An adaptive detection model for IPv6 extension header threats based on deterministic decision automaton.

The IPv6 extension header mechanism, a new feature of the IPv6 protocol, enhances flexibility and scalability but introduces numerous security threats like firewall evasion and covert channels. Existing threat detection methods face limitations in detection types, universality, and speed. Hence, an adaptive detection model for IPv6 extension header threats (ADM-DDA6) is proposed. Firstly, standard rule sets are designed for common IPv6 extension headers, successfully detecting 70 types of threats from THC-IPv6 and ExtHdr tools using only 20 rules. Secondly, by parsing IPv6 extension headers, matching rules, establishing transition relationships, and deciding packet threat status based on final states (Normal or Abnormal), complex threats like header disorder and header repetition can be detected. Finally, an adaptive rule matching method is introduced, which dynamically selects rule sets based on IPv6 extension header types, effectively reducing rule matching time. Experimental results show that under different threat magnitudes, ADM-DDA6 is 32% faster than Suricata v6.0.12 and 21.2% faster than Snort v3.1.61.0 in detection speed. Additionally, as the number of threats increases, on commodity hardware, ADM-DDA6 incurs only a 0.7% increase in CPU overhead with no significant memory consumption increase, maintains maximum throughput, and exhibits minor performance changes under low and moderate network load conditions.

Effects of high-intensity interval training on depressive symptoms: A systematic review and meta-analysis.

The objective of this systematic review and meta-analysis is to investigate the effect of high-intensity interval training (HIIT) on depressive symptoms, including an examination of its impact across different populations, intervention durations, and control groups through subgroup analysis. METHODS: A systematic literature search was conducted using the following databases: Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform. The search covered the period from January 1, 2000, to December 31, 2022. RESULTS: The meta-analysis included 34 randomized controlled trials, involving a total of N = 1607 participants. HIIT had a small but significant effect on depressive symptoms compared to the control group [SMD = -0.40, 95%CI (-0.60, -0.20), I2 = 73%]. However, subgroup analyses revealed no moderating effect of health status or exercise duration on depressive symptoms. HIIT did not have a statistically significant effect on depressive symptoms when compared with other types of exercise [SMD = -0.15, 95% CI (-0.30, 0.01), I2 = 10%]. HIIT demonstrated a medium effect size in reducing depressive symptoms compared to a non-active control group [SMD = -0.53, 95% CI (-0.84, -0.21), I2 = 80%]. CONCLUSIONS: HIIT confers benefits in mitigating depressive symptoms. Compared to non-active control group, HIIT yields moderate improvements in depressive symptoms. We look forward to exploring more moderating effects in the future, such as HIIT modalities, frequency, and so on. In summation, these findings substantiate the use of HIIT as a means to alleviate symptoms of depression.

Rapid Generation of Recombinant Flaviviruses Using Circular Polymerase Extension Reaction.

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

Evaluation of Zika virus DNA vaccines based on NS1 and domain III of E.

