Acupuncture-induced oxygen therapy inhibits oxyradical injury and improves microcirculation following brain injury

BACKGROUND： Acupuncture-induced oxygen therapy combines acupoint theory in traditional Chinese medicine and modern oxygen therapy. Clinical studies have shown that acupuncture-induced oxygen therapy results in favorable outcomes for brain injury. However, the mechanisms of action remain poorly understood. OBJECTIVE： To determine pathological changes and malondialdehyde （MDA） content, superoxide dismutase （SOD） and nitric oxide synthase （NOS） activity, as well as hemorheological brain alterations following acupuncture-induced oxygen therapy, and to explore possible mechanisms of acupuncture-induced oxygen therapy on brain injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experimental Center of Xi＇an Medical University from January 2006 to April 2009. MATERIALS： An oxygen delivery device, through the use of acupuncture （oxygen delivery machine ＋ silver hollowed needle, 0.5 mm inner diameter）, was purchased from Research Center ol Machine, Shaanxi University of Science and Technology in China. METHODS： A total of 180 Sprague Dawley rats were randomly assigned to six groups （n = 30）： normal, sham-surgery （dura mater exposure）, model （brain injury induced by free-falling of heavy object to head）, Xiantaimixture （0.417 mL/100 g following brain injury）, electroacupuncture [acupuncture at Baihui （DU 20）, Housanfi （ST 36）, Yanglingquan （GB 34）, and Sanyinjiao （SP 6） following brain injury], and acupuncture-induced oxygen therapy （oxygen delivery through hollowed needle to Baihui （DU 20）, Housanfi （ST 36）, Yanglingquan （GB 34）, and Sanyinjiao （SP 6） following brain injury, 0.01 mL/minute）. Group intervention was performed once a day for 14 consecutive days. MAIN OUTCOME MEASURES： Pathological changes, MDA content, SOD and NOS activity, and hemorheological alterations in the brain. RESULTS： Obvious pathological changes were observed, such as hemorrhage, edema, and cell necrosis, following brain injury. These alterations were significantly improved following 14 days of treatment with Xiantai mixture, electroacupuncture, and acupuncture-induced oxygen therapy. In particular, acupuncture-induced oxygen therapy resulted in recovery to normal conditions. In the Xiantai mixture, electroacupuncture, and acupuncture-induced oxygen therapy groups, MDA content was significantly reduced （P 〈 0.01）, SOD activity was significantly increased （P 〈 0.01）, NOS activity was significantly decreased （P 〈 0.01）, and hemorheological indices were reduced, compared with the model group, in particular, acupunture-induced oxygen therapy resulted in the most obvious changes （P 〈 0.01）. CONCLUSION： Acupuncture-induced oxygen therapy improved pathological changes following brain injury by possibly improving blood supply, ameliorating ischemia/hypoxia, and inhibiting peroxidation and free radicals.

Apoptosis of endothelial cells of cerebral basilar arteries in symptomatic cerebral vasospasm rabbit models Electron microscopic observation

