Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer.

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.

Diagnosing and tracking depression based on eye movement in response to virtual reality.

Introduction: Depression is a prevalent mental illness that is primarily diagnosed using psychological and behavioral assessments. However, these assessments lack objective and quantitative indices, making rapid and objective detection challenging. In this study, we propose a novel method for depression detection based on eye movement data captured in response to virtual reality (VR). Methods: Eye movement data was collected and used to establish high-performance classification and prediction models. Four machine learning algorithms, namely eXtreme Gradient Boosting (XGBoost), multilayer perceptron (MLP), Support Vector Machine (SVM), and Random Forest, were employed. The models were evaluated using five-fold cross-validation, and performance metrics including accuracy, precision, recall, area under the curve (AUC), and F1-score were assessed. The predicted error for the Patient Health Questionnaire-9 (PHQ-9) score was also determined. Results: The XGBoost model achieved a mean accuracy of 76%, precision of 94%, recall of 73%, and AUC of 82%, with an F1-score of 78%. The MLP model achieved a classification accuracy of 86%, precision of 96%, recall of 91%, and AUC of 86%, with an F1-score of 92%. The predicted error for the PHQ-9 score ranged from -0.6 to 0.6.To investigate the role of computerized cognitive behavioral therapy (CCBT) in treating depression, participants were divided into intervention and control groups. The intervention group received CCBT, while the control group received no treatment. After five CCBT sessions, significant changes were observed in the eye movement indices of fixation and saccade, as well as in the PHQ-9 scores. These two indices played significant roles in the predictive model, indicating their potential as biomarkers for detecting depression symptoms. Discussion: The results suggest that eye movement indices obtained using a VR eye tracker can serve as useful biomarkers for detecting depression symptoms. Specifically, the fixation and saccade indices showed promise in predicting depression. Furthermore, CCBT demonstrated effectiveness in treating depression, as evidenced by the observed changes in eye movement indices and PHQ-9 scores. In conclusion, this study presents a novel approach for depression detection using eye movement data captured in VR. The findings highlight the potential of eye movement indices as biomarkers and underscore the effectiveness of CCBT in treating depression.

Proteomic profiling of ovarian clear cell carcinomas identifies prognostic biomarkers for chemotherapy.

Clear cell ovarian carcinoma (CCOC) is a relatively rare subtype of ovarian cancer (OC) with high degree of resistance to standard chemotherapy. Little is known about the underlying molecular mechanisms, and it remains a challenge to predict its prognosis after chemotherapy. Here, we first analyzed the proteome of 35 formalin-fixed paraffin-embedded (FFPE) CCOC tissue specimens from a cohort of 32 patients with CCOC (H1 cohort) and characterized 8697 proteins using data-independent acquisition mass spectrometry (DIA-MS). We then performed proteomic analysis of 28 fresh frozen (FF) CCOC tissue specimens from an independent cohort of 24 patients with CCOC (H2 cohort), leading to the identification of 9409 proteins with DIA-MS. After bioinformatics analysis, we narrowed our focus to 15 proteins significantly correlated with the recurrence free survival (RFS) in both cohorts. These proteins are mainly involved in DNA damage response, extracellular matrix (ECM), and mitochondrial metabolism. Parallel reaction monitoring (PRM)-MS was adopted to validate the prognostic potential of the 15 proteins in the H1 cohort and an independent confirmation cohort (H3 cohort). Interferon-inducible transmembrane protein 1 (IFITM1) was observed as a robust prognostic marker for CCOC in both PRM data and immunohistochemistry (IHC) data. Taken together, this study presents a CCOC proteomic data resource and a single promising protein, IFITM1, which could potentially predict the recurrence and survival of CCOC.

NHC-Catalyzed Chemo- and Enantioselective Reaction between Aldehydes and Enals for Access to Axially Chiral Arylaldehydes.

