Blocking proteinase-activated receptor 2 signaling relieves pain, suppresses nerve sprouting, improves tissue repair, and enhances analgesic effect of B vitamins in rats with Achilles tendon injury.

ABSTRACT: Tendon injury produces intractable pain and disability in movement, but the medications for analgesia and restoring functional integrity of tendon are still limited. In this study, we report that proteinase-activated receptor 2 (PAR2) activation in dorsal root ganglion (DRG) neurons contributes to chronic pain and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI). Tendon partial transection injury increases the expression of PAR2 protein in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon. Activation of PAR2 promotes the primary sensory neuron plasticity by activating downstream cAMP-PKA pathway, phosphorylation of PKC, CaMKII, and CREB. Blocking PAR2 signaling by PAR2 small-interference RNA or antagonistic peptide PIP delays the onset of TTI-induced pain, reverses the ongoing pain, as well as inhibits sensory nerve sprouting, and promotes structural remodeling of the injured tendon. Vitamin B complex (VBC), containing thiamine (B1), pyridoxine (B6), and cyanocobalamin (B12), is effective to ameliorate TTI-induced pain, inhibit ectopic nerve sprouting, and accelerate tendon repair, through suppressing PAR2 activation. These findings reveal a critical role of PAR2 signaling in the development of chronic pain and histopathological alterations of injured tendon following Achilles tendon injury. This study suggests that the pharmaceuticals targeting PAR2, such as VBC, may be an effective approach for the treatment of tendon injury-induced pain and promoting tendon repair.

Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala.

The primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; prefrontal, multisensory and autonomic aspects of these circuits are mediated predominantly via the basal (BA), lateral (LA), and central (CeA) nuclei, respectively. Based on recent electrophysiological evidence suggesting mesoscale (millimeters-scale) nature of intra-amygdala functional organization, we have investigated the connectivity of these nuclei using infrared neural stimulation (INS) of single mesoscale sites coupled with mapping in ultrahigh field 7T functional magnetic resonance imaging (fMRI), namely INS-fMRI. Following stimulation of multiple sites within amygdala of single individuals, a 'mesoscale functional connectome' of amygdala connectivity (of BA, LA, and CeA) was obtained. This revealed the mesoscale nature of connected sites, the spatial patterns of functional connectivity, and the topographic relationships (parallel, sequential, or interdigitating) of nucleus-specific connections. These findings provide novel perspectives on the brainwide circuits modulated by the amygdala.

Chromosomal mapping of a major genetic locus from Agropyron cristatum chromosome 6P that influences grain number and spikelet number in wheat.

KEY MESSAGE: A novel locus on Agropyron cristatum chromosome 6P that increases grain number and spikelet number was identified in wheat-A. cristatum derivatives and across 3 years. Agropyron cristatum (2n = 4x = 28, PPPP), which has the characteristics of high yield with multiple flowers and spikelets, is a promising gene donor for wheat high-yield improvement. Identifying the genetic loci and genes that regulate yield could elucidate the genetic variations in yield-related traits and provide novel gene sources and insights for high-yield wheat breeding. In this study, cytological analysis and molecular marker analysis revealed that del10a and del31a were wheat-A. cristatum chromosome 6P deletion lines. Notably, del10a carried a segment of the full 6PS and 6PL bin (1-13), while del31a carried a segment of the full 6PS and 6PL bin (1-8). The agronomic characterization and genetic population analysis confirmed that the 6PL bin (9-13) brought about an increase in grain number per spike (average increase of 10.43 grains) and spikelet number per spike (average increase of 3.67) over the three growing seasons. Furthermore, through resequencing, a multiple grain number locus was mapped to the physical interval of 593.03-713.89 Mb on chromosome 6P of A. cristatum Z559. The RNA-seq analysis revealed the expression of 537 genes in the del10a young spike tissue, with the annotation indicating that 16 of these genes were associated with grain number and spikelet number. Finally, a total of ten A. cristatum-specific molecular markers were developed for this interval. In summary, this study presents novel genetic material that is useful for high-yield wheat breeding initiatives to meet the challenge of global food security through enhanced agricultural production.

