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Objective To explore the expression and clinical significance of autophagy related proteins Beclin-1, microtubule-associated protein 1 light chain 3(LC3) in placenta tissues of pregnant women with fetal growth restriction(FGR). Methods A total of 40 pregnant women undergoing delivery due to FGR and 40 pregnant women undergoing normal delivery in the Second Affiliated Hospital of Zhengzhou University were enrolled as FGR group and healthy group between August 2022 and August 2023. The general clinical data in the two groups were collected. The levels of Beclin-1 and LC3 mRNA in placenta tissues were detected by PCR, and expressions of Beclin-1 and LC3 proteins were detected by immunohistochemistry. The differences in positive of Beclin-1 and LC3 proteins among patients with different clinical data were analyzed. Results The placental thickness, placental mass and neonatal weight in FGR group were lower than those in healthy group(P＜0.05). The mRNA levels of Beclin-1 and LC3 in FGR group were higher than those in healthy group(P＜0.05) and positive expression rates of Beclin-1 and LC3 proteins were significantly higher than those in healthy group(P＜0.05). There was significant difference in positive expression profile of Beclin-1 and LC3 proteins among patients with different placental thickness, placental mass and neonatal weight(P＜0.05). Conclusions The positive expressions of autophagy genes(Beclin-1 and LC3) are related to FGR, and their specific expression levels are closely related to fetal growth and development.

It is an important trend for the development of shaped charge (SC) technology to use energetic material in liner. As a new metastable energetic material, zirconium (Zr) based amorphous alloy has incomparable advantages over other energetic materials. In order to understand the jet forming law of Zr-based amorphous alloy liner and acquire an accurate understanding of the influence of key factors such as cone angle and wall thickness on the jet parameters of this kind of liner, the conical ZrCuNiAlAg amorphous alloy liner is taken as a research object and some numerical simulation of the jet forming process are carried out including 5 cone angles under certain wall thickness conditions and 5 kinds of wall thicknesses under certain cone angle conditions based on AUTODYN software. The static explosion tests of Zr-based amorphous alloy liner against steel target plate are carried out as well. The results show that the conical ZrCuNiAlAg amorphous alloy liner can form a stable and continuous jet with a spindle shape under the action of explosive products. In a certain range, both the tip velocity and length diameter ratio (LDR) of the jet decrease with the increasing cone angle and wall thickness of the liner. The average penetration depth of a conical ZrCuNiAlAg amorphous alloy liner with 40° cone angle and 1.2mm wall thickness against 45# steel target plate is 97.5mm at the stand-off distance of 3 times of charge diameter (CD). The diameter of perforation entrance is 25mm. The deflagration reaction and the deflagration products' reverse flight and strong erosion through the orifice are the main reasons for the formation of "large diameter, small penetration depth" perforation by the jet, which shows obvious energy-releasing characteristics in the process of penetration. The above results have certain guiding significance for the structural design of Zr-based amorphous alloy liner and the SC. [ABSTRACT FROM AUTHOR]

It is an important trend for the development of shaped charge (SC) technology to use energetic material in liner. As a new metastable energetic material, zirconium (Zr) based amorphous alloy has incomparable advantages over other energetic materials. In order to understand the jet forming law of Zr-based amorphous alloy liner and acquire an accurate understanding of the influence of key factors such as cone angle and wall thickness on the jet parameters of this kind of liner, the conical ZrCuNiAlAg amorphous alloy liner is taken as a research object and some numerical simulation of the jet forming process are carried out including 5 cone angles under certain wall thickness conditions and 5 kinds of wall thicknesses under certain cone angle conditions based on AUTODYN software. The static explosion tests of Zr-based amorphous alloy liner against steel target plate are carried out as well. The results show that the conical ZrCuNiAlAg amorphous alloy liner can form a stable and continuous jet with a spindle shape under the action of explosive products. In a certain range, both the tip velocity and length diameter ratio (LDR) of the jet decrease with the increasing cone angle and wall thickness of the liner. The average penetration depth of a conical ZrCuNiAlAg amorphous alloy liner with 40° cone angle and 1.2mm wall thickness against 45# steel target plate is 97.5mm at the stand-off distance of 3 times of charge diameter (CD). The diameter of perforation entrance is 25mm. The deflagration reaction and the deflagration products' reverse flight and strong erosion through the orifice are the main reasons for the formation of "large diameter, small penetration depth" perforation by the jet, which shows obvious energy-releasing characteristics in the process of penetration. The above results have certain guiding significance for the structural design of Zr-based amorphous alloy liner and the SC. [ABSTRACT FROM AUTHOR]

