PGG.SV: a whole-genome-sequencing-based structural variant resource and data analysis platform.

Structural variations (SVs) play important roles in human evolution and diseases, but there is a lack of data resources concerning representative samples, especially for East Asians. Taking advantage of both next-generation sequencing and third-generation sequencing data at the whole-genome level, we developed the database PGG.SV to provide a practical platform for both regionally and globally representative structural variants. In its current version, PGG.SV archives 584 277 SVs obtained from whole-genome sequencing data of 6048 samples, including 1030 long-read sequencing genomes representing 177 global populations. PGG.SV provides (i) high-quality SVs with fine-scale and precise genomic locations in both GRCh37 and GRCh38, covering underrepresented SVs in existing sequencing and microarray data; (ii) hierarchical estimation of SV prevalence in geographical populations; (iii) informative annotations of SV-related genes, potential functions and clinical effects; (iv) an analysis platform to facilitate SV-based case-control association studies and (v) various visualization tools for understanding the SV structures in the human genome. Taken together, PGG.SV provides a user-friendly online interface, easy-to-use analysis tools and a detailed presentation of results. PGG.SV is freely accessible via https://www.biosino.org/pggsv.

Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations.

BACKGROUND: A large number of challenging medically relevant genes (CMRGs) are situated in complex or highly repetitive regions of the human genome, hindering comprehensive characterization of genetic variants using next-generation sequencing technologies. In this study, we employed long-read sequencing technology, extensively utilized in studying complex genomic regions, to characterize genetic alterations, including short variants (single nucleotide variants and short insertions and deletions) and copy number variations, in 370 CMRGs across 41 individuals from 19 global populations. RESULTS: Our analysis revealed high levels of genetic variants in CMRGs, with 68.73% exhibiting copy number variations and 65.20% containing short variants that may disrupt protein function across individuals. Such variants can influence pharmacogenomics, genetic disease susceptibility, and other clinical outcomes. We observed significant differences in CMRG variation across populations, with individuals of African ancestry harboring the highest number of copy number variants and short variants compared to samples from other continents. Notably, 15.79% to 33.96% of short variants were exclusively detectable through long-read sequencing. While the T2T-CHM13 reference genome significantly improved the assembly of CMRG regions, thereby facilitating variant detection in these regions, some regions still lacked resolution. CONCLUSION: Our results provide an important reference for future clinical and pharmacogenetic studies, highlighting the need for a comprehensive representation of global genetic diversity in the reference genome and improved variant calling techniques to fully resolve medically relevant genes.

The causal effects of lifestyle, circulating, pigment, and metabolic factors on early age-related macular degeneration: a comprehensive Mendelian randomization study.

PURPOSE: Early detection of lifestyle factors, skin and hair color, circulating parameters, and metabolic comorbidities is crucial for personalized prevention and treatment of early age-related macular degeneration (AMD). This study aimed to assess the relationships between genetically predicted comprehensive risk factors and early AMD. METHODS AND RESULTS: Publicly available genome-wide association study (GWAS) data were utilized to identify genetic variants significantly associated with each trait. We applied a Bonferroni-corrected significance level of P < 0.0017. P values between 0.0017 and 0.05 were considered suggestive associations. Univariable Mendelian randomization (MR) analyses revealed that elevated serum HDL-C, lower serum TG, and decreased three circulating fatty acids levels were robust indicators of an increased risk of early AMD (all P < 0.0017), with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.218 (1.140-1.303), 0.784 (0.734-0.837), 0.772 (0.698-0.855), 0.776 (0.706-0.852), and 0.877 (0.798-0.963), respectively. Additionally, the "never eat wheat products", "age started wearing glasses", and "skin color" were significantly associated with the risk of early AMD (both P < 0.0017), with ORs (95% CIs) of 23.853 (2.731-208.323), 1.605 (1.269-2.030) and 1.190 (1.076-1.317), respectively. Multivariable MR analysis confirmed that elevated serum HDL-C (OR = 1.187, 1.064-1.324) increased the risk of early AMD, while higher serum TG (OR = 0.838, 0.738-0.950) was associated with a significantly lower risk. Furthermore, validation results indicated that serum HDL-C 1.201 (1.101-1.310) and TG 0.795 (0.732-0.864) were significantly associated with the risk of early AMD. There were suggestive associations of smoothies, chronotype, and hair color (0.0017 < P < 0.05), but sun/UV protection, smoking, BMI, diabetes, high blood pressure, cardiovascular diseases, fresh fruit intake, fish oil/cod liver oil supplement, sleeplessness, serum C-reactive protein level, and iron level were not associated with the risk of early AMD. CONCLUSIONS: Our comprehensive MR analysis demonstrated that elevated circulating HDL-C levels increase the risk of early AMD, while TG and fatty acid levels are associated with a decreased risk. These findings provide robust evidence for improved diagnosis and personalized prevention and treatment of early AMD.

