Wrecking neutrophil extracellular traps and antagonizing cancer-associated neurotransmitters by interpenetrating network hydrogels prevent postsurgical cancer relapse and metastases.

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective ß-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

Associated factors leading to misdiagnosis of a combined diagnostic model of different types of strain imaging and conventional ultrasound in evaluation of breast lesions: Selection strategy for using different types of strain imaging in evaluation of breast lesions.

OBJECTIVE: To evaluate the effectiveness of a decision tree that integrates conventional ultrasound (CUS) with two different strain imaging (SI) techniques for diagnosing breast lesions, and to analyze the factors contributing to false negative (FN) and false positive (FP) in the decision tree's outcomes. MATERIALS AND METHODS: Imaging and clinical data of 796 cases in the training set and 351 cases in the validation set were prospectively collected. A decision tree model that combines two types of SI and CUS was constructed, and its diagnostic performance was analyzed. Univariate analysis and multivariate analysis were applied to identify independent risk factors associated with FP and FN results of the decision tree model. RESULTS: Size, shape, margin, vascularity, the types of internal calcifications, EI score and VTI pattern were found to be significantly independently associated with the diagnosis of benign and malignant breast lesions. Therefore, size, shape, margin, vascularity, EI score and VTI pattern were used to construct decision tree models. The Tree (EI+VTI) model had the highest AUC. Both in the training and validation groups, the AUC of Tree (EI+VTI) was significantly higher compared with that of EI, VTI, and BI-RADS (all, P < 0.05). Orientation, posterior acoustic features and the types of internal calcifications were significantly positively associated with misdiagnosis results of Tree (EI+VTI) in evaluation of breast lesions (all P < 0.05). CONCLUSION: The diagnostic model based on a decision tree that integrates two distinct types of SI with CUS enhances the diagnostic accuracy of each method when used individually. This integration lowers the misdiagnosis rate, potentially assisting radiologists in more effective lesion assessments. When applying the decision tree model, attention should be paid to the orientation, posterior acoustic features, and the types of internal calcifications of the lesions.

Antitumor effects of Cypaliuruside F from Cyclocarya paliurus on HepG2 cells.

An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.

Identification of a prognosis-related gene signature and ceRNA regulatory networks in lung adenocarcinoma.

The ceRNA network, consisting of both noncoding RNA and protein-coding RNA, governs the occurrence, progression, metastasis, and infiltration of lung adenocarcinoma. Signatures comprising multiple genes can effectively determine survival stratification and prognosis of patients with lung adenocarcinoma. To explore the mechanisms of lung adenocarcinoma progression and identify potential biological targets, we carried out systematic bioinformatics analyses of the genetic profiles of lung adenocarcinoma, such as weighted gene co-expression network analysis (WGCNA), differential expression (DE) assessment, univariate and multivariate Cox proportional hazard regression models, ceRNA modulatory networks generated using the ENCORI and miRcode databases, nomogram models, ROC curve assessment, and Kaplan-Meier survival curve analysis. The ceRNA network encompassed 37 nodes, comprising 12 mRNAs, 22 lncRNAs, and three miRNAs. Simultaneously, we performed integration analysis using the 12 genes from the ceRNA network. Our findings revealed that the signature established by these 12 genes serves as an adverse element in lung adenocarcinoma, contributing to unfavorable patient prognosis. To ensure the credibility of our results, we used in vitro experiments for further verification. In conclusion, our study delved into the potential mechanisms underlying lung adenocarcinoma via the ceRNA regulatory network, specifically focusing on the PIF1 and has-miR-125a-5p axis. Additionally, a signature comprising 12 genes was identified as a biomarker related to the prognosis of lung adenocarcinoma.

A Model Combining Conventional Ultrasound Characteristics, Strain Elastography and Clinicopathological Features to Predict Ki-67 Expression in Small Breast Cancer.

