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Abstract: Lipid metabolism is a complex biochemical process that regulates normal cell activity and death. Ferroptosis is a novel mode of programmed cell death different from apoptosis, pyroptosis, and autophagy. Abnormal lipid metabolism may lead to lipid peroxidation and cell rupture death, which are regulated by lipoxygenase (LOX), long-chain acyl-coA synthases, and antioxidant enzymes. Alternatively, Fe2+ and Fe3+ are required for the activity of LOXs and ferroptosis, and Fe2+ can significantly accelerate lipid peroxidation in ferroptosis. Abnormal lipid metabolism is a certain risk factor for cardiovascular disease. In recent years, the important role of ferroptosis in developing cardiovascular disease has been increasingly reported. Reducing lipid accumulation could reduce the occurrence of ferroptosis, thus alleviating cardiovascular disease deterioration. This article reviews the relationship of lipid peroxidation to the general mechanism of ferroptosis and highlights lipid peroxidation as the common point of ferroptosis and cardiovascular disease.

Atherosclerosis, a chronic inflammatory disease, is a leading cause of death worldwide. Vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs) and macrophages play extremely vital roles in the formation of atherosclerotic plaques and subsequent atherosclerosis. Necroptosis, a caspase-independent programmed cell necrosis, occurs in advanced atherosclerotic plaques and has been implicated in VEC, VSMC and macrophage function. Although necroptosis may have considered as a defensive line against intracellular infection, it can induce a pro-inflammatory state, which will accelerate the disease process. Accordingly, necroptosis plays an important pathophysiologic role. In this review, we explore the role of necroptosis in VECs, VSMCs and macrophages in atherosclerotic plaques and their connection to atherosclerosis.

Abstract: Long non-coding RNA (lncRNA) is a kind of biomolecule that can regulate important life activities such as cell proliferation, apoptosis, differentiation, aging, and body development. It has been found that lncRNAs are closely related to various diseases. In cardiovascular diseases, lncRNAs affect the expression level of related genes in atherosclerotic plaques, which are closely related to endothelial dysfunction, smooth muscle cell proliferation, macrophage dysfunction, abnormal lipid metabolism, and cellular autophagy, thus participating in regulating the occurrence and development of AS. In view of this, investigating the role of lncRNAs in regulating cardiac gene networks on cardiovascular system diseases has attracted much clinical attention and may be a novel target for AS therapy. This paper focuses on lncRNAs related to AS, explores the relationship between lncRNAs and AS, suggests the role of lncRNAs in the prevention and treatment of AS, and expects the application of more lncRNAs as the marker in the clinical diagnosis and treatment of AS.

OBJECTIVES According to retrospective studies, oesophageal carcinoma is the second deadliest gastrointestinal cancer after gastric cancer. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve the inflammatory response of patients undergoing oesophagectomy; however, conclusions across studies remain unclear. We aimed to evaluate the effect of EIN on the clinical and immunological outcomes of patients undergoing oesophagectomy. METHODS Four electronic databases (MEDLINE, Embase, Web of Science and Cochrane Library) were used to search articles in peer-reviewed, English-language journals. The mean difference, relative risk or standard mean difference with 95% confidence interval were calculated. Heterogeneity was assessed by the Cochran’s Q test and I2 statistic combined with the corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS Six articles were finally included, with a total of 320 patients with oesophageal cancer. The meta-analysis results showed that EIN did not improve clinical outcomes (such as infectious complications, pneumonia, surgical site infection, anastomotic leak and postoperative hospital stay) or immune indices [referring to C-reactive protein, interleukin (IL)-6, IL-8, tumour necrosis factor-α]. Descriptive analysis suggested that EIN also increased the serum concentrations of IgG and the percentage of the B-cell fraction. Thus, its impact on IL-8 and IL-6 remains inconsistent. CONCLUSIONS The early-stage impact of EIN on immunological status in patients undergoing oesophagectomy is still unclear. According to the results of this meta-analysis, whether EIN could improve the clinical outcomes or biological status after oesophagectomy compared to standard enteral nutrition is uncertain. Since the impact of EIN is unclear, current guidelines that strongly advise the use of EIN should be changed, as the utility of EIN is very uncertain. More appropriately powered clinical studies are warranted to confirm its effectiveness.

