NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling.

Precision oncology hinges on linking tumour genotype with molecularly targeted drugs1; however, targeting the frequently dysregulated metabolic landscape of cancer has proven to be a major challenge2. Here we show that tissue context is the major determinant of dependence on the nicotinamide adenine dinucleotide (NAD) metabolic pathway in cancer. By analysing more than 7,000 tumours and 2,600 matched normal samples of 19 tissue types, coupled with mathematical modelling and extensive in vitro and in vivo analyses, we identify a simple and actionable set of 'rules'. If the rate-limiting enzyme of de novo NAD synthesis, NAPRT, is highly expressed in a normal tissue type, cancers that arise from that tissue will have a high frequency of NAPRT amplification and be completely and irreversibly dependent on NAPRT for survival. By contrast, tumours that arise from normal tissues that do not express NAPRT highly are entirely dependent on the NAD salvage pathway for survival. We identify the previously unknown enhancer that underlies this dependence. Amplification of NAPRT is shown to generate a pharmacologically actionable tumour cell dependence for survival. Dependence on another rate-limiting enzyme of the NAD synthesis pathway, NAMPT, as a result of enhancer remodelling is subject to resistance by NMRK1-dependent synthesis of NAD. These results identify a central role for tissue context in determining the choice of NAD biosynthetic pathway, explain the failure of NAMPT inhibitors, and pave the way for more effective treatments.

mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT.

Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) kinase, promotes glutamate secretion, cystine uptake, and incorporation into glutathione, linking growth factor receptor signaling with amino acid uptake and utilization. These results identify an unanticipated mechanism regulating amino acid metabolism in cancer, enabling tumor cells to adapt to changing environmental conditions.

Step-by-step desolvation enables high-rate and ultra-stable sodium storage in hard carbon anodes.

Hard carbon is regarded as the most promising anode material for sodium-ion (Na-ion) batteries, owing to its advantages of high abundance, low cost, and low operating potential. However, the rate capability and cycle life span of hard carbon anodes are far from satisfactory, severely hindering its industrial applications. Here, we demonstrate that the desolvation process defines the Na-ion diffusion kinetics and the formation of a solid electrolyte interface (SEI). The 3A zeolite molecular sieve film on the hard carbon is proposed to develop a step-by-step desolvation pathway that effectively reduces the high activation energy of the direct desolvation process. Moreover, step-by-step desolvation yields a thin and inorganic-dominated SEI with a lower activation energy for Na+ transport. As a result, it contributes to greatly improved power density and cycling stability for both ester and ether electrolytes. When the above insights are applied, the hard carbon anode achieves the longest life span and minimum capacity fading rate at all evaluated current densities. Moreover, with the increase in current densities, an improved plateau capacity ratio is observed. This step-by-step desolvation strategy comprehensively enhances various properties of hard carbon anodes, which provides the possibility of building practical Na-ion batteries with high power density, high energy density, and durability.

Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity.

In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs). NF-κB and survivin are coordinately up-regulated in GBM patient tumors, and functional inhibition of either protein or BRD4 in in vitro and in vivo models restores sensitivity to EGFR TKIs. These results provide a rationale for improving anti-EGFR therapeutic efficacy through pharmacological uncoupling of a convergence point of NF-κB-mediated survival that is leveraged by an interclonal circuitry mechanism established by intratumoral mutational heterogeneity.

Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

The Globodera rostochiensis Gr29D09 Effector with a Role in Defense Suppression Targets the Potato Hexokinase 1 Protein.