A chiral carbene-catalyzed chemo- and enantioselective reaction with racemic biaryl aldehydes and α-bromoenals is developed for access to axially chiral 2-arylbenzaldehydes through atroposelective dynamic kinetic resolution (DKR) processes. This atroposelective DKR strategy can tolerate a broad scope of substrates with diverse functionalities. The axially chiral 2-aryl benzaldehyde products generally afford moderate to good yields and enantioselectivities. The axially chiral molecules afforded from the current approach are variable through simple transformations to afford axially chiral functional molecules with excellent optical purities.

A first-in-human study of Brozopentyl Sodium, following single and multiple ascending intravenous infusion in Chinese healthy volunteers.

BACKGROUND: Brozopentyl Sodium (BZP), a novel agent for ischemic stroke, has shown promising results in preclinical pharmacological studies, prompting the initiation of the first-in-human investigation. PURPOSE: This study aimed to assess the safety, tolerability, and pharmacokinetic (PK) characteristics of BZP in Chinese healthy volunteers. METHODS: The study consisted of two parts. Part I was a single-center, randomized, single-blinded, placebo-controlled, single-ascending study with six BZP dose cohorts (SAD: 25, 50, 100, 200, 300, and 400 mg). Part II was a single-center, randomized, single-blinded, placebo-controlled, multi-dose- and dose-elevated study with three BZP dose cohorts (MAD: 50, 100, and 200 mg). Doses were administered once daily on days 1 and 7 and twice daily on days 2-6. The PK properties of BZP and its bioactive metabolites, BNBP, were assessed. Safety and tolerability evaluations were also conducted. RESULTS: In the SAD study, BZP reached peak plasma concentrations (Tmax) at the end of administration, with median Tmax values ranging from 1 to 1.03 h, while BNBP reached Tmax between 1.25 to 1.38 h. The terminal half-lives (T1/2) were approximately 8 h for BZP and 15 h for BNBP. In the MAD study, steady-state plasma concentrations of BZP were reached by day 5. There was minimal accumulation of both BZP and BNBP after 7 days of administration. The area under the plasma concentration-time curve from 0 to time of the last measurable concentration (AUC0-t) and maximum plasma drug concentration (Cmax) showed dose-proportional increases for BZP but not for BNBP in both study parts. Single and multiple doses of BZP demonstrated a good safety profile and were well-tolerated. CONCLUSION: BZP displayed safety, good tolerability and predictable PK characteristics following both single and multiple ascending intravenous administrations. These findings provide a basis for further clinical development of BZP for ischemic stroke patients.

The Development of Aldehyde Catalytic System.

Aldehyde catalysts have proven to be highly effective in facilitating and accelerating a wide range of challenging transformations in organic chemistry. This article is structured into three main sections, focusing on the utilization of aldehydes as organocatalysts, the aldehydes/transition metals catalytic systems, and photochemical initiators. Finally, we provide a concise summary of the advancements in this fascinating research field, offering our perspectives and insights.

Exposure to Butylparaben Induces Craniofacial Bone Developmental Toxicity in Zebrafish (Danio rerio) Embryos.

Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.

DPHL v.2: An updated and comprehensive DIA pan-human assay library for quantifying more than 14,000 proteins.

A comprehensive pan-human spectral library is critical for biomarker discovery using mass spectrometry (MS)-based proteomics. DPHL v.1, a previous pan-human library built from 1,096 data-dependent acquisition (DDA) MS data of 16 human tissue types, allows quantifying of 10,943 proteins. Here, we generated DPHL v.2 from 1,608 DDA-MS data. The data included 586 DDA-MS data acquired from 18 tissue types, while 1,022 files were derived from DPHL v.1. DPHL v.2 thus comprises data from 24 sample types, including several cancer types (lung, breast, kidney, and prostate cancer, among others). We generated four variants of DPHL v.2 to include semi-tryptic peptides and protein isoforms. DPHL v.2 was then applied to two colorectal cancer cohorts. The numbers of identified and significantly dysregulated proteins increased by at least 21.7% and 14.2%, respectively, compared with DPHL v.1. Our findings show that the increased human proteome coverage of DPHL v.2 provides larger pools of potential protein biomarkers.

Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer.

The present study sought to investigate the correlation between CAAP1 and platinum resistance in ovarian cancer and to preliminarily explore the potential biological function of CAAP1. Proteomic analysis was used to analyze differentially expressed proteins in platinum-sensitive and -resistant tissue samples of ovarian cancer. The Kaplan-Meier plotter was used for prognostic analysis. Immunohistochemistry assay and chi-square test were employed to explore the relationship between CAAP1 and platinum resistance in tissue samples. Lentivirus transfection, immunoprecipitation-mass spectrometry, and bioinformatics analysis were used to determine the potential biological function of CAAP1. Based on results, the expression level of CAAP1 was significantly higher in platinum-sensitive tissues compared to that in resistant tissues. Chi-square test demonstrated that there is a negative correlation between high expression of CAAP1 and platinum resistance. Overexpression of CAAP1 increased cis­platinum sensitivity of the A2780/DDP cell line likely via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. In summary, there is a negative correlation between high expression of CAAP1 and platinum resistance. CAAP1 might be a potential biomarker for platinum resistance in ovarian cancer. SIGNIFICANCE: Platinum resistance is a key factor affecting the survival of ovarian cancer patients. Understanding the mechanisms of platinum resistance is highly important for ovarian cancer management. Here, we performed the DIA- and DDA-based proteomics to analyze differentially expressed proteins in tissue and cell samples of ovarian cancer. We found that the protein identified as CAAP1, which was first reported to be involved in the regulation of apoptosis, may be negatively correlates with platinum resistance in ovarian cancer. In addition, we also found that CAAP1 enhanced the sensitivity of platinum-resistant cells to cis­platinum via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. Our data would be useful to reveal novel molecular mechanisms of platinum resistance in ovarian cancer.

Resistance prediction in high-grade serous ovarian carcinoma with neoadjuvant chemotherapy using data-independent acquisition proteomics and an ovary-specific spectral library.

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5-year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced-stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high-quality ovary-specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan-human spectral library (DPHL), this spectral library provides 10% more ovary-specific and 3% more ovary-enriched proteins. This library was then applied to analyze data-independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six-protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log-rank test, P = 0.002). The classifier was validated with 57 patients from an independent clinical center (P = 0.014). Thus, we have developed an ovary-specific spectral library for targeted proteome analysis, and propose a six-protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT-IDS treatment.

Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation.

BACKGROUND: Cisplatin-based chemotherapy often results in ovarian cancer (OC) chemical resistance and treatment failure. The combination of natural compounds with platinum-based agents is a new strategy for overcoming cisplatin resistance. At present, the synergistic effects and mechanism of combination of shikonin and cisplatin to overcome cisplatin resistance in OC are still unknown. PURPOSE: This study was to evaluate the synergistic effects of shikonin and cisplatin on cisplatin-resistant OC cells and to assess the underlying molecular basis for these effects. METHODS: Cell counting kit-8 assay, colony-formation assay, proteomic analysis, reactive oxygen species (ROS) detection, lipid peroxidation (LPO) detection, Fe2+ detection, western blot, and quantitative real-time reverse transcription PCR (qRT-PCR) were performed to evaluate the effects of shikonin and cisplatin on cisplatin-resistant OC cells. Underlying mechanisms of action were investigated in vitro using small molecule inhibitors and siRNA. In vivo, the effect of shikonin and cisplatin combination on tumor growth in BALB/c nude mice was evaluated, with tumor immunohistochemical (IHC) staining performed to detect ferroptosis-related proteins. RESULTS: In vitro, shikonin and cisplatin were shown to synergistically reduce the viability of cisplatin-resistant OC cells. Proteomic results demonstrated that the combination of the two drugs induced a ferroptotic process, as evidenced by increased levels of ROS, LPO, and Fe2+, with downregulation of glutathione peroxidase 4 (GPX4). Heme oxygenase 1 (HMOX1) inhibition and siRNA interference attenuated the combined effect of the two drugs on cell viability. Accumulation of Fe2+ was attenuated by siRNA interference of HMOX1. In vivo, combination treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice and increased the expression of ferroptosis-related proteins in tumor tissue. CONCLUSION: We report for the first time that the co-treatment of shikonin and cisplatin overcomes cisplatin resistance in OC through ferroptosis. Mechanistic analysis reveals the co-treatment induces ferroptosis through upregulation of HMOX1 that promotes Fe2+ accumulation.