The causal relationship between blood cell indices and 28-day mortality in sepsis: a retrospective study and bidirectional Mendelian randomization analysis.

BACKGROUND: Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients. METHODS: Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data. RESULTS: Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06-1.26; P < 0.05). Multivariable analysis further substantiated PDW's robust association with mortality risk (OR 1.23; 95% CI, 1.03-1.48; P < 0.05). Conversely, our analysis did not uncover significant correlations between the genetic predispositions to other BCIs-including red blood cell count, erythrocyte distribution width, platelet count, mean platelet volume, white blood cell count, neutrophil count, neutrophil percentage, lymphocyte count, and lymphocyte percentage-and 28-day mortality in sepsis. Additionally, an inverse MR analysis did not establish a causal impact of 28-day mortality in sepsis on PDW (OR 1.00; 95% CI, 1.00-1.07; P = 0.29). Moreover, a similar result was observed in the retrospective study. CONCLUSIONS: The study underscores the independent causal role of PDW in predicting 28-day mortality in sepsis, suggesting its potential utility in early patient assessment, risk stratification, and tailoring of therapeutic interventions.

HCC subtypes based on the activity changes of immunologic and hallmark gene sets in tumor and nontumor tissues.

The prognostic role of adjacent nontumor tissue in hepatocellular carcinoma (HCC) patients is still not clear. The activity changes of immunologic and hallmark gene sets in adjacent nontumor tissues may substantially impact on prognosis by affecting proliferation of liver cells and colonization of circulating tumor cells after HCC treatment measures such as hepatectomy. We aimed to identify HCC subtypes and prognostic gene sets based on the activity changes of gene sets in tumor and nontumor tissues, to improve patient outcomes. We comprehensively revealed the activity changes of immunologic and hallmark gene sets in HCC and nontumor samples by gene set variation analysis (GSVA), and identified three clinically relevant subtypes of HCC by nonnegative matrix factorization method (NMF). Patients with subtype 1 had good overall survival, whereas those with subtype 2 and subtype 3 had poor prognosis. Patients with subtype 1 in the validation group also tended to live longer. We also identified three prognostic gene sets in tumor and four prognostic gene sets in nontumor by least absolute shrinkage and selection operator method (LASSO). Interestingly, functional enrichment analysis revealed that in nontumor tissues, genes from four gene sets correlated with immune reaction, cell adhesion, whereas in tumor tissue, genes from three gene sets closely correlated with cell cycle. Our results offer new insights on accurately evaluating prognosis-the important role of gene sets in both tumor and adjacent nontumor tissues, suggesting that when selecting for HCC treatment modality, changes in tumor and nontumor tissues should also be considered, especially after hepatectomy.

Classification and survival prediction in early-stage cirrhosis by gene expression profiling.

