Fracture Mode Transition during Assembly of TC4 High-Lock Bolt under Tensile Load: A Combined Experimental Study and Finite Element Analysis

Fracture during the assembly process is an important failure mode for high-lock bolts used in the aviation industry, which greatly increases the potential of unpredictable accidents during service. In the current study, the underlying reasons for fracture during the assembly of a TC4 high-lock bolt was investigated using a tensile test and finite element analysis (FEA). The microstructure of the as-received bolt consisted of a high proportion of α phase, some β phase, and a small amount of α′ phase formed via martensite phase transformation during the rammer process. The experimental force–displacement curves revealed an average yield load of 55.9 kN and a breaking load of 67.65 kN. The corresponding yield strength was calculated to be 0.9 GPa, which was smaller than the standard value of TC4. This was attributed to the preload-induced stress concentration on the thread surface, leading to obvious strain hardening, which can lead to crack initiation. The effect of preload was further confirmed by the fractographies in which the initial crack was observed on the thread surface. The fractographies suggested that hybrid fracture occurred on the tensile loaded bolt. The initial failure was brittle fracture on the thread surface, transforming into ductile fracture in the screw. The results can contribute to understanding the effect of preload on the load carry capacity of high-lock bolts and provide a strategy to design its assembly specification.     

Rust Distribution of Non-Uniform Steel Corrosion Induced by Impressed Current Method

The non-uniform corrosion of steel bars is the main factor affecting the durability of concrete. The cracking pattern of concrete due to corrosion is closely related to the distribution of the corrosion products. Research on the thickness distribution of the rust layer and the cracking pattern of concrete under different influencing factors is of great significance in the prediction of the service life of existing reinforced concrete structures and the avoidance of the premature cracking of the reinforced concrete structures to be built. This paper studies the thickness distribution of the rust layer on the surface of single and multiple corroded reinforcements under non-uniform corrosion. The electrochemical analysis of the electrified corrosion process was carried out by using the finite element analysis software, and the distribution of the current density was obtained. The effects of geometric parameters, steel bar position, and steel bar spacing and shape on the corrosion expansion cracking pattern were studied. The results indicated that as the position of the steel bar differed, the crack pattern of the concrete changed, depending on the number of corrosion peaks (i.e., the maximum thickness of the rust layer). In terms of the corner-located steel, the number of corrosion peaks varied in the cases of different geometrical parameters (i.e., the diameter of the steel bar and the distance between the steel bars and the stainless steel wire). Nevertheless, the critical corrosion degrees of the side-located and corner-located steel bars, with respect to the cracking of the outer concrete surface, were basically the same. Additionally, the ribbed steel bar presented a lower critical corrosion degree than that of the plain steel bar, while little influence was exhibited with the varying angles of the rib.     

Ultra-High-Performance Concrete (UHPC): A State-of-the-Art Review

The interest of researchers in UHPC has increased over the past decade. It is crucial to understand the structural behavior of reinforced UHPC (R/UHPC) components under various loading conditions before they can be used as a replacement for conventional concrete. Although several studies on ultra-high-performance concrete (UHPC) have been conducted, the knowledge is scattered, and no one can easily judge the performance and methodology of UPHC. Therefore, the purpose of this study was to review the research studies already carried out on UHPC. The review focuses on the materials’ physical and chemical composition, mechanical and durability characteristics, fire resistance, and environmental benefits of UHPC. Design considerations for effectively utilizing UHPC in structural elements are also presented. The best UHPFRC mixture is obtainable with a steel fiber content of 2–3% and a water-to-cement ratio of 0.2–0.3. The review also discusses the essentials recommendation for future research on UHPC.     

Dasatinib and interferon alpha synergistically induce pyroptosis-like cell death in philadelphia chromosome positive acute lymphoblastic leukemia

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is a high-risk disease subtype with a dismal prognosis. Inhibiting BCR-ABL kinase alone is insufficient to eradicate Ph+ALL clones, and alternative BCR-ABL-dependent and -independent pathways need to be targeted as an effective strategy. Our study revealed that the combination of dasatinib and interferon-α showed synergistic activity against Ph+ALL, inducing mitochondrial dysfunction and causing necrosis-like cell lysis. Mechanistic studies showed that the induced cell death was caspase-3-independent. Canonical necroptosis signals, such as RIP1 and MLKL, were not activated; instead, the pyroptosis executor Gasdermin D was upregulated expression and activated. The expression levels of extracellular ATP and IL-1β were also upregulated, both of which are markers of pyroptotic cell death. In a murine Ph+ALL model, the dual drug treatment prolonged the survival of tumor-bearing mice. More importantly, we incorporated the dual drugs to maintenance therapy in 39 patients who were unfit for allogeneic stem cell transplantation (allo-HSCT). The median follow-up was 28.5 months, the 4-year disease-free survival and overall survival rates were 52.2% and 65.2%, respectively. Our data suggest that the combination of dasatinib and interferon-α has potential synergistic activity against Ph+ALL and shows promise as a maintenance therapy for Ph+ALL patients who are unfit for allo-HSCT.     