BACKGROUND: A large-scale outbreak of Zika virus (ZIKV) has occurred in Brazil and other South American countries, and has rapidly spread to 60 countries and regions worldwide since 2015, but no approved anti-ZIKV vaccines are available as of 2021. METHODS: We developed four types of anti-ZIKV DNA vaccine candidates: VPC-NS1, VPC-prME, VPC-prME-NS1, and VPC-EIII-NS1. They were developed against the structural proteins prM and E, and non-structural protein 1 (NS1) of ZIKV using the mammalian cell expression vector pcDNA3.1(+) as the backbone. For immunization, we intramuscularly injected mice with each vaccine candidate (n = 12 to 15 per group) on day 0 and day 14, with mice injected with phosphate-buffered saline (PBS) and pcDNA3.1(+) backbone vector as controls. On day 7, 21, and 35 after initial immunization, the effect of DNA vaccines was evaluated by ZIKV-specific humoral immunity determined by enzyme-linked immunosorbent assay (ELISA), ZIKV-specific T cell immunity determined by intracellular cytokine staining by flow cytometry and serum neutralization capacity determined by plaque reduction neutralization test (PRNT50) assay. RESULTS: The sequencing results showed that DNA vaccine vectors were successfully constructed. Western blotting and immunofluorescence results demonstrated the successful expression of immunogens carried by the DNA vaccines. On day 21 and 35 after the initial immunization, the levels of serum total immunoglobulin (Ig)G in all vaccine-given groups were slightly higher (approximately 1.5- to 2-fold) than those in the control groups. By contrast, ZIKV-specific IgG levels of all vaccine-given groups were significantly higher (approximately 10- to 1000- fold) than those of the control groups. The PRNT50 assay showed that the average serum dilution factors for neutralizing half ZIKV virions from vaccine-given groups were at least 32-fold (highest, 93-fold), while the sera from control group showed no protection. For cellular immunity, the proportions of CD11b+ myeloid cells, CD19+ B lymphocytes and CD3+ T lymphocytes in the mouse spleens as well as the percentages of CD4+ and CD8+ subsets of T cell were not changed 35 days after initial immunization. By contrast, the proportions of ZIKV-specific CD4+T cell and CD8+T cell in all vaccine-given groups were 2- to 10-folds and 2- to 30-fold than those in the control groups, respectively. CONCLUSION: All four DNA vaccines designed for the ZIKV induced neutralizing IgGs and cellular immune responses against ZIKV. Particularly, VPC-EIII-NS1 induced high level of humoral response comparable to the vaccine candidate containing prM, E and NS1 polyprotein, suggesting a potent reduced ADE effect and reserved neutralizing activity. Our findings may provide guidance for improving safety of anti-ZIKV vaccines in the future.

Executive control of freestyle skiing aerials athletes in different training conditions.

Introduction: Due to the actual limitation of training conditions, the freestyle skiing aerials winter training term is short. Training tasks such as adaptability training and developing new skills are needed in summer training. When facing different training environments, freestyle skiing aerial athletes' executive control over their abilities could be affected, which can affect their performance. Therefore, we want to research the effect of training conditions on executive control in freestyle skiing aerials athletes and its neural mechanism. Materials and methods: Thirty-two freestyle skiing aerials athletes were recruited. We evaluated their executive control and used fNIRS to measure oxygenated hemoglobin concentration changes in the prefrontal cortex during a rapid event-related design go/nogo task with different training condition-activated materials. Results: Athletes' behavior control in the summer condition has a lower accuracy than it is in the control condition. Athletes' behavior control in the summer and winter training conditions had a longer reaction time than that in the control condition. The activation of the bilateral dlPFC and orbitofrontal cortex had a significant main effect across training conditions when freestyle skiing aerial athletes completed executive control tasks. The activation of athletes' bilateral vlPFC and left dlPFC had an interaction between training conditions and behavioral control. Conclusion: Different training conditions can lead to freestyle skiing aerial athletes executive control ability to drop, players in different training conditions show less activation on both sides of the vlPFC and orbitofrontal. The bilateral vlPFC and left dlPFC have an integrated effect on behavior inhibition across training conditions.

The Effects of Physical Exercise on the Quality of Life of Healthy Older Adults in China: A Systematic Review.

Objective: To systematically evaluate the effects of physical exercise on the quality of life (QOL) of healthy older adults in China. Methods: Relevant articles published until December 2021 were retrieved from China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, EBSCO, Web of Science, and the Library of Congress. Inclusion criteria were studies in which the subjects were healthy Chinese older adults (aged ≥ 60 years), the reported sample size was clear, and the study design was a randomized controlled trial or a research study. In addition, studies were included if they reported the use of at least one QOL questionnaire and investigated at least one form of physical exercise. Results: In total, 19 studies met the inclusion criteria, which included six studies that used comprehensive physical exercise type as an intervention and 13 studies that used regular physical exercise as an intervention. All 19 studies compared intervention and control groups, of which 12 (63%) were investigative studies and seven (37%) were experimental studies. Of the experimental studies, five used a positive control group and two used a negative control group. All 19 studies reported that physical exercise had varying degrees of positive effects on the QOL in older adults. Body-mind exercise was effective in improving the physical and mental health (MH) of older adults, whereas Xiyangcao only had a positive effect on physical health. Compared with no exercise or other exercise (exercise not used in the intervention group), the exercise group in the survey had a positive effect on the QOL of older adults. Regardless of the type of control group used, the exercise group in the experimental studies showed a positive effect of exercise on the QOL of older adults. Conclusion: Physical exercise has a positive impact on the QOL of healthy older adults. However, due to the wide and varied scope of the included studies, more randomized controlled trials are needed to examine the effects of different types, intensities, durations, and the frequency of exercise on QOL. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220115], identifier: [CRD42020220115].