The enzyme cyclic GMP-AMP synthase (cGAS) is a key sensor for detecting misplaced double-stranded DNA (dsDNA) of genomic, mitochondrial, and microbial origin. It synthesizes 2'3'-cGAMP, which in turn activates the stimulator of interferon genes pathway, leading to the initiation of innate immune responses. Here, we identified Listerin as a negative regulator of cGAS-mediated innate immune response. We found that Listerin interacts with cGAS on endosomes and promotes its K63-linked ubiquitination through recruitment of the E3 ligase TRIM27. The polyubiquitinated cGAS is then recognized by the endosomal sorting complexes required for transport machinery and sorted into endosomes for degradation. Listerin deficiency enhances the innate antiviral response to herpes simplex virus 1 infection. Genetic deletion of Listerin also deteriorates the neuroinflammation and the ALS disease progress in an ALS mice model; overexpression of Listerin can robustly ameliorate disease progression in ALS mice. Thus, our work uncovers a mechanism for cGAS regulation and suggests that Listerin may be a promising therapeutic target for ALS disease. [ABSTRACT FROM AUTHOR]

Background Traditional Chinese medicine (TCM) has become an important option for patients with advanced esophageal cancer (EC) who are not able to undergo surgery, radiotherapy, chemotherapy, or with disease progression after chemotherapy. The purpose of this study is to investigate the application effects of Dingxiang Guanshitong Hanhua Pills alone and its combination with Fugui Guanshitong Granules, in order to improve the quality of life of patients with advanced EC, and provide an effective TCM treatment schemes for EC. Objective To evaluate the effects of Dingxiang Guanshitong Hanhua Pills alone and its combination with Fugui Guanshitong Granules on survival rate and quality of life of patients with EC after 6 weeks of treatment. Methods A total of 109 patients with advanced EC admitted to nine centers such as the First Affiliated Hospital of Henan University of CM, Linzhou Hospital of Traditional Chinese Medicine and Jia County Hospital of Traditional Chinese Medicine from January 2020 to April 2021 were selected as the research objects and divided into the control group, experimental group 1 and experimental group 2 by block randomization method. The control group received Danggui Buxue Decoction and Guizhi Renshen Decoction Granules, the experimental group 1 received Fugui Guanshitong Granules and Dingxiang Guanshitong Hanhua Pills, the experimental group 2 received Dingxiang Guanshitong Hanhua Pills, with the course of 6 weeks in the above three groups. The survival rate after 6 weeks of treatment, Quality of Life (QOL) score, Karnofsky Performance Status (KPS) score, TCM syndrome score (dysphagia, poststernal chest pain, mucus vomiting, loss of appetite, fatigue) before and after treatment of the three groups were compared, and safety evaluation was conducted. Results After 6 weeks of treatment, the survival rate was 72.7% in the control group, 88.6% in the experimental group 1, and 86.8% in the experimental group 2, and there was no statistically significant difference in the survival rates among the three groups after 6 weeks of treatment (χ2=4.036, P=0.133). There was no interaction effect of group and time on QOL score, KPS score, and TCM syndrome score (Pinteraction>0.05). The main effect of group was not significant on QOL score, KPS score and TCM syndrome score (Pinterclass>0.05). The main effect of time was significant on QOL score, KPS score and TCM syndrome score (Ptime

