Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study.

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Efficacy of Oxy-Ionic Solutions With Varying pH Levels Against Streptococcus mutans In Vitro.

Background Chlorhexidine (CHX) is a widely used antimicrobial agent known for its ability to inhibit cariogenic bacteria, reduce plaque formation, neutralize acidity, and promote remineralization. However, the effectiveness of oxy-ionic solutions at different pH levels as an alternative antimicrobial treatment requires further exploration. This study aims to compare the antimicrobial effects of oxy-ionic solutions at various pH levels with those of CHX and fluoride. Methodology This study employed disc diffusion tests to measure the inhibition zone diameters of each solution and broth dilution assays to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results The oxy-ionic solutions exhibited varying degrees of antimicrobial effectiveness depending on their pH levels. The solution at pH 5 demonstrated the best antimicrobial performance among the oxy-ionic solutions, with inhibition zones comparable to those of CHX. The MIC and MBC values indicated that oxy-ionic solutions in mildly acidic environments generally resulted in better antimicrobial activity. Conclusions The study concludes that while CHX remains highly effective against cariogenic bacteria, oxy-ionic solutions, particularly at pH 5, offer a promising alternative. The antimicrobial efficacy of oxy-ionic solutions is influenced by their pH levels. Further research is recommended to explore the long-term effects and clinical applications of oxy-ionic solutions in maintaining oral health and preventing disease.

Nonnegligible Contribution of Nonlymphoid Tissue to Viral Reservoir During the Short-Term Early cART in SIVmac239-Infected Chinese Rhesus Macaques.

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.

Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

The salt-tolerance of perennial ryegrass is linked with root exudate profiles and microflora recruitment.

Salinity poses a significant threat to plant growth and development. The root microbiota plays a key role in plant adaptation to saline environments. Nevertheless, it remains poorly understood whether and how perennial grass plants accumulate specific root-derived bacteria when exposed to salinity. Here, we systematically analyzed the composition and variation of rhizosphere and endophytic bacteria, as well as root exudates in perennial ryegrass differing in salt tolerance grown in unsterilized soils with and without salt. Both salt-sensitive (P1) and salt-tolerant (P2) perennial ryegrass genotypes grew better in unsterilized soils compared to sterilized soils under salt stress. The rhizosphere and endophytic bacteria of both P1 and P2 had lower alpha-diversity under salt treatment compared to control. The reduction of alpha-diversity was more pronounced for P1 than for P2. The specific root-derived bacteria, particularly the genus Pseudomonas, were enriched in rhizosphere and endophytic bacteria under salt stress. Changes in bacterial functionality induced by salt stress differed in P1 and P2. Additionally, more root exudates were altered under salt stress in P2 than in P1. The content of important root exudates, mainly including phenylpropanoids, benzenoids, organic acids, had a significantly positive correlation with the abundance of rhizosphere and endophytic bacteria under salt stress. The results indicate that the interactions between root-derived bacteria and root exudates are crucial for the salt tolerance of perennial ryegrass, which provides a potential strategy to manipulate root microbiome for improved stress tolerance of perennial grass species.

The Recent Progress of Oxygen Reduction Electrocatalysts Used at Fuel Cell Level.

Proton exchange membrane fuel cells (PEMFCs) are gaining significant interest as an attractive substitute for traditional fuel cells, with higher energy density, lower environmental pollution, and better operation efficiency. However, the cathode reaction, i.e., the oxygen reduction reaction (ORR), is widely proved to be inefficient, and therefore an obstacle to the widespread development of PEMFCs. The requirement for affordable highly-efficient ORR catalysts is extremely urgent to be met, especially at fuel cell level. Unfortunately, most previous reports focus on the ORR performance at rotating disk electrodes (RDE) level instead of membrane electrode assembly (MEA) level, making it harder to evaluate ORR catalysts operating under real vehicle conditions. Obviously, it is extremely necessary to develop an in-depth understanding of the structure-activity relationship of highly-efficient ORR catalysts applied at MEA level. In this work, an overview of the latest advances in ORR catalysts is provided with an emphasis on their performance at MEA level, hoping to cover the novel and systemic insights for innovative and efficient ORR catalyst design and applications in PEMFCs.

Study on Reaction Mechanism and Process Safety for Epoxidation.