Mesoscale organization of ventral and dorsal visual pathways in macaque monkey revealed by 7T fMRI.

In human and nonhuman primate brains, columnar (mesoscale) organization has been demonstrated to underlie both lower and higher order aspects of visual information processing. Previous studies have focused on identifying functional preferences of mesoscale domains in specific areas; but there has been little understanding of how mesoscale domains may cooperatively respond to single visual stimuli across dorsal and ventral pathways. Here, we have developed ultrahigh-field 7 T fMRI methods to enable simultaneous mapping, in individual macaque monkeys, of response in both dorsal and ventral pathways to single simple color and motion stimuli. We provide the first evidence that anatomical V2 cytochrome oxidase-stained stripes are well aligned with fMRI maps of V2 stripes, settling a long-standing controversy. In the ventral pathway, a systematic array of paired color and luminance processing domains across V4 was revealed, suggesting a novel organization for surface information processing. In the dorsal pathway, in addition to high quality motion direction maps of MT, MST and V3A, alternating color and motion direction domains in V3 are revealed. As well, submillimeter motion domains were observed in peripheral LIPd and LIPv. In sum, our study provides a novel global snapshot of how mesoscale networks in the ventral and dorsal visual pathways form the organizational basis of visual objection recognition and vision for action.

Design of a Zn-based nanozyme injectable multifunctional hydrogel with ROS scavenging activity for myocardial infarction therapy.

The existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply, often disregarding the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS) that accompanies myocardial infarction. This microenvironment entails cardiomyocytes apoptosis, substantial vascular cell death, excessive inflammatory infiltration and fibrosis. In such situation, the present study introduces a zinc-based nanozyme injectable multifunctional hydrogel, crafted from ZIF-8, to counteract ROS effects after myocardial infarction. The hydrogel exhibits both superoxide dismutase (SOD)-like and catalase (CAT)-like enzymatic activities, proficiently eliminating surplus ROS in the infarcted region and interrupting ROS-driven inflammatory cascades. Furthermore, the hydrogel's exceptional immunomodulatory ability spurs a notable transformation of macrophages into the M2 phenotype, effectively neutralizing inflammatory factors and indirectly fostering vascularization in the infarcted region. For high ROS and demanding for zinc of the infarcted microenvironment, the gradual release of zinc ions as the hydrogel degrades further enhances the bioactive and catalytic performance of the nanozymes, synergistically promoting cardiac function post myocardial infarction. In conclusion, this system of deploying catalytic nanomaterials within bioactive matrices for ROS-related ailment therapy not only establishes a robust foundation for biomedical material development, but also promises a holistic approach towards addressing myocardial infarction complexities. STATEMENT OF SIGNIFICANCE: Myocardial infarction remains the leading cause of death worldwide. However, the existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply. These therapies often ignore the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS). Hence, we designed an injectable Zn-Based nanozyme hydrogel with ROS scavenging activity for myocardial infarction therapy. ALG-(ZIF-8) can significantly reduce ROS in the infarcted area and alleviate the ensuing pathological process. ALG-(ZIF-8) gradually releases zinc ions to participate in the repair process and improves cardiac function. Overall, this multifunctional hydrogel equipped with ZIF-8 makes full use of the characteristics of clearing ROS and slowly releasing zinc ions, and we are the first to test the therapeutic efficacy of Zinc-MOFs crosslinked-alginate hydrogel for myocardial infarction.

Development of lymph node metastasis-related prognostic markers in breast cancer.

