Lactate and Lactylation in Sepsis: A Comprehensive Review.

Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation of lysine residues, fueled by lactate, plays a pivotal role in its pathophysiology. In conducting a literature review on sepsis-related research, we employed a systematic approach to ensure comprehensiveness and accuracy. Initially, we conducted an extensive literature search through the PubMed database, utilizing a range of keywords including "sepsis", "lactate", "lactylation", and "epigenetic modification". The aim was to capture the most recent research related to the pathophysiological mechanisms of sepsis, metabolic disorders, and the role of lactylation. The results of the literature review revealed a close link between sepsis and metabolic dysfunction, particularly the pivotal role of lactylation in regulating immune responses and inflammatory processes. Lactate, not only an energy metabolic byproduct produced during glycolysis, affects the activity of various proteins, including those involved in immune regulation and cell signaling, through lactylation. In the context of sepsis, changes in the levels of lactylation may be closely associated with the severity and prognosis of the disease. In summary, lactylation, as an emerging type of epigenetic modification, provides a new perspective for the diagnosis and treatment of sepsis. Future research needs to further elucidate the exact mechanisms of lactylation in sepsis and explore its potential as a therapeutic target.

The annual incidence and mortality rates associated with sepsis are on the rise, and to date, no medications or therapies have been proven effective in clinical practice. Glycolysis plays a pivotal role in regulating lactylation, a process derived from lactate generated by cellular glucose metabolism. In the context of sepsis, elevated lactate levels are indicative of a poor prognosis. It is imperative to delve into the mechanisms underlying lactylation alterations during sepsis to enhance our comprehension of its complex pathophysiology and to pinpoint innovative therapeutic targets for the condition.

The role of evidence-based practice and empathy in shared decision-making attitudes among newly graduated nurses: A cross-sectional study.

AIM: Examine the levels of variables and explore drivers associated with shared decision-making attitudes among newly graduated nurses. DESIGN: This was a descriptive and cross-sectional study. METHODS: From August 2022 to October 2022, a cross-section of 216 newly graduated nurses from four comprehensive A-level hospitals in northern China was recruited using convenience sampling. Newly graduated nurses are generally defined as nurses with a service period of six months to one year. Data were collected using an online questionnaire support platform, including the Nursing Shared Decision-Making Attitude scale, Jefferson scale of Empathy-Health profession students and the Health Sciences Evidence-Based Practice questionnaire. All data were analysed descriptively, and correlational analysis and hierarchical regression were used to make identical connections between variables. RESULTS: Newly graduated nurses supported shared decision-making. Perceptions of shared decision-making were correlated with the experiences of empathy and evidence-based practice. Additionally, perspective-taking of empathy and beliefs, and the ability to search for and apply existing scientific findings of evidence-based practice had a significant impact on more positive attitudes. CONCLUSION: The survey showed that acceptance of shared decision-making was positive among newly graduated nurses. Clinical nursing managers and teachers should pay attention to cultivating the evidence-based practice and empathy of newly graduated nurses to adopt an optimistic attitude towards shared decision-making in the long term. IMPACT: The survey addresses attitudes of shared decision-making among newly graduated nurses and determines whether empathy and evidence-based practice has an impact on it. The main finding is that newly graduated nurses have an optimistic outlook on the implementation of shared decision-making. This survey showed that empathy and evidence-based practice competencies are associated with shared decision-making attitudes among newly graduated nurses. The results of this survey have an impact on educational institutions and hospitals in the form of recommendations. Several training programmes on empathy and evidence-based practice can help adopt the shared decision-making attitudes of newly graduated nurses. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Protein modification by short-chain fatty acid metabolites in sepsis: a comprehensive review.

