A new diterpenoid alkaloid with antimicrobial activity from Aconitum brachypodum Diels.

A new C20-denudatine-type diterpenoid alkaloid (DA) 11S-aconicarnine D (1) and fifteen known DAs were isolated from the lateral roots of Aconitum brachypodum Diels. Their structures were identified on the basis of extensive spectroscopic analyses, NMR calculations and DP4+ analysis. The antimicrobial activities of compound 1 was evaluated, compound 1 exhibited potent antimicrobial activity against Alternaria panax and Fusarium solani with MICs of 2.00 and 16.00 µg/mL (Nystatin, 1.00 µg/mL), respectively.

The Diterpene Isopimaric Acid Modulates the Phytohormone Pathway to Promote Oryza sativa L. Rice Seedling Growth.

Many plant secondary metabolites are active and important in the regulation of plant growth. Certain plant-derived diterpenes are known to promote plant growth, but the pathways by which this promotion occurs are still unknown. Activity screening revealed that the plant-derived diterpene isopimaric acid exhibits growth-promoting activity in rice (Oryza sativa L.) seedlings. Furthermore, 25 µg/mL of isopimaric acid promoted the growth of 15 self-incompatible associated populations from different rice lineages to different extents. Quantitative analyses revealed a significant decrease in the concentration of the defense-related phytohormone abscisic acid (ABA) following treatment with isopimaric acid. Correlation analysis of the phytohormone concentrations with growth characteristics revealed that the length of seedling shoots was significantly negatively correlated with concentrations of 3-indole-butyric acid (IBA). Moreover, the total root weight was not only negatively correlated with ABA concentrations but also negatively correlated with concentrations of isopentenyl adenine (iP). These data suggest that isopimaric acid is able to influence the phytohormone pathway to balance energy allocation between growth and defense in rice seedlings and also alter the correlation between the concentrations of phytohormones and traits such as shoot and root length and weight. We provide a theoretical basis for the development and utilization of isopimaric acid as a plant growth regulator for rice.

Genome-Wide Association Studies Reveal That the Abietane Diterpene Isopimaric Acid Promotes Rice Growth through Inhibition of Defense Pathways.

Plants are an important source for the discovery of novel natural growth regulators. We used activity screening to demonstrate that treatment of Nipponbare seeds with 25 µg/mL isopimaric acid significantly increased the resulting shoot length, root length, and shoot weight of rice seedlings by 11.37 ± 5.05%, 12.96 ± 7.63%, and 27.98 ± 10.88% and that it has a higher activity than Gibberellin A3 (GA3) at the same concentration. A total of 213 inbred lines of different rice lineages were screened, and we found that isopimaric acid had different growth promotional activities on rice seedlings of different varieties. After induction with 25 µg/mL isopimaric acid, 15.02% of the rice varieties tested showed increased growth, while 15.96% of the varieties showed decreased growth; the growth of the remaining 69.02% did not show any significant change from the control. In the rice varieties showing an increase in growth, the shoot length and shoot weight significantly increased, accounting for 21.88% and 31.25%. The root length and weight significantly increased, accounting for 6.25% and 3.13%. Using genome-wide association studies (GWASs), linkage disequilibrium block, and gene haplotype significance analysis, we identified single nucleotide polymorphism (SNP) signals that were significantly associated with the length and weight of shoots on chromosomes 2 and 8, respectively. After that, we obtained 17 candidate genes related to the length of shoots and 4 candidate genes related to the weight of shoots. Finally, from the gene annotation data and gene tissue-specific expression; two genes related to this isopimaric acid regulation phenotype were identified as OsASC1 (LOC_Os02g37080) on chromosome 2 and OsBUD13 (LOC_Os08g08080) on chromosome 8. Subcellular localization analysis indicated that OsASC1 was expressed in the plasma membrane and the nuclear membrane, while OsBUD13 was expressed in the nucleus. Further RT-qPCR analysis showed that the relative expression levels of the resistance gene OsASC1 and the antibody protein gene OsBUD13 decreased significantly following treatment with 25 µg/mL isopimaric acid. These results suggest that isopimaric acid may inhibit defense pathways in order to promote the growth of rice seedlings.

Adaptation of Ustilago maydis to phenolic and alkaloid responsive metabolites in maize B73.