BACKGROUND: Lymph node metastasis (LNM) from Breast cancer (BC) is commonly seen in BC progression. Currently, the identification of genes linked with LNM in BC remains in mystery. METHODS: Genes related to BC LNM were screened, and a risk model was constructed based on LASSO-Cox analysis. Combined with the Kaplan-Meier curve, the ability of riskscore to distinguish different baseline characteristics was evaluated, and model was verified by the receiver operating characteristic (ROC) curve. The expression levels of prognostic marker genes were analyzed by qRT-PCR and western blot (WB). RESULTS: A higher survival rate and longer survival time in low-risk BC patients. The 1, 3 and 5 year AUC values of the training set were 0.79, 0.74, and 0.73, respectively. Results for the validation set was similar to the training set. The differentially expressed genes between the high- and low-risk groups were significantly enriched in immune pathways. In addition, the low-risk group had higher levels of immune infiltration. qRT-PCR and WB results showed that in BC, CDH10, SMR3A, POU3F2, and FABP7 were down-regulated, and LHX1 was up-regulated. CONCLUSIONS: We built a prognostic model of BC based on LNM-related genes, proffering evaluation for prognosis and precise cure of BC. SIGNIFICANCE: At present, the genes related to lymph node metastasis in BC are still largely unknown and need to be further explored. Searching for potential lymph node metastasis-related genes of BC will provide meaningful biomarkers for BC treatment. Based on TCGA-BRCA data, we established an effective 11-gene prognostic risk model that could predict patient outcomes independently. Our model could classify BC patients and distinguish patients with poor prognosis effectively. Besides, the feature genes we identified might exert a predictive function in immunotherapy. The results of this study provide a new reference for the prognosis and treatment of BC patients with lymph node metastasis.

Effects of traditional Chinese culture-based bibliotherapy on the spiritual health of patients with liver cancer.

BACKGROUND: Liver cancer is a serious global health problem and is associated with poor spiritual health. Bibliotherapy is beneficial in improving health outcomes in cancer patients, yet there is a lack of empirical evidence of its effect on the spiritual health of liver cancer patients in China. The study aimed to investigate the effects of bibliotherapy based on Chinese traditional culture on the spiritual health of patients with liver cancer in China. This study was approved by the Ethics Committee of Hunan Normal University School of Medicine and registered with the Chinese Clinical Trial Registry with the registration (No: 2021260), which registration in June 30th 2021. METHODS: A total of 60 patients with liver cancer were divided into the intervention group (n = 30) and the control group (n = 30) through WeChat. The intervention group received bibliotherapy therapy based on traditional Chinese culture, while the control group received routine care. Spiritual health was assessed using the Spiritual Attitude and Involvement List (SAIL) and compared before and after the intervention between the two groups. The chi-square test and t-test were used to analyze the intervention effects. RESULTS: The two groups were comparable in all baseline characteristics including the SAIL score. After 5 weeks of intervention, the score of SAIL increased significantly from 96.76 ± 15.08 to 106.93 ± 13.82 in the intervention group (t = - 29.380, p < 0.001), while no significant difference in SAIL score was observed in the control group (from 95.27 ± 16.40 to 95.31 ± 16.24, t = - 0.189, p = 0.852). Similar patterns were also observed in its three dimensions of connecting with oneself, connecting with the environment, and connecting with transcendence. CONCLUSIONS: Our study showed that bibliotherapy based on traditional Chinese culture using the WeChat platform can greatly improve the spiritual health of patients with liver cancer and has the potential to be widely applied to cancer patients to improve their well-being.

Unraveling the genetic basis of grain number-related traits in a wheat-Agropyron cristatum introgressed line through high-resolution linkage mapping.