To establish a predictive model incorporating conventional ultrasound, strain elastography and clinicopathological features for Ki-67 expression in small breast cancer (SBC) which defined as maximum diameter less than2 cm. In this retrospective study, 165 SBC patients from our hospital were allocated to a high Ki-67 group (n = 104) and a low Ki-67 group (n = 61). Multivariate regression analysis was performed to identify independent indicators for developing predictive models. The area under the receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff value were compared. Conventional ultrasound parameters (spiculated margin, absence of posterior shadowing and Adler grade 2-3), strain elastic scores and clinicopathological information (HER2 positive) were significantly correlated with high expression of Ki-67 in SBC (all p < .05). Model 2, which incorporated conventional ultrasound features and strain elastic scores, yielded good diagnostic performance (AUC = 0.774) with better sensitivity than model 1, which only incorporated ultrasound characteristics (78.85%vs. 55.77%, p = .000), with specificities of 77.05% and 62.30% (p = .035), respectively. Model 3, which incorporated conventional ultrasound, strain elastography and clinicopathological features, yielded better performance (AUC = 0.853) than model 1 (AUC = 0.694) and model 2 (AUC = 0.774), and the specificity was higher than model 1 (86.89% vs. 77.05%, p = .001). The predictive model combining conventional ultrasound, strain elastic scores and clinicopathological features could improve the predictive performance of Ki-67 expression in SBC.

A nomogram based on multimodal ultrasound and clinical features for the prediction of central lymph node metastasis in unifocal papillary thyroid carcinoma.

OBJECTIVES: To build a predictive model for central lymph node metastasis (CLNM) in unifocal papillary thyroid carcinoma (UPTC) using a combination of clinical features and multimodal ultrasound (MUS). METHODS: This retrospective study, included 390 UPTC patients who underwent MUS between January 2017 and October 2022 and were divided into a training cohort (n = 300) and a validation cohort (n = 90) based on a cut-off date of June 2022. Independent indicators for constructing the predictive nomogram models were identified using multivariate regression analysis. The diagnostic yield of the 3 predictive models was also assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Both clinical factors (age, diameter) and MUS findings (microcalcification, virtual touch imaging score, maximal value of virtual touch tissue imaging and quantification) were significantly associated with the presence of CLNM in the training cohort (all P < .05). A predictive model (MUS + Clin), incorporating both clinical and MUS characteristics, demonstrated favourable diagnostic accuracy in both the training cohort (AUC = 0.80) and the validation cohort (AUC = 0.77). The MUS + Clin model exhibited superior predictive performance in terms of AUCs over the other models (training cohort 0.80 vs 0.72, validation cohort 0.77 vs 0.65, P < .01). In the validation cohort, the MUS + Clin model exhibited higher sensitivity compared to the CLNM model for ultrasound diagnosis (81.2% vs 21.6%, P < .001), while maintaining comparable specificity to the Clin model alone (62.3% vs 47.2%, P = .06). The MUS + Clin model demonstrated good calibration and clinical utility across both cohorts. CONCLUSION: Our nomogram combining non-invasive features, including MUS and clinical characteristics, could be a reliable preoperative tool to predict CLNM treatment of UPTC. ADVANCES IN KNOWLEDGE: Our study established a nomogram based on MUS and clinical features for predicting CLNM in UPTC, facilitating informed preoperative clinical management and diagnosis.

lncRNA FAS-AS1 served as a diagnostic biomarker of end-stage renal disease and mediated vascular calcification via regulating oxidative stress and inflammation.

PURPOSE: Vascular calcification is a frequently occurring complication of end-stage renal disease (ESRD). This study focused on the significance of long non-coding RNA Fas cell surface death receptor-antisense 1(lncRNA FAS-AS1) in ESRD-related vascular calcification aiming to explore a potential biomarker for the detection. METHODS: The study enrolled 65 healthy individuals, 79 ESRD patients (48 patients with vascular calcification), and 93 early-stage (I-IV) chronic kidney disease (CKD) patients. The expression of FAS-AS1 in serum was evaluated by real-time quantitative polymerase chain reaction (PCR). The diagnostic potential of FAS-AS1 was assessed in discriminating ESRD patients, vascular calcification, and the severity of vascular calcification. In vitro, the vascular smooth muscle cells (VSMCs) were treated with a hyperphosphatemia medium to evaluate the effect of FAS-AS1 on VSMCs calcification. RESULTS: Elevated serum FAS-AS1 was observed in ESRD patients, which could discriminate from healthy individuals and early-stage CKD patients. FAS-AS1 was associated with the development of ESRD and the occurrence of vascular calcification. FAS-AS1 was also upregulated in vascular calcification patients, especially the patients with severe calcification, which showed diagnostic significance in evaluating vascular calcification degrees. Calcified VSMCs showed significantly increased levels of Ca2+, reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), which was attenuated by silencing FAS-AS1. CONCLUSIONS: FAS-AS1 discriminated ERSD patients and was associated with the occurrence of vascular calcification. The knockdown of FAS-AS1 suppressed hyperphosphatemia-induced vascular calcification via alleviating oxidative stress and inflammation.

