Effects of evidence-based nursing care interventions on wound pain and wound complications following surgery for finger tendon injury.

We conducted this study aimed to examine the impact of evidence-based nursing interventions on postoperative wound pain and complications after surgery for finger tendon injury. A total of 86 patients treated for finger tendon injuries at our hospital from January 2021 to October 2023 were selected and randomly divided into an experimental group and a control group. The control group received conventional nursing care, while the experimental group received evidence-based nursing interventions. The study compared the postoperative wound pain intensity, incidence of complications and patient satisfaction with nursing care between the two groups. The analysis revealed that compared with conventional care, evidence-based nursing interventions significantly reduced the level of wound pain (p = 0.034) and the incidence of complications (4.65% vs. 18.60%, p = 0.043). It also increased patient satisfaction with the nursing care (97.67% vs. 83.72%, p = 0.026). The study indicates that the application of evidence-based nursing interventions for patients with finger tendon injuries can reduce postoperative wound pain, decrease the incidence of complications and enhance patient satisfaction with nursing care.

Diagnostic value of niacin skin blunting response in adolescent patients with depression.

OBJECTIVE: To investigate the differences in the niacin skin flushing response of adolescent depressed patients and healthy adolescents and its diagnostic value in adolescent depression. METHODS: Thirty-eight cases of acute episodes of depression in unmedicated adolescents and 47 age- and sex-matched healthy controls were included as study subjects, and sociodemographic and clinical data were collected, all of which were stimulated with six concentration gradients (up to 60 mmol/L, followed by sequential 3-fold gradient dilution to a minimum of 0.25 mmol/L) of niacin solution on the forearm skin, and the skin flushing area was applied as an assessment index. RESULTS: The total area of redness of the skin in response to niacin was significantly lower in the adolescent depression group than in the healthy adolescent group (Z=-3.36, p = 0.001) and was able to distinguish the adolescent depression group from the healthy adolescent group (area under curve = 0.713, sensitivity 51.1%, specificity 83.2%). CONCLUSIONS: Niacin sensitivity is reduced in adolescent depressed patients, and the niacin skin flush response has potential clinical value as a diagnostic biomarker for adolescent depression.

Efficient construction of diverse spiro[indoline-3,4'-pyrrolo[3,4-b]pyridines] via [3 + 3] cycloaddition of MBH carbonates of isatins with ß-enamino maleimides.

An efficient method to construct unique spiro[indoline-3,4'-pyrrolo[3,4-b]pyridines] was successfully developed via a DABCO promoted formal [3 + 3] cycloaddition reaction of MBH carbonates of isatins with ß-enamino maleimides in acetonitrile at room temperature. This reaction afforded multifunctionalized spiro[indoline-3,4'-pyrrolo[3,4-b]pyridines] and spiro[dipyrrolo[3,4-b:3',4'-e]pyridine-8,3'-indolines] in good yields and with lower diastereoselectivity. The relative configuration of the two diasteromers of the spiro compounds was clearly elucidated by the determination of eight single crystal structures.

Theoretically evaluating two-dimensional tetragonal Si2Se2 and SiSe2 nanosheets as anode materials for alkali metal-ion batteries.

In this work, based on first-principles calculations, we theoretically predict two kinds of two-dimensional tetragonal Si-Se compounds, Si2Se2 and SiSe2, as the anode materials for alkali metal-ion batteries. The results show that Si2Se2 and SiSe2 are thermally and dynamically stable and have good electronic conductivity. The diffusion barriers of Li, Na and K atoms are 0.07 eV, 0.17 eV and 0.17 eV on the surface of Si2Se2, and 0.45 eV, 0.43 eV and 0.30 eV on the surface of SiSe2, respectively, which indicate excellent rate capability. Most remarkably, Si2Se2 and SiSe2 can deliver high specific capacities. The predicted specific capacities of Si2Se2 are 1252 mA h g-1, 501 mA h g-1 and 250 mA h g-1 for Li, Na and K storage, respectively, and the corresponding specific capacities of SiSe2 are 1441 mA h g-1, 865 mA h g-1 and 180 mA h g-1. In addition, the highest plateaus of open-circuit voltages are 0.50 V vs. Li+/Li, 0.60 V vs. Na+/Na and 1.01 V vs. K+/K for Si2Se2, and 1.13 V vs. Li+/Li, 1.09 V vs. Na+/Na and 1.01 V vs. K+/K for SiSe2, which are beneficial for achieving the high discharge voltage in full cells. Considering these advantages, Si2Se2 and SiSe2 monolayers can be competitive candidates as anode materials for alkali metal-ion batteries.