The adaptation of pathogenic fungi to plant-specialized metabolites is necessary for their survival and reproduction. The biotrophic fungus Ustilago maydis can cause maize smut and produce tumors in maize (Zea mays), resulting in reduced maize yield and significant economic losses. Qualitative analysis using UPLC-MS/MS revealed that the infection of maize variety B73 with U. maydis resulted in increased levels of phytohormones, phenolics, and alkaloids in maize seedling tissues. However, correlation analysis showed that nearly all compounds in the mechanical damage group were significantly negatively correlated with the shoot growth indexes of maize B73. The correlation coefficients of 2-hydroxy-7-methoxy-1,4-benzoxazin-3-one (HMBOA) and maize B73 shoot length and shoot weight were r = -0.56 (p < 0.01) and r = -0.75 (p < 0.001), respectively. In the inoculation group, these correlations weakened, with the correlation coefficients between HMBOA and maize B73 shoot length and shoot weight being r = 0.02 and r = -0.1, respectively. The correlation coefficients between 6-methoxy-2-benzoxazolinone (MBOA) and the shoot weight were r = -0.73 (p < 0.001) and r = -0.15 in the mechanical damage group and inoculation group, respectively. These findings suggest that increased concentrations of these compounds are more positively associated with mechanical damage than with U. maydis infection. At high concentrations, most of these compounds had an inhibitory effect on U. maydis. This study investigated the ability of U. maydis to regulate various compounds, including phytohormones, phenolic acids, and alkaloids in maize B73, providing evidence that U. maydis has adapted to the specialized metabolites produced by maize B73.

Diagnostic efficacy of the contrast-enhanced ultrasound thyroid imaging reporting and data system classification for benign and malignant thyroid nodules.

Background: The contrasted-enhanced ultrasound thyroid imaging reporting and data system (CEUS TI-RADS) is the first international risk stratification system for thyroid nodules based on conventional ultrasound (US) and CEUS. This study aimed to evaluate the diagnostic efficacy of CEUS TI-RADS for benign and malignant thyroid nodules and to assess the related interobserver agreement. Methods: The study recruited 433 patients who underwent thyroid US and CEUS between January 2019 and June 2023 at the Affiliated Hospital of Guangdong Medical University. A retrospective analysis of 467 thyroid nodules confirmed by fine-needle aspiration (FNA) and/or surgery was performed. Further, a CEUS TI-RADS classification was assigned to each thyroid nodule based on the CEUS TI-RADS scoring criteria for the US and CEUS features of the nodule. The nodules were grouped based on their sizes as follows: size ≤1 cm, group A; size >1 and ≤4 cm, group B; and size >4 cm, group C. Multivariate logistic regression was used to analyze independent risk factors for malignant thyroid nodules. Pathological assessment was the reference standard for establishing the sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of CEUS TI-RADS in diagnosing malignant thyroid nodules. The area under the curve (AUC) in the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the scoring system in predicting malignancy in three groups of nodules. The intragroup correlation coefficient (ICC) was adopted to assess the interobserver agreement of the CEUS TI-RADS score. Results: Out of the 467 thyroid nodules, 262 were malignant and 205 were benign. Logistic regression analysis revealed that the independent risk factors for malignant thyroid nodules included punctate echogenic foci (P<0.001), taller-than-wide shape (P=0.015), extrathyroidal invasion (P=0.020), irregular margins/lobulation (P=0.036), hypoechoicity on US (P=0.038), and hypoenhancement on CEUS (P<0.001). The AUC for the CEUS TI-RADS in diagnosing malignant thyroid nodules was 0.898 for all nodules, 0.795 for group A, 0.949 for group B, and 0.801 for group C, with the optimal cutoff values of the CEUS TI-RADS being 5 points, 6 points, 5 points, and 5 points, respectively. Among these groups of nodules, group B had the highest AUC, with the SEN, SPE, ACC, PPV, and NPV for diagnosing malignant nodules being 95.9%, 88.1%, 92.8%, 92.6%, and 93.2%, respectively. The ICC of the CEUS TI-RADS classification between senior and junior physicians was 0.862 (P<0.001). Conclusions: In summary, CEUS TI-RADS demonstrated significant efficacy in distinguishing thyroid nodules. Nonetheless, there were variations in its capacity to detect malignant nodules across diverse sizes, and it demonstrate optimal performance in 1- to 4-cm nodules. These findings may serve as important insights for clinical diagnoses.

