Association between clusters of antibodies against periodontal microorganisms and Alzheimer disease mortality: Evidence from a nationally representative survey in the USA.

BACKGROUND: Alzheimer disease (AD) has been linked with periodontal microorganisms such as Porphyromonas gingivalis in observational and mechanistic studies. IgG antibodies against periodontal microorganisms which are markers of past and current periodontal infection have been correlated with cognitive impairment. We examined associations between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and AD mortality. METHODS: Individuals participating in the Third National Health and Nutrition Examination Survey (NHANES III) with complete data on IgG titers were followed up between 1988 and December 31, 2019. The outcome was AD mortality, and the main exposures were IgG antibodies against periodontal microorganisms classified into four mutually exclusive groups using cluster analysis. Survey-weighted Cox proportional hazard models were used to evaluate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the relationship between clusters and AD mortality. RESULTS: With up to 21 years of follow-up, 160 AD-related deaths were documented. In the multivariable-adjusted model, AD mortality overall was not associated with the Red-Green (aHR 1.18; 95% CI, 0.46-3.07), Yellow-Orange (aHR 1.36; 95% CI, 0.58-3.19), Orange-Blue (aHR 0.63; 95%, CI, 0.33-1.21), and the Orange-Red (aHR 0.79; 95% CI, 0.37-1.70) when the upper tertiles were compared to the bottom tertiles. However, the subgroup of middle-aged individuals in the highest tertile of the Red-Green cluster, but not older individuals, had a 13% higher risk of AD mortality (aHR 1.13; 95% CI, 1.02-1.26) compared with those in the bottom tertile. CONCLUSION: Clusters of IgG antibodies against periodontal microorganisms did not predict AD mortality in this study.

[Clinical Characteristics of Nontuberculous Mycobacterium Infection Cases in Sichuan, China in 2016-2021: A Retrospective Study].

Objective: To study the distribution of nontuberculous mycobacterium (NTM) strains, clinical characteristics and drug sensitivity data of NTM infections so as to provide support for the prevention and treatment of diseases caused by NTM infection in Sichuan. Methods: The clinical data of NTM infection cases treated at the Public Health Clinical Center of Chengdu between July 2016 and July 2021 were collected and the characteristics of the infections were retrospectively reviewed. Results: There were differences in sex, age and underlying diseases among the NTM infection cases in Sichuan. Specifically, young and middle-aged men aged between 20 and 40 were susceptible to AIDS, older men aged over 60 were susceptible to lung diseases, and middle-aged and older women over 40 were susceptible to bronchiectasis. Respiratory tract was the main route of NTM infection. The dominant strain in Sichuan was M. chelonae/ abscessus. The drug resistance rate of M. avium and M. chelonae/ abscessus were relatively higher. Conclusion: For NTM infection patients with different demographic characteristics and underlying diseases, the NTM infection sites, strains, and drug resistance are also different. Definite etiological diagnosis is essential to the treatment of NTM infection. We should highlight the importance of adopting individualized treatment for different NTM infections.

Transcriptomic analysis reveals the regulatory role of quorum sensing in the Acinetobacter baumannii ATCC 19606 via RNA-seq.

BACKGROUND: Acinetobacter baumannii has emerged as the major opportunistic pathogen in healthcare-associated infections with high-level antibiotic resistance and high mortality. Quorum sensing (QS) system is a cell-to-cell bacterial communication mediated by the synthesis, secretion, and binding of auto-inducer signals. It is a global regulatory system to coordinate the behavior of individual bacteria in a population. The present study focused on the QS system, aiming to investigate the regulatory role of QS in bacterial virulence and antibiotic resistance. METHOD: The auto-inducer synthase gene abaI was deleted using the A. baumannii ATCC 19606 strain to interrupt the QS process. The RNA-seq was performed to identify the differentially expressed genes (DEGs) and pathways in the mutant (△abaI) strain compared with the wild-type (WT) strain. RESULTS: A total of 380 DEGs [the adjusted P value < 0.05 and the absolute value of log2(fold change) > log21.5] were identified, including 256 upregulated genes and 124 downregulated genes in the △abaI strain. The enrichment analysis indicated that the DEGs involved in arginine biosynthesis, purine metabolism, biofilm formation, and type VI secretion system (T6SS) were downregulated, while the DEGs involved in pathways related to fatty acid metabolism and amino acid metabolism were upregulated. Consistent with the expression change of the DEGs, a decrease in biofilm formation was observed in the △abaI strain compared with the WT strain. On the contrary, no obvious changes were found in antimicrobial resistance following the deletion of abaI. CONCLUSIONS: The present study demonstrated the transcriptomic profile of A. baumannii after the deletion of abaI, revealing an important regulatory role of the QS system in bacterial virulence. The deletion of abaI suppressed the biofilm formation in A. baumannii ATCC 19606, leading to decreased pathogenicity. Further studies on the role of abaR, encoding the receptor of auto-inducer in the QS circuit, are required for a better understanding of the regulation of bacterial virulence and pathogenicity in the QS network.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: An effective method for identification and phylogenetic analysis of Leishmania species.