Liver cirrhosis has been increasingly diagnosed at an early stage owing to the non-invasive diagnostic techniques. However, it is difficult to identify patients at high risk of disease progression. Screening cirrhotic patients with poor prognosis who are most in need of surveillance is still challenging. Gene expression data GSE15654 and GSE14520 were downloaded for performing unsupervised clustering analysis. The prognostic differences between the different clusters were explored by Cox regression. Integrative analysis of gene expression signature, immune cell enrichments and clinical characterization was performed for different clusters. Two distinctive subclasses were identified in HCV-related GSE15654, and Kaplan-Meier analysis indicated that subtype 2 had lower survival rates than subtype 1 (p = 0.0399). Further analysis revealed subtype 2 had a higher density of follicular T helper cells, resting natural killer cells and M0, M2 macrophages while subtype 1 with a higher fraction of naive B cells, memory B cells, resting memory CD 4 T cells, activated natural killer cells and monocytes. 226 differentially expressed genes were identified between the two subtypes, and Reactome analysis showed the mainly enriched pathways were biological oxidations and fatty acid metabolism. Five hub genes (AKT1, RPS16, CDC42, CCND1 and PCBP2) and three significant modules were extracted from the PPI network. The results were validated in HBV-related GSE14520 cohort. We identified two subtypes of patients with different prognosis for hepatitis C-related early-stage liver cirrhosis. Bioinformatics analysis of the gene expression and immune cell profile may provide fresh insight into understanding the prognosis difference.

Tumor necrosis factor-α-inducible protein 8-like protein 3 (TIPE3): a novel prognostic factor in colorectal cancer.

BACKGROUND: To explore the correlation of tumor necrosis factor-α-induced protein 8-like protein 3 (TIPE3) expressions in colorectal cancer (CRC) with tumor-immune infiltration and patient prognosis. METHODS: Formalin-fixed paraffin-embedded tumor samples from CRC patients (n = 110) were used in this study. Immunohistochemistry staining of TIPE3 and three prognostic immune biomarkers (CD8, CD20, and CD66b) was conducted in the tumor tissues and adjacent normal tissues. A Cox regression analysis of univariate and multivariate variables was performed to assess the correlation between TIPE3 and patient prognosis. RESULT: We found that TIPE3 was mainly expressed in the cytoplasm, with a small amount in the nucleus. The expression of TIPE3 in tumor tissues is significantly higher than in adjacent normal tissues, and it is significantly correlated with the survival rate of patients in tumor tissues (p = 0.0038) and adjacent normal tissues (p<0.0001). Patients with a high TIPE3 expression had a lower survival rate, while patients with a low TIPE3 expression had a higher survival rate. Univariate regression analysis showed that the TIPE3 expression in tumor tissues (p = 0.007), the TIPE3 expression in adjacent normal tissues (p<0.001), the number of CD8+ T cells in tumor tissues (p = 0.020), the number of CD20+ B cells in tumor tissues (p = 0.023), the number of CD20+ B cells in adjacent normal tissues (p = 0.023), the number of CD66b+ neutrophils in tumor tissues (p = 0.005), the number of CD66b+ neutrophils in adjacent normal tissues (p<0.001), lymphatic metastasis (p = 0.010), TNM stage (p = 0.013), and tumor grade (p = 0.027) were significantly correlated with overall survival (OS). These prognostic factors were then subjected to multivariate regression analysis, and the results showed that the expression of TIPE3, the number of CD8+ T cells, and the number of CD66b+ neutrophils were prognostic factors affecting the OS rate of CRC patients. CONCLUSION: We found that the TIPE3 protein is upregulated in CRC cancer tissues and is correlated with survival rate.

Environment-induced same-sex mating in the yeast Candida albicans through the Hsf1-Hsp90 pathway.

