging mice, the mechanism of which, to some extent, is associated with enhancing the antioxidant defenses, reducing oxidative stress, and improving the immune function of aging model mice.

Microarray expression profile analysis of mRNAs and long non-coding RNAs in pulmonary tuberculosis with different traditional Chinese medicine syndromes.

BACKGROUND: Combination chemotherapy with Western anti-tuberculosis (TB) drugs is the mainstay of TB treatment. Chinese herbal medicines with either heat clearing and detoxifying effects or nourishing Yin and reducing fire effects have been used to treat TB based on the Traditional Chinese Medicine (TCM) syndromes of TB patients. This study analyzed the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs in TB patients with different TCM syndromes. METHODS: TB patients were classified as pulmonary Yin deficiency (PYD) syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, and deficiency of Qi and Yin (DQY) syndrome. Total RNA from 44 TB patients and healthy controls was extracted and hybridized with a human lncRNA microarray containing 30586 lncRNAs and 26109 mRNAs probes. Bioinformatics analyses, including gene ontology (GO) and pathways, were performed. Related clinical data were also analyzed. RESULTS: Differentially expressed mRNAs and lncRNAs were identified (fold change >2, and P < 0.05) in PYD (634 mRNAs and 566 lncRNAs), HFYD (47 mRNAs and 55 lncRNAs), and DQY (63 mRNAs and 60 lncRNAs) patients. The most enriched pathways were the hippo signaling pathway (P = 0.000164) and the protein digestion and absorption pathway (P = 5.89017E-05). Clinical analyses revealed that the lipid indexes of TB patients were abnormal and that the triglyceride concentration was significantly higher in DQY patients (P = 0.0252). Our study is the first to acquire the microarray expression profiles of lncRNAs and mRNAs and analyze pathway enrichment in PYD, HFYD, and DQY patients with TB. CONCLUSIONS: Our analyses of the expression profiles of lncRNAs and mRNAs may represent a novel method to explore the biological essence of TCM syndromes of TB.

Serum protein S100A9, SOD3, and MMP9 as new diagnostic biomarkers for pulmonary tuberculosis by iTRAQ-coupled two-dimensional LC-MS/MS.

This study aimed to discover the novel noninvasive biomarkers for the diagnosis of pulmonary tuberculosis (TB). We applied iTRAQ 2D LC-MS/MS technique to investigate protein profiles in patients with pulmonary TB and other lung diseases. A total of 34 differentially expressed proteins (24 upregulated proteins and ten downregulated proteins) were identified in the serum of pulmonary TB patients. Significant differences in protein S100-A9 (S100A9), extracellular superoxide dismutase [Cu-Zn] (SOD3), and matrix metalloproteinase 9 (MMP9) were found between pulmonary TB and other lung diseases by ELISA. Correlations analysis revealed that the serum concentration of MMP9 in the pulmonary TB was in moderate correlation with SOD3 (r = 0.581) and S100A9 (r = 0.471), while SOD3 was in weak correlation with S100A9 (r = 0.287). The combination of serum S100A9, SOD3, and MMP9 levels could achieve 92.5% sensitivity and 95% specificity to discriminate between pulmonary TB and healthy controls, 90% sensitivity and 87.5% specificity to discriminate between pulmonary TB and pneumonia, and 85% sensitivity and 92.5% specificity to discriminate between pulmonary TB and lung cancer, respectively. The results showed that S100A9, SOD3, and MMP9 may be potential diagnostic biomarkers for pulmonary TB, and provided experimental basis for the diagnosis of pulmonary TB.

Association of the miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms with susceptibility to pulmonary tuberculosis in the Chinese Uygur, Kazak and Southern Han populations.

BACKGROUND: Single nucleotide polymorphisms (SNPs) within precursor microRNAs (miRNAs) can affect miRNAs expression, and may be involved in the pathogenesis of pulmonary tuberculosis (TB). This study aimed to investigate potential associations between the four precursor miRNA SNPs (miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 T > C) and susceptibility to pulmonary TB in the Chinese Uygur, Kazak, and Southern Han populations. METHODS: A case-control study was performed on Chinese Uygur (n = 662), Kazak (n = 612), and Southern Han (n = 654) populations using the PCR-PFLR method. The allele and genotype frequencies for all populations were analyzed. Linkage disequilibrium was performed, and different models of inheritance were tested. RESULTS: The allele and genotype frequencies of the miR-499 SNP were significantly different between the TB patients group and the healthy control group in the Uygur population, and were found to be codominant, dominant, recessive and additive models in association with pulmonary TB. The haplotype CTCC showed significant correlation with pulmonary TB. The allele and genotype frequencies of miR-146a and miR-196a2 SNPs were significantly different between the two groups in the Kazak population. The miR-146a SNP was found to be codominant, recessive and additive models, whereas, the miR-196a2 SNP was found to be codominant, dominant, and additive models in association with pulmonary TB. The haplotypes TCCC and CCCT showed significant correlation with pulmonary TB. CONCLUSIONS: The results suggested that susceptibility to pulmonary TB may be closely related to individual differences caused by genetic factors among different ethnic groups in China.