A greenhouse field experiment involving tomato (Solanum lycopersicum) was performed using different nitrogen (N) management regimes: sole application of differing rates of chemical N fertilizer (SC) (SC treatments: N0, N1, N2, and N3) and combined application of manure and chemical N fertilizer (MC) (MC treatments: MN0, MN1, MN2, and MN3). These were used to understand the relationship between comprehensive fruit composition, yield, and N fractions (soil mineral N; soil soluble organic N; soil microbial biomass N, and soil fixed ammonium) under greenhouse conditions. The results showed that the MC treatments significantly increased vitamin C and soluble sugar content compared with SC treatments. In addition, the MN2 treatment produced a high yield and had a positive effect on fruit composition. The N3 (563 kg N/ha) and MN3 (796 kg N/ha) treatments resulted in a high loss of N below the root zone (0-30 cm), consequently reducing N use efficiency. Soil mineral N, soil soluble organic N, and soil fixed ammonium tended to be higher during the first fruiting period, whereas soil microbial biomass N tended to be higher during the second fruiting period. MC treatments significantly increased the N fraction in the 0- to 30-cm soil layer; N fractions tended to be higher with the MN2 treatment. According to an optimum regression equation, soil fixed ammonium during the first fruiting period and soil microbial biomass N during the second fruiting period had a more significant influence on tomato yield and fruit composition. Overall, application MC at an appropriate rate (MN2: 608 kg N/ha) is a promising approach to achieving high yields and optimum taste, and it offers a more sustainable fertilizer management strategy compared with chemical N fertilization. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the beneficial effect of alpha-lipoic acid (ALA) during pregnancy and lactation on susceptibility to ovalbumin (OVA)-induced neonatal asthma, and the mechanism of involved. Methods: Pregnant BALB/c mice were administered ALA (1 % mixed with mouse chow) or standard mouse chow from 6th day of gestation to 21st day of lactation (postnatal). The offspring (neonatal pups) from the OVA and ALA+OVA groups were sensitized on 1st, 7th and 14th postnatal days (PNDs) via intraperitoneal (i.p.) injection of OVA (0.5 µg). Control mice pups were not exposed to OVA. On PND 21, all pubs were again exposed to 1 % OVA aerosol using a nebulizer. Results: Neonatal mice exposed to ALA showed a significant decline (p < 0.05) in the number of inflammatory cells (eosinophils), levels of inflammatory markers (IL-4, IL-13, IL-5 and TNF-a) as well as OVA-specific IgE and total IgE, when compared to neonatal mice from pregnant mice that did not receive ALA (control). Moreover, the antioxidant profiles of ALA-treated mice offspring were significantly improved (p < 0.05). Marked downregulation (p < 0.05) of the protein expressions of NF-κB p-p65 subunit and TNF-a were observed in ALA-treated mice pups. Conclusion: ALA exposure during pregnancy (maternal exposure) markedly decreases OVA-induced asthmatic airway inflammatory response in pups. Thus, ALA might be beneficial for use along with standard anti-asthmatic drugs in the management of pediatric asthmatic patients. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is one of the most commonly inherited heart diseases and the leading cause of sudden cardiac death among adolescents and young adults. Circulating long noncoding RNAs (lncRNAs) have demonstrated potential as diagnostic and therapeutic targets in several cardiovascular diseases. However, the circulating extracellular lncRNA expression profile of patients with HCM remains unclear. Plasma lncRNA expression was evaluated in patients with HCM and healthy controls using a human lncRNA microarray. A weighted correlation network analysis (WGCNA) and linear models for microarray data (Limma) were used. GSE68316 data from cardiac tissue in the Gene Expression Omnibus database were analysed for further validation. Using WGCNA, two modules (referred to as the magenta and the light‑yellow module) were identified that were positively associated with HCM. Gene Ontology analysis revealed that lncRNAs in the magenta module targeted ‘heart growth’. Using Limma, a total of 290 lncRNAs were differentially expressed (210 upregulated and 80 downregulated) in the plasma of HCM patients, compared with controls. Moreover, combined WGCNA and Limma analysis demonstrated that 27 hub lncRNAs in the magenta module and 13 hub lncRNAs in the light‑yellow module were significantly upregulated, compared with the controls. Moreover, of the 40 differentially expressed hub lncRNAs identified in the two modules, three circulating lncRNAs (lnc‑P2RY6‑1:1, ENST00000488040 and ENST00000588047) were also significantly upregulated in the HCM cardiac tissue validation dataset. These lncRNAs may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of HCM. [ABSTRACT FROM AUTHOR]