BACKGROUND： Recent researchers report that vasospasm is caused by that, on one hand, damage of endothelial cells reduces synthesis and liberation of vessel dilator; on the other hand, defluxion of endothelial cells directly exposure vascular smooth muscles in active materials of vasoconstriction in blood. OBJECTIVE： To study whether apoptosis of cerebrovascular cells occurs in symptomatic cerebral vasospasm （CVS） rabbit models by using transmission electron microscope. DESIGN： Contrast observation. SETTINGS： The Fifth Endemic Area, the 89 Hospital of Chinese PLA; Minimally Invasive Neurosurgical Center, Tangdu Hospital, the Fourth Military Medical University of Chinese PLA. MATERIALS： A total of 24 New Zealand rabbits, of either sex, weighing 2.4 - 3.0 kg, of clear grade, were selected from the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA. JEM-2000EX transmission electron microscope was made in Japan. METHODS： The experiment was carried out in the Laboratory of Anatomy （National Key Laboratory）, the Fourth Military Medical University of Chinese PLA from April 2001 to April 2002. ①Preparation of symptomatic CVS models： Eighteen animals which were successfully modeled were randomly divided into experimental group （n =13） and control group （n =5）. Animals in the experimental group were poured with blood into cavitas subarachnoidealis; while, animals in the control group were poured with the same volume of saline into cavitas subarachnoidealis. At the 5^th day injection, three rabbits selected from the experimental group were anesthetized and perfused into left ventricle. And then, aorta pectoralis and caval vein were blocked by using ring clamp. Cranium was rapidly cut open to obtain cerebral basilar artery and a few of brain tissues. Both of them were fixed for 8 hours. Two rabbits selected from the control group were perfused with the same method to obtain basilar artery and brain tissues and fix. ②After fixation by using optic microscope, samples were stained with lead citrate uranyl acetate staining, observed with electron microscope and photographed. MAIN OUTCOME MEASURES： Morphological changes of cytoplasm and nucleus of vascular endothelial ceils and smooth muscle celts in the two groups. RESULTS： Morphology of vascular endothelial cells in cerebral basilar artery was not changed in the control group. However, vascular endothelial cells in the experimental group showed that cytochondria were swelling; endocytoplasmic reticulum was amplified; chromatin margination was clear; nucleus was in pyknosis; endothelial cells fell down from basal membrane; cell-cell junction was broken. Changes of smooth muscle cells were similar to those of endothelial cells. Severely, it was shown that nuclear pyknosis was obvious, and this was like early apoptosis. CONCLUSION： Apoptosis of endothelial cells may occur in spasmodic vessels.

Enterprise Management Innovation and Organizational Model Investigation Based on the E-commerce Environment

Nowadays,the development of e-commerce in China is changing rapidly,and the innovation of enterprise management model based on e-commerce has become a new development requirement,leading Chinese e-commerce companies to find the way to develop business innovation.Taking this as the starting point,firstly,we analyze the significance of enterprise management model innovation under the background of e-commerce development,and on this basis,we summarize the way of enterprise organization management mode innovation under the context of e-commerce,and total related personnel think about it.

Based on the Emerging E-commerce Ecosystem Synergy and Innovation Mechanism Investigation

E-commerce is a new business model based on Internet information technology,and its internal operation mechanism can be studied in depth from the perspective of the knowledge ecosystem according to the law of knowledge ecology.The various knowledge elements in the e-business knowledge ecosystem interact and influence each other,continue to exchange materials and energy according to specific rules,and develop and circulate autonomously so that users can acquire,transfer,share and sublimate knowledge in the business system.Finally,knowledge innovation and new value creation are realized to complete the final value sublimation.Based on this,this paper elaborates on three aspects of e-business ecosystem system synergy theory,e-business ecosystem,and e-business ecosystem synergy and innovation model for the reference of relevant personnel.

Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and nephropathy.However,their activity in diabetic retinopathy(DR)remains unclear.Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR treatment.By single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic conditions.Treatment of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic mice.GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs.Additionally,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial DNA.Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes.Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling.This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe^(-/-)mice

Atherosclerosis is the major contributor to cardiovascular mortality worldwide.Alternate day fasting(ADF)has gained growing attention due to its metabolic benefits.However,the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models.The present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient(Apoe^(-/-))mice.Eleven-week-old male Apoe^(-/-)mice fed with Western diet(WD)were randomly grouped into ad libitum(AL)group and ADF group,and ADF aggravated both the early and advanced atherosclerotic lesion formation,which might be due to the disturbed cholesterol profiles caused by ADF intervention.ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response(ISR)in the liver.The hepatic expression of activating transcription factor 3(ATF3)was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^(-/-)mice.Moreover,the expression of ATF3 could be regulated by Krüppel-like factor 6(KLF6)and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway.In conclusion,ADF aggravates atherosclerosis progression in Apoe^(-/-)mice fed on WD.ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6,subsequently inhibiting ATF3 expression.The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^(-/-)mice.The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.