Stem cell transplantation (SCT) holds great promise for overcoming diseases by regenerating damaged cells, tissues and organs. The potential for self-renewal and differentiation is the key to SCT. RNA methylation, a dynamic and reversible epigenetic modification, is able to regulate the ability of stem cells to differentiate and regenerate.

Isogenic cells cultured together show heterogeneity in their proliferation rate. To determine the differences between fast and slow-proliferating cells, we developed a method to sort cells by proliferation rate, and performed RNA-seq on slow and fast proliferating subpopulations of pluripotent mouse embryonic stem cells (mESCs) and mouse fibroblasts. We found that slowly proliferating mESCs have a more naïve pluripotent character. We identified an evolutionarily conserved proliferation-correlated transcriptomic signature that is common to all eukaryotes: fast cells have higher expression of genes for protein synthesis and protein degradation. This signature accurately predicted growth rate in yeast and cancer cells, and identified lineage-specific proliferation dynamics during development, using C. elegans scRNA-seq data. In contrast, sorting by mitochondria membrane potential revealed a highly cell-type specific mitochondria-state related transcriptome. mESCs with hyperpolarized mitochondria are fast proliferating, while the opposite is true for fibroblasts. The mitochondrial electron transport chain inhibitor antimycin affected slow and fast subpopulations differently. While a major transcriptional-signature associated with cell-to-cell heterogeneity in proliferation is conserved, the metabolic and energetic dependency of cell proliferation is cell-type specific., Author summary By performing RNA sequencing on cells sorted by their proliferation rate, this study identifies a gene expression signature capable of predicting proliferation rates in diverse eukaryotic cell types and species. This signature, applied to single-cell RNA sequencing data from embryos of the roundworm C. elegans, reveals lineage-specific proliferation differences during development. In contrast to the universality of the proliferation signature, mitochondria and metabolism related genes show a high degree of cell-type specificity; mouse pluripotent stem cells (mESCs) and differentiated cells (fibroblasts) exhibit opposite relations between mitochondria state and proliferation. Furthermore, we identified a slow proliferating subpopulation of mESCs with higher expression of pluripotency genes. Finally, we show that fast and slow proliferating subpopulations are differentially sensitive to mitochondria inhibitory drugs in different cell types. Highlights: A FACS-based method to determine the transcriptomes of fast and slow proliferating subpopulations.A universal proliferation-correlated transcriptional signature indicates high protein synthesis and degradation in fast proliferating cells across cell types and species.Applied to scRNA-seq, the expression signature predicts the global proliferation slowdown during C. elegans development.Mitochondria membrane potential predicts proliferation rate in a cell-type specific manner, with ETC complex III inhibitor having distinct effects on fibroblasts vs mESCs.

Purpose The goal of present study is to document our single-center experience with chimney technique for aortic arch diseases. Patients and methods From August 2012 to October 2017, 226 patients (mean age 54±12 years; 197 men) with aortic arch diseases underwent thoracic endovascular aortic repair combined with chimney stents. The aortic stent-grafts were deployed in zone 0 (n=22), zone 1 (n=13), or zone 2 (n=191). Results The technical success rate was 84% (189/226) and immediate type Ia endoleak (ELIa) happened in 37 (16%) patients. The 30-day mortality and morbidity rates were 2% (4/226) and 4% (8/226), respectively. Major adverse events include four major strokes, three spinal cord ischemia and one aortic rupture in the early-term. The clinical and imaging follow-up rates were 98% (218/222) and 78% (173/222), respectively. The average lengths of clinical and imaging follow-up were 22±16 months and 20±15 months, respectively. Chimney stent obstructions in left subclavian arteries were recorded in six (3%) patients. During follow-up, five patients died (2%) and two major strokes occurred (1%). One patient (0.5%) underwent reintervention. Conclusion The current study documented that the chimney technique is effective and safe for treating aortic arch diseases in different aortic zones. Cautions are needed to assess the permanency of chimney stent and to reduce the immediate ELIa rate.

