Large-Scale Proteome Profiling Identifies Biomarkers Associated with Suspected Neurosyphilis Diagnosis.

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

Exploring the expression and clinical significance of the miR-140-3p-HOXA9 axis in colorectal cancer.

PURPOSE: This study aims to investigate the expression patterns and clinical significance of miR-140-3p and homeobox A9 (HOXA9) in colorectal cancer (CRC) selected by bioinformatic study, while elucidating their potential interplay. METHODS: The microRNA expression profiles of paired colorectal cancer and matched normal tissues were retrieved from the Gene Expression Omnibus Database. Differentially expressed microRNAs and microRNA candidates were filtered and subjected to further analysis. Clinicopathological data, along with paraffin-embedded samples of colorectal tumor tissues were collected to facilitate comprehensive analysis. Expression levels of miR-140-3p and HOXA9 were quantified using qRT-PCR and immunohistochemistry. Survival rates were determined using the Kaplan-Meier method, and the COX regression model was utilized to identify independent prognostic factors that impact the overall prognosis. RESULTS: MiR-140-3p was significantly downregulated in colorectal tumors compared to normal tissue, and HOXA9 was identified as a previously unreported potential downstream target. HOXA9 expression was elevated in tumors compared to normal tissues. Reduced miR-140-3p expression was associated with lymph node metastasis, while high HOXA9 expression correlated with both lymph node metastasis and lympho-vascular invasion. Patients with low miR-140-3p and high HOXA9 expression had a poorer prognosis. HOXA9 was identified as an independent risk factor for CRC patient survival. CONCLUSION: The miR-140-3p-HOXA9 signaling disruption is closely linked to lymph node metastasis and unfavorable prognosis in CRC. This axis shows promise as a clinical biomarker for predicting the CRC patient survival and a potential therapeutic target.

Identification of potential biomarkers for diagnosis of syphilis from the cerebrospinal fluid based on untargeted metabolomic analysis.

The infection rate of syphilis continues to rise globally, and the difficulty in diagnosis of neurosyphilis promptly needs to be resolved. More specific and sensitive diagnostic markers for latent syphilis and neurosyphilis should be found. Here the metabolic profiles of 88 cerebrospinal fluid samples from syphilis patients and controls were analyzed by LC/MS-based untargeted metabolomics. In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. The experimental process was evaluated by principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-oxo-octadecadienoic acid and 9,10,13-trihydroxyoctadecenoic acid, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl-N-formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration. Our results may promote the development of biomarkers for diagnosis of latent syphilis from neurosyphilis, and for that of asymptomatic neurosyphilis from symptomatic neurosyphilis in the future.

Effect of Mid-Basilar Artery Angle and Plaque Characteristics on Pontine Infarction in Patients with Basilar Artery Plaque.

AIMS: The basilar artery (BA) geometry and plaque characteristics may play an important role in the development of atherosclerosis. This study was performed to explore the relationship between the mid-BA angle and plaque characteristics and its effect on pontine infarction using high-resolution magnetic resonance imaging and three-dimensional time-of-flight magnetic resonance angiography. METHODS: In total, 77 patients with BA plaques were included in this study. According to the presence of acute pontine infarction on diffusion-weighted imaging, the patients were divided into a pontine infarction group and pontine non-infarction group. The mid-BA angle, plaque burden, stenosis ratio, positive remodeling, and intraplaque hemorrhage were evaluated to investigate their effects on stroke. RESULTS: The pontine infarction group had a greater plaque burden, stenosis ratio, positive remodeling, and mid-BA angle than the pontine non-infarction group. The correlation between the plaque burden and mid-BA angle was the highest (r=0.441, P＜0.001). Multivariate logistic regression analysis showed that the plaque burden (odds ratio, 1.164; 95% confidence interval, 1.093-1.241; P＜0.001) was an independent risk factor for pontine infarction. CONCLUSION: The mid-BA angle may increase the incidence of pontine infarction by increasing the plaque burden.

Nitrate Nitrogen and pH Correlate with Changes in Rhizosphere Microbial Community Assemblages during Invasion of Ambrosia artemisiifolia and Bidens pilosa.