The proteomics and metabolomics studies of GZU001 on promoting the Merisis of maize (Zea mays L.) roots.

BACKGROUND: Plant growth regulators are chemicals that regulate plant growth and development, which can regulate hormonal balance and affect plant growth, thereby increasing crop yield and improving crop quality. Our studies have revealed a new compound, GZU001, which could be used as a plant growth regulator. This compound has been observed to affect root elongation in maize significantly. However, the exact mechanism of this phenomenon is still being investigated. RESULTS: Metabolomics and proteomics were used in unison in this study to explore the response pathway and regulation mechanism of GZU001 in promoting maize root elongation. From the appearance, we can see that both roots and plants of maize treated with GZU001 are significantly improved. Maize root metabolism revealed 101 differentially abundant proteins and 79 differentially expressed metabolites. The current study identified altered proteins and metabolites associated with physiological and biochemical processes. GZU001 treatment has been demonstrated to promote primary metabolism, essential for carbohydrates, amino acids, energy, and secondary metabolism. The result suggests that the stimulation of primary metabolism is beneficial for the growth and development of maize and plays a significant role in sustaining metabolism and growth. CONCLUSIONS: This study recorded the changes of related proteins and metabolites in maize roots after GZU001 treatment and provided evidence for this compound's action mode and mechanism in plants.

Sustainable alginate lyases catalyzed degradation of bio-based carbohydrates.

Alginate is a water-soluble and acidic polysaccharide derived from the cell wall and intercellular substance of brown algae. It is widely distributed in brown algae, such as Laminaria, Sargassum, and Macrocystis, etc. Alginate lyase can catalytically degrade alginate in a ß-eliminating manner, and its degradation product-alginate oligosaccharide (AOS) has been widely used in agriculture, medicine, cosmetics and other fields due to its wide range of biological activities. This article is mainly to make a brief introduction to the classification, source and application of alginate lyase. We hope this minireview can provide some inspirations for its development and utilization.

Genome Analysis of a Novel Polysaccharide-Degrading Bacterium Paenibacillus algicola and Determination of Alginate Lyases.

Carbohydrate-active enzymes (CAZymes) are an important characteristic of bacteria in marine systems. We herein describe the CAZymes of Paenibacillus algicola HB172198T, a novel type species isolated from brown algae in Qishui Bay, Hainan, China. The genome of strain HB172198T is a 4,475,055 bp circular chromosome with an average GC content of 51.2%. Analysis of the nucleotide sequences of the predicted genes shows that strain HB172198T encodes 191 CAZymes. Abundant putative enzymes involved in the degradation of polysaccharides were identified, such as alginate lyase, agarase, carrageenase, xanthanase, xylanase, amylases, cellulase, chitinase, fucosidase and glucanase. Four of the putative polysaccharide lyases from families 7, 15 and 38 were involved in alginate degradation. The alginate lyases of strain HB172198T exhibited the maximum activity 152 U/mL at 50 °C and pH 8.0, and were relatively stable at pH 7.0 and temperatures lower than 40 °C. The average degree of polymerization (DP) of the sodium alginate oligosaccharide (AOS) degraded by the partially purified alginate lyases remained around 14.2, and the thin layer chromatography (TCL) analysis indicated that it contained DP2-DP8 oligosaccharides. The complete genome sequence of P. algicola HB172198T will enrich our knowledge of the mechanism of polysaccharide lyase production and provide insights into its potential applications in the degradation of polysaccharides such as alginate.