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid and reproducible method that has been widely applied for the identification of bacteria and fungi. However, this technique has not yet been applied in clinical laboratories for parasitology, such as for the study of the protozoan Leishmania. METHODOLOGY: By using MALDI-TOF MS, mass spectra database entries (MSPs) were created with 7 World Health Organization reference strains in order to establish a rapid method for Leishmania species identification. Furthermore, cluster analysis was performed with 18 Chinese Leishmania isolates. PRINCIPAL FINDINGS: The MSPs of Leishmania corresponded well with our past identification results, and the dendrogram analysis result was more or less similar to that of the phylogenetic analysis performed by multi-locus sequence typing. CONCLUSIONS/SIGNIFICANCE: MALDI-TOF MS is a promising method that offers both rapidity and efficiency for the identification and dendrogram analysis of Leishmania species.

Association between groups of immunoglobulin G antibodies against periodontal microorganisms and diabetes-related mortality.

BACKGROUND: Immunoglobulin G (IgG) antibodies against periodontal microorganisms can be markers of periodontal infection because their levels rise following infection and remain elevated several years later. METHODS: We evaluated the relationship between groups of IgG antibodies against 19 periodontal microorganisms and diabetes-related mortality over 27 years among participants of the National Health and Nutrition Examination Survey III (1988 to 1992) aged ≥40 years at the time of examination (N = 8,153). RESULTS: Individuals in the highest versus lowest antibody tertiles were at 86% higher risk of dying due to diabetes-related causes in the Red-Green antibody cluster (T. forsythia, T. denticola, A. actinomycetemcomitans, E. corrodens, S. noxia, V. parvula, C. rectus) (hazard ratio [HR], 1.86; 95% CI, 1.09 to 3.20) and 55% lower in the Orange-Blue antibody cluster (E. nodatum, A. naeslundii) (HR, 0.45, 95% CI, 0.32 to 0.63) in multivariable models. In these models, individuals with diabetes at the time of examination had a 16-fold higher risk of dying due to diabetes-related causes (HR, 16.4; 95% CI, 11.0 to 24.7). CONCLUSION: As a subset of periodontal microorganisms are associated with adverse systemic outcomes, antibody profiles may help in prediction of diabetes-related mortality and identify subgroups of individuals among whom periodontal treatment may impact diabetes-related outcomes.

Cystoisospora belli infection in an AIDS patient in China: Need for cautious interpretation of mNGS.

Cystoisospora belli (C. belli) is an opportunistic coccidian parasite. This case is the first reported C. belli infection associated with AIDS in China. C. belli infection of this case was diagnosed with the presence of oocysts using direct wet mount and Ziehl-Neelsen acid-fast stain method, and confirmed by polymerase chain reaction (PCR) and Sanger sequencing, ruling out the result of metagenomic next-generation sequencing (mNGS). This case demonstrates that C. belli infection in AIDS could be a potential risk factor for persistent diarrhea, and should not be neglected in non-endemic area and emphaise the necessity of accurate mNGS databases.

Differences in gene expression and variable splicing events of ovaries between large and small litter size in Chinese Xiang pigs.

BACKGROUND: Although lots of quantitative trait loci (QTLs) and genes present roles in litter size of some breeds, the information might not make it clear for the huge diversity of reproductive capability in pig breeds. To elucidate the inherent mechanisms of heterogeneity of reproductive capability in litter size of Xiang pig, we performed transcriptome analysis for the expression profile in ovaries using RNA-seq method. RESULTS: We identified 1,419 up-regulated and 1,376 down-regulated genes in Xiang pigs with large litter size. Among them, 1,010 differentially expressed genes (DEGs) were differently spliced between two groups with large or small litter sizes. Based on GO and KEGG analysis, numerous members of genes were gathered in ovarian steroidogenesis, steroid biosynthesis, oocyte maturation and reproduction processes. CONCLUSIONS: Combined with gene biological function, twelve genes were found out that might be related with the reproductive capability of Xiang pig, of which, eleven genes were recognized as hub genes. These genes may play a role in promoting litter size by elevating steroid and peptide hormones supply through the ovary and facilitating the processes of ovulation and in vivo fertilization.

Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Stimulated by Mycobacterium tuberculosis PPE57 Identifies Characteristic Genes Associated With Type I Interferon Signaling.