Penicimides A and B, two novel diels-alder [4 + 2] cycloaddition ergosteroids from Penicillium herquei.

Two novel naturally occurring [4 + 2] Diels-Alder cycloaddition ergosteroids (1 and 2), three undescribed oxidized ergosteroids (3-5), and eleven known analogs (6-16) were isolated from Penicillium herquei. Compounds 1 and 2 represent the first reported cycloadducts of a steroid with 1,4,6-trimethyl-1,6-dihydropyridine-2,5-dione or 4,6-dimethyl-1,6-dihydropyridine-2,5-dione to date. Compound 3 is the C-15 epimer of (22E,24R)-9α,11ß-dihydroxyergosta-4,6,8(14),22-tetraen-3-one (14). The chemical structures of these compounds were elucidated through widespread spectroscopic analyses, mainly including HRESIMS and 1D and 2D NMR data, calculated 13C NMR-DP4+ analysis, and electronic circular dichroism (ECD) data analyses. Biological evaluations of Compounds 1-16 revealed that 3, 9-11, and 15 inhibited the production of NO in LPS-induced RAW264.7 cells with an IC50 value from 7.37 ± 0.69 to 38.9 ± 2.25 µM (the positive control dexamethasone IC50: 9.54 ± 0.71 µM). In addition, Compound 3 exhibited a potent inhibitory effect on the secretion of the proinflammatory cytokines TNF-α and IL-6, the transcription level of the proinflammatory macrophage markers TNF-α, and the expression of the iNOS protein.

Value of Intrauterine Autologous Platelet-Rich Plasma Therapy on Endometrial Receptivity: A Literature Review.

Endometrial receptivity is an important factor that influences embryo implantation. Thus, it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology. Recently, growing evidence has indicated that intrauterine platelet-rich plasma (PRP) infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity. Therefore, the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.

SDA-Net: Self-distillation driven deformable attentive aggregation network for thyroid nodule identification in ultrasound images.

Early detection and accurate identification of thyroid nodules are the major challenges in controlling and treating thyroid cancer that can be difficult even for expert physicians. Currently, many computer-aided diagnosis (CAD) systems have been developed to assist this clinical process. However, most of these systems are unable to well capture geometrically diverse thyroid nodule representations from ultrasound images with subtle and various characteristic differences, resulting in suboptimal diagnosis and lack of clinical interpretability, which may affect their credibility in the clinic. In this context, a novel end-to-end network equipped with a deformable attention network and a distillation-driven interaction aggregation module (DIAM) is developed for thyroid nodule identification. The deformable attention network learns to identify discriminative features of nodules under the guidance of the deformable attention module (DAM) and an online class activation mapping (CAM) mechanism and suggests the location of diagnostic features to provide interpretable predictions. DIAM is designed to take advantage of the complementarities of adjacent layers, thus enhancing the representation capabilities of aggregated features; driven by an efficient self-distillation mechanism, the identification process is complemented with more multi-scale semantic information to calibrate the diagnosis results. Experimental results on a large dataset with varying nodule appearances show that the proposed network can achieve competitive performance in nodule diagnosis and provide interpretability suitable for clinical needs.

Risk of second primary cancers in patients with rectal neuroendocrine neoplasms: a surveillance, epidemiology, and end results analysis.