BACKGROUND: Grain number per spike (GNS) is a pivotal determinant of grain yield in wheat. Pubing 3228 (PB3228), a wheat-Agropyron cristatum germplasm, exhibits a notably higher GNS. RESULTS: In this study, we developed a recombinant inbred line (RIL) population derived from PB3228/Gao8901 (PG-RIL) and constructed a high-density genetic map comprising 101,136 loci, spanning 4357.3 cM using the Wheat 660 K SNP array. The genetic map demonstrated high collinearity with the wheat assembly IWGSC RefSeq v1.0. Traits related to grain number and spikelet number per spike were evaluated in seven environments for quantitative trait locus (QTL) analysis. Five environmentally stable QTLs were detected in at least three environments. Among these, two major QTLs, QGns-4A.2 and QGns-1A.1, associated with GNS, exhibited positive alleles contributed by PB3228. Further, the conditional QTL analysis revealed a predominant contribution of PB3228 to the GNS QTLs, with both grain number per spikelet (GNSL) and spikelet number per spike (SNS) contributing to the overall GNS trait. Four kompetitive allele-specific PCR (KASP) markers that linked to QGns-4A.2 and QGns-1A.1 were developed and found to be effective in verifying the QTL effect within a diversity panel. Compared to previous studies, QGns-4A.2 exhibited stability across different trials, while QGns-1A.1 represents a novel QTL. The results from unconditional and conditional QTL analyses are valuable for dissecting the genetic contribution of the component traits to GNS at the individual QTL level and for understanding the genetic basis of the superior grain number character in PB3228. The KASP markers can be utilized in marker-assisted selection for enhancing GNS. CONCLUSIONS: Five environmentally stable QTLs related to grain number and spikelet number per spike were identified. PB3228 contributed to the majority of the QTLs associated with GNS.

Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study.

Background and Objectives: Age is a significant determinant of susceptibility to breast cancer. Currently, the available evidence regarding the non-linear correlation between the age of diagnosis and the prognosis of breast cancer patients is contradictory. Insufficient data currently exist regarding the influence of age at diagnosis on the prognosis of breast cancer. The objective of our investigation was to examine the relationship between age at diagnosis and overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Methods: This retrospective cohort study included 1054 patients diagnosed with breast cancer between March 7, 2013 and December 31, 2019. The hazard ratios (HRs) and 95% confidence interval (CI) for OS, BCSS, DFS were assessed using Cox proportional hazard ratio models and restricted cubic splines (RCS). Results: The study included 1054 breast cancer patients who met the criteria. With a median follow-up of 4.86 years, 71 patients (6.74%) died and 144 patients (13.66%) relapsed. After multivariable adjustment, age showed a U-shaped association with OS, BCSS, and DFS, with significantly higher risk at two ends, with age inflection points of 44, 44, and 41 years for OS, BCSS, and DFS, respectively. For OS, Quartile 1 (HR, 2.09; 95% CI: 0.90-4.84), Quartile 3 (HR, 2.44; 95% CI: 1.05-5.65) and Quartile 4 (HR, 3.38; 95% CI: 1.51-7.54) had poorer OS compared with Quartile 2. Similar results were found for BCSS and DFS. Conclusions: This study confirmed a U-shaped association between age at diagnosis and breast cancer outcome.

Construction of a high-density genetic map and mapping of a spike length locus for rye.

Genetic maps provide the foundation for QTL mapping of important traits of crops. As a valuable food and forage crop, rye (Secale cereale L., RR) is also one of the tertiary gene sources of wheat, especially wild rye, Secale cereale subsp. segetale, possessing remarkable stress tolerance, tillering capacity and numerous valuable traits. In this study, based on the technique of specific-locus amplified fragment sequencing (SLAF-seq), a high-density single nucleotide polymorphism (SNP) linkage map of the cross-pollinated (CP) hybrid population crossed by S. cereale L (female parent) and S. cereale subsp. segetale (male parent) was successfully constructed. Following preprocessing, the number of 1035.11 M reads were collected and 2425800 SNP were obtained, of which 409134 SNP were polymorphic. According to the screening process, 9811 SNP markers suitable for constructing linkage groups (LGs) were selected. Subsequently, all of the markers with MLOD values lower than 3 were filtered out. Finally, an integrated map was constructed with 4443 markers, including 1931 female mapping markers and 3006 male mapping markers. A major quantitative trait locus (QTL) linked with spike length (SL) was discovered at 73.882 cM on LG4, which explained 25.29% of phenotypic variation. Meanwhile two candidate genes for SL, ScWN4R01G329300 and ScWN4R01G329600, were detected. This research presents the first high-quality genetic map of rye, providing a substantial number of SNP marker loci that can be applied to marker-assisted breeding. Additionally, the finding could help to use SLAF marker mapping to identify certain QTL contributing to important agronomic traits. The QTL and the candidate genes identified through the high-density genetic map above may provide diverse potential gene resources for the genetic improvement of rye.

The efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome: A retrospective analysis.

PURPOSE: Clinical efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome (PCOS) was expected to be retrospectively analyzed in this study. METHODS: In this paper, 100 infertility patients with PCOS were selected and divided into the observation and control groups based on different medications. Firstly, clinical data of both groups of patients were acquired. Then, the uterine receptivity and ovarian status, the levels of sex hormones, inflammation and oxidative stress, and the pregnancy outcomes between the 2 groups were compared and analyzed before and after treatment. RESULTS: After a variety of comparisons and analyses, Fuke Qianjin tablets combined with clomiphene citrate were confirmed to improve the uterine receptivity and ovarian status, levels of sex hormone, inflammation and oxidative stress, and pregnancy outcomes in infertility patients with PCOS. CONCLUSIONS: Overall, Fuke Qianjin tablets + clomiphene citrate treatment shows good clinical efficacy and is worth promotion in clinical practice.

The Genomic Variation and Differentially Expressed Genes on the 6P Chromosomes in Wheat-Agropyron cristatum Addition Lines 5113 and II-30-5 Confer Different Desirable Traits.

Wild relatives of wheat are essential gene pools for broadening the genetic basis of wheat. Chromosome rearrangements and genomic variation in alien chromosomes are widespread. Knowledge of the genetic variation between alien homologous chromosomes is valuable for discovering and utilizing alien genes. In this study, we found that 5113 and II-30-5, two wheat-A. cristatum 6P addition lines, exhibited considerable differences in heading date, grain number per spike, and grain weight. Genome resequencing and transcriptome analysis revealed significant differences in the 6P chromosomes of the two addition lines, including 143,511 single-nucleotide polymorphisms, 62,103 insertion/deletion polymorphisms, and 757 differentially expressed genes. Intriguingly, genomic variations were mainly distributed in the middle of the chromosome arms and the proximal centromere region. GO and KEGG analyses of the variant genes and differentially expressed genes showed the enrichment of genes involved in the circadian rhythm, carbon metabolism, carbon fixation, and lipid metabolism, suggesting that the differential genes on the 6P chromosome are closely related to the phenotypic differences. For example, the photosynthesis-related genes PsbA, PsbT, and YCF48 were upregulated in II-30-5 compared with 5113. ACS and FabG are related to carbon fixation and fatty acid biosynthesis, respectively, and both carried modification variations and were upregulated in 5113 relative to II-30-5. Therefore, this study provides important guidance for cloning desirable genes from alien homologous chromosomes and for their effective utilization in wheat improvement.

Identification of predictors for the comprehensive clinical risk and severity of coronary lesions of acute coronary syndrome.

Background: Acute coronary syndrome (ACS) is the most common cause of death in patients with coronary artery disease. The aim of the study was to identify the predictors of both comprehensive clinical risk and severity of coronary lesions by comprehensive use of GRACE and SYNTAX scores in patients with ACS. Methods: Clinical data of 225 ACS patients who underwent coronary angiography between 2015 and 2016 were collected. Multiple logistic regression analysis (stepwise) was used to identify the predictors. The predictive ability of predictors and the model were determined using receiver operating characteristics analyses. Results: Multivariable logistic regression analyses showed that high aspartate aminotransferase (AST) predicted the comprehensive clinical risk with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.011 (1.002-1.021). High total cholesterol (TC) and red blood cell distribution width (RDW) predicted the severity of coronary lesions with ORs and 95% CIs of 1.517 (1.148-2.004) and 1.556 (1.195-2.028), respectively. Low prealbumin predicted both severity of coronary lesions and comprehensive clinical risk of ACS patients with ORs and 95% CIs of 0.743 (0.672-0.821) and 0.836 (0.769-0.909), respectively. The model with a combination of prealbumin and AST had the highest predictive efficacy for comprehensive clinical risk, and the combination of prealbumin, TC, and RDW had the highest predictive efficacy for the severity of coronary lesions. The sensitivity and specificity, and the optimal cut-off values of these four indexes were determined. Conclusions: Four predictors for the comprehensive clinical risk and severity of coronary lesions of ACS were identified, which provided important information for the early diagnosis and appropriate treatment of ACS.

