Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

Potential Approach to Quantifying the Volume of the Ischemic Core in Truncated Computed Tomography Perfusion Scans: A Preliminary Study.

OBJECTIVE: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice. METHODS: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis. RESULTS: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068). CONCLUSIONS: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.

A novel spider venom peptide from the predatory mite Neoseiulus barkeri shows lethal effect on phytophagous pests.

The long-term use of pesticides in the field, and the high fertility and adaptability of phytophagous mites have led to resistance problems; consequently, novel safe and efficient active substances are necessary to broaden the tools of pest mite control. Natural enemies of arthropods typically secrete substances with paralytic or lethal effects on their prey, and those substances are a resource for future biopesticides. In this study, two putative venom peptide genes were identified in a parasitic mite Neoseiulus barkeri transcriptome. Recombinant venom NbSP2 peptide injected into Tetranychus cinnabarinus mites was significantly more lethal than recombinant NBSP1. NbSP2 was also lethal to Spodoptera litura when injected but not when fed to third instar larvae. The interaction proteins of NbSP2 in T. cinnabarinus and S. litura were identified by affinity chromatography. Among these proteins, ATP synthase subunit ß (ATP SSß) was deduced as a potential target. Four binding sites were predicted between NBSP2 and ATP SSß of T. cinnabarinus and S. litura. In conclusion, we identified a venom peptide with activity against T. cinnabarinus and S. litura. This study provides a novel component for development of a new biological pesticide.

Predictors of ghost infarct core on baseline computed tomography perfusion in stroke patients with successful recanalization after mechanical thrombectomy.

OBJECTIVES: To assess the predictors of ghost infarct core (GIC) in stroke patients achieving successful recanalization after mechanical thrombectomy (MT), based on final infarct volume (FIV) calculated from follow-up diffusion-weighted imaging (DWI). METHODS: A total of 115 consecutive stroke patients who had undergone baseline computed tomography perfusion (CTP) scan, achieved successful recanalization after MT, and finished follow-up DWI evaluation were retrospectively enrolled. Ischemic core volume was automatically generated from baseline CTP, and FIV was determined manually based on follow-up DWI. Stroke-related risk factors and demographic, clinical, imaging, and procedural data were collected and assessed. Univariate and multivariate analyses were applied to identify the predictors of GIC. RESULTS: Of the 115 included patients (31 women and 84 men; median age, 66 years), 18 patients (15.7%) showed a GIC. The GIC group showed significantly shorter time interval from stroke onset to CTP scan and that from stroke onset to recanalization (both p < 0.001), but higher ischemic core volume (p < 0.001), hypoperfused area volume (p < 0.001), mismatch area volume (p = 0.006), and hypoperfusion ratio (p = 0.001) than the no-GIC group. In multivariate analysis, time interval from stroke onset to CTP scan (odds ratio [OR], 0.983; p = 0.005) and ischemic core volume (OR, 1.073; p < 0.001) were independently associated with the occurrence of GIC. CONCLUSIONS: In stroke patients achieving successful recanalization after MT, time interval from stroke onset to CTP and ischemic core volume are associated with the occurrence of GIC. Patients cannot be excluded from MT solely based on baseline CTP-derived ischemic core volume, especially for patients with a shorter onset time. KEY POINTS: • Ghost infarct core (GIC) was found in 15.7% of patients with acute ischemic stroke (AIS) in our study cohort. • GIC was associated with stroke onset time, volumetric parameters derived from CTP, and collateral status indicated by HIR. • Time interval from stroke onset to CTP scan and ischemic core volume were independent predictors of GIC.

Spatial accuracy of computed tomography perfusion to estimate the follow-up infarct on diffusion-weighted imaging after successful mechanical thrombectomy.