Design, synthesis, and bioactivity of ferulic acid derivatives containing an ß-amino alcohol.

BACKGROUND: Plant diseases caused by viruses and bacteria cause huge economic losses due to the lack of effective control agents. New potential pesticides can be discovered through biomimetic synthesis and structural modification of natural products. A series of ferulic acid derivatives containing an ß-amino alcohol were designed and synthesized, and their biological activities were evaluated. RESULT: Bioassays results showed that the EC50 values of compound D24 against Xanthomonas oryzae pv. oryzae (Xoo) was 14.5 µg/mL, which was better than that of bismerthiazol (BT, EC50 = 16.2 µg/mL) and thiodiazole copper (TC, EC50 = 44.5 µg/mL). The in vivo curative and protective activities of compound D24 against Xoo were 50.5% and 50.1%, respectively. The inactivation activities of compounds D2, D3 and D4 against tobacco mosaic virus (TMV) at 500 µg/mL were 89.1, 93.7 and 89.5%, respectively, superior to ningnanmycin (93.2%) and ribavirin (73.5%). In particular, the EC50 value of compound D3 was 38.1 µg/mL, and its molecular docking results showed that compound D3 had a strong affinity for TMV-CP with a binding energy of - 7.54 kcal/mol, which was superior to that of ningnanmycin (- 6.88 kcal /mol). CONCLUSIONS: The preliminary mechanism research results indicated that compound D3 may disrupt the three-dimensional structure of the TMV coat protein, making TMV particles unable to self-assemble, which may provide potential lead compounds for the discovery of novel plant antiviral agents.

Trifluoromethylpyridine: An Important Active Fragment for the Discovery of New Pesticides.

Trifluoromethylpyridine (TFMP) is a biologically active fragment formed by connecting trifluoromethyl and pyridine ring. As a result of its unique physical and chemical properties and outstanding biological activity, a variety of pesticide compounds with the TFMP fragment have been discovered and marketed and have played important roles in crop protection research. It is therefore a timely and valuable task to summarize the rationality on how to create new molecules containing TFMP fragments based on the structure-activity relationships, design mentality, and potential mechanism. This review gives a brief summary on the pesticides containing TFMP fragments in the past 5 years and introduces the latest progress of our group in this field. The aim is to provide readers with a convenient route to touch this topic and hopefully serve some educational purpose for graduate students as well.

1,3,4-Oxadiazole Contained Sesquiterpene Derivatives: Synthesis and Microbiocidal Activity for Plant Disease.

A series of 1,3,4-oxadiazole contained sesquiterpene derivatives were synthesized, and the activity of the target compounds against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and tobacco mosaic virus (TMV) were evaluated. The biological activity results showed that the EC50 values of compounds H4, H8, H11, H12, H14, H16, and H19 for Xac inhibitory activity were 33.3, 42.7, 56.1, 74.5, 37.8, 43.8, and 38.4 µg/ml, respectively. Compounds H4, H8, H15, H19, H22, and H23 had inhibitory effects on Xoo, with EC50 values of 51.0, 43.3, 43.4, 50.5, 74.6, and 51.4 µg/ml, respectively. In particular, the curative and protective activities of compound H8 against Xoo in vivo were 51.9 and 49.3%, respectively. In addition, the EC50 values of the inactivation activity of compounds H4, H5, H9, H10, and H16 against TMV were 69.6, 58.9, 69.4, 43.9, and 60.5 µg/ml, respectively. The results of molecular docking indicated that compound H10 exhibited a strong affinity for TMV-coat protein, with a binding energy of -8.88 kcal/mol. It may inhibit the self-assembly and replication of TMV particles and have an anti-TMV effect, which supports its potential usefulness as an antiviral agent.

Oxyfluorfen induces hepatotoxicity through lipo-sugar accumulation and inflammation in zebrafish (Danio rerio).