Effects of Exogenous α-Naphthaleneacetic Acid and 24-Epibrassinolide on Fruit Size and Assimilate Metabolism-Related Sugars and Enzyme Activities in Giant Pumpkin.

Size is the most important quality attribute of giant pumpkin fruit. Different concentrations and application frequencies of α-naphthaleneacetic acid (NAA) and 24-epibrassinolide (EBR) were sprayed on the leaves and fruits of giant pumpkin at different growth stages to determine their effects and the mechanism responsible for fruit size increase. NAA+EBR application improved source strength, and further analysis indicated that NAA+EBR markedly boosted net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr) and the expression level and activity of galactitol synthetase (GolS), raffinose synthetase (RS), and stachyose synthetase (STS), resulting in an increase in the synthesis of photoassimilate, especially stachyose. Concomitantly, NAA+EBR spray increased stachyose and sucrose contents throughout pumpkin fruit growth and the concentrations of glucose and fructose at 0 and 20 days post-anthesis (DPA) in peduncle phloem sap, implying that such treatment improved the efficiency of assimilate transport from the peduncle to the fruit. Furthermore, it improved the expression and activity of alkaline α-galactosidase (AGA), facilitating assimilate unloading, providing carbon skeletons and energy for fruit growth, and increasing fruit weight by more than 44.1%. Therefore, exogenous NAA and EBR increased source capacity, transportation efficiency, and sink strength, overall promoting the synthesis and distribution of photoassimilate, ultimately increasing fruit size.

Stroke of antiplatelet and anticoagulant therapy in patients with coronary artery disease: a meta-analysis of randomized controlled trials.

BACKGROUND: We performed a meta-analysis sought to investigate the risk of stroke with antiplatelet and anticoagulant therapies among patients with coronary artery disease (CAD). METHODS: We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials from January 1995 to March 2020. Studies were retrieved if they reported data of stroke for patients with CAD and were randomized to receive intensive versus conservative antithrombotic therapies, including antiplatelet and oral anticoagulant (OAC). Analyses were pooled by random-effects modeling. A total of 42 studies with 301,547subjects were enrolled in this analysis. RESULTS: Intensive antithrombotic therapy significantly reduced risk of all stroke (RR 0.86, 95% CI 0.80-0.94) and ischemic stroke (RR 0.80, 95% CI 0.71-0.91), but increased risk of hemorrhagic stroke (RR 1.36, 95% CI 1.00-1.86) and intracranial hemorrhage (RR 1.46, 95% CI 1.17-1.81). Subgroup analyses indicated that OAC yields more benefit to all stroke than antiplatelet therapy (OAC: RR 0.73, 95% CI 0.58-0.92; Antiplatelet: RR 0.90, 95% CI 0.83-0.97; Between-group heterogeneity P value = 0.030). The benefit of antiplatelet therapy on all stroke and ischemic stroke were mainly driven by the studies comparing longer versus shorter duration of dual antiplatelet therapy (All stroke: RR 0.86, 95% CI 0.78-0.95; ischemic stroke: RR 0.84, 95% CI 0.75-0.94). CONCLUSIONS: Among CAD patients who have already received antiplatelet therapy, either strengthening antiplatelet or anticoagulant treatments significantly reduced all stroke, mainly due to the reduction of ischemic stroke, although it increased the risk of hemorrhagic stroke and intracranial hemorrhage. OAC yields more benefit to all stroke than antiplatelet therapy.

Invivo zearalenone exposure dose-dependently compromises mouse oocyte competence by impairing chromatin configuration and gene transcription.