The potato cyst nematode (Globodera rostochiensis) is an obligate root pathogen of potatoes. G. rostochiensis encodes several highly expanded effector gene families, including the Gr4D06 family; however, little is known about the function of this effector family. We cloned four 29D09 genes from G. rostochiensis (named Gr29D09v1/v2/v3/v4) that share high sequence similarity and are homologous to the Hg29D09 and Hg4D06 effector genes from the soybean cyst nematode (Heterodera glycines). Phylogenetic analysis revealed that Gr29D09 genes belong to a subgroup of the Gr4D06 family. We showed that Gr29D09 genes are expressed exclusively within the nematode's dorsal gland cell and are dramatically upregulated in parasitic stages, indicating involvement of Gr29D09 effectors in nematode parasitism. Transgenic potato lines overexpressing Gr29D09 variants showed increased susceptibility to G. rostochiensis. Transient expression assays in Nicotiana benthamiana demonstrated that Gr29D09v3 could suppress reactive oxygen species (ROS) production and defense gene expression induced by flg22 and cell death mediated by immune receptors. These results suggest a critical role of Gr29D09 effectors in defense suppression. The use of affinity purification coupled with nanoliquid chromatography-tandem mass spectrometry identified potato hexokinase 1 (StHXK1) as a candidate target of Gr29D09. The Gr29D09-StHXK1 interaction was further confirmed using in planta protein-protein interaction assays. Plant HXKs have been implicated in defense regulation against pathogen infection. Interestingly, we found that StHXK1 could enhance flg22-induced ROS production, consistent with a positive role of plant HXKs in defense. Altogether, our results suggest that targeting StHXK1 by Gr29D09 effectors may impair the positive function of StHXK1 in plant immunity, thereby aiding nematode parasitism. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Factors that determine glucose variability, defined by the coefficient of variation in continuous glucose monitoring values, in a Chinese population with type 2 diabetes.

AIMS: To elucidate the clinical determinants of the coefficient of variation (CV) of glucose by analysing the pancreatic ß-cell function of subjects with type 2 diabetes mellitus (T2DM). METHODS: A total of 716 Chinese subjects with T2DM were included. Continuous glucose monitoring (CGM) was used to assess blood glucose, and the CV was calculated. C-peptide concentration at 0, 0.5, 1, 2 and 3 hours (Cp0h, Cp0.5h, Cp1h, Cp2h and Cp3h, respectively) was measured after a standard 100-g steamed bun meal test to assess pancreatic ß-cell function. The determinants of glucose variability defined by the CV of CGM values were explored from two perspectives: the CV of qualitative variables and the CV of quantitative variables. RESULTS: Our data revealed that C-peptide concentration (Cp0h, Cp0.5h, Cp1h, Cp2h, Cp3h), area under the curve for C-peptide concentration at 0.5 and 3 hours (AUC-Cp0.5h and AUC-Cp3h) decreased with increasing CV quartile (P < 0.05). The CV was negatively correlated with homeostatic model assessment of ß-cell function index, C-peptide concentration at all timepoints, and AUC-Cp0.5h and AUC-Cp3h (P < 0.001). Quantile regression analysis showed that AUC-Cp0.5h had an overall negative effect on the CV in the 0.05 to 0.95 quartiles, and AUC-Cp3h tended to have a negative effect on the CV in the 0.2 to 0.65 quartiles. After adjusting for confounders, multinomial logistic regression showed that each 1-unit increase in AUC-Cp0.5h was associated with a 31.7% reduction in the risk of unstable glucose homeostasis (CV > 36%; P = 0.036; odds ratio 0.683; 95% confidence interval 0.478-0.976). We also identified the AUC-Cp0.5h (0.735 ng/mL) and AUC-Cp3h (13.355 ng/mL) cut-off values for predicting unstable glucose homeostasis (CV >36%) in T2DM subjects. CONCLUSION: Our study suggests that impaired pancreatic ß-cell function may be a clinical determining factor of CV of glucose in people with T2DM.

Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7.