Risk Factors for Depression in Tuberculosis Patients: A Meta-Analysis.

Purpose: Tuberculosis (TB) is a life threatening global infection. However, not only does TB have a high global prevalence, but it is also associated with several comorbidities. Depression is one of the most common and lethal comorbidities of TB patients. Therefore, in order to prevent depression in TB patients more effectively, it is necessary to investigate the factors associated with depression in TB patients by studying the pooled effect of each factor statistically. By concluding the associated factors through statistical analysis, it not only offers accurate guidance for further studies about programs targeted at preventing depression in TB patients, but provides health-care workers useful suggestions and warnings when treating TB patients. Methods: We searched the published literatures from PubMed, Web of Science, EMBASE, and Cochrane Library to collect studies. The meta-analysis included articles from observational studies, including cross-sectional studies, cohort studies and case control studies that had information about factors associated with depression in tuberculosis patients. When the heterogeneity is defined as significant (I2>50%), a random-effect model with 95% confidence interval (CI) was used to estimate risk factors; otherwise, a fixed-effect model was used to combine the effect. A sensitivity test was conducted to examine which one of the studies may have potential bias that can affect the validity and reliability of the result. The funnel plots and Begg's and Egger's statistical tests were performed to assess the publication bias. Subgroup analysis was performed according to the prespecified variables in each group. Results: Totally, 25 studies were included in the meta-analysis. The studies were conducted in various countries around the world between 2011 and 2021, representing the situation in the previous ten years. The final associated factors include female gender [OR=1.319, 95% CI=1.132-1.536, p<0.001], poor social support [OR=4.109, 95% CI=1.431-11.799, p<0.01], marriage status [OR=1.362, 95% CI=1.154-1.608, p<0.001], low education level [OR=1.921, 95% CI=1.475-2.503, p<0.001], residence in rural areas [OR=1.408, 95% CI=1.122-1.767, p<0.01], retreatment status [OR=2.515, 95% CI=1.226-5.159, p<0.01], and having perceived stigma[OR=4.131, 95% CI=1.412-12.088, p<0.05]. Conclusion: Depression prevention programs targeted at women TB patients are supposed to be carried out. Patients in retreatment status are supposed to be paid more attention of their psychological health by caring about their mental status. More social support is ought to be given to tuberculosis patients to reduce their chance of getting depressed. It is necessary to provide patients with a lower education level with psychological related courses to help them learn about their mental status. For patients living in rural areas, governments are supposed to offer psychotherapy for treatment as well as enhancing living condition. Suitable psychotherapy programs and plans is ought to be studied to eradicate perceived stigma of TB patients.

Increased yield of AP-3 by inactivation of asm25 in Actinosynnema pretiosum ssp. auranticum ATCC 31565.

Asamitocins are maytansinoids produced by Actinosynnema pretiosum ssp. auranticum ATCC 31565 (A. pretiosum ATCC 31565), which have a structure similar to that of maytansine, therefore serving as a precursor of maytansine in the development of antibody-drug conjugates (ADCs). Currently, there are more than 20 known derivatives of ansamitocins, among which ansamitocin P-3 (AP-3) exhibits the highest antitumor activity. Despite its importance, the application of AP-3 is restricted by low yield, likely due to a substrate competition mechanism underlying the synthesis pathways of AP-3 and its byproducts. Given that N-demethylansamitocin P-3, the precursor of AP-3, is regulated by asm25 and asm10 to synthesize AGP-3 and AP-3, respectively, asm25 is predicted to be an inhibitory gene for AP-3 production. In this study, we inactivated asm25 in A. pretiosum ATCC 31565 by CRISPR-Cas9-guided gene editing. asm25 depletion resulted in a more than 2-fold increase in AP-3 yield. Surprisingly, the addition of isobutanol further improved AP-3 yield in the asm25 knockout strain by more than 6 times; in contrast, only a 1.53-fold increase was found in the WT strain under the parallel condition. Thus, we uncovered an unknown function of asm25 in AP-3 yield and identified asm25 as a promising target to enhance the large-scale industrial production of AP-3.

