Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer.

BACKGROUND: Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC). METHODS: Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n = 472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls). RESULTS: Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer's disease, liver iron content, sex hormone binding global levels, naive CD4-CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs. CONCLUSION: This study provides potential intervention measures for preventing LTL-induced PCs.

The Role of Extracellular Vesicles in the Treatment of Prostate Cancer.

Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because of a lack of a durable response, especially in advanced disease states. Extracellular vesicles (EVs) are lipid-bilayer encircled nanoscale vesicles that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating the transfer of information. The past decade has witnessed a wide range of EV applications in both diagnostics and therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers in various clinical scenarios to guide treatment; EVs can facilitate the grading and staging of patients for appropriate treatment selection. Second, EVs play a pivotal role in pathophysiological processes via intercellular communication. Targeting key molecules involved in EV-mediated tumor progression (e.g., proliferation, angiogenesis, metastasis, immune escape, and drug resistance) is a potential approach for curbing PCa. Third, EVs are promising drug carriers. Naïve EVs from various sources and engineered EV-based drug delivery systems have paved the way for the development of new treatment modalities. This review discusses the recent advancements in the application of EV therapies and highlights EV-based functional materials as novel interventions for PCa.

Research progress on the application of different controlling strategies to minimizing ethyl carbamate in grape wine.

Ethyl carbamate (EC) is a probable carcinogenic compound commonly found in fermented foods and alcoholic beverages and has been classified as a category 2A carcinogen by the International Agency for Research on Cancer (IARC). Alcoholic beverages are one of the main sources of EC intake by humans. Therefore, many countries have introduced a standard EC limit in alcoholic beverages. Wine is the second largest alcoholic beverage in the world after beer and is loved by consumers for its rich taste. However, different survey results showed that the detection rate of EC in wine was almost 100%, while the maximum content was as high as 100 µg/L, necessitating EC content regulation in wine. The existing methods for controlling the EC level in wine mainly include optimizing raw fermentation materials and processes, using genetically engineered strains, and enzymatic methods (urease or urethanase). This review focused on introducing and comparing the advantages, disadvantages, and applicability of methods for controlling EC, and proposes two possible new techniques, that is, changing the fermentation strain and exogenously adding phenolic compounds. In the future, it is hoped that the feasibility of this prospect will be verified by pilot-scale or large-scale application to provide new insight into the regulation of EC during wine production. The formation mechanism and influencing factors of EC in wine were also introduced and the analytical methods of EC were summarized.

Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.

Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

Mulberry Ethanol Extract and Rutin Protect Alcohol-Damaged GES-1 Cells by Inhibiting the MAPK Pathway.

Mulberry extract has been proven to have the effect of resisting alcohol damage, but its mechanism is still unclear. In this study, the composition of mulberry ethanol extract (MBE) was identified by LC-MS/MS and the main components of MBE were ascertained by measuring. Gastric mucosal epithelial (GES-1) cells were used to elucidate the mechanism of MBE and rutin (the central part of MBE) helped protect against alcohol damage. The results revealed that phenolics accounted for the majority of MBE, accounting for 308.6 mg/g gallic acid equivalents and 108 substances were identified, including 37 flavonoids and 50 non-flavonoids. The treatment of 400 µg/mL MBE and 320 µM rutin reduced early cell apoptosis and the content of intracellular reactive oxygen species, malondialdehyde and increased glutathione. The qPCR results indicated that the MBE inhibits the expression of genes in the mitogen-activated protein kinase (MAPK) pathway, including p38, JNK, ERK and caspase-3; rutin inhibits the expression of p38 and caspase-3. Overall, MBE was able to reduce the oxidative stress of GES-1 cells and regulated apoptosis-related genes of the MAPK pathway. This study provides information for developing anti-ethanol injury drugs or functional foods.

Analysis of Ion Motion and Diffusion Confinement in Inverted Drift Tubes and Trapped Ion Mobility Spectrometry Devices.

Ion motion in trapped ion mobility spectrometers (TIMS) and inverted drift tubes (IDT) has been investigated. The two-dimensional (2D) axisymmetric analytical solution to the Nernst-Planck equation for constant gas flows and opposed linearly increasing fields is presented for the first time and is used to study the dynamics of ion distributions in the ramp region. It is shown that axial diffusion confinement is possible and that broad packets of ions injected initially into the system can be contracted. This comes at the expense of the generation of a residual radial field that pushes the ions outward. This residual electric field is of significant importance as it hampers sensitivity and resolution when parabolic velocity profiles form. When radio frequency (RF) is employed at low pressures, this radial field affects the stability of ions inside the mobility cell. Trajectories and frequencies for stable motion are determined through the study of Mathieu's equation. Finally, effective resolutions for the ramp and plateau regions of the TIMS instrument are provided. While resolution depends on the inverse of the square root of mobility, when proper parameters are used, resolutions in the thousands can be achieved theoretically for modest distances and large mobilities.