Purpose Eukaryotic initiation factor 2α (eIF2α) plays important roles in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in animal hypoxia-induced pulmonary hypertension models. However, the underlying mechanism remains unknown at large. Autophagy has been reported to play a key role in the vascular remodeling in pulmonary arterial hypertension (PAH). The purposes of this study are to determine the functions of eIF2α and autophagy in the vascular remodeling of the monocrotaline-induced PAH rats and to clarify the correlation between eIF2α and autophagy. Methods We established a rat model of monocrotaline-induced PAH, and we established a cell model of platelet derived growth factor (PDGF)-induced PASMCs proliferation. The vascular morphology and the expression of eIF2α, LC3B, and p62 were assessed in the pulmonary arterial tissue of Sprague-Dawleyrats and PDGF-induced PASMCs. Results Autophagy was significantly active in monocrotaline model group (MCT)-induced PAH rats, which obviously promotes vascular remodeling in MCT-induced PAH rats. Furthermore, the proliferation of PASMCs was induced by PDGF in vitro. The expression of LC3B, eIF2α was increased in the PDGF-induced PASMCs proliferation, and the expression of p62 was reduced in the PDGF-induced PASMCs proliferation. Moreover, eIF2α siRNA downregulated the expression of eIF2α and LC3B, and upregulated the expression of p62 in PDGF-induced PASMCs proliferation. eIF2α siRNA inhibited the PDGF-induced PASMCs proliferation. Finally, chloroquine can upregulate the protein expression of LC3B and p62, it also can inhibit proliferation in PDGF-induced PASMCs. Conclusion Based on these observations, we conclude that eIF2α promotes the proliferation of PASMCs and vascular remodeling in monocrotaline-induced PAH rats through accelerating autophagy pathway.

OBJECTIVES Pulmonary sequestration is a rare congenital pulmonary malformation. The aim of this study was to explore the effect of different therapeutic strategies on the clinical outcome of asymptomatic intralobar pulmonary sequestration. METHODS We retrospectively reviewed the clinical data of 37 patients diagnosed with intralobar sequestration. All the patients were asymptomatic. Seventeen patients underwent video-assisted thoracoscopic surgery (VATS) once diagnosed and 20 patients chose to undergo observation. Of these 20 patients, 16 patients developed symptoms during the observation period and also underwent VATS; 4 patients never showed symptoms and did not have surgery. The 33 patients who had VATS were divided into 2 groups: group 1, patients who underwent VATS once diagnosed; group 2, patients who underwent VATS once symptoms appeared. Postoperative data and respiratory function data were compared between the 2 groups. RESULTS Twenty of the patients were men and 17 were women (mean age 37.05 ± 7.89 years). Results of a comparative analysis of the 2 groups indicated that patients in group 1 had better values for median estimated blood loss, median duration of chest tube insertion, postoperative hospital stay and postoperative hospital stay than those in group 2. Postoperative complications were reported in 1 patient in group 1 and in 3 patients in group 2. Meanwhile, the loss of lung function between group 1 and group 2 was statistically significant, which also suggested that patients benefited from surgery once diagnosed. CONCLUSIONS For asymptomatic intralobar sequestration, VATS could be effective and safe. The surgical intervention should be performed once the condition is diagnosed to avoid manifestations occurring and to preserve patients’ quality of life.

Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665–miR98–AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.

Oakleaf butterflies in the genus Kallima have a polymorphic wing phenotype, enabling these insects to masquerade as dead leaves. This iconic example of protective resemblance provides an interesting evolutionary paradigm that can be employed to study biodiversity. We integrated multi-omic data analyses and functional validation to infer the evolutionary history of Kallima species and investigate the genetic basis of their variable leaf wing patterns. We find that Kallima butterflies diversified in the eastern Himalayas and dispersed to East and Southeast Asia. Moreover, we find that leaf wing polymorphism is controlled by the wing patterning gene cortex, which has been maintained in Kallima by long-term balancing selection. Our results provide macroevolutionary and microevolutionary insights into a model species originating from a mountain ecosystem.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Nevertheless, the detailed molecular mechanisms of the progression of LUAD remain largely unknown. The present bioinformatics analysis reported that FAM83A and FAM83A-AS1 were upregulated in LUAD tissues and associated with prognosis in patients with LUAD. The purpose of the current study was to investigate the role of FAM83A and its antisense long non-coding (lnc)RNA FAM83A-AS1 in LUAD. Gene Expression Profiling Interactive Analysis was used to screen for potential oncogenes in LUAD and to analyze the clinical significance of FAM83A and FAM83A-AS1. Small interfering RNAs were constructed and transfected into LUAD cells to knock down the expression of FAM83A and FAM83A-AS1. EdU, Cell Counting Kit-8, Transwell and Matrigel assays were performed to detect the proliferation, migration and invasion of LUAD cells. The interaction between FAM83A-AS1, microRNA (miR)-495-3p and FAM83A was explored using a luciferase reporter assay. FAM83A and FAM83A-AS1 were both overexpressed in LUAD tissues compared with adjacent normal tissues. High expression of FAM83A and FAM83A-AS1 predicted worse survival and more advanced clinical stage. Knockdown of FAM83A or FAM83A-AS1 could inhibit the proliferation, migration and invasion of LUAD cells. Moreover, lncRNA FAM83A-AS1 regulated the expression of FAM83A by functioning as competing endogenous RNA for miR-495-3p. These results implicated that FAM83A and FAM83A-AS1 both played oncogenic roles in LUAD and FAM83A-AS1 could regulate the expression of FAM83A by sponging miR-495-3p. The study revealed a novel regulatory mechanism of tumor development in LUAD and FAM83A and FAM83A-AS1 may be novel biomarkers and therapeutic targets for LUAD.

