Data Mining Mycobacterium tuberculosis

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide. In Mycobacterium tuberculosis, changes in gene expression are highly variable and involve many genes, so traditional single-gene screening of M. tuberculosis targets has been unable to meet the needs of clinical diagnosis. In this study, using the National Center for Biotechnology Information (NCBI) GEO Datasets, whole blood gene expression profile data were obtained in patients with active pulmonary tuberculosis. Linear model-experience Bayesian statistics using the Limma package in R combined with t-tests were applied for nonspecific filtration of the expression profile data, and the differentially expressed human genes were determined. Using DAVID and KEGG, the functional analysis of differentially expressed genes (GO analysis) and the analysis of signaling pathways were performed. Based on the differentially expressed gene, the transcriptional regulatory element databases (TRED) were integrated to construct the M. tuberculosis pathogenic gene regulatory network, and the correlation of the network genes with disease was analyzed with the DAVID online annotation tool. It was predicted that IL-6, JUN, and TP53, along with transcription factors SRC, TNF, and MAPK14, could regulate the immune response, with their function being extracellular region activity and protein binding during infection with M. tuberculosis

Tunable plasmonic reflection by bound 1D electron states in a 2D Dirac metal

We show that surface plasmons of a two-dimensional Dirac metal such as graphene can be reflected by line-like perturbations hosting one-dimensional electron states. The reflection originates from a strong enhancement of the local optical conductivity caused by optical transitions involving these bound states. We propose that the bound states can be systematically created, controlled, and liquidated by an ultranarrow electrostatic gate. Using infrared nanoimaging, we obtain experimental evidence for the locally enhanced conductivity of graphene induced by a carbon nanotube gate, which supports this theoretical concept.Comment: 14 pages, 12 figures, submitted to PR

Antihuman T Lymphocyte Porcine Immunoglobulin Combined With Cyclosporine As First-Line Immunosuppressive Therapy for Severe Aplastic Anemia in China: A Large Single-Center, 10-Year Retrospective Study

BACKGROUND: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009. OBJECTIVES: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019. DESIGN: This is a single-center retrospective study of medical records. METHODS: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to 2019 at our department. RESULTS: The median age of the patients was 24 (4-75) years, and the median follow-up time was 57.2 months (3 days-137.5 months). There was an early mortality rate of 2.8% with a median death time of 0.9 months (3 days-2.9 months). The overall response rates were 40.6% and 56.1% at 3 and 6 months, respectively. The 5-year cumulative incidences of relapse and clonal evolution were 9.0% [95% confidence interval (CI) = 4.2-16.0%] and 4.5% (95% CI = 1.4-10.6%), respectively. The 5-year overall survival (OS) and event-free survival rates were 83.7% (95% CI = 81.1-86.0%) and 50.4% (95% CI = 47.1-53.5%), respectively. CONCLUSION: p-ATG combined with CsA for the treatment of AA is effective and safe, and p-ATG can be used as an alternative ATG preparation for the standard IST regimen in areas in which h-ATG is not available

Metabolomics analysis unveils important changes involved in the salt tolerance of Salicornia europaea

Salicornia europaea is one of the world’s salt-tolerant plant species and is recognized as a model plant for studying the metabolism and molecular mechanisms of halophytes under salinity. To investigate the metabolic responses to salinity stress in S. europaea, this study performed a widely targeted metabolomic analysis after analyzing the physiological characteristics of plants exposed to various NaCl treatments. S. europaea exhibited excellent salt tolerance and could withstand extremely high NaCl concentrations, while lower NaCl conditions (50 and 100 mM) significantly promoted growth by increasing tissue succulence and maintaining a relatively stable K+ concentration. A total of 552 metabolites were detected, 500 of which were differently accumulated, mainly consisting of lipids, organic acids, saccharides, alcohols, amino acids, flavonoids, phenolic acids, and alkaloids. Sucrose, glucose, p-proline, quercetin and its derivatives, and kaempferol derivatives represented core metabolites that are responsive to salinity stress. Glycolysis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis were considered as the most important pathways responsible for salt stress response by increasing the osmotic tolerance and antioxidant activities. The high accumulation of some saccharides, flavonoids, and phenolic acids under 50 mM NaCl compared with 300 mM NaCl might contribute to the improved salt tolerance under the 50 mM NaCl treatment. Furthermore, quercetin, quercetin derivatives, and kaempferol derivatives showed varied change patterns in the roots and shoots, while coumaric, caffeic, and ferulic acids increased significantly in the roots, implying that the coping strategies in the shoots and roots varied under salinity stress. These findings lay the foundation for further analysis of the mechanism underlying the response of S. europaea to salinity

