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Abstract The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P

Abstract Background Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. Findings We performed a genome-wide association analysis in the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age

The interturn short circuit fault is one of the common faults in power transformers. At present, research on interturn short circuit faults focuses on high, medium, and low voltage windings, while there is relatively little research on interturn short circuit in regulating windings. Specifically, there is a lack of reported studies on the transient electromagnetic processes, magnetic field distribution, and electromagnetic force characteristics of interturn short circuits in regulating windings unconnected to the circuit. This study presents an actual fault scenario involving interturn short circuits occurring in the untapped portion of the regulating windings of a specific power transformer. A field-circuit coupled model was established to analyze the transient electromagnetic processes during the fault, and the model’s effectiveness was validated by comparing its results with actual fault recording data. Additionally, the magnetic field distribution and electromagnetic force characteristics during the fault were analyzed, and discussions were carried out regarding various ratios of short-circuit turns in the regulating windings. The results indicate that even when an interturn short circuit occurs in the portion of the regulating winding that is not connected to the circuit, the current in the short-circuited turns can reach several tens of times the rated value. Additionally, the leakage magnetic field and the electromagnetic force experienced by the short-circuited ring also increase significantly. The short-circuit ratio has a significant impact on the current of the short-circuited ring, leakage magnetic field intensity, and electromagnetic force. This study contributes to a better understanding of the impact of interturn short-circuit faults in the untapped portion of the regulating windings, offering crucial technical support for fault diagnosis and prevention of power transformers.

To clarify the preferences of employees seeking influenza vaccination, a discrete choice experiment aims to understand the essential factors that close the gap between intention and behavior. A total of 866 employees with vaccination willingness willing to participated in a discrete choice experiment (DCE) between October 31st and December 6th, 2022 in China including the following attributes: price, vaccination setting, appointment mode, and service time. The data was analyzed using mixed logit models. Employees from smaller enterprises were more likely to get vaccinated collectively. For employees willing to get the influenza vaccine, 95.08 % of their choice was dominated by price. Employees’ behavior varied according to their socioeconomic characteristics. Only female employees strongly favored work-site-based vaccination. Price was the primary factor considered by employees for getting the influenza vaccine. DCE would help to develop influenza vaccination intervention targeted at different groups in future studies.

Pavement performance models are an essential component of a pavement management system (PMS) and have a direct impact on future pavement condition prediction, selection of pavement maintenance and rehabilitation (M&R) methods, and budget planning and allocations. Therefore, it is critical to develop and maintain pavement performance models as accurate as possible. The California Department of Transportation (Caltrans) has implemented a modern pavement management system called PaveM. To maintain the intended functions of PaveM, regular updates of its databases and key components are necessary, including pavement performance models. This paper aims to evaluate the network-level pavement performance models in PaveM by utilizing the concept of deterioration rate and the most recent automated pavement condition survey (APCS) data. First, the concept of pavement deterioration rate was defined. The actual deterioration rates were calculated using two latest cycles of APCS data and then compared to the predicted deterioration rates obtained using APCS data and the current configurations of PaveM. Two typical pavement distresses (International Roughness Index and Caltrans’ asphalt pavement alligator B cracking) for one selected pavement treatment (thin overlay) were predicted using PaveM and compared to the actual APCS measurements. The results from this study show that the concept of deterioration rate was effective in evaluating the overall quality of performance models in PaveM as well as identifying the time spans in which the models may over- or under-predict pavement performance.