Serum protein gamma-glutamyl hydrolase, Ig gamma-3 chain C region, and haptoglobin are associated with the syndromes of pulmonary tuberculosis in traditional Chinese medicine.

BACKGROUND: Traditional Chinese Medicine (TCM) has been applied in treating tuberculosis (TB) based on the TCM syndromes with the effects of inhibiting Mycobacterium, strengthening the body immune system, and reducing the pulmonary toxicity. We used bioinformatic methods to study the clinical and pathological characteristics of pulmonary TB patients with TCM syndromes. Isobaric tags for relative and absolute quantification - coupled two dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) methods were applied to screen differentially expressed serum proteins. METHODS: Pulmonary TB cases were divided into four distinctive TCM syndromes: pulmonary Yin deficiency (PYD) syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, deficiency of Qi and Yin (DQY) syndrome, and deficiency of Yin and Yang (DYY) syndrome. The serum samples from 214 pulmonary TB patients were collected, and the clinical and pathological data was analyzed by using iTRAQ-2DLC-MS/MS. Finally, the differentially expressed proteins were screened and tested by ELISA. Only 5 patients with DYY syndrome were recruited in 3 years, which were not enough for further research. RESULTS: The DQY cases had higher erythrocyte sedimentation rate (ESR) compared to the PYD and HFYD cases (P=0.0178). 94.44% (12 PYD, 18 HFYD, and 4 DQY before anti-TB treatment) of 36 treated TB cases were transformed to PYD accompanied with the reduction of ESR and absorption of pulmonary lesions. A total of 39 differentially expressed proteins (ratios of >1.3 or <0.75) were found among the three TCM syndromes. Proteomic studies revealed that gamma-glutamyl hydrolase (GGH), Ig gamma-3 chain C region (IGHG3), and haptoglobin (HPT) were specifically over-expressed in PYD (P<0.01), HFYD (P<0.001), and DQY cases (P<0.01), respectively. Furthermore, GGH was significantly higher in PYD cases compared to the HFYD and DQY cases (P<0.01, P<0.001, respectively), whereas IGHG3 was significantly higher in HFYD cases than PYD and DQY cases (P<0.001, P<0.01, respectively). CONCLUSIONS: The results suggest that TCM syndromes are significantly correlated with the pulmonary lesions and ESR. GGH was associated with folate metabolism in PYD cases, IGHG3 was linked to the control of Mycobacterium infection in HFYD patients, and HPT was involved in hypoxia in DQY patients. The present study provides new biological basis to understand the pathological changes and proteomic differences of TB syndromes.

[A Novel Method of Infrared Radiative Parameters Calculation in High Temperature Flow Field].

Infrared radiative parameters under high temperature was calculated using RJMCMC method under Bayesian framework presumed Smeared Rotational Band model (SRB), in order to solve the problem of radiation calculation for high speed vehicle infrared signature research. The process of calculation does not need any database of parameter or priors about transition. The experiment from simulation and measured data demonstrates that the position of vibrational transition have been estimated precisely. Simultaneously, the change law of parameter estimation was consistent with theoretic SRB model, from which the integration of radiative parameters under different temperature approximated the line by line calculation (LBL) result very well.

Discovery and identification of serum potential biomarkers for pulmonary tuberculosis using iTRAQ-coupled two-dimensional LC-MS/MS.