BACKGROUND: Volumetric accuracy of using computed tomography perfusion (CTP) to estimate the post-treatment infarct in stroke patients with successful recanalization after mechanical thrombectomy (MT) has been studied a lot, however the spatial accuracy and its influence factors has not been fully investigated. METHODS: This retrospective study reviewed the data from consecutive anterior large vessel occlusion (LVO) patients who had baseline CTP, successful recanalization after MT, and post-treatment diffusion-weighed imaging (DWI). Ischemic core on baseline CTP was estimated using relative cerebral blood flood (CBF) of < 30%. The infarct area was outlined manually on post-treatment DWI, and registered to CTP. Spatial agreement was assessed using the Dice similarity coefficient (DSC) and average Hausdorff distance. According to the median DSC, the study population was dichotomized into high and low Dice groups. Univariable and multivariable regression analyses were used to determine the factors independently associated with the spatial agreement. RESULTS: In 72 included patients, the median DSC was 0.26, and the median average Hausdorff distance was 1.77 mm. High Dice group showed significantly higher median ischemic core volume on baseline CTP (33.90 mL vs 3.40 mL, P < 0.001), lower proportion of moderate or severe leukoaraiosis [27.78% vs 52.78%, P = 0.031], and higher median infarct volume on follow-up DWI (51.17 mL vs 9.42 mL, P < 0.001) than low Dice group. Ischemic core volume on baseline CTP was found to be independently associated with the spatial agreement (OR, 1.092; P < 0.001). CONCLUSIONS: CTP could help to spatially locate the post-treatment infarct in anterior LVO patients who achieving successful recanalization after MT. Ischemic core volume on baseline CTP was independently associated with the spatial agreement.

CT perfusion with increased temporal sampling interval to predict target mismatch status in patients with acute ischemic stroke.

PURPOSE: To evaluate the feasibility of using CT perfusion (CTP) with increased temporal sampling interval to predict the target mismatch status in acute ischemic stroke (AIS) patients with anterior circular large-vessel occlusion (LVO). METHODS: CTP with a sampling interval of 1.7 s (CTP1.7 s) was scanned in 77 AIS patients for pre-treatment evaluation. Simulated CTP data with sampling interval of 3.4 s (CTP3.4 s) or 5.1 s (CTP5.1 s) were reconstructed, respectively. Target mismatch was defined according to the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial criteria, respectively. Pearson correlation analysis, Mann-Whitney U test, Bland-Altman analysis, and chi-square test were used for statistical analysis as appropriate. RESULTS: Significant correlations were found on the volume of ischemic core, hypo-perfused area, mismatch area, and ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p < 0.001). There was no significant difference on the volume of ischemic core, hypo-perfused area, mismatch area, and mismatch ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p > 0.05). Compared with CTP1.7 s, CTP3.4 s or CTP5.1 s showed comparable performance in predicting the target mismatch status in the AIS patients with LVO (both p > 0.05). CONCLUSIONS: CTPs with increased temporal sampling intervals that lead to reduced radiation doses are feasible and may provide comparable performance in predicting target mismatch status in AIS patients with LVO.

Use of ABC/2 method for rapidly estimating the target mismatch on computed tomography perfusion imaging in patients with acute ischemic stroke.

BACKGROUND: Target mismatch (ischemic core, mismatch volume and mismatch ratio) in patients with acute ischemic stroke (AIS) highly relies on the automated perfusion analysis software. PURPOSE: To evaluate the feasibility and accuracy of using the ABC/2 method to rapidly estimate the target mismatch on computed tomography perfusion (CTP) imaging in patients with AIS, using RAPID results as a reference. MATERIAL AND METHODS: In total, 243 patients with anterior circulation AIS who underwent CTP imaging were retrospectively reviewed. Target mismatch associated perfusion parameters were derived from RAPID results and calculated using the ABC/2 method. Paired t-test was used to assess the difference of volumetric parameters between the two methods. The ability of using the ABC/2 method to predict the important cutoff volumetric metrics was also evaluated. RESULT: There was no significant difference in the volumes of ischemic core (P = 0.068), ischemic area (P = 0.209), and mismatch volume (P = 0.518) between ABC/2 and RAPID. Using RAPID results as reference, the ABC/2 method showed high accuracy for predicting perfusion parameters (70 mL and 90 mL: sensitivity=98.5% and 98.5%, specificity=100% and 100%, positive predictive value [PPV]=100% and 100%, negative predictive value [NPV]=93.8% and 92.9%; 10 mL and 15mL: sensitivity=99.6% and 99.5%, specificity=55.6% and 50.0%, PPV=96.6% and 94.8%, NPV=90.9% and 92.3%; 1.2 and 1.8: sensitivity=99.6% and 94.8%, specificity=75.0% and 96.9%, PPV=98.7% and 99.5%, NPV=90.0% and 73.8%). CONCLUSION: The ABC/2 method may be a feasible alternative to RAPID for estimation of target mismatch parameters on CTP in patients with AIS.

Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways.

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

Prognostic value of ASPECTS on post-treatment diffusion-weighted imaging for acute ischemic stroke patients after endovascular thrombectomy: comparison with infarction volume.

OBJECTIVES: To assess the prognostic value of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on post-treatment diffusion-weighted imaging (DWI) for acute ischemic stroke (AIS) patients after endovascular thrombectomy (EVT) and compare it with that of infarction volume. METHODS: Ninety-eight consecutive AIS patients who underwent EVT and post-treatment DWI were retrospectively enrolled. ASPECTS and infarction volume were evaluated based on post-treatment DWI, respectively. Good clinical outcome was defined as modified Rankin Scale score of 0-2 at 90 days. Predictors of good clinical outcome were evaluated using univariate and multivariate logistic regression analysis. Prognostic value of post-treatment DWI ASPECTS and infarction volume were assessed and compared using receiver-operating-characteristic curves and the DeLong method. RESULTS: Favorable outcome was achieved in 62 (63.3%) patients. A strong correlation was found between post-treatment DWI ASPECTS and infarction volume (ρ = -0.847). Due to strong correlation and potential collinearity, two multivariate logistic regression models were respectively developed which included post-treatment DWI ASPECTS or infarction volume. As a result, post-treatment DWI ASPECTS (OR, 2.401; 95%CI, 1.567-3.678; p < 0.001) and infarction volume (OR, 0.982; 95%CI, 0.846-0.998; p = 0.002) were both independent predictors of good clinical outcome. Setting post-treatment DWI ASPECTS ≥ 6 as a cut-off value, optimal performance (AUC = 0.836; sensitivity, 87.1%; specificity, 66.7%) could be obtained in predicting good clinical outcome, which was comparable with that of infarction volume (cut-off volume, ≤ 94.87 ml; AUC = 0.821; sensitivity, 90.3%; specificity, 55.6%). CONCLUSIONS: Post-treatment DWI ASPECTS might be a potential surrogate of infarction volume and be effective in predicting the clinical outcome of AIS patients after EVT. KEY POINTS: • Post-treatment DWI ASPECTS correlated significantly with infarction volume. • A post-treatment DWI ASPECTS ≥ 6 best predicts good outcomes for AIS patients after EVT. • Post-treatment DWI ASPECTS has the potential in substituting infarction volume in predicting the clinical outcome of AIS patients.

Prognostic value of post-treatment fluid-attenuated inversion recovery vascular hyperintensity in ischemic stroke after endovascular thrombectomy.

OBJECTIVES: To explore the value of post-treatment fluid-attenuated inversion recovery vascular hyperintensity (FVH) in predicting clinical outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). METHODS: This retrospective study reviewed data from consecutive patients with large vessel occlusion of anterior circulation between July 2017 and February 2021. Together with other variables, status of post-treatment FVH was assessed for each patient. Good outcome was defined as a 3-month modified Rankin Scale score of 0-2. Chi-square test, Fisher's exact test, independent-samples t test, multivariate logistic regression analysis, and receiver operating characteristic analysis were used as appropriate. RESULTS: Among 84 included patients, 48 (57.1%) patients showed post-treatment FVH. Post-treatment FVH significantly correlated with incomplete recanalization (p < 0.05) and low Alberta Stroke Project Early CT Changes Score on post-treatment diffusion-weighted imaging (p < 0.05). Higher incidence of hemorrhage transformation was observed in patients with post-treatment FVH than those without (27.1% vs. 16.7%); however, the difference did not reach significance (p = 0.259). Successful recanalization (odds ratio [OR], 0.024; 95% confidence interval [CI] 0.003-0.194; p < 0.05), lower National Institutes of Health Stroke Scale scores at admission (NIHSSpre) (OR, 1.196; 95% CI, 1.017-1.406; p < 0.05), and no post-treatment FVH (OR, 74.690; 95% CI, 4.624-1206.421; p < 0.05) were found to be independent predictors of good outcomes. Combined models integrating all three independent predictors (recanalization+NIHSSpre+post-treatment FVH) significantly outperformed the combined model without post-treatment FVH (recanalization+NIHSSpre) in predicting clinical outcome (p = 0.004). CONCLUSIONS: Post-treatment FVH may be an effective prognostic marker associated with clinical outcome in patients with AIS after EVT. KEY POINTS: • Post-treatment FVH correlates with incomplete recanalization and higher infarct volume. • Post-treatment FVH is independently associated with an unfavorable outcome. • Post-treatment FVH may provide prognostic information in patients with AIS after EVT.