While sexual reproduction is pervasive in eukaryotic cells, the strategies employed by fungal species to achieve and complete sexual cycles is highly diverse and complex. Many fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, are homothallic (able to mate with their own mitotic descendants) because of homothallic switching (HO) endonuclease-mediated mating-type switching. Under laboratory conditions, the human fungal pathogen Candida albicans can undergo both heterothallic and homothallic (opposite- and same-sex) mating. However, both mating modes require the presence of cells with two opposite mating types (MTLa/a and α/α) in close proximity. Given the predominant clonal feature of this yeast in the human host, both opposite- and same-sex mating would be rare in nature. In this study, we report that glucose starvation and oxidative stress, common environmental stresses encountered by the pathogen, induce the development of mating projections and efficiently permit same-sex mating in C. albicans with an "a" mating type (MTLa/a). This induction bypasses the requirement for the presence of cells with an opposite mating type and allows efficient sexual mating between cells derived from a single progenitor. Glucose starvation causes an increase in intracellular oxidative species, overwhelming the Heat Shock transcription Factor 1 (Hsf1)- and Heat shock protein (Hsp)90-mediated stress-response pathway. We further demonstrate that Candida TransActivating protein 4 (Cta4) and Cell Wall Transcription factor 1 (Cwt1), downstream effectors of the Hsf1-Hsp90 pathway, regulate same-sex mating in C. albicans through the transcriptional control of the master regulator of a-type mating, MTLa2, and the pheromone precursor-encoding gene Mating α factor precursor (MFα). Our results suggest that mating could occur much more frequently in nature than was originally appreciated and that same-sex mating could be an important mode of sexual reproduction in C. albicans.

Reappraisal of the diagnostic value of alpha-fetoprotein for surveillance of HBV-related hepatocellular carcinoma in the era of antiviral therapy.

This study was designed to explore if antiviral treatment influences the performance of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) among the high-risk chronic HBV-infected patients. A total of 5936 patients who had evidence of chronic HBV infection were enrolled from four independent centres in this retrospective study, including 1721 chronic hepatitis B (CHB), 2286 liver cirrhosis (LC), 798 HCC within Milan criteria and 1131 HCC beyond Milan criteria patients. Stratified by whether they received treatment or not, the patients were further divided into antiviral and non-antiviral groups. Then, the performance of AFP for discriminating HCC was evaluated. Patients receiving antivirals had significantly lower median levels of AFP compared with the non-antiviral patients (P < .001), and there were significantly less patients with abnormal AFP levels in antiviral groups (P < .001). Antiviral therapy improved the AUROCs of AFP for discriminating HCC within Milan criteria. When setting the cut-off values at 20 ng/mL and 100 ng/mL as surveillance and confirmatory tests respectively for HCC among patients receiving antiviral treatment, AFP exhibited a significantly higher sensitivity than those of 200 ng/mL and 400 ng/mL, which are currently recommended by some guidelines, without compromising specificity. Further analysis in antiviral patients revealed that serum AFP had better performance for discriminating HCC within Milan criteria in ALT ≤ 1ULN patients than that in ALT > 1ULN patients. In conclusion, in the era of antiviral therapy, serum AFP's surveillance performance was substantially improved for HCC within Milan criteria among the high-risk population of CHB and LC patients.

Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and the leading cause is persistent hepatitis B virus (HBV) infection. We aimed to identify some core genes and pathways for HBV-related HCC. METHODS: Gene expression profiles of GSE62232, GSE121248, and GSE94660 were available from Gene Expression Omnibus (GEO). The GSE62232 and GSE121248 profiles were the analysis datasets and GSE94660 was the validation dataset. The GEO2R online tool and Venn diagram software were applied to analyze commonly differentially expressed genes between HBV-related HCC tissues and normal tissues. Then, functional enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Gene and Genome (KEGG) as well as the protein-protein interaction (PPI) network was conducted. The overall survival rates and the expression levels were detected by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Next, gene set enrichment analysis (GSEA) was performed to verify the KEGG pathway analysis. Furthermore, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to validate the levels of these three core genes in tumor tissues and adjacent non-tumor liver tissues from 12 HBV related HCC patients, HBV-associated liver cancer cell lines and normal liver cell lines, and HepG2 with p53 knockdown or deletion, respectively. RESULTS: Fifteen highly expressed genes associated with significantly worse prognoses were selected and CCNB1, CDK1, and RRM2 in the p53 signaling pathway were identified as core genes. GSEA results showed that samples highly expressing three core genes were all enriched in the p53 signaling pathway in a validation dataset (P < 0.0001). The expression of these three core genes in tumor tissue samples was higher than that in relevant adjacent non-tumor liver tissues (P < 0.0001). Furthermore, we also found that the above genes were highly expressed in liver cancer cell lines compared with normal liver cells. In addition, we found that the expression of these three core genes in p53 knockdown or knockout HCC cell lines was lower than that in negative control HCC cell lines (P < 0.05). CONCLUSIONS: CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway and could be potential biomarkers and therapeutic targets for HBV-related HCC.