Proline-glutamic acid (PE)- and proline-proline-glutamic acid (PPE)-containing proteins are exclusive to Mycobacterium tuberculosis (MTB), the leading cause of tuberculosis (TB). In this study, we performed global transcriptome sequencing (RNA-Seq) on PPE57-stimulated peripheral blood mononuclear cells (PBMCs) and control samples to quantitatively measure the expression level of key transcripts of interest. A total of 1367 differentially expressed genes (DEGs) were observed in response to a 6 h exposure to PPE57, with 685 being up-regulated and 682 down-regulated. Immune-related gene functions and pathways associated with these genes were evaluated, revealing that the type I IFN signaling pathway was the most significantly enriched pathway in our RNA-seq dataset, with 14 DEGs identified therein including ISG15, MX2, IRF9, IFIT3, IFIT2, OAS3, IFIT1, IFI6, OAS2, OASL, RSAD2, OAS1, IRF7, and MX1. These PPE57-related transcriptomic profiles have implications for a better understanding of host global immune mechanisms underlying MTB infection outcomes. However, more studies regarding these DEGs and type I IFN signaling in this infectious context are necessary to more fully clarify the underlying mechanisms that arise in response to PPE57 during MTB infection.

Comprehensive quality evaluation of the lateral root of Aconitum carmichaelii Debx. (Fuzi): Simultaneous determination of nine alkaloids and chemical fingerprinting coupled with chemometric analysis.

Amino alcohol alkaloids are the active components in the lateral root of Aconitum carmichaelii Debx. (Fuzi), and they have a variety of pharmacological activities. However, the chemical fingerprints of the ester alkaloids reported to date were mainly obtained from high-performance liquid chromatography coupled with ultraviolet detection, and it is difficult to obtain information about amino alcohol alkaloids in Fuzi from such chromatograms. In this paper, a comprehensive fingerprinting method was established using high-performance liquid chromatography coupled with an evaporative light-scattering detector for the simultaneous quantitative analysis of both the amino alcohol alkaloids and ester alkaloids. A total of 42 samples of Fuzi from four production areas were analyzed by constructing high-performance liquid chromatography fingerprints. Then, the quantitative results of the chemical fingerprints combined with chemometrics methods were employed to reveal the factors affecting the geo-authentic Fuzi and to determine characteristic components that can be used to identify these samples. The results indicated distinct differences in the alkaloid contents among samples from the four regions; the geographical origin may be the primary factor affecting the geo-authentic Fuzi, and 15 major components (including songorine, neoline, and hypaconitine, which were quantitatively determined) were found to be characteristic components for the discrimination of Fuzi samples from various regions. Neoline might be a critical component for identifying geo-authentic Fuzi. This approach is convenient, reproducible and provides a promising method for the quality evaluation of Fuzi.

Analysis of alternative splicing events by RNA sequencing in the ovaries of Xiang pig at estrous and diestrous.

Alternative splicing (AS) is an important mechanism for controlling gene expression, which regulates multiple biological processes in higher organisms. Chinese indigenous Xiang pig has distinctive biological characteristics, such as small size, early sexual maturity, lower litter size and not very clear exhibition of estrous behaviors. To further understand how AS responds to estrous cycles in Xiang pig, the genome-wide analysis of AS events was performed by RNA-seq method in Xiang pig ovaries at diestrous and estrous. Using ASprofile program, we analyzed twelve basic AS events in Xiang pig ovaries and identified 68,775 AS events in 15,142 genes from diestrous ovaries and 69,493 AS events in 15,291 genes from the estrous ovaries with average 4.54 splicing events. 94.4-95.5% of expressed genes underwent alternative splicing in this tissues. The frequencies of AS events were similar to each other at diestrous and estrous. Transcription start site (TSS) was the predominant type of AS events, followed by transcription terminal site (TTS), and skipped exon (SKIP). The remaining type of AS events, e.g., intron retention (IR) and alternative exon ends (AE), showed the lower frequencies. Further comparison analysis of gene expression indicated that 4,433 genes had at least one splice variant differentially expressed during estrous, whereas only 2,382 of them were differentially expressed at gene level. Numerous genes involved in gonad development and hormone metabolism were differentially regulated through AS. Twelve genes with different types of alternatively splicing were validated by using RT-PCR method. The GO annotation and KEGG pathway analysis clearly revealed that a lot of DEGs (differentially expressed genes) and DSGs (differentially spliced genes) were involved in follicular development and ovarian steroid biosynthesis. A large number of DSGs, although not differentially expressed, were enriched in circadian rhythm and several signaling pathways. These pathways potentially regulated the female animal reproductive function in gene and/or AS level. Our results suggested that alternative splicing play an essential role in regulation of gene expression in female pigs during estrous. Numerous genes involved in gonad development, hormone metabolism, circadian rhythm were differentially regulated through alternative splicing.