The rhizosphere of invasive plants presumably develops different soil microbial assemblages compared with native plants, which may hinder or promote their invasion. However, to date, no studies have clearly explored rhizosphere microbial community assemblages during invasion. The invasive species Ambrosia artemisiifolia L. and Bidens pilosa L. are widely distributed in China and are known to reduce local biodiversity and cause agricultural losses. Monoculture of A. artemisiifolia or B. pilosa, a mixture of each invasive and native species, and monoculture of native species were established to simulate different degrees of invasion. Metagenomic sequencing techniques were used to test microbial community structure and function. The aim was to explore the drivers of the assembly of peculiar functional microbes in the rhizosphere soil of invasive species during the long-term invasive-native species interaction. Compared with the native species, the relative abundance of 34 microbial genera was higher in the rhizosphere soil of the invasive species. The NO3-N concentration in the rhizosphere soil from the A. artemisiifolia and B. pilosa monocultures was lower than that from monocultures of the three native plants, whereas pH followed the opposite trend. The NO3-N concentration was significantly and negatively correlated with Sporichthya, Afipia, Actinokineospora, and Pseudolabrys. pH was positively correlated with Bradyrhizobium, Actinoplanes, Micromonospora, Steroidobacter, Burkholderia, and Labilithrix. The differences in soil microbes, NO3-N concentrations, and pH between native and invasive species suggest that the rhizosphere soil microbial assemblages may vary. The reduced NO3-N concentration and increased pH corelated with changes in rhizosphere microbial community during A. artemisiifolia and B. pilosa invasion. IMPORTANCE Soil microbial communities play a vital role in the growth of invasive plants. Invasive species may shape peculiar functional microbes in the rhizosphere soil of an invasive species to benefit its growth. However, the drivers of the assembly of soil microbial communities in the rhizosphere soil of invasive species remain unclear. Our study established the relationship between soil microbial communities and soil chemical properties during invasion by A. artemisiifolia and B. pilosa. Additionally, it showed that the presence of the invasive plants correlated with changes in NO3-N and pH, as well as in rhizosphere microbial community assemblage. Furthermore, the study provided important insights into the difference in the microbial community assembly between native and invasive plant species.

Bacillus benefits the competitive growth of Ambrosia artemisiifolia by increasing available nutrient levels.

Bacillus can help plants to acquire nutrients either directly or indirectly. However, the role of Bacillus community on the competitive growth of invasive Ambrosia artemisiifolia is poorly understood. Native Setaria viridis is often found in areas that have been invaded by A. artemisiifolia. We sought to determine whether the quantitative and/or qualitative differences in the Bacillus community present on the invasive A. artemisiifolia and native S.viridis provide a competitive advantage to the invasive over native species. A field experiment was established to imitate the invasion of A. artemisiifolia. The 16S rRNA gene was commercially sequenced to identify the bacilli isolated from the rhizosphere soil of field-grown A. artemisiifolia and S. viridis. The Bacillus communities in their rhizosphere were compared, and their effects on the competitive growth of A. artemisiifolia and S. viridis were tested in the pot experiments. Bacillus in the rhizosphere soil of A. artemisiifolia significantly enhanced its intra-specific competitive ability. The relative abundance of B. megaterium in the rhizosphere soil of A. artemisiifolia was significantly higher than that of S. viridis. Inoculation with B. megaterium that was isolated from the rhizosphere soil of both A. artemisiifolia and S. viridis significantly enhanced the relative competitiveness of A. artemisiifolia and inhibited that of S. viridis. The higher abundance of B. megaterium in the rhizosphere of A. artemisiifolia creates higher levels of available nutrients than that in the native S. viridis, which enhance the competitive growth of A. artemisiifolia. The result helps to discover the mechanism of Bacillus community in the invasion of A. artemisiifolia.

Advances in Metagenomics and Its Application in Environmental Microorganisms.

Metagenomics is a new approach to study microorganisms obtained from a specific environment by functional gene screening or sequencing analysis. Metagenomics studies focus on microbial diversity, community constitute, genetic and evolutionary relationships, functional activities, and interactions and relationships with the environment. Sequencing technologies have evolved from shotgun sequencing to high-throughput, next-generation sequencing (NGS), and third-generation sequencing (TGS). NGS and TGS have shown the advantage of rapid detection of pathogenic microorganisms. With the help of new algorithms, we can better perform the taxonomic profiling and gene prediction of microbial species. Functional metagenomics is helpful to screen new bioactive substances and new functional genes from microorganisms and microbial metabolites. In this article, basic steps, classification, and applications of metagenomics are reviewed.