Reproduction-Associated Hormones and Adult Hippocampal Neurogenesis.

The levels of reproduction-associated hormones in females, such as estrogen, progesterone, prolactin, and oxytocin, change dramatically during pregnancy and postpartum. Reproduction-associated hormones can affect adult hippocampal neurogenesis (AHN), thereby regulating mothers' behavior after delivery. In this review, we first briefly introduce the overall functional significance of AHN and the methods commonly used to explore this front. Then, we attempt to reconcile the changes of reproduction-associated hormones during pregnancy. We further update the findings on how reproduction-related hormones influence adult hippocampal neurogenesis. This review is aimed at emphasizing a potential role of AHN in reproduction-related brain plasticity and its neurobiological relevance to motherhood behavior.

A comprehensive analysis of the MAGE family as prognostic and diagnostic markers for hepatocellular carcinoma.

The Melanoma Antigen Gene (MAGE) family is a large, highly conserved group of proteins which was reported to participate in the progression of multiple cancers in humans. However, the function of distinct MAGE genes in hepatocellular carcinoma (HCC) is largely unclear. In this study, we comprehensively evaluated the expression, clinical significance, genetic alteration, interaction network and functional enrichment of MAGEs in HCC. Our research showed that many MAGE genes were dysregulated in HCC. Among them, MAGEA1, MAGEC2, MAGED1, MAGED2, MAGEF1 and MAGEL2 were significantly associated with clinical stage and differentiation of HCC. MAGED1, MAGED2, MAGEA6, MAGEA12, MAGEA10, MAGEB4, MAGEL2 and MAGEC3 significantly correlated with HCC prognosis. Further functional enrichment analysis suggested the dysregulated MAGEs may play important roles in signal transduction. These results indicate that multiple dysregulated MAGEs might play important roles in the development of HCC and can be exploited as useful biomarkers for diagnosis and treatment in HCC.

A Tool for Early Prediction of Severe Coronavirus Disease 2019 (COVID-19): A Multicenter Study Using the Risk Nomogram in Wuhan and Guangdong, China.

BACKGROUND: Because there is no reliable risk stratification tool for severe coronavirus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identification of cases at high risk of progression to severe COVID-19. METHODS: In this retrospective multicenter study, 372 hospitalized patients with nonsevere COVID-19 were followed for > 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and those who maintained a nonsevere state were assigned to the severe and nonsevere groups, respectively. Based on baseline data of the 2 groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluated its performance. RESULTS: The training cohort consisted of 189 patients, and the 2 independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.4%) patients developed severe COVID-19. Older age; higher serum lactate dehydrogenase, C-reactive protein, coefficient of variation of red blood cell distribution width, blood urea nitrogen, and direct bilirubin; and lower albumin were associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the training cohort (area under the curve [AUC], 0.912 [95% confidence interval {CI}, .846-.978]; sensitivity 85.7%, specificity 87.6%) and the validation cohort (AUC, 0.853 [95% CI, .790-.916]; sensitivity 77.5%, specificity 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analyses indicated that nomogram conferred high clinical net benefit. CONCLUSIONS: Our nomogram could help clinicians with early identification of patients who will progress to severe COVID-19, which will enable better centralized management and early treatment of severe disease.