Leaf mimicry is a fascinating phenomenon in nature. Among the widespread leaf mimics, Kallima butterflies display cryptic dead leaf-like wing patterns and have served as a classic case of protective resemblance supporting the theory of natural selection. Here, we integrated multi-omics data analyses and functional validation to uncover the evolutionary history of Kallima butterflies and investigated the genetic basis of their leaf mimicry. We found evidence for the differentiation and radiation of Kallima butterflies from Eastern Himalaya to East Asia and Southeast Asia. Moreover, we show that the leaf wing polymorphism is controlled by the wing patterning gene, cortex, which has been maintained in the Kallima genus due to balancing selection. Further, we demonstrate the involvement of another wing toolkit gene, WntA, in main leaf vein patterning resulting from a shared ancestral character. Our results reveal that the Kallima leaf wing formation is a typical case of Darwinian gradualism.

Significance: Perivascular adipose tissue (PVAT), which is present surrounding most blood vessels, from the aorta to the microvasculature of the dermis, is mainly composed of fat cells, fibroblasts, stem cells, mast cells, and nerve cells. Although the PVAT is objectively present, its physiological and pathological significance has long been ignored. Recent Advances: PVAT was considered as a supporting component of blood vessels and a protective cushion to the vessel wall from the neighboring tissues during relaxation and contraction. Nonetheless, further extensive research found that PVAT actively regulates blood vessel tone through PVAT-derived vasoactive factors, including both relaxing and contracting factors. In addition, PVAT contributes to atherosclerosis through paracrine secretion of a large number of bioactive factors such as adipokines and cytokines. Thereby, PVAT regulates the functions of blood vessels through various mechanisms operating directly on PVAT or on the underlying vessel layers, including vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Critical Issues: PVAT is a unique adipose tissue that plays an essential role in maintaining the vascular structure and regulating vascular function and homeostasis. This review focuses on recent updates on the various PVAT roles in hypertension and atherosclerosis. Future Directions: Future studies should further investigate the actual contribution of alterations in PVAT metabolism to the overall systemic outcomes of cardiovascular disease, which remains largely unknown. In addition, the messengers and underlying mechanisms responsible for the crosstalk between PVAT and ECs and VSMCs in the vascular wall should be systematically addressed, as well as the contributions of PVAT aging to vascular dysfunction.

Angiogenesis is a core hallmark of advanced cancers, especially in lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of lncRNAs in tumor angiogenesis remain largely unknown. Here we found that linc00665 depletion could markedly depressed proliferation and capillary tube formation of HUVECs in vitro. Mechanistically, linc00665 directly interacted with YB-1 protein, enhanced its stability through inhibiting ubiquitination-dependent proteolysis and stimulated its nuclear translocation in LUAD cells. The accumulated nuclear YB-1 activated expression of ANGPT4, ANGPTL3 and VEGFA by binding to their promoters, contributing to tumor-related angiogenesis in vitro and in vivo. Collectively, we conclude that linc00665 induces tumor-related angiogenesis in LUAD by directly interacting with YB-1 and activating YB-1-ANGPT4/ANGPTL3/VEGFA axis, which provides promising anti-angiogenic targets for cancer therapy.