Mechanochemical activation-assisted synthesis, compared to conventional wet methods, exhibits advantages such as higher chemical homogeneity and better quality of the resulting nano-crystals, in preparing nano-sized aluminum hydride (AlH 3). Solid/liquid state milling is effective and convenient for production of α - AlH 3 /LiCl nano-composites through a mechanochemical reaction of LiH and AlCl 3 in [2-Eim] OAc. However, the kinetics of this process has not been thoroughly studied. In this work, we studied the kinetics of mechanochemical synthesis of α - AlH 3 /LiCl nano-composite to understand the reaction process and find the optimum milling parameters (including shortest time to achieve high-quality product). We performed isothermal desorption tests for as-milled samples at 80 °C. Structures of the products were analyzed using X-ray powder diffraction. Johnson-Mehl-Avrami (JMA) model was adopted to describe the process, which contains transformation fraction and chemical reaction controlled regime. Kinetics of mechanochemical reaction at the beginning was limited by diffusion rate of the reagent, and later controlled by nucleation of AlH 3. By fitting the experimental data, apparent activation energy for the mechanochemical reaction was calculated as 39.6 kJ/mol. • The nano-sized α -AlH 3 was synthesized by a mechanochemical method. • Kinetics of mechanically activated reaction is investigated systemically. • The surface nanocrystallization regulates this mechanochemical reaction kinetics. • The activation energy for this mechanochemical reaction is 39.6 kJ/mol. [ABSTRACT FROM AUTHOR]

Chronic benzene exposure is associated with hematotoxicity and the development of aplastic anemia and leukemia. However, the signaling pathways underlying benzene-induced hematotoxicity remain to be defined. Here, we investigated the role of protein phosphatase 2A (PP2A) in the regulation of benzeneinduced hematotoxicity in a murine model. Male mice with a hepatocyte-specific homozygous deletion of the Ppp2r1a gene (encoding PP2A Aα subunit) (HO) and matched wildtype (WT) mice were exposed to benzene via inhalation at doses of 1, 10, and 100 ppm for 28 days. Peripheral white blood cell counts and activation of bone marrow progenitors were attenuated in the HOmice, indicating that Ppp2r1a deletion protects against benzene-induced hematotoxicity. Moreover, elevation of urinary S-phenyl mercapturic acid, a benzene metabolite, was much greater inWTmice than inHOmice. Real-time exhalation analysis revealed more exhaled benzene but fewer benzene metabolites in HO mice than in WT mice, possibly because of the down-regulation of Cyp2e1, encoding cytochrome P4502E1, in hepatocytes of the HO mice. Loss-of-function screening disclosed that PP2A complexes containing the B56α subunit participate in regulating Cyp2e1 expression. Notably, PP2A-B56α suppressioninHepG2cellsresultedinpersistentγ-cateninphosphorylation at Ser33-Ser37-Thr41 in response to CYP2E1 agonists. In parallel, nuclear translocation of β-catenin was inhibited, concomitant with a remarkable decrease of Cyp2e1 expression. These findings support the notion that a regulatory cascade comprising PP2A-B56α, β-catenin, and Cyp2e1 is involved in benzene-induced hematotoxicity, providing critical insight into the role of PP2A in responses to the environmental chemicals. [ABSTRACT FROM AUTHOR]