Mammalian cardiomyocytes (CMs) undergo maturation during postnatal heart development to meet the increased demands of growth. Here, we found that omentin-1, an adipokine, facilitates CM cell cycle arrest and metabolic maturation. Deletion of omentin-1 causes mouse heart enlargement and dysfunction in adulthood and CM maturation retardation in juveniles, including delayed cell cycle arrest and reduced fatty acid oxidation. Through RNA sequencing, molecular docking analysis, and proximity ligation assays, we found that omentin-1 regulates CM maturation by interacting directly with bone morphogenetic protein 7 (BMP7). Omentin-1 prevents BMP7 from binding to activin type II receptor B (ActRIIB), subsequently decreasing the downstream pathways mothers against DPP homolog 1 (SMAD1)/Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK). In addition, omentin-1 is required and sufficient for the maturation of human embryonic stem cell-derived CMs. Together, our findings reveal that omentin-1 is a pro-maturation factor for CMs that is essential for postnatal heart development and cardiac function maintenance.

A key virulence effector from cyst nematodes targets host autophagy to promote nematode parasitism.

Autophagy, an intracellular degradation system conserved in eukaryotes, has been increasingly recognized as a key battlefield in plant-pathogen interactions. However, the role of plant autophagy in nematode parasitism is mostly unknown. We report here the identification of a novel and conserved effector, Nematode Manipulator of Autophagy System 1 (NMAS1), from plant-parasitic cyst nematodes (Heterodera and Globodera spp.). We used molecular and genetic analyses to demonstrate that NMAS1 is required for nematode parasitism. The NMAS1 effectors are potent suppressors of reactive oxygen species (ROS) induced by flg22 and cell death mediated by immune receptors in Nicotiana benthamiana, suggesting a key role of NMAS1 effectors in nematode virulence. Arabidopsis atg mutants defective in autophagy showed reduced susceptibility to nematode infection. The NMAS1 effectors contain predicted AuTophaGy-related protein 8 (ATG8)-interacting motif (AIM) sequences. In planta protein-protein interaction assays further demonstrated that NMAS1 effectors specifically interact with host plant ATG8 proteins. Interestingly, mutation in AIM2 of GrNMAS1 from the potato cyst nematode Globodera rostochiensis abolishes its interaction with potato StATG8 proteins and its activity in ROS suppression. Collectively, our results reveal for the first time that cyst nematodes employ a conserved AIM-containing virulence effector capable of targeting a key component of host autophagy to promote disease.

Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy, although newly developing targeted therapy and immunotherapy have been showing promising effects in clinical treatment, the effective biomarkers for immune response prediction are still lacking. The study is to construct a gene signature according to ccRCC immune cells infiltration landscape, thus aiding clinical prediction of patients response to immunotherapy. METHODS: Firstly, ccRCC transcriptome expression profiles from Gene Expression Omnibus (GEO) database as well as immune related genes information from IMMPORT database were combine applied to identify the differently expressed meanwhile immune related candidate genes in ccRCC comparing to normal control samples. Then, based on protein-protein interaction network (PPI) and following module analysis of the candidate genes, a hub gene cluster was further identified for survival analysis. Further, LASSO analysis was applied to construct a signature which was in succession assessed with Kaplan-Meier survival, Cox regression and ROC curve analysis. Moreover, ccRCC patients were divided as high and low-risk groups based on the gene signature followed by the difference estimation of immune treatment response and exploration of related immune cells infiltration by TIDE and Cibersort analysis respectively among the two groups of patients. RESULTS: Based on GEO and IMMPORT databases, a total of 269 differently expressed meanwhile immune related genes in ccRCC were identified, further PPI network and module analysis of the 269 genes highlighted a 46 genes cluster. Next step, Kaplan-Meier and Cox regression analysis of the 46 genes identified 4 genes that were supported to be independent prognosis indicators, and a gene signature was constructed based on the 4 genes. Furthermore, after assessing its prognosis indicating ability by both Kaplan-Meier and Cox regression analysis, immune relation of the signature was evaluated including its association with environment immune score, Immune checkpoint inhibitors expression as well as immune cells infiltration. Together, immune predicting ability of the signature was preliminary explored. CONCLUSIONS: Based on ccRCC genes expression profiles and multiple bioinformatic analysis, a 4 genes containing signature was constructed and the immune regulation of the signature was preliminary explored. Although more detailed experiments and clinical trials are needed before potential clinical use of the signature, the results shall provide meaningful insight into further ccRCC immune researches.