Background: While an elevated risk of second primary cancers (SPCs) has been observed in many other cancers, risk of SPCs has not been quantified in patients with rectal neuroendocrine neoplasms (NENs). Methods: Survivors of primary rectal NENs diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER)-18 registries. Relative risk of SPCs was estimated as the standardized incidence ratio (SIR), which was calculated using SEER*Stat software. Results: Between 2000 and 2018, a total of 15836 patients diagnosed with rectal NENs, of whom 1436 (9.1%) received diagnosis of SPCs (SIR: 1.19, 95%CI: 1.13-1.26). The majority of patients were aged 50-69 and had their first cancer diagnosed at the localized stage. Male survivors had a higher propensity for developing SPCs overall, while female survivors exhibited higher risks of specific SPCs. Age at diagnosis of rectal NENs influenced the risk of SPCs, with younger patients having greater risks. A statistically significant increase in the incidence of SPCs was observed among patients aged 30-64 years. Black patients had higher relative risks of certain SPCs, while White patients had a lower risk of subsequent melanoma. Trend analysis revealed that the highest excess burden of SPCs was observed in the years 2000 to 2002. Risk of SPCs remained elevated within the first four years post-diagnosis for survivors of rectal NENs, but diminished thereafter. Conclusion: The study revealed that individuals who survived rectal NENs were at an elevated risk of developing SPCs compared to the general population. Our results hold important implications for the formulation of lifelong surveillance recommendations for cancer survivors.

A nomogram based on the risk factors of cervical lymph node metastasis in papillary thyroid carcinoma coexistent with Hashimoto's thyroiditis.

OBJECTIVE: The purpose of this study was to explore the risk factors of cervical lymph node metastasis(LNM) in papillary thyroid carcinoma(PTC) coexistent with Hashimoto's thyroiditis(HT). METHODS: The clinical data of patients who underwent thyroid operation between November 2016 and January 2020 in our hospital were analyzed retrospectively. The association between sonographic features and the risk factors of cervical LNM in PTC coexistent with HT was analyzed and a nomogram based on the risk factors was built. RESULTS: Age, US features as calcification, blood flow type, distance between thyroid nodule and fibrous capsule were risk factors of cervical LNM(P < 0.05).Size, SWVmax and SWVmean of thyroid nodule, SWVratio between thyroid nodule and thyroid gland were higher in PTCs with LNM than those without LNM(P < 0.05). The ROC curve showed that the cutoff value of SWVratio for predicting LNM was 1.29 (Sensitivity = 0.806, Specificity = 0.775, AUC = 0.823, P < 0.001). Based on the risk factors above, a relevant nomogram prediction model was established. The model verification showed that the C-index of the modeling set was 0.814, indicating that the nomogram model had good predicted accuracy. CONCLUSION: Based on the risk factors above, a relevant nomogram prediction model was established. The model verification showed that the C-index of the modeling set was 0.814, indicating that the nomogram model had good predicted accuracy. The nomogram based on the risk factors above had good prediction ability, which could optimize thyroidectomy and cervical lymph node dissection and improving prognosis.

Adenophorone, An Unprecedented Sesquiterpene from Eupatorium adenophorum: Structural Elucidation, Bioinspired Total Synthesis and Neuroprotective Activity Evaluation.

(-)-Adenophorone (1), a caged polycyclic sesquiterpene featuring an unprecedented tricyclo[4.3.1.05,9 ]decane skeleton, was isolated from Eupatorium adenopharum Spreng. The structure of 1 was unambiguously established by a combination of spectroscopic analysis, X-ray crystallography, and bioinspired total synthesis. Key synthetic features include a sequential Reformatsky/oxidation/regio- and stereoselective hydrogenation, and subsequent merged MBH-Tsuji-Trost cyclization. The concise synthetic sequence efficiently constructs the bicyclic skeleton of cadinene sesquiterpene (+)-euptox A (2) in 8 steps from commercially available monoterpene (-)-carvone (6), with outstanding performance on diastereocontrol. The bioinspired synthesis of 1 was achieved from 2, a plausible biogenetic precursor, via transannular Michael addition. This work provides experimental evidence of our proposed biosynthetic hypothesis of 1. Additionally, compound 1 showed potent neuroprotective activity in H2 O2 -treated SH-SY5Y and PC12 cells.

Diagnostic performance of endorectal ultrasound combined with shear wave elastography for rectal tumors staging.

