Associations between blood antioxidant levels and femoral neck strength.

BACKGROUND: Studies have confirmed that antioxidants contribute to a lower risk of osteoporosis, which is an independent factor for femoral neck fracture (FNF). However, the associations between blood antioxidant levels and femoral neck strength remain unclear. OBJECTIVE: Our aim was to test the hypothesis that levels of blood antioxidants are positively associated with composite indices of bone strength in femoral neck, which integrate the bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI), in a population of middle-aged and elderly individuals. METHODS: This cross-sectional study utilized data from the Midlife in the United States (MIDUS) study. Blood levels of antioxidants were measured and analyzed. RESULTS: In total, data from 878 participants were analyzed. Results of Spearman correlation analyses indicated that blood levels of 6 antioxidants (total lutein, zeaxanthin, alpha-carotene, 13-cis-beta-carotene, trans-beta-carotene and total lycopene) were positively associated with CSI, BSI, or ISI in middle-aged and elderly individuals. Conversely, blood gamma-tocopherol and alpha-tocopherol levels were negatively associated with CSI, BSI, or ISI scores. Furthermore, linear regression analyses suggested that only blood zeaxanthin levels remained positively associated with CSI (odds ratio, OR 1.27; 95% CI: 0.03, 2.50; p = 0.045), BSI (OR, 0.54; 95% CI: 0.03-1.06; p = 0.037), and ISI (OR, 0.06; 95% CI: 0.00, 0.13; p = 0.045) scores in the study population after adjusting for age and sex. CONCLUSIONS: Our results indicated that elevated blood zeaxanthin levels were significantly and positively associated with femoral neck strength (CSI, BSI, or ISI) in a population of middle-aged and elderly individuals. These findings suggest that zeaxanthin supplementation may reduce FNF risk independently.

Discovery of Anti-Inflammatory Triterpenoid Glucosides from the Heritiera littoralis Dryand.

Two new triterpenoid glucosides, Heritiera A (1) and Heritiera B (2), and six known triterpenoid analogs (3-8) were isolated from Heritiera littoralis Dryand. Their structures were identified by comprehensive spectroscopic analyses and comparisons with the literature. The anti-inflammatory activity of the isolates from H. littoralis was evaluated using a lipopolysaccharide (LPS) stimulated RAW 264.7 cells model. The result showed that four triterpenoids exhibited potent anti-inflammatory activity. Among these compounds, compound 2 substantially inhibits the release of nitric oxide (NO) with an IC50 value of 10.33 µM. The triterpenoids from H. littoralis could be used as potential candidates for the development of new anti-inflammatory agents.

Effects of different energy diets on DNA methylation and mRNA expression in follicle stimulating hormone receptor gene promoter region of Duolang sheep during estrus.

BACKGROUND: The aim of this study was to study the relationship between the methylation level of the promoter region of follicle-stimulating hormone receptor (FSHR) gene and the mRNA expression of Duolang sheep fed different energy diets. METHODS: In this study, polyembryo estrus Duolang sheep under different energy levels were selected as the experimental subjects. Dietary nutrient level reference (NY/T 816-2004), medium energy level was 10.88 MJ/day, high and low energy groups were increased and decreased by 15% on the basis of medium energy level, respectively 12.51 MJ/day, 9.25 MJ/day. Through RNA and DNA extraction, qPCR, bisulfitegenomicse-quencing PCR (BSP), sequence matching and other analysis of ovarian tissue of Duolang sheep. The difference of DNA methylation level and mRNA expression of FSHR gene during estrus in Duolang sheep fed with different energy diets was detected. RESULTS: The results showed the expression level of FSHR in high energy group was significantly higher than that in low energy group (P < 0.01), the expression level of FSHR in high energy group was significantly higher than that in medium energy group (P < 0.05), and the expression level of FSHR in medium energy group was significantly higher than that in low energy group (P < 0.05). In the target fragment of the promoter region of the FSHR gene, the methylation rate was 25% in the high energy group, 50% in the normal group, and 75% in the low energy group. CONCLUSIONS: This study revealed that different dietary energy levels had certain effects on the FSHR gene DNA methylation level and mRNA expression, and the expression level was negatively correlated with methylation level.

MIA-Directed 2-Pyridione-Enabled Selective Ortho-C-H Arylation of Phenylalanine: A Mechanistic Study.

The 2-methoxyiminoacyl-mediated arylation of substituted phenylalanines has been examined. Selective monoarylation at the ortho position was achieved using pyridone ligands which decelerate the arylation process. Density functional theory (DFT) study of a continuous C-H arylation process that included the first and second arylation stage was performed. The computational result shows that the introduction of a pyridone ligand obviously disfavors the second arylation stage, which directly contributes to the selectivity between the mono/diarylated products. Furthermore, results of the kinetic isotope effect and a control experiment are agreed with DFT study.