NIGT1 represses plant growth and mitigates phosphate starvation signaling to balance the growth response tradeoff in rice.

Inorganic phosphate (Pi) availability is an important factor which affects the growth and yield of crops, thus an appropriate and effective response to Pi fluctuation is critical. However, how crops orchestrate Pi signaling and growth under Pi starvation conditions to optimize the growth defense tradeoff remains unclear. Here we show that a Pi starvation-induced transcription factor NIGT1 (NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1) controls plant growth and prevents a hyper-response to Pi starvation by directly repressing the expression of growth-related and Pi-signaling genes to achieve a balance between growth and response under a varying Pi environment. NIGT1 directly binds to the promoters of Pi starvation signaling marker genes, like IPS1, miR827, and SPX2, under Pi-deficient conditions to mitigate the Pi-starvation responsive (PSR). It also directly represses the expression of vacuolar Pi efflux transporter genes VPE1/2 to regulate plant Pi homeostasis. We further demonstrate that NIGT1 constrains shoot growth by repressing the expression of growth-related regulatory genes, including brassinolide signal transduction master regulator BZR1, cell division regulator CYCB1;1, and DNA replication regulator PSF3. Our findings reveal the function of NIGT1 in orchestrating plant growth and Pi starvation signaling, and also provide evidence that NIGT1 acts as a safeguard to avoid hyper-response during Pi starvation stress in rice.

Risk factors of non-sentinel lymph node metastasis in breast cancer with 1-2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study.

BACKGROUND: The randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1-2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1-2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1-2 SLN macrometastases undergoing TM. METHODS: The clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis. RESULTS: A total of 273 patients with 1-2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019-1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302-36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1-2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%. CONCLUSIONS: The breast cancer patients with cT1/2N0 stage, undergoing TM and 1-2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.

Correlation of asprosin and Nrg-4 with type 2 diabetes Mellitus Complicated with Coronary Heart Disease and the Diagnostic Value.

PURPOSE: Asprosin is a newly discovered adipose factor secreted by white fat, which is involved in glucose metabolism and inflammation. Neuregulin-4 (Nrg-4) is a new adipose factor released from brown adipose tissue and is considered to play an important role in metabolism. This study aims to explore the association between serum Asprosin, Nrg-4 level and coronary heart disease(CHD) in patients with type 2 diabetes mellitus(T2DM) and the diagnostic value. PATIENTS AND METHODS: 157 patients with T2DM were enrolled from Affiliated Hospital of Chengde Medical University between December 2020 to July 2021. These patients were divided into T2DM without CHD group (T2DM-0, n = 80) and T2DM with CHD (T2DM-CHD, n = 77). Serum Asprosin and Nrg-4 expression was detected by enzyme-linked immunosorbent assay, and the correlations between Asprosin or Nrg-4 and clinical and biochemical indicators were analyzed. A receiver operating characteristics curve analysis and area under the curve (AUC) were used to evaluate diagnostic accuracy. RESULTS: Serum Asprosin level of the T2DM-CHD group were significantly higher and Nrg-4 level significantly lower than those of the T2DM-0 group.Spearman correlation analysis showed that serum Asprosin levels were significantly positively correlated with diabetes course,history of hypertension, fasting plasma glucose(FPG), glycosylated hemoglobin A1c(HbA1C), triglycerides(TG),triglyceride glucose index(TyG index) and urea, and negatively correlated with ALT (all p < 0.05). Nrg-4 was negatively correlated with history of hypertension, body mass index(BMI), FPG, HbA1C, TG, and TyG indexes (all p < 0.05), and positively correlated with high-density lipoprotein cholesterol(HDL-C)(p < 0.05).Logistic regression analysis showed that after adjusting potential confounders, Asprosin was a risk factor for diabetes mellitus, Nrg-4 was a protective factor.The AUC of Asprosin for diagnosing T2DM-CHD was 0.671 (95% confidence interval [CI] 0.584-0.759), and the AUC of the Nrg4 index for diagnosing T2DM-CHD was 0.772 (95% CI 0.700-0.844). The AUC of Asprosin and Nrg-4 for the combined diagnosis of T2DM-CHD was 0.796 (95% CI 0.726-0.864). CONCLUSION: Asprosin and Nrg-4 may be novel diagnostic biomarkers for T2DM with CHD, as they effectively improved the diagnostic accuracy for T2DM-CHD.