The reaction mechanism and process safety for epoxidation were investigated in this study. 1-(2-Chlorophenyl)-2-(4-fluorophenyl)-3-(1,2,4-triazole) propene (triazolene), a typical representative of high steric olefinic compounds, was chosen as the raw material. In addition, hydrogen peroxide was chosen as the oxygen source in the reaction. Online Raman spectroscopy combined with high-performance liquid chromatography (HPLC) was used for the process monitoring analysis. The results of this study indicated that the epoxidation process is exothermic, and the apparent reaction heat was 1340.0 kJ·kg-1 (measured by the mass of triazolene). The heat conversion rate was 39.7% immediately after hydrogen peroxide dosing to a triazolene and maleic anhydride mixture solution in chloroform. This result indicated that a considerable amount of heat is accumulated during the epoxidation reaction, which leads to a potential high safety concern. The study of the reaction mechanism showed that maleic anhydride reacts with hydrogen peroxide quickly to form maleic acid peroxide, which is controlled by hydrogen peroxide feeding, and the formed maleic acid peroxide further reacts with triazolenes slowly, which is a kinetically controlled reaction. Decomposition kinetics studies revealed that the temperatures corresponding to the time of maximum reaction rate for 8 and 24 h are TD24 = 89.9 °C and TD8 = 104.1 °C, respectively.

Observation of peripheral refraction in myopic anisometropia in young adults.

AIM: To investigate the differences in retinal refraction difference values (RDVs) of adult patients with myopic anisometropia compared with those without myopic anisometropia, and to investigate the relationship between ocular biometric measurements and relative peripheral refraction. METHODS: This clinical observation study included 130 patients with myopia (-0.25 to -10.00 D) between October 2022 and January 2023 aged between 18 and 40y. The patients were divided into anisometropia (n=63; difference in binocular anisometropia ≥1.00 D) and non-anisometropia (n=67; difference in binocular anisometropia <1.00 D) groups accordingly. Ocular biometric measurements were performed by optical biometrics and corneal topography to assess the steep keratometry (Ks), flap keratometry (Kf), axial length (AL), corneal astigmatism (CYL; Ks-Kf), surface regularity index (SRI), surface asymmetry index (SAI), and central corneal thickness (CCT). The RDV was measured at five retinal areas from the fovea to 53 degrees (RDV-0-10, RDV-10-20, RDV-20-30, RDV-30-40, and RDV-40-53), the total RDV (TRDV) of 53 degrees, and four regions, including RDV-superior, RDV-inferior, RDV-temporal, and RDV-nasal. An analysis of Spearman correlation was carried out to examine the correlation between RDV and the spherical equivalent (SE) and ocular biological parameters. RESULTS: Within RDV-20-53, both groups showed relative hyperopic defocus, and the increase in RDV corresponds to the increase in eccentricity. In the myopic anisometropia group, the TRDV, RDV-20-53, RDV-superior, and more myopic eyes had significantly higher RDV-temporal values than less myopic eyes. (P<0.05). In the non-anisometropia group, there was no significant difference in the RDV between the more and less myopic eyes at different eccentricities (P>0.05). There was a negative correlation between SE and TRDV (r=-0.205, P=0.001), RDV-20-53 (r=-0.281, -0.183, -0.176, P<0.05), RDV-superior (r=-0.251, P<0.001), and RDV-temporal (r=-0.230, P<0.001), a negative correlation between CYL and RDV-10-30 (r=-0.147, -0.180, P<0.05), and a negative correlation between SRI and RDV-0-20 (r=-0.190, -0.170, P<0.05). AL had a positive correlation with RDV-20-30 (r=0.164, P=0.008) and RDV-temporal (r=0.160, P=0.010). CONCLUSION: More myopic eyes in patients with myopic anisometropia show more peripheral hyperopic defocus. Diopter and corneal morphology may affect peripheral retinal defocus.

The Predictive Value of Serum NT-proBNP on One-Year All-Cause Mortality in Geriatrics Hip Fracture: A Cohort Study.