Mixed exposure effect of seminal metals on semen quality, mediation of total antioxidant capacity, and moderation of GSTM1/GSTT1 gene deletion in Chinese reproductive-aged men.

BACKGROUND: The effects of metal exposure on semen quality and the role of oxidative damage in this process remain unclear. METHODS: We recruited 825 Chinese male volunteers, and 12 seminal metals (Mn, Cu, Zn, Se, Ni, Cd, Pb, Co, Ag, Ba, Tl, and Fe), the total antioxidant capacity (TAC), and reduced glutathione were measured. Semen parameters and GSTM1/GSTT1-null genotypes were also detected. Bayesian kernel machine regression (BKMR) was applied to evaluate the effect of the mixed exposure to metals on semen parameters. The mediation of TAC and moderation of GSTM1/GSTT1 deletion were analyzed. RESULTS: Most seminal metal concentrations were correlated with each other. The BKMR models revealed a negative association between the semen volume and metal mixture, with Cd (cPIP = 0.60) and Mn (cPIP = 0.10) as the major contributors. Compared to fixing all scaled metals at their median value (50th percentiles), fixing the scaled metals at their 75th percentiles decreased the TAC by 2.17 units (95%CI: -2.60, -1.75). Mediation analysis indicated that Mn decreased the semen volume, with 27.82% of this association mediated by TAC. Both the BKMR and multi-linear models showed that seminal Ni was negatively correlated with sperm concentration, total sperm count, and progressive motility, which was modified by GSTM1/GSTT1. Furthermore, Ni and the total sperm count showed a negative association in GSTT1 and GSTM1 null males (ß[95%CI]: 0.328 [-0.521, -0.136]) but not in males with GSTT1 and/or GSTM1. Although Fe and the sperm concentration and total sperm count were positively correlated, they showed inverse "U" shapes in univariate analysis. CONCLUSION: Exposure to the 12 metals was negatively associated with semen volume, with Cd and Mn as the major contributors. TAC may mediate this process. GSTT1 and GSTM1 can modify the reduction in the total sperm count caused by seminal Ni exposure.

EGFR Mutation Promotes Glioblastoma through Epigenome and Transcription Factor Network Remodeling.

Epidermal growth factor receptor (EGFR) gene amplification and mutations are the most common oncogenic events in glioblastoma (GBM), but the mechanisms by which they promote aggressive tumor growth are not well understood. Here, through integrated epigenome and transcriptome analyses of cell lines, genotyped clinical samples, and TCGA data, we show that EGFR mutations remodel the activated enhancer landscape of GBM, promoting tumorigenesis through a SOX9 and FOXG1-dependent transcriptional regulatory network in vitro and in vivo. The most common EGFR mutation, EGFRvIII, sensitizes GBM cells to the BET-bromodomain inhibitor JQ1 in a SOX9, FOXG1-dependent manner. These results identify the role of transcriptional/epigenetic remodeling in EGFR-dependent pathogenesis and suggest a mechanistic basis for epigenetic therapy.

The mediating role of menstrual irregularity on obesity and sexual function in Chinese women with pelvic floor disorders: a cross-sectional study.

BACKGROUND: Sexual problems are common among women with pelvic floor disorders (PFD). Few studies have explored the relationship between obesity and sexual function in women with PFD. This study aimed to prove that obesity was a risk factor for worse sexual function in women with PFD, and to investigate the mediating role of menstrual irregularity. METHODS: This was a cross-sectional study involving 783 women with PFD from Shandong Province, China between June 2020 and February 2021. Female sexual function was assessed using the Pelvic Organ Prolapse/UI Sexual Questionnaire-12 (PISQ-12). Obesity was defined as BMI ≥ 28.0. Menstrual irregularity was defined as menstrual cycles ≥ 35 or menstrual cycles < 25 days. Logistic regression and multiple linear regression were employed to explore the association among obesity, menstrual irregularity and sexual function. RESULTS: Obesity was associated with worse PISQ-12 scores compared with normal- weight women (mean score 28.14 ± 7.03 versus 32.75 ± 5.66, p < 0.001). After adjusting for controlling variables, women with obesity (ß= -3.74, p < 0.001) and menstrual irregularity (ß= -3.41, p < 0.001) had a worse sexual function. Menstrual irregularity had a mediation effect on the association between obesity and sexual function. CONCLUSIONS: This study provided evidence that obesity was associated with worse sexual function in women with PFDs, and the effect of obesity on sexual function was partially mediated by menstrual irregularity. Weight control may have potential benefits for improving sexual function and preventing female sexual dysfunction. It's also important to pay attention to the menstrual cycle.