To investigate the immune regulation and antioxidation effects of polysaccharide from Ilex kudingcha C.J. Tseng on mouse spleen lymphocytes in vitro. The proliferation, antioxidant capacity (SOD, T-AOC, GSH-Px and CAT) activity and malonic dialdehyde (MDA) content, as well as the secretion of cytokines (TNF-α, IFN-γ and IL-1β) were detected after treating with polysaccharide from Ilex kudingcha C.J. Tseng. The results showed that polysaccharide from Ilex kudingcha C.J. Tseng could promote the proliferation of spleen lymphocytes dose-dependently. Compared to the OD value of control group (0.31), the OD values at the concentration of 80 and 160 μg/mL were increased significantly (P

Babesia microti is an obligate intraerythrocytic protozoan transmitted by an Ixodes tick. Infections caused by protozoa, including Plasmodium yoelii and Toxoplasma gondii, are shown to inhibit tumor development by activating immune responses. Th1 immune response and macrophages not only are essential key factors in Babesia infection control but also play an important role in regulating tumor development. In this study, we investigated the effects of B. microti infection on melanoma in tumor-bearing mice. The results showed that B. microti infection could inhibit the growth of melanoma, significantly enlarge the spleen size (p ≤ 0.0001), and increase the survival period (over 7 days) of tumor-bearing mice. Mouse spleen immune cell analysis revealed that B. microti-infected tumor-bearing mice could increase the number of macrophages and CD4+ T cells, as well as the proportion of CD4+ T cells and M1 macrophages in the tumor. Immunohistochemical assays showed that B. microti infection could inhibit tumor angiogenesis (p ≤ 0.0032). Meanwhile, both B. microti-infected erythrocytes and culture supernatant were observed to significantly (p ≤ 0.0021) induce the mRNA expression of iNOS, IL-6, and TNF-α in macrophages. Moreover, B. microti culture supernatant could also repolarize IL-4-induced M2 macrophages to the M1 type. Overall, B. microti exerted antitumor effects by stimulating the immune system of tumor-bearing mice and inducing the polarization of immunosuppressive M2 macrophages to pro-inflammatory M1 macrophages.

Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG methylation sites associated with prostate cancer.

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

The apicomplexan Babesia microti is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase (PYK) plays a central metabolic regulatory role in most living organisms and catalyzes the essentially irreversible step in glycolysis that converts phosphoenolpyruvate (PEP) to pyruvate. Hence, PYK is recognized as an attractive therapeutic target in cancer and human pathogens such as apicomplexans. In this study, we cloned, expressed, and purified B. microti PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of B. microti with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the Km value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC50 value 0.49 μM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of in vitro-cultured B. microti with IC50 values of 0.77, 2.10, 1.73, and 1.15 μM. Overall, the present study provides a theoretical basis for the design and development of new anti-Babesia drugs.

Background: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. Methods: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. Findings: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P

The problem of sulfur corrosion has seriously affected the safe and stable operation of the power transformers. Currently, adding passivators into the transformer oil is the most effective method to suppress the problem. However, no explicit provisions have been made for the optimum concentration of the specific passivators. In this paper, the transformer oils with different corrosive sulfurs and different aging degrees were used to study the protective performance of three different passivators. By comparing the copper surface, the optimum concentrations for each passivators were acquired. Moreover, by testing the breakdown voltage, dielectric loss factor, volume resistivity, and moisture content of the insulating oil after adding passivators with the optimal concentration, the effect of three passivators on the oil quality was obtained. Results show that the three passivators have different protective performance on different types of corrosive sulfurs. Irgamet 39 has a better protective effect at lower concentrations than the other two. The protective effect of all three passivators on dodecyl mercaptan is poor, and a new type of passivator capable of protecting against dodecyl mercaptan needs to be developed. Moreover, the three passivators have different protection performance on the transformer oils with different aging degrees. The protective performance is poor especially for the oils with longer running years or passivators with lower concentrations. Among the three passivators, Irgamet 39 had the smallest impact on the oil quality, followed by T571 and then TTA. The above research can provide some references for guiding the passivator addition in actual projects and preventing the occurrence of sulfur corrosion failures.

Babesia orientalis, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by Rhipicephalus haemaphysaloides. However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of B. orientalis merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in B. orientalis. We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system in vitro further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of B. orientalis. Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.