Objective This study evaluated the association between N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and one-year mortality in geriatric patients with intertrochanteric and femoral neck fractures receiving the operative treatment. Methods Consecutive age ≥65 years patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. The multivariate logistic regression models were used to identify the association between preoperative NT-proBNP concentrations and mortality. All analyses were performed using EmpowerStats and the R software. Result One thousand two hundred nineteen patients were included in the study. The average age was 79.73±6.65 years (range 66-99 years). The mean NT-proBNP concentration was 616.09±1086.85 ng/L (median 313.40 ng/L, range 16.09-20123.00 ng/L). The follow-up was 35.39±15.09 months (median 35.78 months, range 0.10-80.14 months). One hundred and eleven (9.1%) patients died within one year. After adjusting for confounding factors, multivariate logistic regression models showed a curved association between preoperative NT-proBNP concentration and one-year mortality. When the NT-proBNP concentration was below 1099 ng/L, the mortality increased by 10% (OR=1.10, 95%CI: 1.03-1.17, P=0.0025) when NT-proBNP increased by 100 ng/L. When the NT-proBNP concentration was above 1099 ng/L, the mortality did not increase anymore when NT-proBNP increased (OR=1.00, 95%CI: 0.99-1.02, P=0. 7786). Thus, NT-proBNP was a valuable indicator to predict high one-year mortality in practice. Conclusion The NT-proBNP concentrations were nonlinearly associated with mortality in elderly hip fractures with a saturation effect, and NT-proBNP was a risk indicator of all-cause mortality. A well-designed controlled trial to show the role of mortality by decreasing the concentration of NT-proBNP is needed in the future.

[Changes in Plasma Amyloid-ß Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment].

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy: A case report.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a newly described and rare glomerular disease. To date, only approximately 40 cases have been reported globally. CASE SUMMARY: A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years. The patient was diagnosed with PIG. She was prescribed corticosteroid therapy in other hospitals during the initial stage, to which she had responded poorly and had developed femoral head necrosis. Therefore, we administered immunosuppressants, renin-angiotensin system inhibitors, combined with traditional Chinese medicine. The patient was followed for 1 year, during which her clinical condition improved. CONCLUSION: Integrated Chinese and Western medicine may be effective for PIG treatment, which requires active intervention to improve prognosis.

The serum NT-proBNP is associated with all-cause mortality in geriatric hip fracture: a cohort of 1354 patients.

Geriatric hip fracture patients often have increased N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. This study found a curved association between preoperative NT-proBNP level and all-cause mortality. There was an inflection point of NT-proBNP 781 ng/L in the saturation effect. Thus, NT-proBNP was a valuable indicator of all-cause mortality. PURPOSE: To explore the relationship between N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level and all-cause mortality in geriatric hip fractures and evaluate the possible predictive role of NT-proBNP level. METHODS: Consecutive older adult patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between NT-proBNP levels and mortality. All analyses were performed using EmpowerStats and the R software. RESULTS: One thousand three hundred fifty-four patients were included in the study. The mean follow-up was 34.35 ± 15.82 months. Four hundred twenty-nine (31.68%) patients died due to all-cause mortality. The preoperative NT-proBNP was median 337.95 (range 16.09-20,123.00) ng/L. Multivariate Cox regression models showed a nonlinearity association between NT-proBNP levels and mortality in elderly hip fractures. An NT-proBNP of 781 ng/L was an inflection point in the saturation effect. When < 781 ng/L, NT-proBNP was associated with mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI]: 1.06-1.18, P < 0.0001), whereas at > 781 ng/L, NT-proBNP was not associated with mortality (HR = 1.00, 95% CI: 0.98-1.01, P = 0.4718). In the stratification analysis, the result was stable. CONCLUSIONS: The NT-proBNP levels were nonlinearly associated with mortality in elderly hip fractures, and NT-proBNP of 781 ng/L was a valuable indicator of all-cause mortality. TRIAL REGISTRATION: ChiCTR2200057323.

Grazing practices affect phyllosphere and rhizosphere bacterial communities of Kobresia humilis by altering their network stability.