Although invivo and invitro zearalenone (ZEN) exposure impaired oocyte quality, the mechanisms by which ZEN damages oocytes and the lowest observed effect level remain unclear. Furthermore, although it is known that premature chromatin condensation may occur in oocytes under proapoptotic conditions, whether ZEN exposure compromises oocyte competence by impairing gene transcription by causing premature chromatin condensation remains to be investigated. This study tested the toxic concentrations of invivo ZEN exposure that impair oocyte preimplantation developmental potential (PIDP) and the hypothesis that ZEN exposure compromises oocyte competence by increasing oxidative stress and changing chromatin configuration and the transcription of related genes. We found that invivo treatment of mice (Kunming strain, 8 weeks after birth) with 0.5-1mg kg-1 ZEN daily for 5 days, impaired the PIDP of mouse oocytes, increased oxidative stress, disturbed spindle assembly and chromosome segregation, caused premature chromatin condensation, impaired global gene transcription and disturbed the expression of genes related to oocyte competence, spindle assembly, redox potential and apoptosis. In conclusion, ZEN dose-dependently compromised the competence of mouse oocytes by causing oxidative stress and impairing chromatin configuration and gene transcription.

Meiotic arrest with roscovitine and sexual maturity improve competence of mouse oocytes by regulating expression of competence-related genes.

We have studied the mechanisms by which meiotic arrest maintenance (MAM) with roscovitine, female sexual maturity, and the surrounded nucleoli (SN) chromatin configuration improve the competence of mouse oocytes by observing the expression of oocyte competence-related genes in non-surrounded nucleoli (NSN) and SN oocytes from prepubertal and adult mice following maturation with or without MAM. The results demonstrated that MAM with roscovitine significantly improved the developmental potential of adult SN and prepubertal NSN oocytes, but had no effect on that of prepubertal SN oocytes. Without MAM, while 40% of the 2-cell embryos derived from prepubertal SN oocytes developed into 4-cell embryos, none of the 2-cell embryos derived from prepubertal NSN oocytes did, and while 42% of the 4-cell embryos derived from adult SN oocytes developed into blastocysts, only 1% of the 4-cell embryos derived from prepubertal SN oocytes developed into blastocysts. Furthermore, MAM with roscovitine, SN configuration, and female sexual maturity significantly increased the mRNA levels of competence-beneficial genes and decreased those of competence-detrimental genes. In conclusion, our results suggest that MAM with roscovitine, SN chromatin configuration, and female sexual maturity improve oocyte competence by regulating the expression of competence-related genes, suggesting that Oct4, Stella, Mater, Zar1, Mapk8, and Bcl2 are oocyte competence-beneficial genes, whereas Foxj2, Ship1, and Bax are competence-detrimental genes.

Meiotic block with roscovitine improves competence of porcine oocytes by fine-tuning activities of different cyclin-dependent kinases.

Successful use of oocytes from small follicles (SFs) is of great importance for animal embryo production and human in vitro fertilization with reduced hormone-related side effects. How in vitro meiotic arrest maintenance (MAM) increases the competence of oocytes is not clear. In this study, pig oocytes recovered from SF of 1-2 mm and medium-follicles (MF) of 3-6 mm in diameter from abattoir ovaries were treated by various MAM treatments to improve their competence. The results showed that 25 µM roscovitine or 1 mM db-cAMP efficiently blocked germinal vesicle breakdown in both SF and MF oocytes suggesting a similar cyclin-dependent kinase (CDK) 1 level between the two oocyte groups. MAM with 15- and 25-µM roscovitine alone or with 1-mM db-cAMP improved competence of SF and MF oocytes, respectively, with a promoted chromatin configuration transition from surrounded nucleoli (SN) to re-decondensation (RDC) pattern that supported substantial gene transcription. However, MAM with db-cAMP alone or with higher concentrations of roscovitine did not improve oocyte competence, could not support an SN-to-RDC transition, and/or evoked a premature chromatin condensation (PMC) that suppressed gene transcription. Both CDK2 and CDK5 contents were higher (p < .05) in MF than in SF oocytes. It is concluded that the competence of pig oocytes, particularly that of SF oocytes can be improved by MAM using a proper roscovitine concentration that promotes gene transcription by inhibiting CDK5 while letting CDK2 off to prevent PMC.