Sepsis is a major life-threatening syndrome of organ dysfunction caused by a dysregulated host response due to infection. Dysregulated immunometabolism is fundamental to the onset of sepsis. Particularly, short-chain fatty acids (SCFAs) are gut microbes derived metabolites serving to drive the communication between gut microbes and the immune system, thereby exerting a profound influence on the pathophysiology of sepsis. Protein post-translational modifications (PTMs) have emerged as key players in shaping protein function, offering novel insights into the intricate connections between metabolism and phenotype regulation that characterize sepsis. Accumulating evidence from recent studies suggests that SCFAs can mediate various PTM-dependent mechanisms, modulating protein activity and influencing cellular signaling events in sepsis. This comprehensive review discusses the roles of SCFAs metabolism in sepsis associated inflammatory and immunosuppressive disorders while highlights recent advancements in SCFAs-mediated lysine acylation modifications, such as substrate supplement and enzyme regulation, which may provide new pharmacological targets for the treatment of sepsis.

Prognostic Nomogram for Patients with Hepatitis E Virus-related Acute Liver Failure: A Multicenter Study in China.

BACKGROUND AND AIMS: Timely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients. METHODS: The nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative ability using time-dependent receiver operating characteristics (td-ROC) analysis, respectively. RESULTS: Multivariate logistic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, international normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95% confidence interval: 0.602-0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and decision curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set. CONCLUSIONS: The novel nomogram is an accurate and efficient mortality prediction method for HEV-ALF patients.

Impact of regulatory T cells on the prognosis of hepatocellular carcinoma: A protocol for systematic review and meta analysis.

BACKGROUND: This meta-analysis aimed to systematically review current available literature to assess the impact of regulatory T cells (Tregs) on the prognosis of hepatocellular carcinoma (HCC). METHODS: We will browse the online databases of PubMed and Cochrane Library. The summary hazard ratio (HR) and their 95% confidence intervals (CIs) will be combined to present the value reported in the study. CONCLUSION: Our meta-analysis will provide useful guidance in treatment of HCC based on the reported evidences regarding the impact of Tregs on the prognosis of HCC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/3Q8PW.

Efficacy of single-session transcranial direct current stimulation on addiction-related inhibitory control and craving: a randomized trial in males with Internet gaming disorder.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.

A role for the right dorsolateral prefrontal cortex in enhancing regulation of both craving and negative emotions in internet gaming disorder: A randomized trial.

Reward-seeking and relief from negative emotions are two central motivational drives underlying addictions. Impaired executive control over craving and negative emotions contributes to compulsive addictive behaviors. Neuroimaging evidence has implicated the prefrontal cortex (PFC) in regulating craving or emotions. This study aims at examining whether anodal transcranial direct current stimulation (tDCS) over a specific region of the PFC would enhance both regulation processes. Thirty-three men with internet gaming disorder received active (1.5 mA for 20 minutes) and sham tDCS over the right dorsolateral PFC (dlPFC) one week apart in a randomized order. During each stimulation session, participants regulated craving for gaming during a regulation of craving (ROC) task and negative emotions during an emotion regulation (ER) task using cognitive reappraisal. Subjective ratings of craving and negative emotions and skin conductance responses (SCRs) were recorded. For both craving and negative emotions, tDCS of the right dlPFC facilitated downregulation and upregulation: active relative to sham tDCS decreased ratings (ROC: 95% CI of difference -1.38 to -0.56, p < 0.001; ER: -1.65 to -0.70, p < 0.001) and/or SCRs (ROC: -1.99 to -0.41 µs, p = 0.004) for downregulation, and increased ratings (ROC: 0.24 to 0.82, p = 0.001; ER: 0.26 to 0.72, p < 0.001) for upregulation. These findings provide the first experimental evidence confirming that tDCS of the right dlPFC enhances both craving- and negative-emotion-regulation. This suggests a promising approach for concurrently enhancing executive control over two central motivational drives underlying addictions.

Impaired regulation of both addiction-related and primary rewards in individuals with internet gaming disorder.