OBJECTIVE: This study aims to analyze the performance of endorectal ultrasound (ERUS) combined with shear wave elastography (SWE) for rectal tumor staging. METHODS: Forty patients with rectal tumors who had surgery were enrolled. They underwent ERUS and SWE examinations before surgery. Pathological results were used as the gold standard for tumor staging. The stiffness values of the rectal tumor, peritumoral fat, distal normal intestinal wall, and distal perirectal fat were analyzed. The diagnostic accuracy of ERUS stage, tumor SWE stage, ERUS combined with tumor SWE stage, and ERUS combined with peritumoral fat SWE stage were compared and evaluated by receiver operating characteristic (ROC) curve to select the best staging index. RESULTS: From T1 to T3 stage, the maximum elasticity (Emax) of the rectal tumor increased gradually (p < 0.05). The cut-off values of adenoma/T1 and T2, T2 and T3 tumors were 36.75 and 85.15kPa, respectively. The diagnostic coincidence rate of tumor SWE stage was higher than that of ERUS stage. Overall diagnostic accuracy of ERUS combined with peritumoral fat SWE Emax restaging was significantly higher than that of ERUS. CONCLUSIONS: ERUS combined with peritumoral fat SWE Emax for tumor restaging can effectively distinguish between stage T2 and T3 rectal tumors, which provides an effective imaging basis for clinical decisions.

Nine undescribed oxidized ergosterols from the endophytic fungus Penicillium herquei and their cytotoxic activity.

A chemical investigation of the EtOAc extract of the endophytic fungus Penicillium herquei led to the isolation of nine undescribed oxidized ergosterols, penicisterols A-I (1-9), along with ten known analogs (10-19). Their structures and absolute configurations were elucidated by a combination of spectroscopic data analysis, quantum-chemical electronic circular dichroism (ECD) calculations and comparisons, [Rh2(OCOCF3)4]-induced ECD experiments, DFT-calculated 13C chemical shifts and DP4+ probability analysis. Compound 1 was a rare example of ergosterol in which the bond between C-8 and C-9 was cleaved to form an enol ether. Moreover, compound 2 possessed a rare (2,5-dioxo-4-imidazolidinyl)-carbamic acid ester group substituted at C-3. All undescribed oxidized ergosterols (1-9) were evaluated for their cytotoxic activity against five cancer cell lines including 4T1 (mouse breast carcinoma), A549 (human pulmonary carcinoma), HCT-116 (human colorectal carcinoma), HeLa (human cervical carcinoma) and Hepg2 (human hepatoma carcinoma) cells. Compounds 2 and 3 displayed moderate cytotoxic activity against 4T1, A549 and HeLa cells, with IC50 values ranging from 17.22 to 31.35 µM.

Combining serum AFP and CEUS LI-RADS for better diagnostic performance in Chinese high-risk patients.

PURPOSE: To evaluate and compare the diagnostic performance of revised contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System version by combining LR-M category and serum alpha-fetoprotein (AFP) under different cut-off values. MATERIAL AND METHODS: This retrospective study enrolled 152 high-risk patients with 152 histology-proven nodules. For revised LI-RADS, nodules in LR-M with different elevated AFP thresholds have been reclassified as the LR-5 category. The diagnostic performances of original and revised CEUS LI-RADS were evaluated and compared. RESULTS: To compare with the original version, the sensitivity of revised LR-5 (adjusted with AFP value > 200 ng/ml or 400 ng/ml) for the diagnosis of hepatocellular carcinoma (HCC) improved from 52.5 to 69.2% or 65.0%, respectively (both p < 0.001) without compromising specificity (87.5% vs. 71.9% or 78.1%, respectively, both p > 0.05). For the diagnosis of non-HCC malignancy, the specificity of the LR-M after reclassification was improved (69.6% vs. 84.4% or 80.7%, respectively, both p < 0.001) with a non-significant sensitivity reduction (100.0 vs. 70.6% or 82.4%, respectively, both p > 0.05). After modification, the sensitivity of LR-5 also increased to 69.1% or 64.9% (both p < 0.001), while the specificity and PPV did not change (both p > 0.05) for larger nodules (> 20 mm). CONCLUSION: The diagnostic performance of CEUS LI-RADS can be further improved by reclassifying LR-M nodules with elevated AFP thresholds to LR-5.

Compounds isolated from the pericarp of Zanthoxylum bungeanum and inhibitory activity against LPS-induced NO production in RAW264.7.