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics.

In this work, the pKa values of 69 polar alkanes (YH2) in acetonitrile were computed using the method developed by Luo and Zhang in 2020, and representative 69 thermodynamic network cards on 22 elementary steps of YH2 and related polar alkenes (Y) releasing or accepting H2 were naturally established. Potential electron reductants (YH-), hydride reductants (YH-), antioxidants (YH2 and YH-), and hydrogen molecule reductants (YH2) are unexpectedly discovered according to thermodynamic network cards. It is also found that there are great differences between YH2 and common hydrogen molecule reductants (XH2), such as Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydro-phenanthridine (PH2), releasing two hydrogen ions to unsaturated compounds. During the hydrogenation process, XH2 release hydrides first, then the oxidation state XH+ release protons. However, in the case of YH2, YH2 release protons first, then YH- release hydrides. It is the differences on acidic properties of YH2 and XH2 that result in the behavioral and thermodynamic differences on YH2 and XH2 releasing two hydrogen ions (H--H+). The redox mechanisms and behaviors of Y, YH-, and YH2 as electron, hydrogen atom, hydride, and hydrogen molecule donors or acceptors in the chemical reaction are reasonably investigated and discussed in this paper using thermodynamics.

Theoretical study for evaluating and discovering organic hydride compounds as novel trifluoromethylation reagents.

Trifluoromethylation reaction is one of the significant and practical organic chemical reactions, and the design and discovery of novel trifluoromethylation reagents have been attracting more and more attention. Trifluoromethyl-substituted organic hydride compounds (XH) have the potential to be novel trifluoromethylation reagents in organic synthesis due to the favorable tendency of XH˙+ releasing ˙CF3 to form stable aromatic structures in terms of thermodynamics. The key elementary step of the trifluoromethylation is the radical cation (XH˙+) generation by catalysis or single-electron activation releasing ˙CF3 to form a stable aromatic structure, which also provides the thermodynamic driving force of the chemical process. In this work, 47 new trifluoromethylation reagent candidates of XHs were designed and calculated for the Gibbs free energy and activation free energy [ΔG‡RD(XH˙+)] of XH˙+ releasing ˙CF3 using the density functional theory (DFT) method, in order to quantitatively measure the reactivity of XHs as trifluoromethylation reagents, and to establish the molecular library as well as reactivity database of novel trifluoromethylation reagents for synthetic chemists. According to the and ΔG‡RD(XH˙+) values, all the XHs can be reasonably divided into 3 classes, including class 1 (excellent trifluoromethylation reagents), class 2 (potential trifluoromethylation reagents) and class 3 (not trifluoromethylation reagents). To our delight, 15 XHs with a 1,4-dihydropyridine structure and 3 XHs with a 3,4-dihydropyrimidin-2-one structure are identified to be novel excellent and potential trifluoromethylation reagents, respectively, according to their reactivity data. The relationship between the structural features, including methylation, heteroatom, substituents, conjugated structure and so on, and the reactivity of XHs as trifluoromethylation reagents are also discussed in this work. The computation results indicate that trifluoromethyl-substituted 1,4-dihydropyridine compounds and 3,4-dihydropyrimidin-2-one analogues could be possible trifluoromethylation reagents in organic synthesis. This work may provide the theoretical basis and references for discovering organic hydride compounds as novel reagents for trifluoromethylation or other alkylation reactions.