Predictive Value of Endometrial Receptivity for Pregnancy Outcomes of In-vitro Fertilization Embryo Transfer for Patients of Different Ages.

Context: In recent years, the number of women with unexplained infertility has increased, and clinicians consider poor endometrial receptivity (ER) to be one of the main reasons. ER can have great predictive value for in-vitro fertilization embryo transfer (IVF-ET)-induced pregnancy. Objective: The study intended to investigate the predictive value of ER-endometrial thickness (EMT) and type and hemodynamic parameters-using color-doppler ultrasound on the pregnancy outcome of IVF-ET for women of different ages. Design: The research team performed a prospective controlled study. Setting: The study took place at the Department of Reproductive Medicine at Hebei Reproductive Hospital in Shijiazhuang, China. Participants: Participants were 841 infertile patients undergoing IVF-ET treatment at the hospital between March 01, 2018 and December 30, 2018. The research team divided participants into two groups: (1) participants diagnosed as having a clinical pregnancy after IVF-ET became the pregnancy group, with 439 participants, and (2) participants who didn't become pregnant became the nonpregnancy group, with 402 participants. Outcome Measures: The research team: (1) measured EMT, (2) determined endometrium types, (3) classified the intimal and subintimal blood flow, and (4) determined the hemodynamic parameters of the endometrium and subendometrium. The team also measured: (1) the systolic blood flow velocity (VS), (2) diastolic blood flow velocity (VD), and (3) average blood flow velocity (VM) three times and recorded the average value. Results: Statistically significant differences existed in the pregnancy and implantation rates among the different age groups for the groups with EMTs of <8 mm and 8-13 mm (P < .05). The results were similar in the endometrial Type A and endometrial Type B groups as well as between the endometrial blood flow Type 1 and Type 2 groups (P < .05). The distribution of endometrial blood flow types was significantly different between the groups (P = .002). In addition, statistically significant differences existed in the implantation rates between the <30 years and 30-34 groups in different blood-flow-type groups (P < .05). Based on the results of the ROC curve, high-quality embryos (0.566, 95%CI: 0.527-0.605) and endometrial blood flow types (0.554, 95%CI: 0.515-0.593) could not predict clinical pregnancy. Conclusions: The pregnancy and implantation rates increased between the <30 and 30-34 age groups and them decreased between the age groups as age increased. EMT, endometrial type, and blood flow type can be valuable parameters in predicting the implantation and pregnancy rates of patients of different ages.

Development and Identification of a Wheat-Rye Breeding Line for Harmonious Improvement Between Powdery Mildew Resistance and High Yield Potential.

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is a devastating disease that seriously threatens wheat yield and quality. To control this disease, host resistance is the preferred measure. However, wheat breeding is a complex process with elusive exchange and recombination of the traits from their parents. Increased resistance often leads to a decline in other key traits, such as yield and quality. Developing breakthrough germplasms with harmonious powdery mildew resistance and other key breeding traits is attractive in wheat breeding. In this study, we developed an ideal wheat breeding line AL46 that pyramided its hexaploid triticale parent-derived desirable yield traits and its wheat parent-derived powdery mildew resistance gene Pm2. Sequential genomic in situ hybridization (GISH), multicolor GISH, multicolor fluorescence in situ hybridization, and molecular marker analyses revealed that AL46 was a wheat-rye T1RS·1BL translocation line. Genetic analysis combined with function marker detection and sequence alignment were used to confirm that AL46 carried the Pm2 gene. Then, we evaluated the powdery mildew resistance and comprehensive traits of AL46, and just as we designed, AL46 showed harmonious powdery mildew resistance with some key breeding traits. This study not only developed an ideal wheat germplasm resource but also provided a successful example for pyramiding breeding, which could be a promising direction for wheat improvement in the future.

