Immunization with Tp0954, an adhesin of Treponema pallidum, provides protective efficacy in the rabbit model of experimental syphilis.

Syphilis, a chronic multisystemic disease caused by spirochete Treponema pallidum subspecies pallidum infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a T. pallidum placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund's adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited T. pallidum dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized, T. pallidum-challenged animals were not infected by T. pallidum, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.

Convenient exosome separation by phosphatidylserine targeting polymer brush materials.

We report phosphatidylserine targeting polymer brush materials to selectively separate exosomes. This method provides an efficient separation strategy with ordinary centrifuge force, which improves the integrity and purity of the exosomes. Compared with the common methods, the content of contaminated lipoprotein in the resulting exosomes decreased obviously.

The diversity analysis and gene function prediction of intestinal bacteria in three equine species.

The intestinal flora has a variety of physiological functions involved in the regulation of host metabolism, immunity and endocrinology, and plays an important role in maintaining the health of the host. In this study, we used high-throughput sequencing technology to analyze the intestinal bacterial diversity and their gene functions in three equine species of the genus Shetland Pony (SP), Mongolian Wild Ass (MA), and Plain Zebra (PZ) in captivity in two wildlife parks in Inner Mongolia Autonomous Region, China. The results showed that only the SP intestinal bacterial abundance index (Chao1) was significantly different (P < 0.05) between the same species in the two wildlife parks, but neither the intestinal bacterial diversity index (Shannon) nor the community composition were significantly different (P > 0.05). The bacterial abundance index (Chao1) was significantly higher in MA than SP (P < 0.05) and highly significantly higher than PZ (P < 0.01); the bacterial diversity index (Shannon) was higher in MA than PZ, but there was no significant difference, but both MA and PZ were significantly higher than SP (P < 0.05). Moreover, the intestinal bacterial community composition was significantly different among the three equine species (P = 0.001). The dominant bacterial phyla for SP, MA, and PZ were Firmicutes and Bacteroidota; among them, the bacterial family with the highest relative abundance was Lachnospiraceae and the bacterial genus was Rikenellaceae_RC9_gut_group. Analysis of the metabolic gene functions of intestinal bacteria revealed that the highest relative abundance at Pathway level 2 was for global and overview maps; at Pathway level 3, the highest relative abundance was for biosynthesis of secondary metabolites. In sum, the intestinal bacterial community composition and diversity of the above three equine species differed significantly, but their metabolic gene functions were similar. Moreover, the results of this manuscript fill the gap in the study of intestinal bacterial diversity in SP, MA, and PZ. It also provides a reference for the study of the dominant bacteria in the intestinal microorganisms of these three equine species and the discovery of novel functional genes.

Assessment of recombinant antigens Tp0100 and Tp1016 of Treponema pallidum for serological diagnosis of syphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

Regulatory Effect of Lactiplantibacillus plantarum 2-33 on Intestinal Microbiota of Mice With Antibiotic-Associated Diarrhea.

Diarrhea is one of the common adverse reactions in antibiotic treatment, which is usually caused by the imbalance of intestinal flora, and probiotics play an important role in the structure of intestinal flora. Therefore, this experiment studied the regulatory effect of Lactiplantibacillus plantarum 2-33 on antibiotic-associated diarrhea (AAD) mice. First, the AAD mice model was established by the mixed antibiotic solution of gentamicin sulfate and cefradine. Then, the physiological indexes and diarrhea of mice were observed and recorded by gastric perfusion of low dose (1.0 × 107 CFU/ml), medium dose (1.0 × 108CFU/ml), and high dose (1.0 × 109 CFU/ml) strain 2-33. 16S rRNA gene V3-V4 regions were sequenced in colon contents of mice in control group, model group, self-healing group, and experimental group, respectively, and the diversity of intestinal flora and gene function prediction were analyzed. The results showed that the intestinal flora of AAD mice was not significantly regulated by gastric perfusion of strain 2-33 to 7 days, but the relative abundance and diversity of intestinal flora of AAD mice were significantly improved by gastric perfusion to 14 days (p < 0.05). In addition, at the genus level, the relative abundance of Lactobacillus increased significantly, and the relative abundance of Enterococcus and Bacillus decreased significantly (p < 0.05). In addition, the regulation of strain 2-33 on intestinal flora of AAD mice was time- and dose-dependent, short-term gastric perfusion, and low dose had no significant effect (p > 0.05). Strain 2-33 can significantly increase the levels of anti-inflammatory cytokines IL-4 and IL-10, significantly decrease the levels of proinflammatory cytokines TNF-α and IFN-γ (p < 0.05), and can also adjust carbohydrate metabolism, amino acid metabolism, and energy metabolism to normal levels, thus accelerating the recovery of intestinal flora structure of AAD mice. In summary, strain 2-33 can improve the structure and diversity of intestinal flora of AAD mice, balance the level of substance and energy metabolism, and play a positive role in relieving diarrhea, maintaining and improving the intestinal microecological balance.