Optimization of long range potential interaction parameters in ion mobility spectrometry.

The problem of optimizing Lennard-Jones (L-J) potential parameters to perform collision cross section (CCS) calculations in ion mobility spectrometry has been undertaken. The experimental CCS of 16 small organic molecules containing carbon, hydrogen, oxygen, nitrogen, and fluoride in N2 was compared to numerical calculations using Density Functional Theory (DFT). CCS calculations were performed using the momentum transfer algorithm IMoS and a 4-6-12 potential without incorporating the ion-quadrupole potential. A ceteris paribus optimization method was used to optimize the intercept σ and potential well-depth ϵ for the given atoms. This method yields important information that otherwise would remain concealed. Results show that the optimized L-J parameters are not necessarily unique with intercept and well-depth following an exponential relation at an existing line of minimums. Similarly, the method shows that some molecules containing atoms of interest may be ill-conditioned candidates to perform optimizations of the L-J parameters. The final calculated CCSs for the chosen parameters differ 1% on average from their experimental counterparts. This result conveys the notion that DFT calculations can indeed be used as potential candidates for CCS calculations and that effects, such as the ion-quadrupole potential or diffuse scattering, can be embedded into the L-J parameters without loss of accuracy but with a large increase in computational efficiency.

Determination of 10 mycotoxins in wine, baijiu, and huangjiu of the Chinese market by liquid chromatography tandem mass spectrometry and exposure estimation.

In this study, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to analyze the prevalence of 10 mycotoxins in 140 samples from the Chinese market, aiming to assess the exposure of Chinese individuals to these mycotoxins through the consumption of wine, baijiu, and huangjiu. Mycotoxins were detected in 98% of the samples, with fumonisins (FBs), deoxynivalenol (DON), and zearalenone (ZEN) exhibiting positive rates exceeding 50%. Regarding the exposure of the Chinese population to mycotoxins resulting from alcoholic beverage consumption, fruit wine intake made a relatively significant contribution to aflatoxin exposure, while baijiu showed a relatively significant contribution to ZEN exposure (1.84%). The analysis of the correlation between grape variety, wine region, and mycotoxin content demonstrated that FBs, ZEN, and DON were significantly influenced by grape variety and wine region. This research holds great significance in protecting human life and health, as well as in the production of safer alcoholic beverages.

Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of 10 mycotoxins in beer of the Chinese market and exposure estimate.

Mycotoxins are important risk factors in beer. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine 10 mycotoxins in beer within 6 min. The method is fast, efficient, and has a simple and quick sample preparation. Validation was conducted based on the performance standards specified in Commission Decision 657/2002/EC, and the results demonstrated excellent linearity (R2 > 0.99), repeatability (RSD < 5 %), quantification limits (0.005-20.246 µg/L), and recovery rates (77 %-118 %). The prevalence of the 10 mycotoxins in 96 beers purchased from the Chinese market was analyzed, and the exposure of the Chinese population to mycotoxins through beer consumption was assessed. Deoxynivalenol (DON) was detected in 93.75 % of the beers, and the incidence of fumonisins (FBs) and zearalenone (ZEN) exceeded 50 %. Beer intake contributed significantly to the exposure of aflatoxins (AFs) and DON, especially in males. Correlation analysis between mycotoxin content in beer, raw materials, and the brewing process revealed that the brewing process significantly affected the content of DON (P < 0.001), while auxiliary materials also had a significant impact on the content of FBs and DON (P < 0.001). This study holds great significance in producing higher quality and safer beer.

Fungal Community Composition and Its Relationship with Volatile Compounds during Spontaneous Fermentation of Cabernet Sauvignon from Two Chinese Wine-Growing Regions.

The microbial community structure associated with wine in a wine-growing region is shaped by diverse ecological factors within that region, profoundly impacting the wine flavor. In wine fermentation, fungi contribute more sensory-active biochemical compounds than bacteria. In this study, we employed amplicon sequencing to measure samples from the spontaneous fermentation process of cabernet sauvignon wines from two wine-growing regions in China to study the diversity and structural evolution of fungi during spontaneous fermentation and analyze the correlation between fungi and volatile compounds. The results showed significant differences in fungal community structure and diversity in cabernet sauvignon musts from different geographical origins, and these differences affected the flavor quality of the wines. As alcoholic fermentation progressed, Saccharomyces became the dominant fungal genus and reshaped the fungal community structure, and the diversity of the fungal community decreased. However, the fungal communities of each wine-growing region remained distinct throughout the fermentation process. Furthermore, the correlation between the fungal community and volatile compounds indicated that wine is a product of fermentation involving multiple fungal genera, and the flavor is influenced by a variety of fungi. Our study enhances the comprehension of fungal communities in Chinese wine-growing regions, explaining the regulatory role of wine-related fungal microorganisms in wine flavor.