Dynamic Modeling and Chaos Control of Informatization Development in Manufacturing Enterprises.

To explore the cooperative evolutionary mechanism among top management support, employees' technical ability, and informatization performance in the process of the "integration of informatization and industrialization (IOII)" in manufacturing enterprises, this study established a three-dimensional dynamic model of informatization development, obtained the model parameters by the expert scoring method of case companies, and analyzed the time series of the dynamic model. After adjusting those parameters of the evolutionary process that do not meet the expectations of the enterprise, combined with management practice, the dynamic system is finally stable at the expected value. For a special state in the evolutionary process, the maximum Lyapunov exponent is used to identify the chaotic characteristics of the system, and a linear controller is designed to manage and control the chaotic system so that it evolves toward the expected value. The results of the case analysis verify the rationality of the model and the effectiveness of the control method, reveal the internal evolutionary mechanism of the informatization development of manufacturing enterprises, and explain the influence of chaos on enterprise management so as to help managers to use and control chaos.

Anatomical Basis of the Intermediate Dorsal Pedal Neurocutaneous Perforator Pedicled Propeller Flap: A Cadaveric Dissection.

Soft tissue defects of the forefoot represent a challenging surgical modality to reconstructive microsurgeons. This study describes the anatomical basis and design of the perforator-based intermediate dorsal pedal neurocutaneous vascular flap. Thirty fresh human lower limb specimens were injected with red latex and used for dissection of the dorsal vascular and neural anatomy of the foot. The direction and distribution of the intermediate dorsal cutaneous nerve and the vascular anatomy of the third dorsal artery of the plantar arch, along with the intermediate dorsal neurocutaneous nutrient vessels, were mapped. A simulated flap elevation procedure was performed on one fresh cadaver specimen. A clinical series of five cases is presented to demonstrate the feasibility of using the perforator-based intermediate dorsal pedal neurocutaneous vascular flap to reconstruct soft-tissue defects of the forefoot. The intermediate dorsal cutaneous nerve usually originates from the lateral branch of the superficial peroneal nerve. Crossing the surface of the cruciate ligament, it descends distally to the proximal part of the fourth intermetatarsal space and divides into the third and fourth dorsal metatarsal branches. The intermediate dorsal cutaneous neural nutrient vessels, which are multi-segmental and polyphyletic, offer innervation to the skin paddle of the flap elevated on the basis of the third dorsal perforator of the plantar arch. This perforator occupies a relatively constant position in the proximal part of the intermetatarsal space. It sends multiple tiny branches toward the intermediate dorsal cutaneous neural or paraneural nutrient vessel chain. In terms of clinical application, all flaps survived completely; one patient had partial loss of the skin graft. The design and anatomical basis of the intermediate dorsal pedal neurocutaneous vascular flap based on the third dorsal perforator of the plantar arch is a reliable reconstructive option for reconstructing small soft tissue defects in the forefoot. Clin. Anat. 31:1077-1084, 2018. © 2018 Wiley Periodicals, Inc.

Association between migraine and venous thromboembolism: a Mendelian randomization and genetic correlation study.

Objective: Previous observational studies have reported an increased risk of venous thromboembolism (VTE) among individuals with migraine. This study aimed to investigate the causal effect of migraine on the development of VTE, as well as explore the genetic correlation between them. Methods: We conducted a two-sample Mendelian randomization (MR) study using publicly available summary statistics from large-scale genome-wide association studies for migraine and VTE. Linkage disequilibrium score regression analysis was performed to estimate the genetic correlation between migraine and VTE. Results: There were several shared risk variants (p-value < 5 × 10-8) between migraine and VTE. Linkage disequilibrium score regression analysis found a significant positive genetic correlation between migraine and VTE. The genetic correlations based on two migraine datasets were 0.208 (se = 0.031, p-value = 2.91 × 10-11) and 0.264 (se = 0.040, p-value = 4.82 × 10-11), respectively. Although main MR analysis showed that migraine was associated with an increased risk of VTE (odds ratio = 1.069, 95% confidence interval = 1.022-1.118, p-value = 0.004), the association attenuated to non-significance when using several other MR methods and using another set of genetic instruments. In addition, evidence of heterogeneity was found. Reverse MR analysis showed VTE was associated with increased risk of migraine with aura (odds ratio = 1.137, 95% confidence interval = 1.062-1.218, p-value = 2.47 × 10-4) with no evidence of pleiotropy and heterogeneity. Conclusion: We showed suggestive evidence indicating an association between migraine and increased risk of VTE. Additionally, we found robust evidence suggesting that VTE is associated with an increased risk of migraine. The positive genetic correlation indicates that migraine and VTE has shared genetic basis. Further investigations will be necessary to address potential sex-specific effects in the analysis.