Two-dimensional phosphorus carbides (ß-PC) as highly efficient metal-free electrocatalysts for lithium-sulfur batteries: a first-principles study.

Li-S batteries are considered as the next-generation batteries due to their exceptional theoretical capacity. However, their practical application is hampered by the shuttling effects of lithium polysulfides (LiPSs) and the sluggish Li2S decomposition, particularly the slow conversion from Li2S2 to Li2S. Addressing these challenges, the quest for effective catalysts that can accelerate the conversion of LiPSs and enhance the performance of Li-S batteries is crucial. In this study, we explored the electrocatalytic activity of two-dimensional phosphorus carbides (ß0-PC and ß1-PC) in Li-S batteries based on first-principles calculations. Our findings reveal that these materials demonstrate optimal binding strengths (ranging from 1.09 to 1.83 eV) with long-chain LiPSs, effectively preventing them from dissolving into the electrolyte. Additionally, they show remarkable catalytic activity during the sulfur redox reaction (SRR), with ΔG being only 0.37 eV for ß0-PC and 0.13 eV for ß1-PC. The low energy barrier induced by ß-PC enhances ion migration barrier and significantly expedites the charge/discharge cycles of Li-S batteries. Furthermore, we investigated the conversion dynamics of Li2S2 to Li2S, employing the computational lithium electrode (CLE) model. The excellent performance in these aspects underscores the potential of these materials as electrocatalysts for Li-S batteries, paving the way for advanced high-efficiency energy storage solutions.

High risk of low birth weight in couples with advanced paternal age in in vitro fertilization treatment.

BACKGROUND: With the development of socio-economic conditions and a shift in attitudes towards fertility, there has been a gradual increase in delayed childbearing since the 2000s. Age plays a significant role in the decline of fertility. However, we know very little about the association of paternal age with reproductive outcomes. OBJECTIVES: To investigate the correlation between advanced paternal age and semen quality, embryo quality, pregnancy, and neonatal outcomes in IVF cycles. MATERIALS AND METHODS: In this study, after excluding female partners aged ≥35 years, we analyzed data from 761 infertile couples who underwent in vitro fertilization cycles at the First Affiliated Hospital of USTC between June 2020 and March 2023. Cases were classified into three groups according to the age of the male: <35 years (530 infertile couples), 35 years ≤ paternal age <40 years (125 infertile couples), and ≥40 years (106 infertile couples). Then, we compared the general clinical data arising from in vitro fertilization cycles between the three groups, including semen parameters, embryonic parameters, and pregnancy and neonatal birth outcomes. RESULTS: Data analysis showed that the duration of infertility and the incidence of secondary infertility were significantly higher in paternal age ≥35 years groups than those aged <35 years (all p < 0.05). We also observed a significant difference between ≥40 years and <35 years groups in terms of the normal fertilization rate, high-quality embryo rate, clinical pregnancy rate, miscarriage rate, live birth rate, Apgar scores, and the low birth weight neonatal rate (all p < 0.05). The group with paternal age ≥40 years showed statistically significant differences in terms of clinical pregnancy rate, miscarriage rate, live birth rate, and low birth weight on multivariable logistic regression (all p < 0.05). CONCLUSION: The results of our study indicate that advanced paternal age (≥40 years) has a significant impact on the embryo quality, pregnancy outcome, and neonatal outcome. Paternal age over 40 years is a risk for in vitro fertilization success rate.

Safety assessment of coronary arteries during left bundle branch area pacing.