Survey of the biogenic amines in craft beer from the Chinese market and the analysis of the formation regularity during beer fermentation.

This study evaluated the levels of eight biogenic amines in 59 craft beers of five styles and monitored the changes during beer fermentation, showing that putrescine and tryptamine were the most abundant at maximum values of 46.14 mg/L and 89.97 mg/L, respectively. This research indicated for the first time that dark beer, such as Stout/Porter, displayed the highest total biogenic amine content due to considerable tryptamine accumulation, with a maximum value of 116.95 mg/L. The total biogenic amine level increased gradually during the segmental saccharification and main fermentation stages, representing the two critical control points for their formation during beer fermentation. This study provides a theoretical basis and technical guidance for the safe and standardized production of craft beer and the formulation of biogenic amines limit standards, which is highly significant for protecting the health of consumers.

Hanseniaspora uvarum FS35 degrade putrescine in wine through the direct oxidative deamination pathway of copper amine oxidase 1.

Putrescine is abundant in wine and have toxicological risks for the health of consumers. Certain microbes with oxidative deamination activity are considered to be one of the most effective ways to degrade putrescine. The characterization and possible mechanism of putrescine degradation by Hanseniaspora uvarum FS35 were studied in this work. Hanseniaspora uvarum FS35 was selected from 111 yeast strains by UPLC analysis and exhibited the ability to eliminate > 44.5 mg/L of putrescine after 12 h of culture. Transcriptome analysis showed that by adding putrescine as a nitrogen source, the gene expression level of copper amine oxidase 1 (CuAO1) increased, leading to a coordinated response in the oxidative deamination of putrescine to 4-amino-butanal and subsequent dehydrogenation to 4-amino-butanoate. The purified recombinant protein CuAO1 could degrade 25.8 and 21.8 mg/L of putrescine in Marselan and Cabernet Sauvignon wines, respectively. H. uvarum FS35 was then inoculated sequentially with Saccharomyces cerevisiae into Cabernet Sauvignon grape juice, and the physiochemical indexes and aroma compounds were detected by HPLC and HS-SPME/GC-MS, respectively. wines produced from sequential inoculations showed significantly lower level of putrescine and higher amounts of glycerol, lactic acid, acetic acid, phenylethyl alcohol, ethyl acetate and ß-phenylethyl acetate compared with the control fermentation of commercial S. cerevisiae, which proved the potential of H. uvarum FS35 as a promising strategy to reduce biogenic amines in wines.

B-cell lymphocyte kinase polymorphisms rs13277113, rs2736340, and rs4840568 and risk of autoimmune diseases: A meta-analysis.

BACKGROUND: B-cell lymphocyte kinase (BLK) is an inhibitor of B cells that has an important influence on several autoimmune diseases, but there is a lack of comprehensive analysis of its association with autoimmune diseases. Hence, it is meaningful to conduct a comprehensive analysis. METHODS: A systematic literature search was performed on the PubMed, ScienceDirect, and Web of Science databases up to June 30, 2016. The data were extracted and quality-assessed before conducting the meta-analysis. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were assessed with the STATA version 12.0 software. Subgroup and sensitivity analysis were conducted to explore potential sources of heterogeneity. RESULTS: Altogether, 33 studies with 68,874 cases and 90,684 controls, 24 studies with 31,095 cases and 39,077 controls for rs13277113, 21 studies with 26,388 cases and 40,635 controls for rs2736340, and 4 studies with 11,391 cases and 10,972 controls for rs4840568 were included in this meta-analysis. The results revealed that the BLK rs13277113 and rs2736340 polymorphisms increased the risk of autoimmune diseases in the total analysis (A vs G: OR = 1.33, 95% CI = 1.27-1.39, P < .01; T vs C: OR = 1.34, 95% CI = 1.27-1.41, P < .01), and rs4840568 was positively associated with systemic lupus erythematosus (SLE) (A vs G: OR = 1.32, 95% CI = 1.22-1.43, P = .01). CONCLUSION: This meta-analysis shows that the BLK (rs13277113, rs2736340, rs4840568) polymorphisms may be a risk factor for developing autoimmune diseases, especially for Asian populations and SLE.