Oxyfluorfen (OXY) is widely used in agriculture as a herbicide, resulting in its continuous accumulation in the environment. The presence of OXY can be detected in soil and rivers. However, until now, the potential toxicity of OXY to aquatic organisms has not been evaluated. In this study, zebrafish was used as a model animal to evaluate OXY-induced liver toxicity. The study found that 0.25, 0.5, and 1 mg/L of OXY affected the early development of zebrafish and severely damaged the lipid and sugar metabolism in the liver of zebrafish larvae. Furthermore, a metabolic function disorder caused liver damage. OXY also caused inflammation by upregulating the inflammatory factors IL-6, IL-8, and TNF-α, and activated the apoptotic pathway to inhibit hepatocyte proliferation, resulting in zebrafish liver toxicity. Our research showed that OXY had certain toxic effects on zebrafish development and liver and could cause potential harm to other aquatic organisms and humans.

Epidural esketamine and morphine for postoperative analgesia after caesarean delivery: A pilot study.

Objective: The aim of this study was to determine whether the addition of esketamine to morphine would improve postoperative analgesia after cesarean section. Methods: Parturients who planned for a cesarean delivery using combined spinal-epidural anesthesia with a request for postoperative anesthesia were randomly divided into four groups (A, B, C, and D). When the surgery was completed, the parturients in groups A, B, C, and D were administered 2 mg morphine, 0.25 mg/kg of esketamine, 0.25 mg/kg of esketamine plus 2 mg morphine hydrochloride, and 0.25 mg/kg of esketamine plus 1 mg morphine through the epidural catheters, respectively. The postoperative pain at rest, pain with movement, the number of rescue analgesics, and adverse effects were evaluated for 48 h after cesarean delivery. Results: A total of 119 parturients were included in this study, including 30 cases in group A, 30 cases in group B, 30 cases in group C, and 29 cases in group D. All visual analog scale (VAS) scores at rest and with movement were much lower in group C as compared with those in group A and group B (P < 0.05). Moreover, VAS scores at rest were also lower in Group C than in group D for 24 h (P < 0.05). Corresponding to the low pain scores, parturients in group C also required less rescue analgesia as compared with the other three groups (P = 0.021 for C vs. A, P < 0.001 for C vs. B, and P < 0.001 for C vs. D). There were no statistically significant differences between the four study groups with regard to the incidence of adverse events (P > 0.05). Conclusions: The addition of esketamine to morphine improved postoperative analgesia after cesarean section without increasing the incidence of adverse events.

Hydrazone modification of non-food natural product sclareolide as potential agents for plant disease.

Plant diseases and their drug resistance pose a serious threat to agricultural production. One way to solve this problem is to discover new and efficient botanical pesticides. Herein, a series of novel hydrazide-hydrazone-containing sesquiterpenoid derivatives were synthesized by simply modifying the structure of the non-food natural product sclareolide. The biological activity results illustrated that compared to ningnanmycin (39.2 µg/mL), compound Z28 had the highest antiviral activity against tobacco mosaic virus (TMV), and the concentration for 50% of maximal effect (EC50) of its inactivation activity was 38.7 µg/mL, followed by compound Z14 (40.6 µg/mL). Transmission electron microscopy (TEM) demonstrated that TMVs treated with compounds Z14 and Z28 were broken into rods of different lengths, and their external morphology was fragmented or even severely fragmented. Autodocking and molecular dynamics (MD) simulations indicated that compound Z28 had a strong affinity for tobacco mosaic virus coat protein (TMV-CP), with a higher binding energy of -8.25 kcal/mol compared to ningnanmycin (-6.79 kcal/mol). The preliminary mechanism revealed that compound Z28 can achieve an antiviral effect by targeting TMV-CP, rendering TMV unable to self-assemble and replicate, and might be a candidate for a novel plant antiviral agent. Furthermore, the curative and protective activities of compound Z22 (EC50 = 16.1 µg/mL) against rice bacterial blight were 51.3% and 50.8%, respectively. Its control effect was better than that of bismerthiazol (BT) and thiadiazole copper (TC), compound Z22 that can be optimized as an active molecule.