Selective Construction of Diverse Polycyclic Spirooxindoles via a Three-Component Reaction of Cyclic Mercapto-Substituted ß-Enamino Esters, Isatins, and Cyclic 1,3-Diketones.

The three-component reaction of alkyl 2-(benzo[b][1,4]thiazin-3-ylidene)acetates, isatins, and 1,3-indanedione (1,3-cyclopentanedione) in ethanol in the presence of acetic acid conveniently afforded spiro[indeno[1,2-b]phenothiazine-6,3'-indolines] or spiro[cyclopenta[b]phenothiazine-4,3'-indolines] in good yields and with high diastereoselectivity. More interestingly, a similar three-component reaction with 4-hydroxychromen-2-one resulted in the unexpected polycyclic spiro[benzo[b]chromeno[3',4':5,6]pyrano[2,3-e][1,4]thiazine-7,3'-indolines] in satisfactory yields. A plausible reaction mechanism was rationally proposed for formation of different kinds of the spiro compounds, and the stereochemistries of the various spiro compounds were clearly elucidated.

Glucose metabolism during in vitro maturation of mouse oocytes: An study using RNA interference.

In previous studies on glucose metabolism during in vitro maturation, intact cumulus-oocyte complexes (COCs) were treated with enzyme inhibitors/activators. Because inhibitors/activators may have non-specificity and/or toxicity, and culture of COCs cannot differentiate whether glucose metabolism of cumulus cells (CCs) or that of the oocyte supports oocyte maturation, results from the previous studies must be verified by silencing genes in either CCs or cumulus-denuded oocytes (DOs). In this study, RNAi was adopted to specify the effects of glucose metabolism in CCs or DOs on oocyte maturation. Although silencing either glyceraldehyde 3-phosphate dehydrogenase (GAPDH) or glucose-6-phosphate dehydrogenase (G6PD) genes in CCs significantly decreased competence of the cocultured DOs, silencing G6PD impaired competence to a greater extent. While silencing G6PD or GAPDH of CCs decreased glutathione and ATP contents of cocultured DOs to similar extents, silencing G6PD increased oxidative stress as well. Analysis on metabolite contents and oxidative stress index and culture of DOs in medium conditioned with gene-silenced CCs indicated that CCs supported oocyte maturation by releasing glucose metabolites. Silencing mitochondrial pyruvate carrier 1 or NADH dehydrogenase (ubiquintone) flavoprotein 1 of DOs significantly impaired their maturation. The results have unequivocally confirmed that CCs promote oocyte maturation by releasing glucose metabolites from both pentose phosphate pathway (PPP) and glycolysis. Pyruvate is transferred into DOs by mitochondrial pyruvate carrier (MPC) and utilized through mitochondrial electron transport to support maturation.

A new classification of the germinal vesicle chromatin configurations in pig oocytes.

Reported classifications of germinal vesicle (GV) chromatin configurations in pig oocytes were not done by uniform standards and they were not well correlated with oocyte competence. In this study, GV chromatin of pig oocytes was classified into nonsurrounded nucleolus (NSN), surrounded nucleolus (SN), partly NSN (pNSN) and SN (pSN), prematurely condensed NSN (cNSN), pNSN (cpNSN) and pSN (cpSN), and early diakinesis (ED) patterns. During in vitro maturation in 199 medium, NSN oocytes from 1 to 2 mm follicles went consecutively through pNSN, pSN, cpSN, and ED before undergoing GV breakdown, and chromatin in some SN oocytes from 3 to 6 mm follicles re-decondensed into a re-decondensation (RDC) configuration. Under unfavorable conditions such as follicle atresia, ovary handling or maturation in simple MEM medium, however, premature chromatin condensation occurred, forming cNSN, cpNSN, and cpSN patterns. While all NSN and pNSN and some pSN and RDC oocytes actively transcribed, no cNSN, cpNSN, or cpSN oocytes showed transcription. Maturation and embryo culture suggested that SN and pSN oocytes were more competent than NSN and pNSN oocytes; cpSN oocytes were more competent than cNSN/cpNSN oocytes; and only RDC oocytes could develop into blastocysts. It is concluded that the newly classified chromatin configurations are more closely correlated with oocyte competence than those reported previously.