Rotenone,an environmental toxin,causes abnormal methylation of the mouse brain organoid's genome and ferroptosis

More and more reports have pointed out that rotenone, as an insecticide, has high neurotoxicity and reproductive toxicity to livestock and mammals. As a highly physiological correlation system of internal organs, quasi-organs have great potential in the fields of drug toxicity and efficacy test, toxicology research, developmental biology and so on. In this study, brain organs (mBOs) derived from mouse neural stem cells were used to investigate the effects of rotenone on the physiological activity and epigenetic modification of mBOs. At the same time, Rotenone could significantly stimulate the increase of the concentration of LPO, lactic acid and hydroxyl radical in mBOs, and inhibit the expression of neuronal marker Tuj1, CHAT, PAX6 and so on. Further analysis showed that Rotenonem could induce mitochondrial damage in mBOs. The results of qPCR and Western blot showed that Rotenone could up-regulate the expressions of ferroptosis promoting protein p53, Cox2 and so on, while inhibit the expressions of negative regulatory protein of ferroptosis GPX4, FTH1, SLC7A11. In addition, the results of RRBS-Seq sequencing showed that the methylation modification at DMR level in Rotenone-treated mBOs group was significantly higher than that in Ctrl group. The results of KEGG analysis showed that compared with Ctrl, the genes with hypermethylation of promoter and Genebody in Rotenone-treated mBOs were mainly located in the Neuro active ligand-receptor interaction signal transduction pathway. In summary, rotenone can significantly lead to abnormal methylation of mouse brain organs, and lead to the loss of normal physiological function of neurons by inducing ferroptosis.     

PBL联合CBL教学法在急诊住院医师规范化培训教学中的应用

目的 探讨PBL联合CBL教学法在急诊住院医师规范化培训教学中的应用效果。方法 选择2019年3—6月在本科室参加住院医师规范化培训的80名学员,随机分为两组,各40名。其中对照组采用PBL教学方法,观察组采用PBL联合CBL教学方法授课。带教结束后,采用DOPS评分、Mini-CEX评分、技能操作和学员满意度调查问卷评估两组学员的教学成果。结果 与对照组相比,观察组学员DOPS各项指标及总分、教学满意度、Mini-CEX考核评分、急救技能操作成绩均高于对照组,且差异均有统计学意义（P <0.05）。结论 PBL联合CBL教学法在急诊住培教学中有助于提高学员的学习能力,提升急诊临床教学质量。     

Prognostic and incremental value of computed tomography-based radiomics from tumor and nodal regions in esophageal squamous cell carcinoma

Objective: This study aimed to evaluate the prognostic value of preoperative radiomics and establish an integrated model for esophageal squamous cell cancer(ESCC).Methods: A total of 931 patients were retrospectively enrolled in this study(training cohort, n=624; validation cohort, n=307). Radiomics features were obtained by contrast-enhanced computed tomography(CT) before esophagectomy. A radiomics index was set based on features of tumor and reginal lymph nodes by using the least absolute shri...     

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.     

Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features. We discovered that female mice prenatally treated with anti-Müllerian hormone (PAMH) display impaired sexual behavior and sexual partner preference over the reproductive age. Blunted female sexual behavior was associated with increased sexual rejection and independent of sex steroid hormone status. Structurally, sexual dysfunction was associated with a substantial loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the ventromedial nucleus of the hypothalamus (VMH) and other areas of hypothalamic nuclei involved in social behaviors. Using in vivo chemogenetic manipulation, we show that nNOS^VMH neurons are required for the display of normal sexual behavior in female mice and that pharmacological replenishment of nitric oxide restores normal sexual performance in PAMH mice. Our data provide a framework to investigate facets of hypothalamic nNOS neuron biology with implications for sexual disturbances in PCOS.