Objective This study was conducted to determine the effects of dietary maifanite supplementation and fecal collection method on the apparent total tract digestibility (ATTD) of calcium (Ca) and phosphorus (P) and blood parameters in growing pigs. Methods Thirty-six growing barrows (Duroc×Landrace×Yorkshire; 27.0±2.6 kg) were allotted to six dietary treatments with 6 pigs per treatment according to body weight in a completely randomized design. The experimental treatments were: i) Low Ca+cornstarch (2.25%), ii) Low Ca+maifanite (2.25%), iii) Medium Ca+cornstarch (1.42%), iv) Medium Ca+maifanite (1.42%), v) High Ca+cornstarch (0.64%), and vi) High Ca+maifanite (0.64%). Feces were collected by the total collection (TC) and indicator method (IM). At the beginning and the end of the experiment, blood samples were collected from each pig. Results For the TC method, there were no difference in Ca intake, fecal Ca output, Ca retention and the ATTD of Ca between cornstarch and maifanite diets at the same dietary Ca level. However, urinary Ca excretion was lower (p = 0.01) in pigs fed low Ca diets without maifanite supplementation compared with other dietary treatments. Dietary maifanite supplementation had no effect on the P metabolism in growing pigs. For the IM method, there was no difference in Ca digestibility between cornstarch and maifanite diets at the same dietary Ca level. The ATTD of P was greater (p

Objective The goal of this study was to investigate the effects of dietary standard ileal digestible (SID) valine:lysine ratios on performance, intestinal morphology, amino acids of liver and muscle, plasma indices and mRNA expression of branched-chain amino acid (BCAA) metabolism enzymes. Methods A total of 144 crossbred pigs (Duroc×Landrace×Large White) weaned at 28±4 days of age (8.79±0.02 kg body weight) were randomly allotted to 1 of 4 diets formulated to provide SID valine:lysine ratios of 50%, 60%, 70%, or 80%. Each diet was fed to 6 pens of pigs with 6 pigs per pen (3 gilts and 3 barrows) for 28 days. Results Average daily gain increased quadratically (p

Objective Two experiments were conducted to determine the content of digestible energy (DE) and metabolizable energy (ME) as well as the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in barley grains obtained from Australia, France or Canada. Methods In Exp. 1, 18 growing barrows (Duroc×Landrace×Yorkshire; 31.5±3.2 kg) were individually placed in stainless-steel metabolism crates (1.4×0.7×0.6 m) and randomly allotted to 1 of 3 test diets. In Exp. 2, eight crossbred pigs (30.9±1.8 kg) were allotted to a replicate 3×4 Youden Square designed experiment with three periods and four diets. Two pigs received each diet during each test period. The diets included one nitrogen-free diet and three test diets. Results The relative amounts of gross energy (GE), CP, and all AA in the Canadian barley were higher than those in Australian and French barley while higher concentrations of neutral detergent fiber, acid detergent fiber, total dietary fiber, insoluble dietary fiber and β-glucan as well as lower concentrations of GE and ether extract were observed in the French barley compared with the other two barley sources. The DE and ME as well as the SID of histidine, isoleucine, leucine and phenylalanine in Canadian barley were higher (p

Objective The hull attached to the barley kernel can be mechanically removed thus reducing the fiber content of the barley. This experiment was carried out to evaluate the effects of partial dehulling on the nutrient digestibility as well as the digestible energy (DE) and metabolizable energy (ME) content of barley in pigs. Methods Two hulled barley samples (high fiber barley [HF] and low fiber barley [LF]) with either high or low fiber contents were obtained from the Hubei and Jiangsu Provinces of China. A portion of the two barleys was mechanically dehulled (dehulled high fiber barley [DHF] and dehulled low fiber barley [DLF]). Thirty barrows (initial BW = 31.5±3.2 kg) were assigned to one of five diets in a randomized complete block design. The five diets consisted of 96.9% corn, HF, LF, DHF, or DLF supplemented with 3.1% minerals and vitamins. Each diet was fed to six barrows housed in individual metabolism crates for a 10-d acclimation period followed by a 5-day total but separate collection of feces and urine. Results The daily loss of gross energy (GE) in feces was lower (p