Expression of hepatic Wnt5a and its clinicopathological features in patients with hepatocellular carcinoma.

BACKGROUD: Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis. However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In the present study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCC progression and outcome. METHODS: Wnt5a expression and cellular distribution in HCCs and their matched paracancerous tissues from 87 patients were analyzed with tissue microarray and immunohistochemistry and compared with hepatic Wnt3a signaling. Wnt5a expression was categorized into low or high based on immunohistochemistry. Overall survival rate of HCC patients was estimated in correlation with the hepatic Wnt5a level using Kaplan-Meier method; the survival difference between patients with low and those with high Wnt5a was compared with log-rank test; and prognostic analysis was carried out with Cox regression. RESULTS: Total incidence of Wnt5a expression in the HCC tissues was 70.1%, which was significantly lower (χ2 = 13.585, P < 0.001) than that in their paracancerous tissues (88.5%). Significant difference of Wnt5a intensity was found between HCC and their paracancerous tissues (Z = 8.463, P < 0.001). Wnt5a intensity was inversely correlated with Wnt3a signaling (r = -0.402, P < 0.001) in HCC tissues. A decrease of Wnt5a expression in relation to the clinical staging from stage I to IV and low or no staining at advanced HCC were observed. Wnt5a level was related to periportal embolus (χ2 = 11.069, P < 0.001), TNM staging (χ2 = 8.852, P < 0.05), 5-year survival (χ2 = 4.961, P < 0.05), and confirmed as an independent prognosis factor of HCC patients (hazard ratio: 1.957; 95% confidence interval: 1.109-3.456; P < 0.05). CONCLUSIONS: The decrease of hepatic Wnt5a signaling is associated with HCC progression and poor prognosis.

Glypican-3 is a biomarker and a therapeutic target of hepatocellular carcinoma.

BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multi-step and complex process. Early diagnosis and effective treatments are of utmost importance. This review summarized the recent studies of oncofetal glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC. DATA SOURCES: English-language reports published from June 2001 to September 2014 were searched from MEDLINE. The key words searched included: GPC-3, biomarker, target and HCC. The sensitivity, specificity, positive and negative predictive values were extracted, and the effect of GPC-3 targeted therapy on HCC was also evaluated. RESULTS: GPC-3 plays a crucial role in HCC cell proliferation and metastasis. It mediates oncogenesis involving signaling pathways during hepatocyte malignant transformation. GPC-3 expression is increased in atypical hyperplasia and cancerous tissues. GPC-3 levels in HCC patients are related to HBV infection, TNM stage, periportal cancerous embolus, and extrahepatic metastasis. The diagnostic accuracy of the combination of serum GPC-3 and alpha-fetoprotein in HCC is up to 94.3%. Down-regulation of GPC-3 with specific siRNA or anti-GPC-3 antibody alters cell migration, metastasis and invasion behaviors. The nude mice xenograft tumor growth is inhibited by silencing GPC-3 gene transcription. CONCLUSION: Oncofetal GPC-3 is a highly specific biomarker for the diagnosis of HCC and a promising target molecule for HCC gene therapy.

[Down-regulated clusterin expression enhances sensitivity of hepatoma cells to anti-cancer drugs].