Diagnostic accuracy of using Alberta Stroke Program Early Computed Tomography Score on CT perfusion map to predict a target mismatch in patients with acute ischemic stroke.

PURPOSE: To assess the diagnostic accuracy of using Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on CT perfusion (CTP) map to predict a volumetric target mismatch in patients with acute ischemic stroke (AIS). METHODS: Three-hundred and seven AIS patients with an onset time within 24h or unclear onset time who underwent CTP evaluation for large vessel occlusion of anterior circulation were enrolled. CTP ASPECTS was evaluated on cerebral blood flow (CBF) and time-to-maximum (Tmax) colored maps, respectively. Automated perfusion analysis software was used to calculate the volumes of ischemic core (volumeCBF<30%) and tissue at risk (volumeTmax>6s). Target mismatch was defined as volumeCBF< 30%<70ml, volumemismatch≥15ml, and volumeTmax >6s/volume CBF< 30%≥1.8. Spearman correlation and receiver operating characteristic curves were used for statistical analyses. RESULTS: Strong correlations were found between CBF ASPECTS and volumeCBF<30%, and between Tmax ASPECTS and volumeTmax>6s for overall population (ρ=-0.872, -0.757) and late-arriving patients (ρ=-0.900, -0.789). Mismatch ASPECTS moderately correlated with mismatch volume for overall population (ρ=0.498) and late-arriving patients (ρ=0.407). A CBF ASPECTS≥5 optimally predicted an ischemic core volume<70ml in overall population (sensitivity, 94.4%; specificity, 80.4%) and late-arriving patients (sensitivity, 89.5%; specificity, 90.5%). A CBF ASPECTS≥6 combined with a Mismatch ASPECTS≥1 optimally identified a target mismatch in overall population (sensitivity, 84.5%; specificity, 77.0%) and late-arriving patients (sensitivity, 83.7%; specificity, 90.0%). CONCLUSION: CTP ASPECTS might be useful in predicting target mismatch derived from automated perfusion analysis software, and assisting in patient selection for endovascular therapy.

Subacute thyroiditis during early pregnancy: a case report and literature review.

BACKGROUND: Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy. CASE PRESENTATION: A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41. CONCLUSION: SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.

Metabolic and Transcriptomic Analyses Reveal the Effects of Ethephon on Taraxacum kok-saghyz Rodin.

The roots of Taraxacum kok-saghyz Rodin (TKS) are well-known and valued for their rubber-producing ability. Therefore, research on the analysis and detection of metabolites from the roots of TKS have been reported in previous studies. However, all of these studies have the shortcoming of focusing on only the rubber of TKS, without profiling the other metabolites in a systematic and comprehensive way. Here, the primary and secondary metabolites from the leaves of TKS were investigated using UPLC-ESI-MS/MS, and a total of 229 metabolites were characterized. Carboxylic acid derivatives, fatty acyls, phenols, and organooxygen compounds were found to be the major metabolites of TKS. The transcriptome data indicated that ribosomal, glycolysis/gluconeogenesis, phenylpropanoid biosynthesis, and linoleic acid metabolism genes were significantly differentially expressed. This study is the first to report the differences in the metabolic and transcriptome profiles of TKS leaves under exogenous ethephon spray, which improves our understanding of the main metabolites and their molecular mechanisms in TKS leaves.

Granulocyte colony-stimulating factor reduces the endoplasmic reticulum stress in a rat model of diabetic cardiomyopathy.