Ultrasimple air-annealed pure graphene oxide film for high-performance supercapacitors.

Realizing both high gravimetric and volumetric specific capacitances (noted as CW and CV, respectively) is an essential prerequisite for the next-generation, high performance supercapacitors. However, the need of electronic/ionic transport for electrochemical reactions causes a "trade-off" between compacted density and capacitance of electrode, thereby impairing gravimetric or volumetric specific capacitances. Herein, we report a high-performance, film-based supercapacitor via a thermal reduction of graphene oxide (GO) in air. The reduced, layer-structured graphene film ensures high electrode density and high electron conductivity, while the hierarchical channels generated from reduction-induced gas releasing process offer sufficient ion transport pathways. Note that the resultant graphene film is employed directly as electrodes without using any additives (binders and conductive agents). As expected, the as-prepared electrodes perform particularly well in both CW (420F g-1) and CV (360F cm-3) at a current density of 0.5 A g-1. Even at an ultrahigh current density of 50 A g-1, CW and CV maintain in 220F g-1 and 189F cm-3, respectively. Furthermore, the corresponding symmetric two-electrode supercapacitor achieves both high gravimetric energy density of 54 W h kg-1 and high gravimetric power density of 1080 W kg-1, corresponding to volumetric energy density of 46 W h L-1 and volumetric power density of 917 W L-1.

Diversity Analysis of Bacterial and Function Prediction in Hurunge From Mongolia.

With the continuous infiltration of industrialization and modern lifestyle into pastoral areas, the types and processing capacity of Hurunge are decreasing, and the beneficial microbial resources contained in it are gradually disappearing. The preservation and processing of Hurunge are very important for herdsmen to successfully produce high-quality koumiss in the second year. Therefore, in this study, 12 precious Hurunge samples collected from Bulgan Province, Ovorkhangay Province, Arkhangay Province, and Tov Province of Mongolia were sequenced based on the V3-V4 region of the 16S rRNA gene, and the bacterial diversity and function were predicted and analyzed. There were significant differences in the species and abundance of bacteria in Hurunge from different regions and different production methods (p < 0.05). Compared with the traditional fermentation methods, the OTU level of Hurunge fermented in the capsule was low, the Acetobacter content was high and the bacterial diversity was low. Firmicutes and Lactobacillus were the dominant phylum and genus of 12 samples, respectively. The sample QHA contained Komagataeibacter with the potential ability to produce bacterial nanocellulose, and the abundance of Lactococcus in the Tov Province (Z) was significantly higher than that in the other three regions. Functional prediction analysis showed that genes related to the metabolism of bacterial growth and reproduction, especially carbohydrate and amino acid metabolism, played a dominant role in microorganisms. In summary, it is of great significance to further explore the bacterial diversity of Hurunge for the future development and research of beneficial microbial resources, promotion, and protection of the traditional ethnic dairy products.

The Predictors of Conduction Disturbances Following Transcatheter Aortic Valve Replacement in Patients With Bicuspid Aortic Valve: A Multicenter Study.

