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The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain.This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis.Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development.The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased.lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors. [ABSTRACT FROM AUTHOR]

Rabbit hepatitis E virus (HEV) has been reported for years and is thought to have the potential for zoonotic transmission from rabbits to humans. As reported, HEV genotype 3 (gt3) is the most prevalent form of HEV in rabbits. To determine the prevalence of HEV in commercial rabbit livers, 176 liver samples were collected from an abattoir in Hebei Province, China. Three (1.7%) samples tested positive for RNA of HEV-ORF2 (open reading frames-2). Sequence analysis showed that the three isolates shared high identities with each other (94.08–98.85%). Further analysis showed that all the rabbit strains clustered together in the branch of HEV gt3. Further study by immunohistochemistry (IHC) assays showed that 131 (74.4%) liver samples were positive for HEV ORF2 protein. Pathological changes including cell degeneration, inflammatory cell infiltration and bile duct epithelial cell hyperplasia were observed under microscopy. These findings indicated the presence of HEV in commercial livers of rabbits. Additional studies should be conducted to investigate the infectivity of rabbit HEV (rHEV) and the potential risks of zoonotic transmission of rHEV from rabbits to human beings.

Abstract Background Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. Methods We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff) was used to estimate the transmission interaction in different age groups. Results A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff = 4.28), followed by group 2 to 3 (R eff = 2.61), and group 2 to 4 (R eff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45–64 years old. Conclusions Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15–64 years should first be vaccinated to prevent transmission in China. Graphical Abstract

In the era of big data,due to information overload,it is difficult for users to find interesting content from massive data.The birth of personalized recommendation system has greatly solved this problem.Collaborative filtering has been widely used in the field of personalized recommendation,but due to the limitations of the model,the recommendation effect has not been further improved.Most existing collaborative filtering introduce presentation learning methods to obtain better user representation vectors and item representation vectors or improve user item match functions to improve the performance of the recommendation system,but such work is devoted to extracting user-item interaction information from a single interaction.This paper proposes a multi-space interactive collaborative filtering recommendation algorithm,which maps user vectors and item vectors to multiple spaces,performs user-item interaction from multiple angles,and then uses a two-layer attention mechanism to aggregate the final user representation vector and item representation vector to make a score prediction.The multi-space interaction collaborative filtering(MSICF) was compared with baseline on the published real dataset,and the evaluation of the MSICF is better than baseline.

A roof?rib pillar support system is often formed in the metal mines that applied to the backfill mining method. In order to ensure the safe mining, it is of great significance to explore the failure mechanism of the roof?rib pillar support system under backfill mining. On the basis of considering the side pressure effect of the backfill on the rib pillar, a mechanical model of the roof?rib pillar support system under backfill mining was established. Furthermore, the catastrophe theory was used to explore the failure mechanism of the supporting system under the action of the filling body, and the influence of the structural parameters of the support system before and after filling on the stability of the stope was analyzed. The research results show that under the condition of certain mechanical properties of the rock mass, the stability of the roof?rib pillar support system under backfill mining is controlled by the stope structure parameters (roof thickness, stope span, rib pillar width, rib pillar height), the overburden load and the side pressure of the backfill. The addition of the filling body will reduce the stiffness ratio of the support system, thereby improving the stability of the stope. When the stope is at an unfilled state, the optimization sequence of the structural parameters of the support system should be roof thickness, stope span, rib pillar width and rib pillar height. When the stope is at the state of filling, the optimization sequence should be roof thickness, rib pillar width, stope span, and rib pillar height. The combination of theoretical derivation and numerical simulation is applied in the supporting project to verify the correctness of theoretical derivation.

Abstract Background Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. Results Herein, we have prepared a new donut-like metal–organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. Conclusions Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration. Graphic abstract

ObjectiveCarotid endarterectomy (CEA) has been considered as “gold standard” treatment for patients with significant carotid stenosis Intra-operative hypotension was a risk factor for post-operative complications in patients undergoing CEA. This study aimed to investigate the predictors for intra-operative hypotension during CEA.MethodsThis retrospective study included consecutive patients underwent CEA from June 1, 2020 to May 31, 2021 in the neurosurgery department of Xuanwu Hospital, Capital Medical University. The intraoperative hypotension was defined as blood pressure (BP) of 20% below standard value for longer than 5 min. Univariable and multivariable analyses were performed to identify the prediction of risk factors for intraoperative hypotension.ResultsOverall, 367 patients were included, and 143 (39.0%) patients had hypotension during CEA procedure. Univariate analysis indicated Grade 3 hypertension (P = 0.002), peripheral artery disease (P = 0.006) and shunting (P = 0.049) were associated with occurrence of intraoperative hypotension during CEA procedure. On multivariable analysis, Grade 3 hypertension (P = 0.005), peripheral artery disease (P = 0.009), and shunting (P = 0.034) were all found to be independent predicting factors of hypotension during the CEA process.ConclusionIntraoperative hypotension is a dynamic phenomenon may be affected by patients with grade 3 hypertension, peripheral artery disease and intra-operative shunting. It is necessary to pay special attention to these patients, both intraoperatively and postoperatively, to improve the final clinical outcome.