Objective To evaluate the safety of early oral feeding in patients with type II diabetes after radical resection of esophageal carcinoma. Methods The clinical data of 121 patients with type II diabetes who underwent radical resection of esophageal carcinoma in the department of cardiothoracic surgery of Jinling Hospital from January 2016 to December 2018 were retrospectively analyzed. According to the median time (7 days) of the first oral feeding after surgery, the patients were divided into early oral feeding group (EOF, feeding within 7 days after surgery, 67 cases) and late oral feeding group (LOF, feeding after 7 days, 54 cases). Postoperative blood glucose level, incidence of complications, nutritional and immune indexes, inflammatory indexes, normalized T12-SMA (the postoperative/preoperative ratio of vertical spinal muscle cross-sectional area at the 12th thoracic vertebra level) and QLQ-C30 (Quality Of Life Questionnaire) scores were recorded and compared in the two groups. Results There was no statistical difference in preoperative nutritional index and postoperative complication rates between the EOF and LOF group (p > 0.05). The postoperative nutritional index (ALB, PA, TRF, Hb) and immune index (IgA, IgG, IgM) of the EOF group were higher than those of the LOF group (p p p Conclusions Early oral feeding is safe and feasible for patients with type II diabetes after radical resection of esophageal cancer, and it can improve short-term nutritional status and postoperative life quality of the patients.

Soundless chemical demolition agents (SCDAs) provide a reliable alternative for demolishing concrete structures in densely populated areas. However, research on the demolition of reinforced concrete member using SCDAs has not been conducted in detail. In this study, 12 concrete beam segments with different parameters were prepared to investigate the method of demolishing concrete beam using SCDAs. The arrangement of single row holes perpendicular to the upper surface of the beam segment was adopted, and the stirrups at the top of the beam segment were cut off along the hole connecting line and its extension line before grouting. The results showed that owing to the defect caused by cutting stirrups, the crack on the upper surface of the beam segment developed at the cutting seam, and the vertical crack on the end surface of the beam segment was also formed at the cutting seam and extended to the bottom of the beam segment. Besides, the average volume expansion rate of SCDAs in all boreholes in the beam segment (i.e. volume expansion rate of SCDAs) was determined to evaluate the impacts of the concrete compressive strength, hole spacing, and hole diameter on the crushing effect. Finally, a new equation for computing the hole spacing was derived, considering the time after grouting, concrete compressive strength, hole diameter, tie reinforcement ratio, ambient temperature, and volume expansion rate of SCDAs. The solution obtained using the proposed equation was in good agreement with the experimental results and was expected to provide guidance for the engineering application of SCDAs.

Perivascular adipose tissue (PVAT), the adipose tissue that surrounds most of the vasculature, has emerged as an active component of the blood vessel wall regulating vascular homeostasis and affecting the pathogenesis of atherosclerosis. Although PVAT characteristics resemble both brown and white adipose tissues, recent evidence suggests that PVAT develops from its own distinct precursors implying a closer link between PVAT and vascular system. Under physiological conditions, PVAT has potent anti-atherogenic properties mediated by its ability to secrete various biologically active factors that induce non-shivering thermogenesis and metabolize fatty acids. In contrast, under pathological conditions (mainly obesity), PVAT becomes dysfunctional, loses its thermogenic capacity and secretes pro-inflammatory adipokines that induce endothelial dysfunction and infiltration of inflammatory cells, promoting atherosclerosis development. Since PVAT plays crucial roles in regulating key steps of atherosclerosis development, it may constitute a novel therapeutic target for the prevention and treatment of atherosclerosis. Here, we review the current literature regarding the roles of PVAT in the pathogenesis of atherosclerosis.

Background: The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation. Methods: Using unique brown adipocyte–specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice. Results: We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte–selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor–dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT. Conclusions: These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.

Soundless chemical demolition as a novel and promising demolition method shows great potential to be applied in the engineering field. However, the demolition effect greatly depends on the hole parameters. In this paper, the influence of three hole parameters (hole diameter, hole depth and surrounding constraint) on the development and distribution of expansive pressure was explored. Meanwhile, constraint factor was introduced to describe the constraint of surrounding materials and quantify the constraint of steel pipes. The dispersion degree of relative expansive pressure was positively correlated with hole diameter, negatively correlated with the hole depth, and had no obvious relationship with the constraint coefficient. The impact of hole diameter and constraint coefficient exhibits an obvious impact on the expansive pressure at middle of the pipes than that of hole depth. Moreover, the expansive pressure increased with the increment of hole diameter and showed a linear relationship within 2 days. However, the development regularity of the expansive pressure is not linear with the constraint coefficient and this trend is moderated with the further increase of the coefficient. This work provides an idea to solve the problem that the proper hole parameters are hard to determine for chemical soundless demolition using expansive pressure measured by steel pipe.