Association between egg consumption and mortality risk in United States adults with established coronary heart disease or stroke: A cohort study using data from NHANES 1999-2018.

BACKGROUND: To investigate the relationship between egg consumption and mortality in individuals with pre-existing coronary heart disease or stroke. METHODS: This study utilized data from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. Egg consumption was evaluated through 24 h dietary recalls at baseline. Mortality status was tracked until December 31, 2019. Survey-weighted Cox proportional hazards models were utilized. RESULTS: The study involved 3,975 participants aged 20 years or older with a median follow-up of 89.00 months. A total of 1,675 individuals died during follow-up. Compared to individuals who did not consume eggs, the consumption of 0-50 g/day (hazard ratio [HR] = 1.033, 95% confidence interval [CI] =0.878-1.214) was not found to have a significant association with all-cause mortality. However, consuming 50-100 g/day (HR = 1.281, 95% CI = 1.004-1.635) and >100 g/day (HR = 1.312, 95% CI =1.036-1.661) exhibited a significant association with an increased risk of all-cause mortality. We identified a non-liner relationship between egg consumption and cardiovascular mortality, where the risk was found to be lowest at an intake of about 50 g/day. For individuals consuming more than 50 g/day, each additional 50 g increment in egg consumption was significantly linked to an elevated risk of cardiovascular mortality (HR = 1.276, 95% CI = 1.009-1.614). CONCLUSION: In U.S. adults with pre-existing cardiovascular disease, a significant positive association was found between consuming over 50 g of eggs per day and the risk of mortality, highlighting the importance of moderate intake.

Identifying novel proteins for migraine by integrating proteomes from blood and CSF with genome-wide association data.

BACKGROUND: Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co-localization analysis methods. METHODS: We utilized cis-protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co-localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins. RESULTS: We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955-0.981, p = 1.27 × 10-6) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024-1.065, p = 1.08 × 10-5) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946-0.982, p = 8.74 × 10-5) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies. CONCLUSIONS: We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms.

Preservation of Simmental bull sperm at 0°C in Tris dilution: effect of dilution ratio and long-distance transport.

OBJECTIVE: This study aimed to assess the impact of the dilution ratio of Tris diluent, storage at 0°C, and long-distance transportation on the spermatozoa of Simmental cattle. It also validated the feasibility of the regional distribution of fresh semen. METHODS: In experiment 1, semen was diluted at four dilution ratios (1:6, 1:9, 1:12, and 1:15) to determine the optimal dilution ratio of Tris diluent. In experiment 2, we assessed sperm viability, progressive motility (objectively assessed by computer-assisted sperm analyzer), and acrosome intactness in Tris dilutions kept at constant 0°C for 1, 3, 6, 9, and 12 days. We compared them to Tianshan livestock dilutions (Commercial diluent). In experiment 3, semen was diluted using Tris diluent, and sperm quality was measured before and after long-distance transport. Artificial insemination of 177 Simmental heifers compared to 156 using Tianshan Livestock dilution. RESULTS: The outcomes demonstrated that 1:9 was the ideal Tris diluent dilution ratio. The sperm viability, Progressive Motility, and acrosome integrity of both Tris and Tianshan dilutions preserved at 0°C gradually decreased over time. sperm viability was above 50% for both dilutions on d 9, with a flat rate of decline. The decrease in acrosome integrity rate was faster for Tianshan livestock dilutions than for Tris dilutions when stored at 0°C for 1 to 6 days. There was no significant difference (p>0.05) in sperm viability between semen preserved in Tris diluent after long-distance transportation and semen preserved in resting condition. The conception rates for Tris dilution and Tianshan livestock dilution were 49.15% and 46.15% respectively, with no significant difference (p>0.05). CONCLUSION: This shows that Tris diluent is a good long-term protectant. It has been observed that fresh semen can be successfully preserved for long-distance transport when stored under 0°C conditions. Additionally, it is feasible to distribute semen regionally.

The regulatory process and practical significance of non-coding RNA in the dissemination of prostate cancer to the skeletal system.

Prostate cancer is a major contributor to male cancer-related mortality globally. It has a particular affinity for the skeletal system with metastasis to bones seriously impacting prognosis. The identification of prostate cancer biomarkers can significantly enhance diagnosis and patient monitoring. Research has found that cancer and metastases exhibit abnormal expression of numerous non-coding RNA. Some of these RNA facilitate prostate cancer bone metastasis by activating downstream signaling pathways, while others inhibit this process. Elucidating the functional processes of non-coding RNA in prostate cancer bone metastasis will likely lead to innovative treatment strategies for this malignant condition. In this review, the mechanistic role of the various RNA in prostate cancer is examined. Our goal is to provide a new avenue of approach to the diagnosis and treatment of bone metastasis in this cancer.