Glucokinase activator improves glucose tolerance and induces hepatic lipid accumulation in mice with diet-induced obesity

Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug development based on glucokinase(GK)activation is an important strategy for lowering blood glucose.This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice.Materials and methods:Mice were fed with a high-fat diet(HFD)for 16 weeks to induce obesity,followed by a GK activator(GKA,AZD1656)or vehicle treatment by gavage for 4 weeks.The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests.Hepatic lipid accumulation was assessed by hematoxylin and eosin staining,Oil Red O staining,and transmission electron microscopy.The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis,with a mechanistic study in mouse livers in vivo and AML12 cells in vitro.Results:GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation.Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase(PERK)-unfolded protein response(UPR)pathway activations in GKA-treated HFD-fed mice.Inhibition of the ACC activity,which is an important protein in lipogenesis,attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro.Conclusions:GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression,which subsequently activated the hepatic PERK-UPR signaling pathway.

Mechanisms of chromatin-based epigenetic inheritance

Multi-cellular organisms such as humans contain hundreds of cell types that share the same genetic information(DNA sequences),and yet have different cellular traits and functions.While how genetic information is passed through generations has been extensively characterized,it remains largely obscure how epigenetic information encoded by chromatin regulates the passage of certain traits,gene expression states and cell identity during mitotic cell divisions,and even through meiosis.In this review,we will summarize the recent advances on molecular mechanisms of epigenetic inheritance,discuss the potential impacts of epigenetic inheritance during normal development and in some disease conditions,and outline future research directions for this challenging,but exciting field.

Induced regulatory T cells suppress Tel cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus

Type 1 diabetes mellitus(T1D)is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells.In addition to well-established pathogenic effector T cells,regulatory T cells(Tregs)have also been shown to be defective in T1D.Thus,an increasing number of therapeutic approaches are being developed to target Tregs.However,the role and mechanisms of TGF-β-induced Tregs(iTregs)in T1D remain poorly understood.Here,using a streptozotocin(STZ)-induced preclinical T1D mouse model,we found that iTregs could ameliorate the development of T1D and preserve β cell function.The preventive effect was associated with the inhibition of type 1 cytotoxic T(Tel)cell function and rebalancing the Treg/Tc1 cell ratio in recipients.Furthermore,we showed that the underlying mechanisms were due to the TGF-β-mediated combinatorial actions of mTOR and TCF1.In addition to the preventive role,the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic(NOD)mouse models were tested,which revealed improved β cell function.Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.

Caenorhabditis elegans mom-4 is required for the activation of the p38 MAPK signaling pathway in the response to Pseudomonas aeruginosa infection

The p38 mitogen-activated protein kinase(MAPK)plays an evolutionarily conserved role in the cellular re-sponse to microbial infection and environmental stress.Activation of p38 is mediated through phosphorylation by upstream MAPKK,which in turn is activated by MAPKKK.In the Caenorhabditis elegans,the p38 MAPK(also called PMK-1)signaling pathway has been shown to be required in its resistance to bacterial infection.However,how different upstream MAP2Ks and MAP3Ks specifically contribute to the activation of PMK-1 in response to bacterial infection still is not clearly un-derstood.By using double-stranded RNA-mediated interference(RNAi)and genetic mutants of C.elegans,we demonstrate that C.elegans MOM-4,a mammalian TAK1 homolog,is required for the resistance of C.elegans to a P.aeruginosa infection.We have also found that the MKK-4 of C.elegans is required for P.aeruginosa resistance,but not through the regulation of DLK-1.In summary,our results indicate that different upstream MAPKKKs or MAPKKs regulate the activation of PMK-1 in response to P.aeruginosa.