Computer-Aid Directed Evolution of GPPS and PS Enzymes.

Pinene, a natural active monoterpene, is widely used as a flavoring agent, perfume, medicine, and biofuel. Although genetically engineered microorganisms have successfully produced pinene, to date, the biological yield of pinene is much lower than that of semiterpenes (isoprene) and sesquiterpenes (farnesene). In addition to the low heterologous expression of geranyl pyrophosphate synthase (GPPS) and pinene synthase (PS), cytotoxicity due to accumulation of the monoterpene also limits the production of pinene in microorganisms. In this study, we attempted to use two strategies to increase the biological yield of pinene. By deleting the random coils of GPPS and PS alone or in combination, a strain with a 335% yield increase was obtained. Additionally, upon computer-guided molecular modeling and docking of GPPS with isopentenyl pyrophosphate (IPP), its substrate, the key sites located within the catalytic pocket for substrate binding, was predicted. After screening, a strain harboring the T273R mutation of GPPS was selected among a batch of mutations of the key sites with a 154% increase in pinene yield.

TEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR phosphorylation.

BACKGROUND: TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown. RESULTS: Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation were found co-located on frozen cancer tissue sections. CONCLUSIONS: Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.

Predicting Athletes' Pre-Exercise Fluid Intake: A Theoretical Integration Approach.

Pre-exercise fluid intake is an important healthy behavior for maintaining athletes’ sports performances and health. However, athletes’ behavioral adherence to fluid intake and its underlying psychological mechanisms have not been investigated. This prospective study aimed to use a health psychology model that integrates the self-determination theory and the theory of planned behavior for understanding pre-exercise fluid intake among athletes. Participants (n = 179) were athletes from college sport teams who completed surveys at two time points. Baseline (Time 1) assessment comprised psychological variables of the integrated model (i.e., autonomous and controlled motivation, attitude, subjective norm, perceived behavioral control, and intention) and fluid intake (i.e., behavior) was measured prospectively at one month (Time 2). Path analysis showed that the positive association between autonomous motivation and intention was mediated by subjective norm and perceived behavioral control. Controlled motivation positively predicted the subjective norm. Intentions positively predicted pre-exercise fluid intake behavior. Overall, the pattern of results was generally consistent with the integrated model, and it was suggested that athletes’ pre-exercise fluid intake behaviors were associated with the motivational and social cognitive factors of the model. The research findings could be informative for coaches and sport scientists to promote athletes’ pre-exercise fluid intake behaviors.

Evaluating the reliability and validity of SF-8 with a large representative sample of urban Chinese.

BACKGROUND: The Short Form-8 (SF-8) is a widely used instrument for measuring health-related quality of life (HRQOL). The purpose of the current study is to evaluate the reliability and validity of the Chinese version SF-8 using a large, representative sample of city residents in mainland China. METHODS: We surveyed residents of 35 major cities in China using random digit dialing of both landlines and cell phones. We adopted a multi-stage stratified sampling scheme and selected a probability sample of 10,885 adults. Internal consistency reliability of the SF-8 was evaluated with item-total correlations and Cronbach's alphas. Construct validity was assessed with factor analysis. Known-groups validity was examined based on known HRQOL differences in age, gender, income, and overall quality of life. RESULTS: We showed that SF-8 has very good internal consistency reliability and known-groups validity. Our results also confirmed that the traditional 2-factor structure of SF-8 (physical and mental health) is reasonable among Chinese city residents. Further, we showed that a 3-factor model (physical, mental, and overall health) fit the data better than the traditional 2-factor model. CONCLUSIONS: This study is the first to confirm the traditional 2-factor structure of SF-8 using a large, representative sample from China. We have shown that the SF-8 Chinese version is feasible, reliable, and valid. Our findings support the use of the SF-8 summary scores for assessing general HRQOL among Chinese. Future studies may further explore the possibility of a 3-factor structure for the SF-8 among the Chinese population.

Protective effects of choline against hypoxia-induced injuries of vessels and endothelial cells.