The primary utilization strategy for meadow grasslands on the Qinghai-Tibet Plateau (QTP) is livestock grazing. This practice is considered as one of the major drivers of plant-associated bacterial community construction and changes in soil properties. The species of Kobresia humilis is considered as the most dominant one in grasslands. However, how different grazing practices affect the phyllosphere and rhizosphere bacterial communities of K. humilis is unknown. To address this issue, the effects of the grazing enclosure (GE), single-species grazing (YG and SG, representing yak only and sheep only, respectively), and different ratios of grazing (ratio of yak to sheep is 1:2, 1:4, and 1:6, represented by MG1:2, MG1:4, and MG1:6, respectively) on the dominant plant of K. humilis, it's phyllosphere and rhizosphere bacteria, and soil properties were investigated using artificially controlled grazing and grazing enclosure. Our data showed that grazing enclosure enhanced vegetation coverage, and rhizosphere bacterial richness and diversity, while reduced plant number and bacterial network stability of K. humilis. The NO3--N, K+, and Cl- concentrations were lower under grazing compared to GE. SG reduced the concentration of NH4+-N, TN, K+, and Na+ compared to YG. Moderate grazing intensity had a lower relative abundance of the r-strategists (Bacteroidota and Gammaproteobacteria) with higher bacterial network stability. Yak and sheep grazing showed reversed impacts on the bacterial network stability between the phyllosphere and rhizosphere of K. humilis. Proteobacteria and Actinobacteriota were identified in the molecular ecological network analysis as keystone taxa in the phyllosphere and rhizosphere networks, respectively, under all treatments. This study explained why sheep grazing has more adverse effects on grazing-tolerant grass species, K. humilis, than yak grazing, and will contribute to a better understanding of the impacts of different grazing practices and grazing enclosure on alpine grassland ecosystems on the QTP.

Adipocyte-derived extracellular vesicles: bridging the communications between obesity and tumor microenvironment.

By the year 2035 more than 4 billion people might be affected by obesity and being overweight. Adipocyte-derived Extracellular Vesicles (ADEVs/ADEV-singular) are essential for communication between the tumor microenvironment (TME) and obesity, emerging as a prominent mechanism of tumor progression. Adipose tissue (AT) becomes hypertrophic and hyperplastic in an obese state resulting in insulin resistance in the body. This modifies the energy supply to tumor cells and simultaneously stimulates the production of pro-inflammatory adipokines. In addition, obese AT has a dysregulated cargo content of discharged ADEVs, leading to elevated amounts of pro-inflammatory proteins, fatty acids, and carcinogenic microRNAs. ADEVs are strongly associated with hallmarks of cancer (proliferation and resistance to cell death, angiogenesis, invasion, metastasis, immunological response) and may be useful as biomarkers and antitumor therapy strategy. Given the present developments in obesity and cancer-related research, we conclude by outlining significant challenges and significant advances that must be addressed expeditiously to promote ADEVs research and clinical applications.

LncRNA PVT1 inhibits endothelial cells apoptosis in coronary heart disease through regulating MAPK1 expression via miR-532-3p.

Background: Coronary atherosclerotic heart disease (CAD) is an inflammatory vascular disease caused by atherosclerosis. Long non-coding RNAs are involved in the pathophysiological process of coronary heart disease. Here we investigated the regulatory effects of lncRNA PVT1 (PVT1) in human coronary artery endothelial cells (HCAECs).Methods: qRT-PCR and western blot were performed to detect gene and protein expressions. CCK-8, flow cytometry and wound healing assays were used to determine cell viability, apoptosis and migration of HCAECs. The binding relationship among miR-532-3p, PVT1 and MAPK1 was verified by dual luciferase reporter assay.Results: Overexpression of PVT1 markedly reduced cell apoptosis and increased cell proliferation and migration. However, miR-532-3p upregulation suppressed cell proliferation and migration and promoted apoptosis of HCAECs. PVT1 suppressed the expression of miR-532-3p via directly targeting miR-532-3p. And miR-532-3p overexpression abolished the effect of PVT1 upregulation on proliferation and apoptosis in HCAECs. Furthermore, MAPK1 acted as a target gene of miR-532-3p and miR-532-3p inhibited MAPK1 expression.Conclusion: PVT1 promoted MAPK1 expression by targeting miR-532-3p, thus inhibiting HCAECs apoptosis and promoting cell proliferation, suggesting PVT1 might have great potential as a therapeutic target for CAD.

Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.

Consumption frequencies of beverages and the hypertension risk in adults: a cohort study in China.