Efficacy of Eltrombopag With Immunosuppressive Therapy for Children With Acquired Aplastic Anemia

BACKGROUND: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. METHODS: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). RESULTS: There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, CONCLUSION: Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates

Genotype-Degree of Hemolysis Correlation in Hereditary Spherocytosis

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt\u27s carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. RESULTS: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). CONCLUSION: The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Simultaneous and Rapid Determination of Main Lignans in Different Parts of Schisandra Sphenanthera by Micellar Electrokinetic Capillary Chromatography

Lignans are imporant active ingredients of Schisandra sphenanthera. A micellar electrokinetic chromatography method was developed for the simultaneous determination of eight lignans – schizandrin, schisandrol B, schisantherin A, schisanhenol, anwulignan, deoxyschizandrin, schizandrin B and schizandrin C – in different parts of S. sphenanthera. The key factors for separation and determination were studied and the best analysis conditions were obtained using a background electrolyte of 10 mM phosphate-37.5 mM SDS-35% v/v acetonitrile (pH 8.0) at the separation voltage of 28 kV and detection at 214 nm, whereby the plant samples could be analyzed within 9.0 min. Analysis yielded good reproducibility (RSD between 1.19-2.28%) and good recovery (between 92.2-103.8%). The detection limits (LOD) and limit of quantification (LOQ) were within 0.4-1.2 mg/L and 1.5-4.0 mg/L. This method is promising to improve the quality control of different parts of S. sphenanthera

Isolation, Purification, Fractionation, and Hepatoprotective Activity of Polygonatum Polysaccharides

In this study, three homogeneous fractions, PSP-N-b-1, PSP-N-b-2, and PSP-N-c-1, were obtained from an aqueous extract of Polygonatum using DEAE cellulose column chromatography, CL-6B agarose gel chromatography, and Sephadex G100 chromatography. Their monosaccharide compositions and molecular weights were analyzed. The results revealed that PSP-N-b-1, PSP-N-b-2, and PSP-N-c-1 are primarily composed of six monosaccharides: Man (mannose), GlcA (glucuronic acid), Rha (rhamnose), GalA (galacturonic acid), Glc (glucose), and Ara (arabinose), with molecular weights of 6.3 KDa, 5.78 KDa, and 3.45 KDa, respectively. Furthermore, we observed that Polygonatum polysaccharides exhibited protective effects against CCL4-induced liver damage in HepG2 cells in vitro, operating through both anti-oxidant and anti-inflammatory mechanisms. Our research findings suggest that Polygonatum polysaccharides may emerge as a promising option in the development of hepatoprotective drugs or functional foods with anti-inflammatory and antioxidant properties

Establishment of a multiplex-PCR detection method and development of a detection kit for five animal-derived components in edible meat

A multiplex polymerase chain reaction (PCR) detection method for the simultaneous detection of animal-derived components from deer, cow, sheep, pig and horse in edible meat was established, and a multiplex PCR detection kit for the rapid detection of animal-derived components was developed. According to the mitochondrial cytochrome b (Cyt b) gene of bovine species, sheep species, pig species and horse species and the mitochondrial cytochrome c oxidase subunit I (COX 1) gene of sika deer and red deer as the target gene sequences of primers, the specific primers of five different species were designed, the PCR system was optimized, and the multiplex PCR identification method of five animal-derived components was established. The minimum detection amount was determined by sensitivity test. The results showed that five meat specific amplification bands could be found at the same time in the same reaction system, including 173 bp fragment for venison, 148 bp for beef, 261 bp for pork, 100 bp for mutton and 424 bp for horse, indicating that the method is specific and stable. The minimum detection limit by this method was 1 ng/μL, showing a high sensitivity. According to the different sites in different areas of animal mitochondrial genes, a multiplex PCR detection method was established and a detection kit was developed, and the rapid, sensitive, stable and high-throughput detection of five animal-derived components and adulterated animal components in edible meat can be realized by using the kit