Identification and Simultaneous Determination of the Main Toxical Pyrrolizidine Alkaloids in a Compound Prescription of Traditional Chinese Medicine: Qianbai Biyan Tablet

Qianbai biyan tablet (QT) is a compound prescription of traditional Chinese medicine which is used to treat nasal congestion, rhinitis, and nasosinusitis, with Senecio scandens as its main plant material. Several pyrrolizidine alkaloids (PAs) were reported in Senecio scandens and others of Senecio species. Although Senecio scandens is assigned as the legal plant material of QT, whether replaced use of it by other Senecio plants can bring toxicity is unknown because of the lack of quantitative data about toxic PAs between different Senecio species. In the present study, adonifoline, senkirkine, and another PA presumed as emiline have been identified in QT; however, there was no senecionine detected in all tablets. PA contents in QTs varied in different companies and different batches. Adonifoline existed only in Senecio scandens, and senecionine was detected in all eight Senecio plants investigated in the present study. Data showed that replaced use of Senecio scandens with a low level of senecionine by other Senecio plants such as Senecio vulgaris containing a high level of senecionine is advertised to be forbidden. Data of the present study may be used as a reference to make new drug quality regularity and recommendation guideline for the safety of QT

Diffusion-weighted imaging lesions after endovascular treatment of cerebral aneurysms: A network meta-analysis

BackgroundThromboembolism is one of the common complications in endovascular treatments including coiling alone, stent-assisted coiling (SAC), balloon-assisted coiling (BAC), and flow-diverting (FD) stents. Such treatments are widely used in intracranial aneurysms (IAs), which usually present as positive lesions in diffusion-weighted imaging (DWI). Whether these adjunctive techniques increase postprocedural DWI-positive lesions after endovascular treatment remains unclear.MethodsA thorough electronic search for the literature published in English between January 2000 and October 2022 was conducted on PubMed, Medline, and EMBASE. Eighteen studies (3 cohort studies and 15 case–control studies) involving 1,843 patients with unruptured IAs (UIAs) were included. We performed a frequentist framework network meta-analysis (NMA) to compare the rank risks of cerebral thromboembolism of the above four endovascular treatments. The incoherence test was used to analyze the statistical disagreement between direct and indirect evidence. Funnel plots were used to analyze publication bias.ResultsThe incidences of DWI lesions in patients who received FD stents, SAC, BAC, and coiling alone were 66.1% (109/165), 37.6% (299/795), 31.1% (236/759), and 25.6% (236/921). The incidence of DWI lesions in patients who received FD stents was higher than that in patients who received SAC [OR: 2.40; 95% CI (1.15, 5.00), P < 0.05], BAC [OR: 2.62; 95% CI (1.19, 5.77), P < 0.05], or coiling alone [OR: 2.77; 95% CI (1.26, 6.07), P < 0.05]. The incoherence test showed preferable consistency in this NMA. No obvious publication bias was found in the funnel plot.ConclusionFD stent placement brings more ischemic lesions identified by DWI than any other procedures for patients with UIA. The characteristics of FD stents may result in a high incidence of DWI lesions

Screening of an individualized treatment strategy for an advanced gallbladder cancer using patient-derived tumor xenograft and organoid models

Gallbladder cancer is a highly aggressive malignancy with poor sensitivity to postoperative radiotherapy or chemotherapy; therefore, the development of individualized treatment strategies is paramount to improve patient outcomes. Both patient-derived tumor xenograft (PDX) and patient-derived tumor organoid (PDO) models derived from surgical specimens can better preserve the biological characteristics and heterogeneity of individual original tumors, display a unique advantage for individualized therapy and predicting clinical outcomes. In this study, PDX and PDO models of advanced gallbladder cancer were established, and the consistency of biological characteristics between them and primary patient samples was confirmed using pathological analysis and RNA-sequencing. Additionally, we tested the efficacy of chemotherapeutic drugs, targeted drugs, and immune checkpoint inhibitors using these two models. The results demonstrated that gemcitabine combined with cisplatin induced significant therapeutic effects. Furthermore, treatment with immune checkpoint inhibitors elicited promising responses in both the humanized mice and PDO immune models. Based on these results, gemcitabine combined with cisplatin was used for basic treatment, and immune checkpoint inhibitors were applied as a complementary intervention for gallbladder cancer. The patient responded well to treatment and exhibited a clearance of tumor foci. Our findings indicate that the combined use of PDO and PDX models can guide the clinical treatment course for gallbladder cancer patients to achieve individualized and effective treatment