BACKGROUND: This study aimed to assess the safety of left bundle branch area pacing (LBBAP) by measuring the distance from the tip of the electrode to the nearby coronary artery with a nine-partition grid method. METHODS: From January 2019 to October 2020, patients who underwent LBBAP and postoperative coronary angiography in the Second Affiliated Hospital of Nanchang University were included in the study. The patients' fluoroscopic images of LBBAP and coronary angiography were collected and analyzed. Changes in the ST­T segment in the electrocardiogram (ECG), serum troponin, and myocardial enzyme profiles were observed before and after the LBBAP procedure. RESULTS: A total of 50 patients were included in this study, of whom 46 patients underwent implantation with a pacemaker and 4 patients received an implantable cardioverter defibrillator (ICD). The pacing electrodes were confined to the posterior-middle (PM), median (M), Posterior inferior (PI), and middle inferior (MI) positions of the two-dimensional nine-square grid or in the junction area of the above positions, and were concentrated in the rectangle formed by the line of the center points of the four positions. The average vertical distances from the electrode tip to the left anterior descending branch artery (LAD), posterior descending branches (PD) and the left posterior ventricular branches (PL) were 19.69 ± 8.72 mm, 26.09 ± 8.02 mm, and 21.11 ± 7.86 mm, respectively; the minimum was 5.28 mm, 9.51 mm, and 8.69 mm, respectively. Coronary angiography in all patients showed no significant injury to the ventricular septal branch; however, we observed elevated serum troponin and changes in ST­T segment in ECG. CONCLUSION: The study demonstrates that pacing electrodes in LBBAP can be safely implanted over a wide range. Coronary arteries are likely to be safe when the pacing electrodes are located within the rectangle formed by the line connecting the PM, M, PI, and MI zone centroids. The left bundle branch can be quickly captured and the safety of the coronary artery can be improved by locating the electrode in the posterior-mid zone. The potential risk of injury to the LAD from the electrode is greater compared with the PD.

The Chemical Ecology of Plant Natural Products.

Plants are excellent chemists with an impressive capability of biosynthesizing a large variety of natural products (also known as secondary or specialized metabolites) to resist various biotic and abiotic stresses. In this chapter, 989 plant natural products and their ecological functions in plant-herbivore, plant-microorganism, and plant-plant interactions are reviewed. These compounds include terpenoids, phenols, alkaloids, and other structural types. Terpenoids usually provide direct or indirect defense functions for plants, while phenolic compounds play important roles in regulating the interactions between plants and other organisms. Alkaloids are frequently toxic to herbivores and microorganisms, and can therefore also provide defense functions. The information presented should provide the basis for in-depth research of these plant natural products and their natural functions, and also for their further development and utilization.

Long-Term Stimulation of the Left Dorsal Branch of the Thoracic Nerve Improves Ventricular Electrical Remodeling in a Canine Model of Chronic Myocardial Infarction.

PURPOSE: To evaluate the ventricular electrophysiologic effects of long-term stimulation of the left dorsal branch of thoracic nerve (LDTN) derived from the left stellate ganglion (LSG) in a canine model of chronic myocardial infarction (MI). METHODS: Seventeen adult male beagles were randomly divided into three groups: the sham group (sham operated, n = 6), the MI group (n = 6), and the MI + LDTN group (MI plus LDTN stimulation, n = 5). The canine model of chronic MI was induced by the occlusion of the left anterior descending artery (LADO). The LDTN was separated and intermittently stimulated immediately after LADO for 2 months. The heart rate variability (HRV) analysis, in vivo electrophysiology, the evaluation of LSG function and neural activity, histological staining, and western blotting (WB) assay were performed to evaluate the effect of LDTN stimulation on the heart. RESULTS: The canine MI model was successfully established by LADO, and the LDTN was separated and stimulated immediately after LADO. The HRV analysis showed that LDTN stimulation reversed the increased LF value and LF/HF ratio of the MI group. LDTN stimulation prolonged the shortening ERP and APD90, decreased the dispersion of ERP and APD90, and increased the VFT. Additionally, LDTN stimulation inhibits the LSG function and neural activity. Furthermore, LDTN stimulation suppressed the activation of Wnt/ß-catenin signaling, which contributed to the LSG neuronal apoptosis by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2. CONCLUSION: LDTN stimulation could attenuate cardiac sympathetic remodeling and improve ventricular electrical remodeling, which may be mediated by suppressing the activated Wnt/ß-catenin signaling pathway and then promoting the LSG neuronal apoptosis.

Four New Furofuran Lignans from Phryma leptostachya Inhibit the Accumulation of Molting Hormones in Armyworm.