Poor executive function (EF) has been implicated in addictions. Among "hot" EFs (i.e., those involving motivations and emotions), poor regulation of craving has been proposed to underlie addiction development in substance-use disorders (SUDs), making such regulation a potential treatment target. However, regulation of craving remains poorly understood in internet gaming disorder (IGD). Additionally, prior studies of cold EFs (e.g., inhibition and cognitive flexibility under neutral conditions) in IGD have provided mixed results and mostly included only male subjects. We addressed these issues by instructing 54 participants (26 with IGD including males and females, and 28 control subjects) to perform a regulation-of-craving (ROC) task and a Stroop color-word-interference task. Compared to control subjects, individuals with IGD revealed deficits in regulation for both gaming- and food-related craving, but no differences in Stroop performance. The current study provides initial empirical support suggesting regulation impairments for both addiction-related and primary rewards among individuals with IGD. The findings are consistent with studies in SUDs, suggesting that impaired regulation of craving may be a relevant transdiagnostic construct across SUDs and behavioral addictions. The findings suggest targeting regulation of "hot" processes should be considered in IGD treatment development.

Is monetary reward processing altered in drug-naïve youth with a behavioral addiction? Findings from internet gaming disorder.

Current models of addiction biology highlight altered neural responses to non-drug rewards as a central feature of addiction. However, given that drugs of abuse can directly impact reward-related dopamine circuitry, it is difficult to determine the extent to which reward processing alterations are a trait feature of individuals with addictions, or primarily a consequence of exogenous drug exposure. Examining individuals with behavioral addictions is one promising approach for disentangling neural features of addiction from the direct effects of substance exposure. The current fMRI study compared neural responses during monetary reward processing between drug naïve young adults with a behavioral addiction, internet gaming disorder (IGD; n = 22), and healthy controls (n = 27) using a monetary incentive delay task. Relative to controls, individuals with IGD exhibited blunted caudate activity associated with loss magnitude at the outcome stage, but did not differ from controls in neural activity at other stages. These findings suggest that decreased loss sensitivity might be a critical feature of IGD, whereas alterations in gain processing may be less characteristic of individuals with IGD, relative to those with substance use disorders. Therefore, classic theories of altered reward processing in substance use disorders should be translated to behavioral addictions with caution.

Negative regulation of Nod-like receptor protein 3 inflammasome activation by T cell Ig mucin-3 protects against peritonitis.

The Nod-like receptor protein 3 (NLRP3) inflammasome plays roles in host defence against invading pathogens and in the development of autoimmune damage. Strict regulation of these responses is important to avoid detrimental effects. Here, we demonstrate that T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, inhibits NLRP3 inflammasome activation by damping basal and lipopolysaccharide-induced nuclear factor-κB-mediated up-regulation of NLRP3 and interleukin-1ß during the priming step and basal and ATP/lipopolysaccharide-induced ATP production, K+ efflux, and reactive oxygen species production during the activation step. Residues Y256/Y263 in the C-terminal region of Tim-3 are required for these inhibitory effects on the NLRP3 inflammasome. In mice with alum-induced peritonitis, blockade of Tim-3 exacerbates peritonitis by overcoming the inhibitory effect of Tim-3 on NLRP3 inflammasome activation, while transgenic expression of Tim-3 attenuates inflammation by inhibiting NLRP3 inflammasome activation. Our results show that Tim-3 is a critical negative regulator of NLRP3 inflammasome and provides a potential target for intervention of diseases with uncontrolled inflammasome activation.

Functional and structural neural alterations in Internet gaming disorder: A systematic review and meta-analysis.