The Als3 Cell Wall Adhesin Plays a Critical Role in Human Serum Amyloid A1-Induced Cell Death and Aggregation in Candida albicans.

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1, respectively) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the present study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1, in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

Nomogram based on blood lipoprotein for estimation of mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a clinic syndrome with substantial high short-term mortality. It is very important to stratify patients according to prognosis to decide management strategy. This study aimed to formulate and validate a nomogram model based on blood lipoprotein for prediction of 3-month mortality in patients with hepatitis B virus (HBV)-related ACLF. METHODS: Data on 393 consecutive patients who were diagnosed as HBV-related ACLF at the Third Affiliated Hospital of Sun Yat-sen University between June 1, 2013, and February 1, 2015, were prospectively collected. Of these, 260 patients who were collected in an earlier period formed the training cohort for the development of nomogram, while 133 patients who were collected thereafter formed the validation cohort for confirming the performance of nomogram. RESULTS: Multivariate analysis showed that low density lipoprotein cholesterol (LDL-C), age, prothrombin time, and creatinine were independently associated with 3-month mortality of patients with HBV-related ACLF. Kaplan-Meier survival analysis revealed that the high LDL-C (LDL-C ≥ 1.0 mmol/L, cut-off value) was significantly associated with elevated overall survival (P < 0.001). All independent factors for survival were selected into the nomogram. The calibration plot for the probability of survival showed good agreement between prediction by nomogram and actual observation. CONCLUSION: This study highlighted that reduction of serum LDL-C level was an independent risk factor for the survival in patients with HBV-related ACLF, and the nomogram based on serum LDL-C was an accurate and practical model for predicting the 3-month mortality in patients with this disease.

Genome-wide patterns of copy number variations in Spodoptera litura.

Spodoptera litura is a polyphagous pest and can feed on more than 100 species of plants, causing great damage to agricultural production. The SNP results showed that there were gene exchanges between different regions. To explore the variations of larger segments in S. litura genome, we used genome resequencing samples from 14 regions of China, India, and Japan to study the copy number variations (CNVs). We identified 3976 CNV events and 1581 unique copy number variation regions (CNVRs) occupying the 108.5 Mb genome of S. litura. A total of 5527 genes that overlapped with CNVRs were detected. Selection signal analysis identified 19 shared CNVRs and 105 group-specific CNVRs, whose related genes were involved in various biological processes in S. litura. We constructed the first CNVs map in S. litura genome, and our findings will be valuable for understanding the genomic variations and population differences of S. litura.

Antifungal Activity of Mammalian Serum Amyloid A1 against Candida albicans.

Mammalian serum amyloid A (SAA) is a major acute phase protein that shows a massive increase in plasma concentration during inflammation. In the present study, we demonstrate that the expression of mouse SAA1 in serum was increased when infected with Candida albicans, a major human fungal pathogen, in a systemic infection model. We then set out to investigate the antifungal activity of SAA proteins against C. albicans Recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) were expressed and purified in Escherichia coli Both rhSAA1 and rmSAA1 exhibited a potent antifungal activity against C. albicans We further demonstrate that rhSAA1 binds to the cell surface of C. albicans, disrupts cell membrane integrity, and induces rapid fungal cell death in C. albicans Our finding expands the known functions of SAA1 and provides new insight into host-Candida interactions during fungal infection.

Serum liver fibrosis markers discriminate significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase.