Mortality of Deep Brain Stimulation and Risk Factors in Patients With Parkinson's Disease: A National Cohort Study in Korea.

BACKGROUND: This study aimed to investigate 1) long-term outcomes of deep brain stimulation (DBS), such as mortality after DBS as well as the causes of death, 2) demographic and socioeconomic factors influencing mortality, and 3) comorbidities affecting mortality after DBS in patients with Parkinson's disease (PD). METHODS: This study analyzed the National Health Insurance Service-National Health Information Database. Data on patients with PD diagnosis codes from 2002 to 2019 were extracted and analyzed. Data on the causes of death were obtained by linking the causes of death to data from Statistics Korea. The Kaplan-Meier method with the log-rank test was used for survival analysis. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and their 95% confidence intervals. Regarding comorbidities such as PD dementia and fracture, which did not satisfy the assumption for the proportional HR, time-dependent Cox analysis with the Mantel-Byar method was used. RESULTS: From 2005 to 2017, among 156,875 patients diagnosed with PD in Korea, 1,079 patients underwent DBS surgery, and 251 (23.3%) had died by 2019. The most common cause of death (47.1%) was PD. In the multivariate Cox regression analysis, the higher the age at diagnosis and surgery, the higher the mortality rate. The men and medical aid groups had significantly higher mortality rates. PD dementia and fracture were identified as risk factors for mortality. CONCLUSION: Older age at diagnosis and surgery, being male, the use of medical aid, and the comorbidity of dementia and fractures were associated with a higher risk of mortality after DBS in patients with PD. Neurologists should consider these risk factors in assessing the prognosis of PD patients undergoing DBS.

Effects of Dietary Protein-to-Energy Ratios on Growth, Immune Response, Antioxidative Capacity, Liver and Intestinal Histology, and Growth-Related Gene Expression in Hybrid Yellow Catfish (Pelteobagrus fulvidraco ♀ × Pelteobagrus vachelli ♂).

This study is aimed at evaluating the effects of dietary protein-to-energy ratios on the growth, immunological response, antioxidative capacity, liver and intestinal histology, and growth-related gene expression of hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × Pelteobagrus vachelli ♂). Eight diets were formulated to form different protein/energy ratios of 84, 88, 90, 93, 95, 96, 99, and 103 mg/kcal (P/E84, P/E88, P/E90, P/E93, P/E95, P/E96, P/E99, and P/E103), respectively. These diets contain different levels of gross energy (GE), ranging from 4.13 to 4.76 kcal g-1. Seven hundred and twenty healthy fish (17.15 ± 0.02 g) were randomly dispersed into 24 rectangular fiberglass tanks with 8 treatments in triplicate groups. The fish fed a P/E ratio of 95 mg/kcal demonstrated the best growth and feed utilization. A significant (P < 0.05) increase in percent weight gain (WG%) and specific growth rate (SGR) was seen as the dietary P/E ratio ameliorated from P/E84 to P/E95, followed by a decreased pattern in these parameters. Feed conversion ratio (FCR) and daily feed intake (DFI) were significantly impacted by dietary P/E ratios (P < 0.05). Additionally, an optimum P/E ratio improved intestinal morphology. However, low or high P/E ratio diets can cause oxidative stress, impaired liver function, and significantly reduced nonspecific immunity. The expression of target of rapamycin (TOR) and insulin-like growth factor-1 (IGF1) genes in the liver was considerably influenced by dietary protein-to-energy ratios (P < 0.05). Based on the statistical analysis of WG% against the dietary P/E ratio, the optimal P/E ratio for the studied species was estimated to be 92.92 mg/kcal.