This meta-analytic study aimed to identify the common and specific neural alterations in Internet gaming disorder (IGD) across different domains and modalities. Two separate meta-analyses for functional neural activation and gray-matter volume were conducted. Sub-meta-analyses for the domains of reward, cold-executive, and hot-executive functions were also performed, respectively. IGD subjects, compared with healthy controls, showed: (1) hyperactivation in the anterior and posterior cingulate cortices, caudate, posterior inferior frontal gyrus (IFG), which were mainly associated with studies measuring reward and cold-executive functions; and, (2) hypoactivation in the anterior IFG in relation to hot-executive function, the posterior insula, somatomotor and somatosensory cortices in relation to reward function. Furthermore, IGD subjects showed reduced gray-matter volume in the anterior cingulate, orbitofrontal, dorsolateral prefrontal, and premotor cortices. These findings suggest that IGD is associated with both functional and structural neural alterations in fronto-striatal and fronto-cingulate regions. Moreover, multi-domain assessments capture different aspects of neural alterations in IGD, which may be helpful for developing effective interventions targeting specific functions.

Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection.

Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI's role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1ß, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.

Diversification of Root Hair Development Genes in Vascular Plants.

The molecular genetic program for root hair development has been studied intensively in Arabidopsis (Arabidopsis thaliana). To understand the extent to which this program might operate in other plants, we conducted a large-scale comparative analysis of root hair development genes from diverse vascular plants, including eudicots, monocots, and a lycophyte. Combining phylogenetics and transcriptomics, we discovered conservation of a core set of root hair genes across all vascular plants, which may derive from an ancient program for unidirectional cell growth coopted for root hair development during vascular plant evolution. Interestingly, we also discovered preferential diversification in the structure and expression of root hair development genes, relative to other root hair- and root-expressed genes, among these species. These differences enabled the definition of sets of genes and gene functions that were acquired or lost in specific lineages during vascular plant evolution. In particular, we found substantial divergence in the structure and expression of genes used for root hair patterning, suggesting that the Arabidopsis transcriptional regulatory mechanism is not shared by other species. To our knowledge, this study provides the first comprehensive view of gene expression in a single plant cell type across multiple species.

Construction and optimization of an efficient amplification method of a random ssDNA library by asymmetric emulsion PCR.

Construction of a random ssDNA sublibrary is an important step of the aptamer screening process. The available construction methods include asymmetric PCR, biotin-streptavidin separation, and lambda exonuclease digestions, in which PCR amplification is a key step. The main drawback of PCR amplification is overamplification increasing nonspecific hybridization among different products and by-products, which may cause the loss of potential high-quality aptamers, inefficient screening, and even screening failure. Cycle number optimization in PCR amplification is the main way to avoid overamplification but does not fundamentally eliminate the nonspecific hybridization, and the decreased cycle number may lead to insufficient product amounts. Here, we developed a new method, "asymmetric emulsion PCR," which could overcome the shortcomings of conventional PCR. In asymmetric emulsion PCR, different templates were separated by emulsion particles, allowing single-molecule PCR, in which each template was separately amplified, and the nonspecific hybridization was avoided. Overamplification or formation of by-products was not observed. The method is so simple that direct amplification of 40 or more cycles can provide a high-quality ssDNA library. Therefore, the asymmetric emulsion PCR would improve the screening efficiency of systematic evolution of ligands by exponential enrichment.

The Prognostic Impact of Heat Shock Proteins Expression in Patients with Esophageal Cancer: A Meta-Analysis.

PURPOSE: Heat shock proteins (HSPs) are highly conserved molecular chaperones. There are various studies that assess the prognostic value of HSPs in patients with esophageal cancer, but the conclusion remains controversial. This is the first meta-analysis study aiming to summarize the evidence on the suitability of HSPs to predict patients' survival. MATERIALS AND METHODS: Searching PubMed, Web of science and Medline until May 31, 2014, data were compared for overall survival in patients with down-regulated HSPs level with those with up-regulated level. We conducted a meta-analysis of 9 studies (801 patients) that correlated HSPs levels with overall survival. Data were synthesized with hazard ratios (HRs). RESULTS: The estimated risk of death was 2.93-fold greater in HSP27 negative patients than HSP27 positive patients [95% confidence interval (CI), 1.12-7.62]. When limited to esophageal squamous cell carcinoma (ESCC), the risk of death in HSP27 negative patients seemed more significant (HR, 3.90; 95% CI, 2.35-6.49). Decreased expression of HSP70 was also associated with worse survival in esophageal cancer (HR, 2.83; 95% CI, 1.90-4.23) and, when limited to ESCC, HR was 3.21 (95% CI, 1.94-5.30). Data collected, however, were not sufficient to determine the prognostic value of HSP90 in patients with ESCC nor esophageal adenocarcinomas (EADC). CONCLUSION: In this meta-analysis, reduced HSP27 and HSP70 expressions were associated with poor survival in patients with esophageal cancer, especially esophageal squamous cell carcinoma.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