Objective: To evaluate the predictors of new-onset conduction disturbances in bicuspid aortic valve patients using self-expanding valve and identify modifiable technical factors. Background: New-onset conduction disturbances (NOCDs), including complete left bundle branch block and high-grade atrioventricular block, remain the most common complication after transcatheter aortic valve replacement (TAVR). Methods: A total of 209 consecutive bicuspid patients who underwent self-expanding TAVR in 5 centers in China were enrolled from February 2016 to September 2020. The optimal cut-offs in this study were generated from receiver operator characteristic curve analyses. The infra-annular and coronal membranous septum (MS) length was measured in preoperative computed tomography. MSID was calculated by subtracting implantation depth measure on postoperative computed tomography from infra-annular MS or coronal MS length. Results: Forty-two (20.1%) patients developed complete left bundle branch block and 21 (10.0%) patients developed high-grade atrioventricular block after TAVR, while 61 (29.2%) patients developed NOCDs. Coronal MS <4.9 mm (OR: 3.08, 95% CI: 1.63-5.82, p = 0.001) or infra-annular MS <3.7 mm (OR: 2.18, 95% CI: 1.04-4.56, p = 0.038) and left ventricular outflow tract perimeter <66.8 mm (OR: 4.95 95% CI: 1.59-15.45, p = 0.006) were powerful predictors of NOCDs. The multivariate model including age >73 years (OR: 2.26, 95% CI: 1.17-4.36, p = 0.015), Δcoronal MSID <1.8 mm (OR: 7.87, 95% CI: 2.84-21.77, p < 0.001) and prosthesis oversizing ratio on left ventricular outflow tract >3.2% (OR: 3.42, 95% CI: 1.74-6.72, p < 0.001) showed best predictive value of NOCDs, with c-statistic = 0.768 (95% CI: 0.699-0.837, p < 0.001). The incidence of NOCDs was much lower (7.5 vs. 55.2%, p < 0.001) in patients without Δcoronal MSID <1.8 mm and prosthesis oversizing ratio on left ventricular outflow tract >3.2% compared with patients who had these two risk factors. Conclusion: The risk of NOCDs in bicuspid aortic stenosis patients could be evaluated based on MS length and prosthesis oversizing ratio. Implantation depth guided by MS length and reducing the oversizing ratio might be a feasible strategy for heavily calcified bicuspid patients with short MS.

PNUTS mediates ionizing radiation-induced CNE-2 nasopharyngeal carcinoma cell migration, invasion, and epithelial-mesenchymal transition via the PI3K/AKT signaling pathway.

PURPOSE: Ionizing radiation (IR) is widely used for treating nasopharyngeal carcinoma (NPC). However, recent studies indicate that IR can also promote the migration and invasion of malignant tumors. Phosphatase 1 nuclear-targeting subunit (PNUTS), a novel interacting protein, was recently demonstrated to be involved in tumorigenesis and metastasis formation. This protein was hypothesized to take part in IR-induced migration and invasion in NPC cells in this study. MATERIALS AND METHODS: Western blotting was used to detect how PNUTS was expressed in NPC cells with or without IR treatment. Wound-healing and Transwell assays were used to measure cell migration and invasion. Quantitative real-time PCR and Western blotting were used to determine the expression levels of PNUTS and epithelial-mesenchymal transition (EMT) proteins, respectively, after CNE-2 cells were infected with an adenovirus vector, ad-PNUTS, or transfected with PNUTS-specific siRNA. Finally, the expression levels of PI3K/AKT signaling-related proteins were detected by Western blotting. RESULTS: IR significantly promoted PNUTS expression and the migration and invasion in CNE-2 cells. Moreover, after exposure to IR, expression of the mesenchymal markers N-cadherin and vimentin increased, while that of the epithelial marker E-cadherin decreased. Silencing PNUTS remarkably attenuated IR-induced increases in cell migration and invasion and reversed the EMT process. Additionally, the overexpression of PNUTS restored the mobility and invasiveness of CNE-2 cells, which regained EMT characteristics. Furthermore, we found that PNUTS regulated IR-induced EMT via the PI3K/AKT signaling pathway. CONCLUSION: Our research illustrates a relationship between PNUTS and IR-induced cell migration and invasion and provides a novel therapeutic target for preventing radiotherapy-induced metastasis in NPC patients.

Effect of pharmaceutical care on clinical outcomes of outpatients with type 2 diabetes mellitus.

BACKGROUND: In the People's Republic of China, outpatients have limited time with their physicians. Thus, compared to inpatients, outpatients have lower medication adherence and are less knowledgeable about their disease. OBJECTIVE: The objective of this study was to evaluate the effect of pharmaceutical care on clinical outcomes of outpatients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: A randomized, controlled, prospective clinical trial was conducted recruiting a total of 240 T2DM outpatients from Zhongda Hospital, Southeast University. The control group (CG) received only common care from medical staff, whereas the inter vention group (IG) received extra pharmaceutical care from clinical pharmacists. Biochemical data such as blood pressure (BP), fasting blood glucose (FBG), glycosylated hemoglobin A1 (HbA1c), and blood lipid were collected before and after 6-month intervention. The primary end points in this study were FBG and HbA1c. RESULTS: After the intervention, most of the baseline clinical outcomes of the patients in IG significantly improved, while only body mass index, diastolic BP, low-density lipoprotein cholesterol, and total cholesterol (TC) improved significantly in patients in the CG. Compared to CG, in IG, there were significant improvements in FBG, HbA1c, TC, the target attainment rates of HbA1c, and BP. CONCLUSION: Pharmaceutical care provided by clinical pharmacists could improve the control of diabetes of outpatients, and clinical pharmacists could play an important role in diabetes management.