The current study aimed to lay a theoretical foundation for further development of choline as an anti-hypoxia damage drug. Wild-type, 3- to 5-month-old male Sprague-Dawley rats, weighing 180-220 g, were used in this study. The rats were randomly divided into a normoxic control group (n=16) and a chronic intermittent hypoxia (CIH) group (n=16). The effects of CIH on acetylcholine (ACh)-mediated endothelium-dependent vasodilatation in the rat cerebral basilar arterioles and mesenteric arterioles, as well as the protective effects of choline on the arterioles damaged by hypoxia were observed. Moreover, the effects of choline on endothelial cell proliferation during hypoxia were observed, and choline's functional mechanism further explored. The ACh-mediated vasodilatation of rat cerebral basilar and mesenteric arterioles significantly reduced during hypoxia (P<0.01). Choline significantly increased dilation in the rat cerebral basilar (P<0.01) and mesenteric arterioles (P<0.05) damaged by CIH compared with those in the control group. In addition, under hypoxic conditions, choline significantly promoted the proliferation of rat aortic endothelial cells (P<0.05) and significantly reduced lactate dehydrogenase activity in the cell culture supernatant in vitro (P<0.05). Furthermore, the effect of choline could be related to its ability to significantly increase the secretion of vascular endothelial growth factor (P<0.01) and activation of α7 non-neuronal nicotinic acetylcholine receptors under hypoxia (P<0.01). This study demonstrated that choline could have protective effects against hypoxic injuries.

Diazoxide protects rat vascular endothelial cells against hypoxia and cold-induced damage.

The present study aimed to examine the effects of hypoxia and cold on vascular endothelial cells (VECs), as well as the protective ability of novel VECs-protective drugs against these injuries. A rat model simulating exposure to hypoxia and cold at high altitude environments was established. Based on these animal experiments, rat aortic VECs were established as injury models and exposed to hypoxia and/or adrenaline (ADR) in vitro. The results revealed that hypoxia significantly altered the levels of nitric oxide and vascular endothelial growth factor, while the cold temperature significantly increased the release of ADR and noradrenaline. Exposure to hypoxia combined with cold temperature significantly affected all these indices. In vitro experiments demonstrated that hypoxia, ADR (which was used to simulate cold in the animal experiments) and the combination of the two factors resulted in damage to the VECs and endothelial dysfunction. In addition, the results also showed that diazoxide, a highly selective mitoKATP opener, protected VECs against these injuries. In conclusion, hypoxia and cold temperature induced endothelial cell dysfunction and endocrine disorders, respectively. Improving endothelial function using diazoxide may be an effective therapeutic strategy in patients with altitude-associated disorders. However, the potential for clinical application requires further study.

Proteomics reveals potential non-neuronal cholinergic receptor-effectors in endothelial cells.

AIM: The non-neuronal acetylcholine system (NNAS) in endothelial cells participates in modulating endothelial function, vascular tone, angiogenesis and inflammation, thus plays a critical role in cardiovascular diseases. In this study, we used a proteomic approach to study potential downstream receptor-effectors of NNAS that were involved in regulating cellular function in endothelial cells. METHODS: Human umbilical vein endothelial cells were incubated in the presence of acetylcholine, oxotremorine, pilocarpine or nicotine at the concentration of 10 µmol/L for 12 h, and the expressed proteins in the cells were separated and identified with two-dimensional electrophoresis (2-DE) and LC-MS. The protein spots with the largest changes were identified by LC-MS. Biowork software was used for database search of the peptide mass fingerprints. RESULTS: Over 1200 polypeptides were reproducibly detected in 2-DE with a pH range of 3-10. Acetylcholine, oxotremorine, pilocarpine and nicotine treatment caused 16, 9, 8 and 9 protein spots, respectively, expressed differentially. Four protein spots were identified as destrin, FK506 binding protein 1A (FKBP1A), macrophage migration inhibitory factor (MIF) and profilin-1. Western blotting analyses showed that treatment of the cells with cholinergic agonists significantly decreased the expression of destrin, FKBP1A and MIF, and increased the expression of profilin-1. CONCLUSION: A set of proteins differentially expressed in endothelial cells in response to cholinergic agonists may have important implications for the downstream biological effects of NNAS.