OBJECTIVE: To investigate the relationship between and underlying mechanistic pathway of clusterin (CLU) and chemo-resistance ofhepatocellular carcinoma (HCC) cells. METHODS: CLU protein expression in HCC cell lines (Hep3B, SMMC7721, PLC, and HepG2) and HepG2/ADM cells was quantified by western blotting. Four short-hairpin (sh)RNAs designed to block CLU-mRNA were generated, screened by RT-PCR, and transfected into the cells to determine effects of CLU on cell viability and apoptosis. Effects of CLU blockade on drug efflux pump activity were measured by flow cytometry. RESULTS: CLU was found to be over-expressed in HCC cell lines and HepG2/ADM cells. The four shRNAs inhibited CLU-mRNA as follows (vs. levels in untransfected cells): shRNA-1: 73.68% (q =23.011, P < 0.01), shRNA-2: 39.26% (q =11.991, P < 0.01), shRNA-3: 62.36% (q =19.392, P < 0.01), and shRNA-4: 55.35% (q =17.149, P < 0.01). shRNA-mediated depletion of CLU led to increased sensitivity to anti-cancer drugs and increased doxorubicin-induced apoptosis in HepG2/ADM cells, as evidenced by the apoptosis ratio of the shRNA-1 group of 39.28% vs. the apoptosis ratio of the untransfected control group of 4.92%. Silencing of CLU also decreased drug etflux pump activity, and the level of MDR1/P-gp expression was significantly reduced (shRNA-1 group vs.untransfected control group: q =14.604, P < 0.01). CONCLUSION: CLU repression may enhance sensitivity of HCC cells to anti-cancers drugs and represents a potential molecular-target for reversal of multidrug-resistant HCC.

[Effects of Brucea javanica oil emulsion on human papilloma virus type 16 infected cells and mechanisms research].

OBJECTIVE: To explore the in vitro inhibitive effect and underlying mechanisms of Brucea Javanica oil emulsion (BJOE) on human papilloma virus (HPV) type 16 infected cells. METHODS: The HPV16 E61E7 immortalized human ectocervical Ect1/E6E7 cell line and the CaSki cell line were selected as the in vitro models of premalignant cervical lesion and cervical cancer respectively. After treated with BJOE at different concentrations (5, 10, 20, and 40 microg/mL) at the operation time points (24, 48, and 72 h), the effects of BJOE on proliferative activities were measured by MTT assay. The morphologic changes of cell apoptosis stained with Hochest 33,258 were observed by fluorescence microscope. The effect on the cell apoptosis rate was analyzed by Annexin V-FITC/PI double-labeled flow cytometry. The mRNA expressions of HPV16 E6 and E7 were determined by semi-quantitative RT-PCR. The protein expressions of HPV16 E6, E7 oncogene, and specifically interacted p53, Rb antioncogene were stained by immunocytochemical staining (Elivison two-step procedure). RESULTS: (1) The proliferative activities of the Ect1/E6E7 cell and the CaSki cell treated with BJOE at different concentrations (5, 10, 20, and 40 p g/mL) at the operation time points (24, 48, and 72 h) were obviously inhibited, showing dose- and time-dependent manners (P <0.05). (2) Typical changes of apoptosis were observed in both HPV 16 positive cell lines after treated with BJOE. The cell apoptosis rates increased markedly after being cultured with BJOE at different concentrations (5, 10, and 20 microg/mL) for 48 h (P < 0.05). (3) After treated with BJOE at different concentrations (5, 10, and 20 microg/mL) for 48 h, the HPV16 E6 and E7 mRNA relative expressions in both HPV 16 positive cell lines decreased significantly (P < 0.05). (4) After treated with BJOE at different concentrations (5, 10, and 20 microg/ mL), the expressions of HPV16 E6, E7, and mutant p53 protein decreased gradually (P < 0.05), while the Rb protein expression increased gradually (P < 0.05). CONCLUSIONS: BJOE showed obvious in vitro inhibitory effects on HPV type 16 infected cells. Its underlying mechanisms might be possibly associated with down-regulating expressions of HPV16 E6 and E7 oncogenes.

Genome-Wide Identification of WD40 Proteins in Cucurbita maxima Reveals Its Potential Functions in Fruit Development.