OBJECTIVE: To explore the associations between the consumption frequencies of alcohol, tea and sugar-sweetened beverages (SSBs) and the hypertension risk among Chinese adults. DESIGN: A longitudinal study of the effect of beverage consumption on hypertension risk. SETTING: Nine provinces in China, including Jiangsu, Hubei, Hunan, Guangxi, Guizhou, Liaoning, Heilongjiang, Shandong and Henan. PARTICIPANTS: The longitudinal data of the China Health and Nutrition Survey from 2004 to 2015 were used. A total of 4427 participants from 9 provinces were included at baseline. OUTCOME: First incidence of hypertension. RESULTS: During a mean follow-up of 8.7 years, 1478 participants developed hypertension. Alcohol consumption more than twice a week in young men (HR 1.86, 95% CI 1.09 to 3.18) or middle-aged men (HR 1.37, 95% CI 1.01 to 1.87) was associated with a higher hypertension risk. Middle-aged women who consumed tea frequently (HR 0.71, 95% CI 0.52 to 0.97), or young women who consumed SSBs less than once a week (HR 0.31, 95% CI 0.14 to 0.67) had a lower risk of hypertension. CONCLUSIONS: High-frequency alcohol consumption increased the risk of hypertension in men, and frequent tea consumption and low-frequency SSBs consumption were associated with lower risk of hypertension in women. Consumption frequency of beverages was also suggested to be considered in the prevention and control of hypertension.

Expression and Clinical Significance of PIEZO2 in Gastric Cancer.

OBJECTIVE: The aim of this research was to investigate the expression of PIEZO2 and its potential clinical significance in gastric cancer (GC). METHODS: In this study, we detected the protein expression levels of PIEZO2 in GC tissues and adjacent normal tissues by immunohistochemistry (IHC) and analysed the relationship between the protein expression levels of PIEZO2 and clinicopathological parameters of GC patients. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter were used to verify the diagnostic and prognostic values of PIEZO2. Proteins interacting with PIEZO2 were predicted using the SRING database. RESULTS: Our results showed that the protein expression levels of PIEZO2 in GC tissues were lower than those in adjacent normal tissues (all P < 0.05), and the protein expression level of PIEZO2 was correlated with lymph node metastasis and TNM stage of GC patients (all P < 0.05). Aberrant overexpression of PIEZO2 was associated with poor prognosis of GC patients. Proteins such as VR1, TRPV1, LHFPL5, STOM, TRPA1 and STOML3 had obvious interactions with PIEZO2 (P = 0.00213). CONCLUSION: In summary, our current study identified PIEZO2 as a promising target for early diagnosis and as a potential prognostic biomarker in GC patients.

Risk factors of seizure presentation in brain arteriovenous malformation patients and seizure outcomes after single-modality treatments.

BACKGROUND: Epileptic seizures are common symptoms in brain arteriovenous malformation patients and seizure control was an important issue in the treatments. This retrospective study attempted to define the risk factors of seizure presentation and to evaluate the effects of treatment modalities on seizure outcomes. METHODS: Patients receiving single treatment modality during 2013-2016 years, followed up more than 2 years were recruited. Logistic regression analysis was used to detect independent predictors. The factors associated with seizure control were analyzed in patients with pre-treatment seizures, and the factors associated with de novo seizures were analyzed in patents without pre-treatment seizures. RESULTS: Multivariate analysis identified that the independent predictors of seizure presentation were unruptured (ruptured vs. unruptured, OR = 0.314), and in the frontal (frontal vs. parietal, OR = 3.982) or temporal lobe (temporal vs parietal, OR = 3.313). In 47 patients with seizure presentation, good seizure outcomes were achieved in 26 cases. Partial obliteration of nidus (partial vs complete, OR = 32.301) and headache presentation were independent predictors of poor outcome. In 169 patients without seizure presentation, de novo seizures occurred in 22 cases. Treatments of microsurgery or radiosurgery led to a higher incidence of de novo seizures than intravascular embolization. CONCLUSIONS: Patients with unruptured and frontal/temporal lobe located nidus were more likely to manifest seizure presentation. Incomplete nidus obliteration was an independent risk factor of poor outcomes in patients with pre-existing seizures. However, compared to microsurgery or radiosurgery, endovascular embolization was less likely to cause de novo seizures in patients without pre-existing seizures.