Seventeen compounds were isolated and identified from the ethyl acetate part of Zanthoxylum bungeanum Maxim., including one new compound 18-acetyloxyneocryptotanshinone (1) and 16 known compounds (2-17). Their structures were elucidated by extensive spectroscopy. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD). All compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, of which 1 and 10 exhibited the most significant inhibitory effect, with IC50 of 17.29 and 10.27 µM, respectively.

Palladium-Catalyzed Synthesis, Acetylcholinesterase Inhibition, and Neuroprotective Activities of N-Aryl Galantamine Analogues.

A series of new N-aryl galantamine analogues (5a-5x) were designed and synthesized by modification of galantamine, using Pd-catalyzed Buchwald-Hartwig cross-coupling reaction in good to excellent yields. The cholinesterase inhibitory and neuroprotective activities of N-aryl derivatives of galantamine were evaluated. Among the synthesized compounds, the 4-methoxylpyridine-galantamine derivative (5q) (IC50 = 0.19 µM) exhibited excellent acetylcholinesterase inhibition activity, as well as significant neuroprotective effect against H2O2-induced injury in SH-SY5Y cells. Molecular docking, staining, and Western blotting analyses were performed to demonstrate the mechanism of action of 5q. Derivative 5q would be a promising multifunctional lead compound for the treatment of Alzheimer's disease.

Compositions analysis and insecticidal activity of Aconitum polycarpum Chang ex W.T.Wang petroleum ether fractions and essential oils.

ETHNOPHARMACOLOGICAL RELEVANCE: The Aconitum genus plants as a natural pesticide for insecticide and rodent control has been recorded in Chinese folk. However, the insecticide effect, mechanism, and active composition of Aconitum polycarpum Chang ex W.T.Wang have not been studied further. AIM OF THE STUDY: This study was designed to analyze the chemical composition, evaluate contact toxicity of petroleum ether extracts (PEEs) and essential oils (EOs) of A. polycarpum, and further explore their possible insecticidal mechanism. MATERIALS AND METHODS: The roots of A. polycarpum were extracted with 90% methanol, and then extracted with petroleum ether to obtain PEEs; the EOs was extracted by distillation. The chemical compositions of PEEs and EOs were analyzed by GC-MS. Contact toxicity was evaluated by the immersion method. Exploring insecticidal mechanisms through in vitro enzyme inhibitory activity. RESULTS: 12 compounds were identified from PEEs by GC-MS, mainly including aliphatic (94.8%), the main compositions were Octadecadienol (ODO) (aliphatic, 53.2%) and L-Ascorbyl dipalmitate (LADP) (aliphatic, 36.1%). 24 compounds were identified in EOs. About 44.6% of the identified components were terpenoids and their derivatives, and the rest were mainly aliphatic (34.7%) and phenols (3.0%). The main chemical components were L (-)-Borneol (LB) (terpenoid, 28.3%), LADP (aliphatic, 19.1%), and Isoborneol (terpenoid, 9.1%). The contact toxicity indicated that the PEEs showed great contact toxicity against Spodoptera exigua (LC50 = 126.2 mg/L). Meanwhile, LADP (LC50 = 128.1 mg/L) and ODO (LC50 = 121.3 mg/L) was similar to that of Cyhalothrin (LC50 = 124.2 mg/L) in contact toxicity. In addition, we found that LADP and ODO exhibited excellent inhibitory activity against CarE (IC50 = 58.0, 56.1 mg/L, respectively) by measuring in vitro enzyme inhibitory activity, which was superior than Cyhalothrin (IC50 = 68.1 mg/L). CONCLUSIONS: The chemical compositions and contact toxicity of EOs and PEEs of A. polycarpum were analyzed and evaluated, and their insecticidal mechanisms were preliminarily discussed for the first time. It proved PEEs of A. polycarpum and its main components (LADP and ODO) exhibited excellent contact toxicity against S. exigua, and CarE was identified as a potential target for contact toxicity. This study indicated that the insecticidal activity of petroleum ether extracts from A. polycarpum is quite promising, and provides a practical and scientific basis for the development and application of botanical pesticides.

Synthesis, antiproliferative and anti-MDR activities of lathyrane diterpene derivatives based on configuration inversion strategy.

A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.