[The correlation between sperm DNA damage and IVF-ET clinical pregnancy outcomes in different BMI population with normal routine semen examination].

OBJECTIVE: To analyze the correlation between sperm DFI, HDS and IVF-ET pregnancy outcomes in different BMI populations with normal routine semen examination. METHODS: The clinical data of 199 cycles of IVF-ET were retrospectively analyzed. Sperm chromatin structure analysis based on flow cytometry was used to detect sperm DFI and HDS. The correlation between sperm DFI, HDS and pregnancy outcome of IVF-ET were analyzed. RESULTS: The sperm DFI was negatively correlated with IVF-ET pregnancy in overweight (24.0 kg/m2≤BMI<28.0 kg/m2) population (OR=0.935, P=0.043). In the normal BMI group (18.5 kg/m2≤BMI < 24.0 kg/m2), the clinical pregnancy outcome of IVF-ET was not significantly correlated with sperm DFI, and was negatively correlated with male age (OR=0.744, P=0.020). In the obese population (BMI ≥ 28.0 kg/m2) , there was no significant correlation between the clinical pregnancy outcome of IVF-ET and sperm DNA fragmentation index (DFI) , but a negative correlation with male BMI (OR = 0.779, P = 0.043). CONCLUSION: The male BMI affected the correlation between sperm DFI and IVF-ET pregnancy outcomes: ①Sperm DFI was only associated with IVF-ET clinical pregnancy outcome in the overweight population; ② In normal BMI and obese populations, male age and male BMI were important factors affecting IVF-ET clinical pregnancy outcome respectively; ③No correlation was found between sperm HDS and IVF-ET pregnancy outcomes.

Clinical, electrophysiological, and genetic characteristics of cerebrotendinous xanthomatosis in South Korea.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder caused by 27-hydroxylase deficiency. We report the clinical characteristics of six Korean CTX patients. The median age of onset was 22.5 years, the median age at diagnosis was 42 years, and the diagnostic delay was 18.1 years. The most common clinical symptoms were tendon xanthoma and spastic paraplegia. Four of five patients exhibited latent central conduction dysfunction. All patients carried the same mutation in CYP27A1 (c.1214 G>A [p.R405Q]). CTX is a treatable neurodegenerative disorder; however, our results revealed that patients with CTX in Korea might receive the diagnosis after a prolonged delay. .

Blood Cell Parameters Combined with Inflammatory Markers in the Early Diagnosis of Pulmonary Embolism.

Venous thrombosis is a semi-solid formation of blood components that coalesce in the venous system, and the pathological process of its formation is called venous thrombosis. The deep veins of the lower extremities are a common site of prevalence, and the clinical diagnosis of lower extremity deep vein thrombosis can occur independently or as a complication of other diseases. There is a clear link between inflammation and coagulation/anticoagulation, with inflammatory mechanisms upregulating pro-inflammatory factors, downregulating natural anticoagulant substances, and inhibiting fibrinolytic activity; systemic inflammation is a strong pro-thrombotic stimulus; and in vivo, natural anticoagulant substances not only prevent thrombosis, but also deter inflammatory processes. The interconnection between inflammation and coagulation plays an important role in venous thrombosis. In this study, we analyzed the relationship between inflammatory markers CRP and Fg, FVIII:C and FIX:C by measuring plasma CRP concentration, Fg level, FVIII:C and FIX:C levels in patients with DVT diagnosed by ultrasound, and explored the role and mechanism of inflammatory response and coagulation factor abnormalities and the interaction between them in the development of DVT. In this paper, human blood DNA was extracted by phenol-chloroform-isoamyl alcohol extraction, and CRP 1059G/C gene polymorphism was detected by polymerase chain reaction-restriction enzyme segment length polymorphism (PCR-RFLP) nucleotide typing technique, and the genotypes of each subject were distinguished according to the bands seen by gel electrophoresis, and the frequency of each genotype was counted. Plasma CRP concentrations were measured by immunoturbidimetric assay, FVIII:C and FIX:C levels were measured by phase I assay, and plasma Fg levels were measured by coagulation assay in 59 cases (38 males and 21 females, aged 21-82 years, mean 49.67±11.12 years) and 26 controls (17 males and 9 females, aged 32-67 years, mean 50.13±8.96 years). The above indexes were compared between the two groups, and the correlation between CRP and FVIII:C, FIX:C and Fg was analyzed. Polymerase chain reaction-restriction enzyme segment length polymorphism nucleotide typing technique was used to detect the relationship between CRP 1059G/C gene polymorphism and DVT, to further search for risk factors of venous thrombosis, thus providing new ideas for the future prevention and treatment of this disease in clinical practice.