An Extended Grey Model GM(1, 1, exp(bk)) and Its Application in Chinese Civil Air Passenger Volume Prediction

In grey models,GM(1,1)is an important prediction model.The grey model GM(1,1)has good prediction results in the case original data change exponentially at a low speed.However in practical cases sometimes,original data show exponential changes or approximately exponential changes change at a high speed.In these cases,the grey model GM(1,1)has poor prediction results because the data fail to meet the laws of traditional model.Therefore,the paper proposes an extended grey model GM(1,1,ebk)and its modeling method.In the final section,the paper builds grey models of GM(1,1,ebk)for a practical problem and the results show the grey model proposed has greatly improved simulation and prediction accuracy compared with the traditional model.

Bacteroides ovatus-mediated CD27^(−)MAIT cell activation is associated with obesity-related T2D progression

Type 2 diabetes(T2D)is highly associated with obesity.However,the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune disorder.Mucosal-associated invariant T(MAIT)cells,which are innate-like T cells that recognize bacterial metabolites,have been reported to be altered in obese people and to lead to metabolic dysfunction during obesity.By studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D,we found an elevation in CD27^(-)negative(CD27−)MAIT cells producing a high level of IL-17 under T2D obese conditions,which could be positively correlated with impaired glucose metabolism in obese people.We further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell abnormalities.Specifically,accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17^(-)producing CD27−MAIT cell expansion and could be associated with T2D risk in obese individuals.Overall,these results suggest that an aberrant gut microbiota–immune axis in obese people may drive or exacerbate T2D.Importantly,CD27−MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional strategies.Our findings extend current knowledge regarding the clinical relevance of body mass index(BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms.

Ultralow-loading single-atom cobalt on graphitic carbon nitrogen with robust Co-N pairs for aerobic cyclohexane oxidation

Selectively aerobic oxidation of cyclohexane using the homogeneous catalysts is an industrially important process,suffering from the difficult catalyst separation,low conversion and selectivity.Herein,a series of single-atom Co catalysts,possessing the ultralow Co loading of below 1.0 wt.‰,supported on mesoporous graphitic carbon nitrogen(Co/g-C_(3)N_(4)-w)were prepared by a simple adsorption method and applied into the cyclohexane oxidation.Characterization results demonstrate that the confinement effect of the voids in g-C_(3)N_(4) facilitates the formation of the single-atom Co,which is stabilized by bonding with the pyridinic nitrogen of g-C_(3)N_(4) and accompanied by the electron transfer from Co to g-C_(3)N_(4).The catalytic performance presents an increasing trend with the increment of the Co loading,and the superior value with the conversion of 23.8%and selectivity of 95.6%is obtained over Co/g-C_(3)N_(4)-0.9.Kinetic study,density functional theory(DFT)calculations,and characterizations reveal that the decreased activation energy of cyclohexane oxidation over Co/g-C_(3)N_(4)-w can be attributed to the favorable dissociation activation of O_(2) molecules and decomposition of cyclohexylhydroperoxide(CHHP)intermediate on the coordination unsaturated single-atom Co as well as the enhanced adsorption of cyclohexane on the electron-rich g-C_(3)N_(4) surface,boosting the cyclohexane oxidation following the surface catalytic mechanism.Distinctively,robust Co-N structures and hydrophobic nature of g-C_(3)N_(4) contribute to the high stability of Co/g-C_(3)N_(4)-0.9 for cyclohexane oxidation.

A Modified CES Production Function Model and Its Application in Calculating the Contribution Rate of Energy and Other Influencing Factors to Economic Growth

In the analysis of economic growth factors, the constant elasticity of substitution(CES)production function model is used to calculate the contribution rates of influencing factors to economic growth. However, the traditional CES production function model fails to consider the staged characteristics of economic growth. Therefore, this study provides a modified model of the CES production function. With regard to its application, a new method for calculating the contribution rates of energy and other influencing factors to economic growth is proposed using a modified CES production function model. This work concludes by calculating the contribution rates of Chinese energy and other influencing factors to economic growth.