WD40 proteins, a super gene family in eukaryotes, are involved in multiple biological processes. Members of this family have been identified in several plants and shown to play key roles in various development processes, including acting as scaffolding molecules with other proteins. However, WD40 proteins have not yet been systematically analyzed and identified in Cucurbita maxima. In this study, 231 WD40 proteins (CmWD40s) were identified in C. maxima and classified into five clusters. Eleven subfamilies were identified based on different conserved motifs and gene structures. The CmWD40 genes were distributed in 20 chromosomes; 5 and 33 pairs of CmWD40s were distinguished as tandem and segmental duplications, respectively. Overall, 58 pairs of orthologous WD40 genes in C. maxima and Arabidopsis thaliana, and 56 pairs of orthologous WD40 genes in C. maxima and Cucumis sativus were matched. Numerous CmWD40s had diverse expression patterns in fruits, leaf, stem, and root. Several genes were involved in responses to NaCl. The expression pattern of CmWD40s suggested their key role in fruit development and abiotic stress response. Finally, we identified 14 genes which might be involved in fruit development. Our results provide valuable basis for further functional verification of CmWD40s in C. maxima.

Comparative transcriptome and metabolome analyses of cherry leaves spot disease caused by Alternaria alternata.

Alternaria alternata is a necrotrophic fungal pathogen with a broad host range that causes widespread and devastating disease in sweet cherry (Prunus avium). We selected a resistant cultivar (RC) and a susceptible cultivar (SC) of cherry and used a combined physiological, transcriptomic, and metabolomic approach to investigate the molecular mechanisms underlying the plant's resistance to A. alternata, of which little is known. We found that A. alternata infection stimulated the outbreak of reactive oxygen species (ROS) in cherry. The responses of the antioxidant enzymes and chitinase to disease were observed earlier in the RC than in the SC. Moreover, cell wall defense ability was stronger in the RC. Differential genes and metabolites involved in defense responses and secondary metabolism were primarily enriched in the biosynthesis of phenylpropanoids, tropane, piperidine and pyridine alkaloids, flavonoids, amino acids, and α-linolenic acid. Reprogramming the phenylpropanoid pathway and the α-linolenic acid metabolic pathway led to lignin accumulation and early induction of jasmonic acid signaling, respectively, in the RC, which consequently enhanced antifungal and ROS scavenging activity. The RC contained a high level of coumarin, and in vitro tests showed that coumarin significantly inhibited A. alternata growth and development and had antifungal effect on cherry leaves. In addition, differentially expressed genes encoding transcription factors from the MYB, NAC, WRKY, ERF, and bHLH families were highly expressed, they could be the key responsive factor in the response of cherry to infection by A. alternata. Overall, this study provides molecular clues and a multifaceted understanding of the specific response of cherry to A. alternata.

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. OBJECTIVES: We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. METHODS: We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. RESULTS: Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. CONCLUSION: Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Control of SOX2 protein stability and tumorigenic activity by E3 ligase CHIP in esophageal cancer cells.

SOX2 is highly expressed and controls tumor initiation and cancer stem cell function in various squamous cell carcinomas including esophageal squamous cancer. However, the molecular mechanism leading to SOX2 overexpression in cancer is incompletely understood. Here, we identified CHIP, a chaperone-associated ubiquitin E3 ligase, as a novel negative regulator of SOX2 protein stability and tumorigenic activity in esophageal squamous carcinoma cells. We showed that CHIP interacted with SOX2 primarily via chaperone HSP70, together they catalyzed SOX2 ubiquitination and degradation via proteasome. In contrast, HSP90 promoted SOX2 stability and inhibition of HSP90 activity induced SOX2 ubiquitination and degradation. Notably, unlike the case in normal esophageal tissues where CHIP was detected in both the cytoplasm and nucleus, CHIP in clinical esophageal tumor specimens was predominantly localized in the cytoplasm. Consistent with this observation, we observed increased expression of exportin-1/CRM-1 in clinical esophageal tumor specimens. We further demonstrated that CHIP catalyzed SOX2 ubiquitination and degradation primarily in the nuclear compartment. Taken together, our study has identified CHIP as a key suppressor of SOX2 protein stability and tumorigenic activity and revealed CHIP nuclear exclusion as a potential mechanism for aberrant SOX2 overexpression in esophageal cancer. Our study also suggests HSP90 inhibitors as potential therapeutic agents for SOX2-positive cancers.