The mediating effect of the prolonged second stage of labor on delivery mode and urinary incontinence among postpartum women: evidence from Shandong, China.

INTRODUCTION AND HYPOTHESIS: This study was aimed at exploring the mediating role of the prolonged second stage of labor (PSSL) in the association between delivery mode and urinary incontinence (UI) among postpartum women in Shandong, China. METHODS: A cross-sectional study involving postnatal women from the Women's Pelvic Floor Functional Health Center in Shandong, China, was conducted. An electronic questionnaire was used to collect the data between June 2020 and February 2021. UI was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Logistic regression and multiple linear regression were employed to explore the association among delivery mode, PSSL, and UI, and the mediating role of PSSL. RESULTS: Among the total of 5,586 postpartum women included in this study, the prevalence of UI was 13.3%. Among the 742 patients with UI, the prevalence of stress urinary incontinence (78.3%) was greater than urge urinary incontinence (8.6%), mixed urinary incontinence (9.3%), and others (3.8%). After adjusting for controlling variables, delivery mode was found to be significantly associated with PSSL, whereby women with vaginal delivery were more likely to be in PSSL, and women with PSSL had a higher probability of suffering from UI. PSSL played a partial mediating effect in delivery mode and UI. CONCLUSIONS: This study provided evidence that the effect of delivery mode on UI was partially mediated by PSSL among postpartum women in Shandong, China. Strategies to prevent PSSL should be actively adopted to reduce the risk of UI in women.

Effects of Dietary Glycinin on Oxidative Damage, Apoptosis and Tight Junction in the Intestine of Juvenile Hybrid Yellow Catfish, Pelteobagrus fulvidraco ♀ × Pelteobaggrus vachelli ♂.

The objective of this study was to examine the influences of glycinin for growth and intestinal structural integrity related to oxidative damage, apoptosis and tight junction of juvenile hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × Pelteobaggrus vachelli ♂). Fish (initial weight, 1.02 ± 0.01 g) were fed diets containing five different levels of glycinin at 0%, 2%, 4%, 6%, and 8% for 8 weeks. The results demonstrated that dietary glycinin levels had a negative correlation with final weight, feed intake, protein efficiency ratio and survival rate of the experiment fish. When the level of dietary glycinin exceeded 4%, the structural integrity of the posterior intestine was observably impaired, characterized by disordered and exfoliated margin of intestinal villi, blurred and broken boundaries of tight junctions, damaged organelles and cell vacuolation. Levels of 4-8% dietary glycinin depressed the total antioxidant capacity and total superoxide dismutase activities of posterior intestine. Furthermore, a high level of dietary glycinin linearly and quadratically down-regulated the mRNA expressions of Claudin-1, Occludin and ZO-1, while it linearly and significantly up-regulated the mRNA expressions of Bax, Cyt C, Caspase 3, Caspase 9 and p53 in the posterior intestine. In conclusion, dietary 4-8% glycinin impaired the morphological structure of the posterior intestine by inducing oxidative stress and cell apoptosis, and eventually impeded the growth performance of juvenile hybrid yellow catfish.