Adiponectin and its receptors in chronic hepatitis B patients with metabolic syndrome in China.

BACKGROUND/AIMS: Adiponectin can initiate a broad range of metabolic and immunological effects. Little is known about the role of adiponectin in hepatitis B related liver disease and metabolic syndrome (MS). METHODOLOGY: We studied 138 patients with untreated chronic hepatitis B (CHB), who were from Beijing Ditan hospital in 2005 to 2009. According to MS, two groups (65 with MS vs. 73 without MS) were established. They were compared with characteristics and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2). RESULTS: In the group of CHB patients with MS, the levels of LDH, γ-GT, FPG, FINS, HOMA-IR, HOMA-ß, TG and HBeAg positive were significantly higher than those in the group without MS (p<0.05). Liver steatosis in the group with MS is significantly more severe than that in the group without MS (p<0.001). With binary logistic regression analyses, BMI and HOMA-IR showed independent predictors to MS in patients with CHB. In patients with chronic HBV, the insulin sensitizing adipokine adiponectin and its receptor AdipoR2 was associated with diabetes in patients with CHB and MS. CONCLUSIONS: Our findings showed the CHB patients with MS may be presence of more severe steatosis. MS in CHB patients may be closely correlated with insulin resistance and less effect of viruses. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with MS.

[Type A/H1N1 influenza: a clinical summary of 24 imported cases].

OBJECTIVE: To study the clinical characteristics and laboratory results of 24 confirmed H1N1 influenza cases. METHODS: The characters of clinical, laboratory, iconography and etiology of 24 patients with A/H1N1 were studied, and the changes of T-lymphocyte subsets that between the pre- and post-treatment were evaluated. RESULTS: The ages of patients were ranged from 6 to 65 years old; average age was 26 years old.15 patients were under 25 years old. 22 (22/24, 91.7%) patients had recently traveled to USA or Canada. The most common presenting symptoms were: fever (22/24, 91.7%); sore throat (22/24, 91.7%); cough (20/24, 83.3%); dry cough (14/24, 58.3%); expectoration (6/24, 25.0%); nasal discharge (6/24, 25.0%). Six had pneumonia in sixteen patients (6/16, 37.5%) who took CT scan; seven (7/24, 29.2%) had headache and four (4/24, 16.7%) had muscular soreness; two (2/24, 8.3%) had sneeze and nasal obstruction; only one(1/24, 4.2%) had diarrhea; one (1/24, 4.2%) had conjunctivitis. The result of 23 patients about T-Lymphocyte subsets: most of CD4 and CD8 were decreased (18/23, 78.3%), ranging from 122 to 691 cells/microl (normal was 706 - 1125 cells/microl), with the average of 408 cells/microl, but ratios of CD4/CD8 were normal. Fourteen patients were detected CD4 and CD8 after received the treatment during 5 to 7 days.the results of CD4 (cells/microl) were different between the pre- and post-treatment: 436.29 +/- 189.06, 976.71 +/- 332.96 (paired-samples t test: t = -5.416, P < 0.05) while the results of CD8 (cells/microl) were: 323.64 +/- 176.47, 703.14 +/- 211.77 (t = -5.319, P < 0.05); the results of leukocytes in 22 patients were different between pre- and post-treatment: (5.13 +/- 1.47) x 10(9)/L, (6.25 +/- 1.37) x 10(9)/L (t = -2.900, P < 0.05) while the results of lymphocytes were: (1.16 +/- 0.43) x 10(9)/L, (2.30 +/- 0.37) x 10(9)/L (t = -6.819, P < 0.05); but the ratios of CD4/CD8 were: 1.44 +/- 0.41, 1.40 +/- 0.26 (t = 0.507, P > 0.05). All the patients were received antivirus treatment (Oseltamivir) and the virus conversed during 1 - 10 days (average 4.5 days). The temperature was normal after onset during 3 - 4 days and the patients were recovered during 3 - 13 days (with the average of 7.3 days). CONCLUSION: Influenza A virus H1N1 subtype was identified as the cause of outbreaks of febrile respiratory infection which was self-limited. There was no evidence to show that the changes of T-Lymphocyte subsets could indicate the prognosis of patients.