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis is a chronic disease. Currently, there are no sufficiently validated biomarkers for early diagnosis of TB infection. In this study, a panel of potential serum biomarkers was identified between patients with pulmonary TB and healthy controls by using iTRAQ-coupled 2D LC-MS/MS technique. Among 100 differentially expressed proteins screened, 45 proteins were upregulated (>1.25-fold at p < 0.05) and 55 proteins were downregulated (<0.8-fold at p < 0.05) in the TB serum. Bioinformatics analysis revealed that the differentially expressed proteins were related to the response to stimulus, the metabolic and immune system processes. The significantly differential expression of apolipoprotein CII (APOCII), CD5 antigen-like (CD5L), hyaluronan-binding protein 2 (HABP2), and retinol-binding protein 4 (RBP4) was further confirmed using immunoblotting and ELISA analysis. By forward stepwise multivariate regression analysis, a panel of serum biomarkers including APOCII, CD5L, and RBP4 was obtained to form the disease diagnostic model. The receiver operation characteristic curve of the diagnostic model was 0.98 (sensitivity = 93.42%, specificity = 92.86%). In conclusion, APOCII, CD5L, HABP2, and RBP4 may be potential protein biomarkers of pulmonary TB. Our research provides useful data for early diagnosis of TB.

Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis.

BACKGROUND: Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation. METHODS: Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups. RESULTS: We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05). CONCLUSIONS: Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB.

Effect of mesenteric lymph duct ligation on gene expression profiles of renal tissue in hemorrhagic shock rats with fluid resuscitation.

BACKGROUND: Acute kidney injury (AKI), a common pathological process following hemorrhagic shock, can lead to an internal milieu disorder, which is an important factor of multiple organ failure (MOF). It has been shown that the mesenteric lymph return plays a deleterious effect on MOF induced by hemorrhagic shock. In this study, we investigated the effects of mesenteric lymph duct ligation (MLDL) on gene expression profiles of renal tissue following hemorrhagic shock with fluid resuscitation. METHODS: After establishment of hemorrhagic shock model and fluid resuscitation in rats of shock and shock ligation groups, the MLDL was performed in shock ligation group, and only threading under the mesenteric lymph duct in the shock group. Then, the fixed position renal tissue was taken out for homogenate in two groups at 3 h after resuscitation, the total mRNA was extracted, reversely transcribed into cDNAs and marked with Cy3 and Cy5. The cDNAs were subjected for microarray scanning with 12,028 cDNA probes; the differentially expressed genes between two groups were analyzed. RESULTS: In the 5812 valid dates of rat genomes transcription, there were 34 known differentially expressed genes between the two groups, of which 11 genes were up-regulated whereas 23 genes were down-regulated by MLDL. These different expressed genes encoding protein function were mainly involved in signal transduction, transcription regulation, metabolism, transport, cell growth, cell cycle, cell adhesion, cell movement, cellular component, and biological process. CONCLUSIONS: The mechanism of MLDL alleviating the AKI aftershock might be associated with up- or down-regulation of the above gene expressions.

Metabolomic analysis of plasma biomarkers in children with autism spectrum disorders.

Autism spectrum disorder (ASD) presents a significant risk to human well-being and has emerged as a worldwide public health concern. Twenty-eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9-O-18:0), DL-2-hydroxystearic acid, and 7(S),17(S)-dihydroxy-8(E),10(Z),13(Z),15(E),19(Z)-docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three-biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.

Identification of pattern recognition receptor genes in peripheral blood mononuclear cells and monocytes as biomarkers for the diagnosis of lupus nephritis.

BACKGROUND: The study aimed to investigate the diagnostic value of lupus-related pattern recognition receptors (PRRs) genes in peripheral blood mononuclear cells (PBMCs) and monocytes (MONs) for lupus nephritis (LN). METHODS: PBMCs were isolated from a cohort with 37 LN patients and 39 healthy controls (HCs), and MONs were derived from another cohort with 70 LN patients and 66 HCs. Q-PCR was used to measure the mRNA levels of CGAS, IFNB1, AIM2, IL1Β, NLRC4, NLRP3, NLRP12 and ZBP1 in the PBMCs and MONs. The Mann-Whitney U test was used to compare the data in LN patients and HCs. Eleven GEO datasets of SLE/LN were used to perform differentially expressed genes (DEGs) analysis to these PRR genes. Receiver operating characteristic (ROC) curve analysis was employed to assess the performance of individual genes or the disease prediction model established by combining multiple genes in LN diagnosis. Spearman correlation method was done to analyze the correlation between these PRRs and other clinical characteristics. RESULTS: The mRNA levels of five genes (AIM2, NLRC4, IL1B, NLRP12 and ZBP1) in PBMCs, and seven genes (CGAS, IFNB1, AIM2, IL1B, NLRP3, NLRP12 and ZBP1) in MONs of LN patients were significantly higher than those of HCs (P < 0.05). DEGs analysis based on the GEO datasets showed that ZBP1, AIM2 and IL1B were significantly increased in several datasets. The ROC curve analysis indicated that the area under curve (AUC) of the LN prediction models derived from PBMCs or MONs were 0.82 or 0.91 respectively. In addition, the expression levels of these PRRs were correlated with other clinical features in LN patients, including Anti-Sm, ESR, serum Cr, and C3. CONCLUSION: Our study suggests that these lupus-related PRRs might be served as potential biomarkers of LN.