Previous studies have investigated various factors that contribute to the severity of work zone crashes. However, little has been done on the specific effects of light conditions. Using the data from the Enhanced Tennessee Roadway Information Management System (E-TRIMS), crashes that occurred in the Tennessee work zones during 2003–2015 are categorized into three light conditions: daylight, dark-lighted, and dark-not-lighted. One commonly used decision tree method—Classification and Regression Trees (CART)—is adopted to investigate the factors contributing to crash severity in highway work zones under these light conditions. The outcomes from the three decision trees with differing light conditions show significant differences in the ranking and importance of the factors considered in the study, thereby indicating the necessity of examining traffic crashes according to light conditions. By separately considering the crash characteristics under different light conditions, some new findings are obtained from this study. The study shows that an increase in the number of lanes increases the crash severity level in work zones during the day while decreasing the severity at night. Similarly, drugs and alcohol are found to increase the severity level significantly under the dark-not-lighted condition, while they have a limited influence under daylight and dark-lighted conditions.

Application of natural herbs with a view to enhancing production performance and health status has created an important demand in poultry production. With the increasing concerns on this issue, greater attention paid to alternatives to antibiotics for organic meat and egg production has led to a great demand. This study was conducted with view to assessing the possible role of M. oleifera as a natural feed supplement in poultry ration. Various scientific findings and published research articles were considered concerning issues including the study background, objectives, major findings, and conclusions of the review. M oleifera is known as a miracle tree because of its wealthy resource of various nutrients with high biological values. M. oleifera has been used as a growth promoter, immune enhancer, antioxidant, and has a hypo-cholesterol effect on chickens. It has both nutritional and therapeutic values. However, there is still much confusion in past published articles involving the major roles of M. oleifera in production performance and health status of chickens. Taking this into account, the present study highlights an outline of the experimental uses of M. oleifera on growth performance, egg production performance, egg quality, and health status in broilers and laying hens justified with the past findings to the present. The knowledge gaps from the past studies are considered, and the feasibility of M. oleifera in poultry ration is suggested. The findings have motivated further study on M. oleifera to find out the most active ingredients and their optimal doses in both broiler and laying hen rations. Finally, the present study highlights that supplementation of M. oleifera may play a role in the immunity, sound health, and production performance in poultry.

The experiment was conducted to determine the chemical composition, digestible energy (DE), metabolisable energy (ME) and the apparent total tract digestibility (ATTD) in sunflower seed meal (SFSM) and to develop reasonable prediction equations for estimating energy digestibility based on chemical composition of these meals for growing pigs. Ten SFSMs were collected and 66 crossbred barrows (initial body weight=36.43±5.25 kg) were randomly allocated to one of eleven diets. The basal diet was based on corn and soybean meal which contained 82.2% corn, 14.8% de-hulled soybean meal and 3% premix. The test diets contained 30% SFSM at the expense of corn and soybean meals. The experiment comprised a 7-d adaptation period followed by a 5-d collection period of faecal matter and urine. On a dry matter (DM) basis, the content of crude protein, neutral and acid detergent fibre, and gross energy (GE) ranged from 29.33 to 39.09%, 38.15 to 55.40%, 24.59 to 37.34% and 18.65 to 21.50 MJ/kg, respectively. The concentration of DE and ME ranged from 10.51 to 12.47 MJ/kg and 10.26 to 12.16 MJ/kg of DM, respectively. The DE values and ATTD of GE among the ten SFSMs significantly differed (P10%) among the ten SFSMs (DM). The results of DE, ME and prediction equations could be applied to evaluate the energy digestibility of SFSM in growing pigs.

Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients1-4. However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness5-11, and existing wearable cardiac devices can only capture signals on the skin12-16. Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.

Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene (Tardbp) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation of Btn1a1 and Xdh mRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency.

Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression. [ABSTRACT FROM AUTHOR]