Expression and function of Toll-like receptors in peripheral blood mononuclear cells from patients with ovarian cancer.

Inflammation has been implicated in the initiation and progression of ovarian cancer (OC), the underlying mechanisms of which are still unclear. We hypothesized that the abnormal expression of Toll-like receptors (TLRs), which were potential activators of nuclear factor-kappa B p65 (NF-κB p65), could promote inflammation and tumorigenesis in OC. In this study, we characterized the expression of TLRs in peripheral blood mononuclear cells (PBMCs) and found TLR2 and TLR6 mRNAs levels to be higher in PBMCs from OC patients than in those from benign disease (BC) or healthy normal controls (NC). Flow cytometry analysis showed that TLR1, TLR2 and TLR6 were highly expressed in monocytes from OC patients, but not in those from control subjects. Consistently, inflammatory cytokines interleukin (IL)-1ß and IL-6 were up-regulated in PBMCs from OC patients upon stimulation with Pam3CSK4 (TLR1 ligand) and HKLM (TLR2 ligand), compared with unstimulated PBMCs. Stimulation of PBMCs with TLR ligands led to activation of downstream signaling molecules in TLRs (MyD88, TRAF6, TANK, NF-κB p65 and p-NF-κB p65). We also discovered that SK-OV-3-secreted factors were potent PBMCs activators, leading to the production of IL-1ß, IL-6 and IL-8 through activation of TLRs and downstream signaling molecules in PBMCs. Before coculturing with SK-OV-3, pretreatment of THP-1 cells or PBMCs with monoclonal antibodies against TLR1, TLR2 or TLR6 inhibited the production of IL-1ß and IL-6 and activation of MyD88, TRAF6, TANK, NF-κB p65 and p-NF-κB p65. Our results provided new evidence that TLR1, TLR2 and TLR6 signaling was linked with inflammation in OC microenvironment.

[Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1ß) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1ß), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.

ZmMYB31 directly represses maize lignin genes and redirects the phenylpropanoid metabolic flux.

Few regulators of phenylpropanoids have been identified in monocots having potential as biofuel crops. Here we demonstrate the role of the maize (Zea mays) R2R3-MYB factor ZmMYB31 in the control of the phenylpropanoid pathway. We determined its in vitro consensus DNA-binding sequence as ACC(T)/(A) ACC, and chromatin immunoprecipitation (ChIP) established that it interacts with two lignin gene promoters in vivo. To explore the potential of ZmMYB31 as a regulator of phenylpropanoids in other plants, its role in the regulation of the phenylpropanoid pathway was further investigated in Arabidopsis thaliana. ZmMYB31 downregulates several genes involved in the synthesis of monolignols and transgenic plants are dwarf and show a significantly reduced lignin content with unaltered polymer composition. We demonstrate that these changes increase cell wall degradability of the transgenic plants. In addition, ZmMYB31 represses the synthesis of sinapoylmalate, resulting in plants that are more sensitive to UV irradiation, and induces several stress-related proteins. Our results suggest that, as an indirect effect of repression of lignin biosynthesis, transgenic plants redirect carbon flux towards the biosynthesis of anthocyanins. Thus, ZmMYB31 can be considered a good candidate for the manipulation of lignin biosynthesis in biotechnological applications.