Hot-Pressing Metal Covalent Organic Frameworks as Personal Protection Films.

Effective personal protection is crucial for controlling infectious disease spread. However, commonly used personal protective materials such as disposable masks lack antibacterial/antiviral function and may lead to cross infection. Herein, a polyethylene glycol-assisted solvent-free strategy is proposed to rapidly synthesize a series of the donor-acceptor metal-covalent organic frameworks (MCOFs) (i.e., GZHMU-2, JNM-1, and JNM-2) under air atmosphere and henceforth extend it via in situ hot-pressing process to prepare MCOFs based films with photocatalytic disinfect ability. Best of them, the newly designed GZHMU-2 has a wide absorption spectrum (200 to 1500 nm) and can efficiently produce reactive oxygen species under sunlight irradiation, achieving excellent photocatalytic disinfection performance. After in situ hot-pressing as a film material, the obtained GZHMU-2/NMF can effectively kill E. coli (99.99%), S. aureus (99%), and H1N1 (92.5%), meanwhile possessing good reusability. Noteworthy, the long-term use of a GZHMU-2/NWF-based mask has verified no damage to the living body by measuring the expression of mouse blood routine, lung tissue, and inflammatory factors at the in-vivo level.

The discovery and identification of a candidate proteomic biomarker of active tuberculosis.

BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.

The novel human MRC1 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis in Chinese Uygur and Kazak populations.

The MRC1 gene, encoding the human mannose receptor (MR), is a member of the C-type lectin receptors family. MR can recognize and bind to Mycobacterium tuberculosis by the extracellular structure, and play a role in antigen-presenting and maintaining a stable internal environment. This study aimed to investigate potential associations of SNPs in exon 7 of the MRC1 gene with pulmonary tuberculosis (TB). G1186A, G1195A, T1212C, C1221G, C1303T and C1323T were genotyped using PCR and DNA sequencing in 595 Chinese Uygur and 513 Kazak subjects. In the Uygur, the frequency of allele G (P=0.031, OR=1.29, 95% CI=1.02-1.62) and AA genotype (P=0.033, OR=1.64, 95% CI=1.04-2.60) for G1186A was lower in the pulmonary TB than healthy control and were significantly correlated with pulmonary TB. After adjustment for age and gender, G1186A was found to be additive models in association with pulmonary TB (P=0.04, OR=1.27, 95% CI=1.01-1.60). By calculating linkage disequilibrium, the frequency of haplotype GGTCCT (P=0.032, OR=0.75, 95% CI=0.57-0.97) and GGTCCC (P=0.044, OR=0.57, 95% CI=0.33-0.99) was significantly associated with pulmonary TB. No association was found between other SNPs and pulmonary TB. In the Kazak, all SNPs were not associated with pulmonary TB. Our results suggest that genetic factors play an important role in susceptibility to pulmonary TB at the individual level, and provide an experimental basis to clarify the pathogenesis of pulmonary TB.

Hereditary breast cancer in the Han Chinese population.

Breast cancer is the most common malignancy among women and has a strong genetic background. So far, 13 breast cancer susceptibility genes of high or moderate penetrance have been identified. This review summarizes findings on these genes in Han Chinese. BRCA1 and BRCA2 are the 2 most important susceptibility genes. They have a relatively low mutation rate, and the most frequent sites of mutation are in exon 11. Frameshift mutations are the main type of mutation. Founder mutations may also exist, and BRCA-associated breast cancer has specific clinicopathologic characteristics. TP53 and PALB2 are relatively rare susceptibility genes. The relationship between the other 9 genes and breast cancer has not been fully elucidated. At present, the mutation spectrum for these susceptibility genes is not well understood in the Chinese population, and there are few reports on prognosis and clinical intervention in high-risk populations. Therefore, the true value of genetic counseling for breast cancer has yet to be realized. This article reviews studies of hereditary breast cancer in the Han Chinese population, highlights potential inadequacies, and provides a foundation for genetic counseling for breast cancer in China.