Prolonged endoplasmic reticulum (ER) stress contributes to the apoptosis of cardiomyocytes, which leads to the development of diabetic cardiomyopathy. Previously, we reported that the granulocyte colony-stimulating factor (G-CSF) reduces the cardiomyocyte apoptosis in diabetic cardiomyopathy; however, the precise mechanisms associated with this process are not yet fully understood. Therefore, in this study, we investigated whether the mechanism of the anti-apoptotic effect of G-CSF was associated with ER stress in a rat model of diabetic cardiomyopathy. Diabetic cardiomyopathy was induced in rats using a high-fat diet combined with the administration of a low-dose of streptozotocin. Diabetic rats were treated with G-CSF or saline for 5 days. Cardiac function was evaluated using serial echocardiography before and 4 weeks after treatment. The rate of cardiomyocyte apoptosis and the expression levels of proteins related to ER stress, including glucose-regulated protein 78 (GRP78), caspase-9, and caspase-12 were analyzed in the cardiac tissue. G-CSF treatment significantly reduced cardiomyocyte apoptosis in the diabetic myocardium and downregulated the expression levels of these proteins in diabetic rats treated with low-dose streptozotocin when compared to that in rats treated with saline. In addition, G-CSF treatment significantly downregulated the expression levels of proteins related to ER stress, such as GRP78, inositol-requiring enzyme-1α (IRE-1α), and C/EBP homologous protein (CHOP) in H9c2 cells under high glucose (HG) conditions. Moreover, G-CSF treatment significantly improved the diastolic dysfunction in serial echocardiography assessments. In conclusion, the anti-apoptotic effect of G-CSF may be associated with the downregulation of ER stress.

Thermodynamic Network Cards of Hantzsch Ester, Benzothiazoline, and Dihydrophenanthridine Releasing Two Hydrogen Atoms or Ions on 20 Elementary Steps.

In this work, thermodynamic driving forces on 20 possible elementary steps of Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydrophenanthridine (PDH2) releasing two hydrogen atoms or ions were measured or derived from the related thermodynamic data using Hess' law in acetonitrile. Furthermore, thermodynamic network cards of HEH2, BTH2, and PDH2 releasing two hydrogen atoms or ions on 20 elementary steps were first established. Based on the thermodynamic network cards, hydride-donating, hydrogen-atom-donating, and electron-donating abilities of XH2 and XH-, and two hydrogen-atom(ion)-donating abilities of XH2 are discussed in detail. Obviously, the thermodynamic network cards of HEH2, BTH2, and PDH2 not only offer rational data guidance for organic synthetic chemists to properly choose an appropriate reducer among the three reducing agents to hydrogenate various unsaturated compounds but also strongly promote elucidatation of the detailed hydrogenation mechanisms.

Downregulation of DLGAP1-Antisense RNA 1 Alleviates Vascular Endothelial Cell Injury Via Activation of the Phosphoinositide 3-kinase/Akt Pathway Results from an Acute Limb Ischemia Rat Model.

OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.

Novel liquid fermentation medium of Cordyceps militaris and optimization of hydrothermal reflux extraction of cordycepin.

In this study, we developed a novel liquid fermentation medium of Cordyceps militaris using pupa powder and wheat bran as nitrogen resources instead of the traditionally used peptone. This process not only reduced the cost by approximately 50%, but increased production by over 30%. Then, we explored a method to extract and purify cordycepin by combining hydrothermal reflux extraction with macroporous resin adsorption, which is inexpensive and suitable for the industrial production. The optimum conditions for hydrothermal reflux were extracting three times at 95 °C with 1:10 sample-to-water ratio, and the cordycepin purity with macroporous resin HPD-100 reached 95.23%.[Formula: see text].

RNAi targeting ecdysone receptor blocks the larva to adult development of Tetranychus cinnabarinus.

RNA interference (RNAi) is a potentially useful pest control method because of its high specificity. Silencing the expression of important RNAi target genes of pests will block important biological processes and reduce pest damage. Ecdysone is a unique arthropod hormone and the ecdysone receptor (EcR) is a key factor in molting pathway. We investigated the possibility that dsRNA targeting of the EcR of Tetranychus cinnabarinus (TcEcR) could effectively block development from larvae to adults. The mRNA level of TcEcR was highest in the larva stage, and 73.1% of the mites failed to survive the larva stage when TcEcR expression was silenced. Only 11.7% of T. cinnabarinus ingesting dsRNA successfully developed into adults, while 86.7% in the control succeeded in molting across each stage. RNAi significantly increased the developmental intervals of T. cinnabarinus. Under the effects of dsRNA, development times for the larva and first nymph doubled. Phenotype of body size change and death were observed during the development of T. cinnabarinus ingesting dsRNA. These findings suggest that RNAi is a potential means for the control of T. cinnabarinus. Genes in hormone pathways such as EcR are possible RNAi targets.