Furofuran lignans have been identified as the main substances responsible for the biological activities of the plant genus Phryma. Here, four new phrymarolin-type leptolignans A-D (7-10) and eight previously known lignans were isolated from P. leptostachya. Of these, nine exhibited significant antifeedant activity against armyworm (Mythimna separata) through a dual-choice bioassay, with the EC50 values ranging from 0.58 to 10.08 µg/cm2. In particular, the newly identified lignan leptolignan A (7) showed strong antifeedant activity, with an EC50 value of 0.58 ± 0.34 µg/cm2. Further investigation found that leptolignan A can inhibit the growth and nutritional indicators in the armyworm M. separata. The concentrations of two molting hormones, 20-hydroxyecdysone and ecdysone, were also found to decrease significantly following the treatment of the armyworms with the lignan, implying that the target of the P. leptostachya lignan may be involved in 20-hydroxyecdysone and ecdysone synthesis. These results enrich our knowledge of P. leptostachya metabolite structural diversity, and provide a theoretical basis for the control of armyworm using lignans.

Polymethoxylated flavones from the leaves of Vitex negundo have fungal-promoting and antibacterial activities during the production of broad bean koji.

Broad bean paste is a popular condiment in Asian countries. Leaves of Vitex negundo Linn. were used extensively in China during the koji-making of broad bean paste. Spreading V. negundo leaves on raw broad beans during fermentation was able to facilitate the rapid growth of fungi to form mature koji. We isolated two strains of fungi from mature koji, and four strains of bacteria from the rotten broad beans resulting from a failed attempt. According to microbial activity assays, two polymethoxylated flavones, 5-hydroxy-3,6,7,8,3',4'-hexamethoxy flavone (HJ-1) and 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxy flavone (HJ-2) were isolated from V. negundo leaves, and the fungal growth promotion and inhibition of bacterial growth of these two compounds were found to improve the production of broad bean koji. This study reveals the compounds present in V. negundo leaves with bioactivity against important microbes in koji manufacture, and provides a theoretical basis for the application of V. negundo in broad bean paste production.

Efficacy and safety of low-dose esketamine for painless gastrointestinal endoscopy in adults: a systematic evaluation and meta-analysis.

Object: The benefits of low-dose esketamine for painless gastrointestinal endoscopy remain unclear. As such, the present study aimed to investigate the efficacy and safety of low-dose esketamine for this procedure. Methods: Seven common databases were searched for clinical studies investigating low-dose esketamine for painless gastrointestinal endoscopy. Subsequently, a meta-analysis was performed to synthesize and analyze the data extracted from studies fulfilling the inclusion criteria. Results: Meta-analysis revealed that, compared with propofol, low-dose esketamine in combination with propofol significantly reduced recovery time by 0.56 min (mean difference [MD] -0.56%, 95% confidence interval (CI) -1.08 to -0.05, p = 0.03), induction time by 9.84 s (MD -9.84, 95% CI -12.93 to -6.75, p < 0.00001), propofol dosage by 51.05 mg (MD -51.05, 95% CI -81.53 to -20.57, p = 0.01), and increased mean arterial pressure by 6.23 mmHg (MD 6.23, 95% CI 1.37 to 11.08, p = 0.01). Meanwhile, low-dose esketamine reduced injection pain by 63% (relative risk [RR] 0.37, 95% CI 0.28 to 0.49, p < 0.00001), involuntary movements by 40% (RR 0.60, 95% Cl 0.42 to 0.85, p < 0.005), choking by 42% (RR 0.58, 95% Cl 0.38 to 0.88, p = 0.01), bradycardia by 68% (RR 0.32, 95% Cl 0.18 to 0.58, p = 0.0002), hypotension by 71% (RR 0.29, 95% Cl 0.21 to 0.40, p < 0.00001), respiratory depression by 63% (RR 0.37, 95% 0.26 to 0.51, p < 0.00001), additional cases of propofol by 53% (RR 0.47, 95% Cl 0.29 to 0.77, p = 0.002), and increased hypertension by 1000% (RR 11.00, 95% Cl 1.45 to 83.28, p = 0.02). There were no significant differences in mean heart rate, mean oximetry saturation, delirium, dizziness, vomiting, tachycardia, and hypoxemia. Subgroup analyses revealed that, compared with other dose groups, 0.25 mg/kg esketamine afforded additional benefits in recovery and induction time, mean arterial pressure, involuntary movements, hypoxemia, and respiratory depression. Conclusion: Low-dose esketamine was found to be safe and effective for providing anesthesia during gastrointestinal endoscopy, with 0.25 mg/kg identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control.