Effects of melatonin on sperm quality, enzyme activity, antioxidant gene expression and fertility of cryopreserved bovine semen.

Melatonin (MLT) has strong antioxidant capacity and can reduce the damage caused by oxidative stress in sperm, but there is still little content in the field we have studied. In this study, we are committed to scientific research on adding melatonin to Belgian blue bull semen diluent for cryopreservation. Different concentrations (0, 0.1, 0.3, 0.5 or 0.7 mg/mL) of MLT were added diluent. Sperm kinetic parameters, enzyme activity, antioxidant gene expression and fertility were analyzed after thawing. The results showed that MLT concentration of 0.3 mg/mL exerted positive effects on post-thaw kinetic parameters. Compared with other groups, 0.3 mg/mL MLT treated sperm acrosome and plasma membrane integrity, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels significantly increased. Meanwhile, the mRNA expression of antioxidant genes SOD2, CAT and GPx increased in the 0.3 mg/mL MLT treatment group, and the mRNA expression of apoptosis genes Caspase-3 and Bax were significantly reduced. In addition, in vitro fertilization (IVF) embryo cleavage, blastocyst rate and artificial insemination (AI) pregnancy rate were higher in 0.3 mg/mL MLT. Therefore, MLT showed cryoprotective capacity to the freezing diluent used for Belgian blue bull sperm during the process of freezing-thawing, and the optimal concentration of MLT for the frozen diluent was 0.3 mg/mL.

Recent advances in cryotolerance biomarkers for semen preservation in frozen form-A systematic review.

Spermatozoa cryopreservation has been practiced for decades and is a very useful technique for long-term preservation of sperm fertility. The capability for semen cryopreservation varies across species, seasons, latitudes, and even for different ejaculates from the same animal. This article summarizes research results on sperm cryotolerance biomarkers in several species, focusing on three areas: spermatozoa cryotolerance biomarkers, seminal plasma proteins cryotolerance biomarkers, and other cryotolerance biomarkers. We discovered that sperm cryoresistance biomarkers are primarily related to sperm plasma membrane stability, the presence of antioxidant substances in sperm or seminal plasma, sperm cell energy metabolism, water and small molecule transport channels in the sperm plasma membrane, and antistress substances in sperm or seminal plasma. The research conducted using diverse livestock models can be employed to enhance the basic and applied reproduction of other mammals through the study of sperm cryotolerance biomarkers, as well as the substantial similarities between livestock and other organisms, including endangered species.

Survival benefit of younger gastric cancer patients in China and the United States: A comparative study.

BACKGROUND: The impact of racial and regional disparity on younger patients with gastric cancer (GC) remains unclear. AIM: To investigate the clinicopathological characteristics, prognostic nomogram, and biological analysis of younger GC patients in China and the United States. METHODS: From 2000 to 2018, GC patients aged less than 40 years were enrolled from the China National Cancer Center and the Surveillance Epidemiology and End Results database. Biological analysis was performed based on the Gene Expression Omnibus database. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 6098 younger GC patients were selected from 2000 to 2018, of which 1159 were enrolled in the China National Cancer Center, and 4939 were collected from the Surveillance Epidemiology and End Results database. Compared with the United States group, younger patients in China revealed better survival outcomes (P < 0.01). For race/ethnicity, younger Chinese cases also enjoyed a better prognosis than that in White and Black datasets (P < 0.01). After stratification by pathological Tumor-Node-Metastasis (pTNM) stage, a survival advantage was observed in China with pathological stage I, III, and IV (all P < 0.01), whereas younger GC patients with stage II showed no difference (P = 0.16). In multivariate analysis, predictors in China involved period of diagnosis, linitis plastica, and pTNM stage, while race, diagnostic period, sex, location, differentiation, linitis plastica, signet ring cell, pTNM stage, surgery, and chemotherapy were confirmed in the United States group. Prognostic nomograms for younger patients were established, with the area under the curve of 0.786 in the China group and of 0.842 in the United States group. Moreover, three gene expression profiles (GSE27342, GSE51105, and GSE38749) were enrolled in further biological analysis, and distinctive molecular characteristics were identified in younger GC patients among different regions. CONCLUSION: Except for younger cases with pTNM stage II, a survival advantage was observed in the China group with pathological stage I, III, and IV compared to the United States group, which might be partly due to differences in surgical approaches and the improvement of the cancer screening in China. The nomogram model provided an insightful and applicable tool to evaluate the prognosis of younger patients in China and the United States. Furthermore, biological analysis of younger patients was performed among different regions, which might partly explain the histopathological behavior and survival disparity in the subpopulations.