[Effect of electroacupuncture on cerebral PKC isozyme expression levels in cerebral ischemia-reperfusion rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Dingzhongxian" (MS 5) and "Dingpangxian" (MS 8) on the expression of cerebral protein kinase C (PKC) isozymes in local cerebral ischemia reperfusion injury (CI/RI) rats so as to explore its underlying mechanism in protecting ischemic brain tissue. METHODS: Seventy-two Wistar rats were randomized into normal control (n = 8), CI/RI model (model, n = 32), and EA (n = 32) groups. The later two groups were further divided into 4, 12, 24 and 72 h subgroups, respectively, with 8 rats in each. CI/RI model was established by occlusion of the middle cerebral artery under anesthesia and reperfusion for 4, 12, 24 and 72 h, respectively. EA (1 mA, 2 Hz/15 Hz) was applied to "Dingzhongxian" (MS5) and "Dingpangxian" (MS8) for 10 min every time, and once again every 12 h after modeling. The expression of PKCgamma and PKCdelta in the ischemic cortex tissue was detected using immunohistochemistry. TdT-mediated dUTP Nick-End Labeling was used to detect neuronal apoptosis of the local ischemic cerebral cortex. RESULTS: In comparison with the normal group, the expression levels of cerebral PKCgamma and PKCdelta proteins as well as the number of the apoptotic neurons at time-points of 4, 12, 24 and 72 h after modeling were increased apparently in the model group (P < 0.01); while compared with the model group, cerebral PKCgamma and PKCdelta protein expressions and the apoptotic neuronal number were decreased considerably in the EA group (P < 0.01, P < 0.05). No significant differences were found among the 4 time-points in the expression levels of PKCgamma and PKCdelta and apoptotic neuronal number in the model group and EA group (P > 0.05). CONCLUSION: EA intervention can effectively down-regulate expressions of cerebral PKCgamma, PKCdelta proteins and apoptotic neuronal number in cerebral ischemia rats, which may contribute to its effect in protecting the ischemic cerebral tissue.

Acetylation of sphingosine kinase 1 regulates cell growth and cell-cycle progression.

Sphingosine kinase 1 (SPK1) is a key enzyme in the sphingolipid metabolic pathway. It forms an essential checkpoint to regulate the relative levels of bioactive sphingolipid metabolites, ceramide, sphingosine, and sphingosine 1-phosphate (S1P). Here, we present evidence that SPK1 is acetylated by the intrinsic acetyltransferase activity of p300/cAMP-response element-binding protein (CREB)-binding protein (CBP) at a conserved acetylation motif (the GK motif). This post-translational modification may be an important regulator of SPK1 protein, as acetylation by p300 or CBP increased its stability. Mutation of two lysine (K) residues in its GK motif to either arginine (R) or glutamine (Q) blocked SPK1 ubiquitination and prevented its degradation by the proteasome. The processes of acetylation and ubiquitination may compete for the same lysine residues and, therefore, form a switch for SPK1 protein regulation. Intriguingly, human embryonic kidney (HEK) 293 cells stably expressed the mutated form of SPK1, in which the K residue was mutated to Q (Q-SPK1), and this mutated form mimicked acetylated SPK1. These cells were larger in size and had a slower growth rate compared to cells that expressed wild-type SPK1 (W-SPK1) or the K/R-mutated SPK1 (R-SPK1). These data suggest that SPK1 acetylation plays a key role in cell growth, cell size, and cell-cycle control.

[Observation on therapeutic effect of comprehensive therapy for acute large area cerebral infarction].

OBJECTIVE: To search for a method for increasing clinical therapeutic effect of acute large area cerebral infarction. METHODS: Ninety-six cases were randomly divided into a comprehensive treatment group and a western medicine group, 48 cases in each group. The western medicine group were treated with routine western methods, dehydration for decreasing intracranial pressure, brain-protection, anti-platelet agglutination, improving circulation and expectant treatment, etc.; the comprehensive treatment group were treated with the routine treatment of western medicine combined with acupuncture, moxibustion and enema of Chinese drugs. The therapeutic effect was observed after treatment for 28 days. RESULTS: The total effective rate was 68.8% in the comprehensive treatment group and 39.6% in the western medicine group with a very significant difference between the two groups (P < 0.01), and the score of the National Institute of Health's Stroke Scale (NIHSS) and the score of the Glasgow Coma Scale (GCS) in the comprehensive treatment group were better than those in the western medicine group (P < 0.001, P < 0.01). CONCLUSION: Combined treatment of Chinese medicine and western medicine for large area cerebral infarction is better than simple western medicine, and it can significantly improve neurological defect of the patient and decrease death rate.