Chronic liver inflammation caused by chronic hepatitis B virus (CHB) infection leads to liver cirrhosis and hepatocellular carcinoma. Recently, the role of alanine aminotransferase (ALT) as a predictor of liver inflammation has been questioned. The aim of this study was to investigate the utility of noninvasive fibrosis markers including hyaluronic acid (HA), collagen type IV (CIV), N-terminal propeptide of type III procollagen (PIIINP), and laminin (LN) in identifying significant liver inflammation in patients with CHB, especially in patients with normal or near-normal ALT. A total of 242 CHB patients who underwent liver biopsy were enrolled. The serum levels of ALT, aspartate aminotransferase, HA, CIV, PIIINP, and LN were quantified and the relationship between histological staging and serum markers was systematically analyzed. Serum CIV, PIIINP, HA, and LN levels increased significantly along with the increasing severity of liver inflammation. Multivariate analysis showed that CIV and LN were independently associated with significant inflammation. CIV, PIIINP, HA, and LN levels were found to have high diagnostic values for predicting significant inflammation in patients with CHB (area under the curve, AUC = 0.807, 0.795, 0.767, and 0.703, respectively). The combined index for the identification of significant inflammation, including CIV, PIIINP, HA, and LN levels, significantly improved diagnostic performance (AUC = 0.851). Moreover, the combined index also achieved excellent diagnostic accuracy (AUC = 0.861) in patients with CHB with normal or near-normal ALT. In conclusion, the combined index may be a strong indicator for discriminating significant liver inflammation, especially in patients with CHB with normal or near-normal ALT.

Rare Meningitis and Epileptic Seizure Infected with Brucella melitensis: a Case Report.

BACKGROUND: Although brucellosis is the most common zoonotic disease worldwide, human meningitis infected with Brucella melitensis is rare and difficult to diagnosis. Herein we describe the clinical aspects of a rare case of Brucella melitensis meningitis accompanied by epileptic seizure. METHODS: Bacterial culture of CSF was utilized to find the pathogen. Serum and CSF agglutination tests were used to detect the capacity of Brucella antigen. Bacterial clone was identified by the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Magnetic resonance imaging (MRI) was used to monitor the recovery changes for meningitis. RESULTS: The bacterial culture was positive for Brucella app. Antigen-antibody agglutination test was also positive with a titer more than 1/200. A reliable identification score of 2.8 for Brucella melitensis was obtained by MALDI-TOF. MRI showed obviously improved meningitis after therapy. CONCLUSIONS: The results of this study suggest the treatments for Brucella meningitis must be planned depending on the patient's clinical conditions and the laboratory identification of pathogen infection as early as possible.

Fasting Serum Low-Density Lipoprotein (LDL) Before Liver Transplantation Predicts Post-Transplant Survival.

BACKGROUND The disordered metabolism of liver function in liver cancer patients can affect postoperative survival after liver transplantation. We assessed whether the levels of various chemicals in liver metabolism prior to receiving a liver transplant were prognostic factors and metabolism markers in predicting survival rate. MATERIAL AND METHODS Seventy-seven patients received a donor liver transplant between June 2012 and April 2016. The basic level of fasting serum GLU, Crea, TBil, TC, TG, HDL, LDL, ApoA1, ApoB100, INR, and MELD scores of 77 patients were retrospectively analyzed. Each patient's survival was monitored to evaluate prognosis and long-term survival. RESULTS The overall survival rates of all patients post-transplant at 6-, 12-, 24-, and 36-month follow-up were 90.9%, 79.2%, 68.8%, and 64.9% respectively. Fasting serum levels of GLU (P=0.004), HDL (P=0.010), LDL (P=0.008), ApoA1 (P=0.028), and MELD scores (P=0.013) prior to liver transplantation were closely associated with the cumulative survival post-transplant in univariate analyses. Controlled fasting GLU of ≤5.12 mmol/L (P=0.019), LDL of ≤2.62 mmol/L (P=0.031), and MELD scores of ≤9 (P=0.013) before LT were significantly and independently associated with increased cumulative survival in the multivariate analyses. CONCLUSIONS Decreased fasting serum GLU, LDL, and MELD scores as independent risk factors prior to liver transplantation markedly increase cumulative survival.