Polycystic ovary syndrome (PCOS) is a highly prevalent disease affecting 5 to 18% of women of reproductive age worldwide (1, 2). PCOS is diagnosed upon the presence of at least two out of three prime features: high circulating levels of androgens (hyperandrogenism), menstrual irregularities (oligo-anovulation), and polycystic-like ovarian morphology (2, 3). Beyond its implications leading to female infertility, the disease is associated with several metabolic disruptions, cardiovascular diseases, and psychosocial disorders (4). Among these neurological implications, it has become clear that approximately 30% or more of patients with PCOS experience sexual dysfunctions, with clinical studies reporting a high risk of low sexual arousal, desire, and satisfaction and impaired lubrication and orgasm (5–9). These symptoms allude to disturbances in brain circuits controlling sexual function in the context of PCOS.Neural circuits driving female sexual behaviors are conserved among vertebrate species operating under the influence of sex steroid hormone modulation, which is paramount for partner interaction, receptivity, and sexual performance (10, 11). Indeed, gonadal sex hormones are implicated in shaping circuit architecture in the hypothalamus during development and activating these neonatally programmed circuits over reproductive adult life in many species (12–16). The hypothalamus integrates sensorial stimuli and autonomic arousal from endogenous sex drive cues (e.g., estrous phase, energy status, hormone milieu, genital stimulation) to convey this information to other brain areas and peripheral nerves (10, 17). The ventromedial nucleus of the hypothalamus (VMH) is considered the hub of specialized neurons, with intrinsic properties driving different components of sexual behavior (18–21). The VMH harbors neurons expressing neuronal nitric oxide synthase (nNOS), the enzyme responsible for the production of nitric oxide (NO), a key gaseous neurotransmitter that stimulates female sexual behavior (22, 23) and communicates with other circuits within the social brain (24, 25). Despite current advances unraveling novel pathways in the female sexual brain with specific behavioral responses, there is a clear lack of knowledge on how disturbances in these circuits may participate in sexual dysfunctions affecting one-third of women with PCOS.Growing evidence indicates that androgen excess in utero induces a developmental reprogramming of the female fetal brain toward the manifestation of PCOS traits later in life (26–29). Some studies have suggested that the clinical signs of hyperandrogenism have detrimental sexual effects (5), indicating a negative correlation between androgen levels and sexual function in PCOS. In recent years, it has been proposed that prenatal anti-Müllerian hormone excess may trigger gestational hyperandrogenism via the inhibition of placental aromatase (29, 30) and that women with PCOS display higher circulating levels of androgens and AMH during pregnancy as compared to healthy women (29, 31). Prenatal AMH-treated mice (PAMH) reliably recapitulate all the mouse equivalents of the PCOS Rotterdam criteria (29, 32) and are thus a preclinical model to mimic the human PCOS condition. PAMH female mice also display pronounced neuroendocrine dysfunction leading to exacerbated luteinizing hormone (LH) secretion (29), as in women with PCOS (33), denoting the presence of prenatally reprogrammed defects within the gonadotropin-releasing hormone (GnRH) neuronal network. Thus, prenatal AMH excess–mediated disruptions in the female brain may be key to understanding the pathophysiology of PCOS.Here, we investigated whether prenatal AMH excess could underpin defects in sex circuits promoting sexual dysfunction in PCOS-like female mice. We uncovered a profound decrease of nNOS and progesterone receptor (PR) expression in the VMH. These anatomical changes were also associated with significant impairment of sexual receptivity in PCOS-like female mice. Nevertheless, normal sexual function in PAMH female mice was restored to control levels upon peripheral injection of NO donor. Performing a series of acute functional manipulations in freely moving female mice, we showed that chemogenetic silencing of nNOS^VMH neurons in control female mice recapitulates PCOS-like sexual dysfunctions. Taken together, we unveiled a brain pathway potentially underpinning the etiology of low sexual drive in PCOS while pointing to prospective therapeutic approaches to rescue normal sexual function in these women.     

三黄片在术后早期炎性肠梗阻治疗中的应用价值探讨

目的探讨三黄片在术后早期炎性肠梗阻治疗中的应用价值。方法对36例术后早期炎性肠梗阻患者的治疗进行回顾性总结。结果治疗组中18例患者经过保守治疗,痊愈15例,有效17例,有效率94．4％;对照组中18例治愈10例,有效率83．3％。结论三黄片在术后早期炎性肠梗阻治疗中具有一定的应用价值,值得推广。