Synergistic Effect of Yak Dung Fiber and Yak Dung Ash on the Mechanical and Shrinkage Properties of Cement Mortar.

The high value use of agricultural and livestock waste resources in the context of a low carbon economy is a challenge that currently plagues many countries. Yak dung, as a waste resource from livestock farming in the plateau, is considered to be a misplaced treasure. In this work, yak dung was processed into yak dung fiber (YDF) and yak dung ash (YDA), respectively, and the microscopic morphology of the YDF and YDA was assessed using scanning electron microscopy (SEM). The elements in the YDA were analyzed by energy dispersive X-ray spectroscopy (EDX). Moreover, cementitious composites were prepared with YDF at 0%, 0.3%, 0.5% and 0.7% and by replacing cement with YDA at 5%, 10% and 15% to assess the workability, mechanical properties and shrinkage properties of cementitious composites containing different YDF types (alkali treated and untreated), contents and different YDA contents. The results showed that alkali-treated YDF and YDA contain a large number of honeycomb structure pores, and the strength of cementitious materials with alkali-treated YDF was higher. The addition of YDF had a negative effect on the fluidity and compressive strength of the cementitious material, but the 0.3% YDF was beneficial in increasing its flexural strength. The compressive strength and flexural strength first increased and then decreased with the increase of YDA content. Both YDF and YDA inhibited the shrinkage of the cement paste, and the shrinkage strain of the cement matrix composites containing 0.3% YDF and 10% YDA was reduced by 51.1% compared to the control group. This work is expected to promote the application of yak dung waste in cementitious materials.

Evodiamine inhibits ESCC by inducing M-phase cell-cycle arrest via CUL4A/p53/p21 axis and activating noxa-dependent intrinsic and DR4-dependent extrinsic apoptosis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignancy with high incidence in several regions of China, and the prognosis of patients with ESCC is unfavorable. Evodiamine (Evo), a small molecule derived from the traditional Chinese herb Evodia rutaecarpa, has shown anti-cancer efficacy in numerous human malignancies but not in ESCC. PURPOSE: To determine whether Evo induces cell-cycle arrest and apoptosis in ESCC in vitro and in vivo and elucidate the underlying mechanisms. METHODS: ATPlite and colony formation assay were used to validate the inhibiting effect of Evo on three ESCC cells in vitro; Two subcutaneous tumor models of ESCC cells were used to evaluate the anti-ESCC effect of Evo and assess the biosafety of Evo in vivo; RNAseq and Database of KEGG pathway analysis provided a direction for the mechanistic study of Evo; FACS was used to detect Evo-induced cell cycle arrest and cell apoptosis in ESCC cells; Western blot and QPCR were respectively used to detect the level of related genes and proteins in Evo-treated ESCC cells; SiRNA and other experimental techniques were used to identify the molecular mechanism of Evo-induced ESCC cell cycle arrest and cell apoptosis. RESULTS: Evo significantly suppressed the growth of ESCC both in vitro and in vivo. Mechanistically, Evo induced M-phase cell-cycle arrest by inactivation of CUL4A E3 ligase, which mediates degradation blockage of p53 and transcriptional activation of p21. With the prolonged treatment time, Evo triggered both Noxa-dependent intrinsic and DR4-dependent extrinsic cell apoptosis in two ESCC cell lines. CONCLUSION: Our findings revealed the anti-tumor efficacy and mechanisms of Evo, providing a solid scientific basis for Evo as an attractive choice for ESCC treatment.