Nematicidal Activity of 20-Deoxyingenol-3-angelate from Euphorbia peplus Latex Through Protein Kinase C Isotype TPA-1.

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.

A novel contact force sensing pulsed field ablation catheter in a porcine model.

BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.

Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction Via the miR-210/ Nox2/ROS Pathway.

BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.

Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal LINC01963 to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells.

BACKGROUND: Hyperglycemia is widespread in the world's population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. METHODS: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1ß, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. RESULTS: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1ß, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1ß, IL-18, ROS, MDA, and LDH. CONCLUSION: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

A new C19-diterpenoid alkaloid in Aconitum georgei Comber.

Nine diterpenoid alkaloids were isolated from Aconitum georgei Comber belonging to the genus Aconitum in Ranunculaceae family. Their structures were determinated by using HR-ESI-MS and 1 D/2D NMR spectra as geordine (1), yunaconitine (2), chasmanine (3), crassicauline A (4), forestine (5), pseudaconine (6), 14-acetylalatisamine (7), austroconitine B (8), and talatisamine (9). Among them, compound 1 is a previously undescribed aconitine-type C19-diterpenoid alkaloid, and compounds 3, and 5-9 have not previously been isolated from this species. The results of in vitro experiments indicated that new compound 1 possesses mild anti-inflammatory activity, which inhibited the production of NO in LPS-activated RAW 264.7 cells with an inhibition ratio of 29.75% at 50 µM.

Chemical Structure Diversity and Extensive Biological Functions of Specialized Metabolites in Rice.

Rice (Oryza sativa L.) is thought to have been domesticated many times independently in China and India, and many modern cultivars are available. All rice tissues are rich in specialized metabolites (SPMs). To date, a total of 181 terpenoids, 199 phenolics, 41 alkaloids, and 26 other types of compounds have been detected in rice. Some volatile sesquiterpenoids released by rice are known to attract the natural enemies of rice herbivores, and play an indirect role in defense. Momilactone, phytocassane, and oryzalic acid are the most common diterpenoids found in rice, and are found at all growth stages. Indolamides, including serotonin, tryptamine, and N-benzoylserotonin, are the main rice alkaloids. The SPMs mainly exhibit defense functions with direct roles in resisting herbivory and pathogenic infections. In addition, phenolics are also important in indirect defense, and enhance wax deposition in leaves and promote the lignification of stems. Meanwhile, rice SPMs also have allelopathic effects and are crucial in the regulation of the relationships between different plants or between plants and microorganisms. In this study, we reviewed the various structures and functions of rice SPMs. This paper will provide useful information and methodological resources to inform the improvement of rice resistance and the promotion of the rice industry.

Prognostic Role of Mitochondrial Transcription Termination Factor 3 in Thyroid Carcinoma.

Background: Studies have shown that the Mitochondrial Transcription Termination Factor 3 (MTERF3) negatively regulates mitochondrial gene expression and energy metabolism, and plays a significant role in many cancer types. Nevertheless, the expression and prognostic role of MTERF3 in patients with thyroid carcinoma (THCA) is still unclear. Thus, we investigated the expression, clinicopathological significance, and prognostic value of MTERF3 in THCA. Methods: The protein and mRNA expression levels of MTERF3 were, respectively, analyzed using immunohistochemistry (IHC) from THCA tissues and RNA-Seq data downloaded from The Cancer Genome Atlas. In addition, the relationships among the expression of MTERF3, the stemness feature, the extent of immune infiltration, drug sensitivity, the expression of ferroptosis, and N6-methyladenosine (m6A) methylation regulators, were evaluated as prognostic indicators for patients with THCA using the Kaplan-Meier plotter database. Results: The IHC and RNAseq results showed that the protein and mRNA expression levels of MTERF3 in adjacent nontumor tissues were significantly higher than in THCA tissues. The survival analysis indicated that decreased expression of MTERF3 was associated with a poorer prognosis. Furthermore, the expression of MTERF3 not only negatively correlated with the enhancement of the stemness of THCA and the reduction of drug sensitivity but also was implicated in ferroptosis and m6A methylation. Conclusion: The data from this study support the hypothesis that decreased expression of MTERF3 in THCA is associated with a poor prognosis.