A Magnetic Bead-Integrated Chip for the Large Scale Manufacture of Normalized esiRNAs

The chemically-synthesized siRNA duplex has become a powerful and widely used tool for RNAi loss-of-function studies, but suffers from a high off-target effect problem. Recently, endoribonulease-prepared siRNA (esiRNA) has been shown to be an attractive alternative due to its lower off-target effect and cost effectiveness. However, the current manufacturing method for esiRNA is complicated, mainly in regards to purification and normalization on a large-scale level. In this study, we present a magnetic bead-integrated chip that can immobilize amplification or transcription products on beads and accomplish transcription, digestion, normalization and purification in a robust and convenient manner. This chip is equipped to manufacture ready-to-use esiRNAs on a large-scale level. Silencing specificity and efficiency of these esiRNAs were validated at the transcriptional, translational and functional levels. Manufacture of several normalized esiRNAs in a single well, including those silencing PARP1 and BRCA1, was successfully achieved, and the esiRNAs were subsequently utilized to effectively investigate their synergistic effect on cell viability. A small esiRNA library targeting 68 tyrosine kinase genes was constructed for a loss-of-function study, and four genes were identified in regulating the migration capability of Hela cells. We believe that this approach provides a more robust and cost-effective choice for manufacturing esiRNAs than current approaches, and therefore these heterogeneous RNA strands may have utility in most intensive and extensive applications

Triptolide Inhibits the Proliferation of Prostate Cancer Cells and Down-Regulates SUMO-Specific Protease 1 Expression

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa

Multi-Objective Scheduling of Electric Vehicles in Smart Distribution Network

Due to the energy savings and environmental protection they provide, plug-in electric vehicles (PEVs) are increasing in number quickly. Rapid development of PEVs brings new opportunities and challenges to the electricity distribution network’s dispatching. A high number of uncoordinated charging PEVs has significant negative impacts on the secure and economic operation of a distribution network. In this paper, a bi-level programming approach that coordinates PEVs’ charging with the network load and electricity price of the open market is presented. The major objective of the upper level model is to minimize the total network costs and the deviation of electric vehicle aggregators’ charging power and the equivalent power. The subsequent objective of the lower level model after the upper level decision is to minimize the dispatching deviation of the sum of PEVs’ charging power and their optimization charging power under the upper level model. An improved particle swarm optimization algorithm is used to solve the bi-level programming. Numerical studies using a modified IEEE 69-bus distribution test system including six electric vehicle aggregators verify the efficiency of the proposed model

Parallel Computation for Inversion Algorithm of 2D ZTEM

ZTEM refers to the Z-axis tipper electromagnetic method. The ZTEM method is an airborne magnetotelluric sounding method based on the difference in rocks’ resistivity using the native electromagnetic field. The method is effective in exploring large-scale structures when the ground is fluctuant. The paper introduces the inversion algorithm of 2D ZTEM named the conjugate gradient method. This method, which avoids solving the Jacobi matrix, is very effective but not effective enough when the model is divided into a big grid. This study can perform further computation using parallel computation and then receive the processed data. We compare the results of the serial algorithm with the result of the parallel algorithm, which proves that the parallel algorithm is correct. When the number of processes is between three and six, the speedup ratio is between 1.74 and 3.19. It improves the effectiveness of the parallel algorithm of 2D ZTEM