[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.

Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). We determined dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC), striatum, and nucleus accumbens (NAc) after drug treatment. DAT availability in the mPFC and NAc significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells were measured following drug treatment. After drug treatment, Spearman rank and Pearson correlation analyses showed a significant difference between the extracellular dopamine level and the ICSS threshold. After drug treatment, Spearman rank correlation analysis showed a significant correlation between Ca2+ signaling and the ICSS threshold. A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.

Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3ß signaling axis.

Psoriasis is a chronic, systemic immune-mediated disease caused by abnormal proliferation, decreased apoptosis, and over-differentiation of keratinocytes. The psoriatic skin lesions due to abnormal keratinocytes are closely associated with ROS produced by inflammatory cells. Peroxiredoxin II (Prx II) is an efficient antioxidant enzyme, which were highly expressed in skin tissues of psoriasis patient. However, the detailed mechanical functions of Prx II on psoriatic skin remain to be elucidated. Present study showed that depletion of Prx II results in alleviation of symptoms of IMQ-induced psoriasis in mice, but no significant differences in the amounts of serum inflammatory factors. Prx II-knockdown HaCaT cells were susceptible to H2O2-induced apoptosis mediated by Ca2+ release from the endoplasmic reticulum through 1,4,5-triphosphate receptors (IP3Rs), the PI3K/AKT pathway and phosphorylated GSK3ß (Ser9) were significant downregulated. Additionally, significantly reduced sensitivity of Prx II-knockdown HaCaT cells to apoptosis was evident post NAC, 2-APB, BAPTA-AM, SC79 and LiCl treated. These results suggest that Prx II regulated apoptosis of keratinocytes via the PI3K/AKT/GSK3ß signaling axis. Furthermore, treatment with the Prx II inhibitor Conoidin A significantly alleviated psoriatic symptoms in IMQ model mice. These findings have important implications for developing therapeutic strategies through regulate apoptosis of keratinocytes in psoriasis, and Prx II inhibitors may be exploited as a therapeutic drug to alleviate psoriatic symptoms.

[Research progress on processing historical evolution, chemical constituents, and pharmacological action of Bombyx Batryticatus].

Bombyx Batryticatus is a precious traditional Chinese animal drug commonly used in clinical practice in China, which has the effects of extinguishing wind, stopping convulsions, dispelling wind, relieving pain, resolving phlegm, and dissipating mass. The processing of Bombyx Batryticatus has a long history. As early as in the Liu Song period of the Southern and Northern Dynasties, there was a record of the processing of Bombyx Batryticatus with rice swill. In addition to the processing with bran, honey bran, and ginger juice, which are still used today, there are also processing methods such as rendering, flour processing, wine processing, salt processing, oil processing, charcoal, and red dates processing in ancient times. After processing, the fishy smell of Bombyx Batryticatus can be removed, and avoid nausea and vomiting caused by the direct taking. Furthermore, processing can also facilitate the removal of surface hairs and toxicity reduction, making the medicinal material crispy and easy to crush. Previous studies have shown that the main chemical constituents of Bombyx Batryticatus include protein polypeptides, sterols, and flavonoids, with anticonvulsant, anticoagulation, antithrombotic, anti-cancer, hypnotic, hypoglycemic, and other pharmacological effects. This paper reviewed the processing historical evolution, chemical constituents, and pharmacological effects of Bombyx Batryticatus to lay a foundation for the research on the processing mechanism, quality control, and active core substances of Bombyx Batryticatus.

Automatic sleep staging of single-channel EEG based on domain adversarial neural networks and domain self-attention.

The diagnosis and management of sleep problems depend heavily on sleep staging. For autonomous sleep staging, many data-driven deep learning models have been presented by trying to construct a large-labeled auxiliary sleep dataset and test it by electroencephalograms on different subjects. These approaches suffer a significant setback cause it assumes the training and test data come from the same or similar distribution. However, this is almost impossible in scenario cross-dataset due to inherent domain shift between domains. Unsupervised domain adaption was recently created to address the domain shift issue. However, only a few customized UDA solutions for sleep staging due to two limitations in previous UDA methods. First, the domain classifier does not consider boundaries between classes. Second, they depend on a shared model to align the domain that could miss the information of domains when extracting features. Given those restrictions, we present a novel UDA approach that combines category decision boundaries and domain discriminator to align the distributions of source and target domains. Also, to keep the domain-specific features, we create an unshared attention method. In addition, we investigated effective data augmentation in cross-dataset sleep scenarios. The experimental results on three datasets validate the efficacy of our approach and show that the proposed method is superior to state-of-the-art UDA methods on accuracy and MF1-Score.

Identification and analysis of miRNAs differentially expressed in male and female Trichosanthes kirilowii maxim.

Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae family of which different sexes have separate medicinal uses. We used Illumina high-throughput sequencing technology to sequence miRNAs from male and female flower buds of TK. We performed bioinformatics analysis, miRNA identification, and target gene prediction on the data obtained from sequencing, and association analysis was performed in combination with the results of a previous transcriptome sequencing study. As a result, there were 80 differentially expressed miRNAs (DESs) between the female and male plants (48 upregulated and 32 downregulated in female plants). Moreover, 27 novel miRNAs in DESs were predicted to have 282 target genes, and 51 known miRNAs were predicted to have 3418 target genes. By establishing a regulatory network between miRNAs and target genes, 12 core genes were screened, including 7 miRNAs and 5 target genes. Among them, tkmiR157a-5p, tkmiR156c, tkmiR156_2, and tkmiR156k_2 jointly target the regulation of tkSPL18 and tkSPL13B. These two target genes are specifically expressed in male and female plants, respectively, and are involved in the biosynthesis process of BR, which is closely related to the sex differentiation process of TK. The identification of these miRNAs will provide a reference for the analysis of the sex differentiation mechanism of TK.

Two new constituents from the aerial parts of Salvia miltiorrhiza Bge.

Two new constituents: a neolignan, salignan A (1) and a phenolic acid, salside A (2), along with two known compounds (3, 4) have been isolated from the aerial parts of Salvia miltiorrhiza Bge. All structures were assigned on the basis of detailed spectroscopic analyses. The absolute configuration of 1 was characterised by electronic circular dichroism (ECD) spectroscopy. Compounds 1 and 3 exhibited moderate inhibitory effects on nitric oxide (NO) production in LPS-induced RAW264.7 cells, and the IC50 values are 11.58 and 10.73 µM, respectively. Compound 4 displayed moderate antioxidant activity to scavenge DPPH and ABTS radicals, and the IC50 values are 7.96 and 1.10 µM, respectively.

[Research progress on processing history evolution, chemical constituents, and pharmacological effects of Hirudo].

As a traditional animal drug, Hirudo is slightly toxic and has the effects of breaking blood stasis, dredging meridians, expelling stasis, and resolving mass. It has a long history of processing, and the early boiling records can be traced back to the Han Dynasty. More than ten processing methods such as frying, roasting, and lime processing appeared later. After processing, Hirudo is deodorized and modified in taste and becomes crispy, which is conducive to crushing and clinical application. At present, the reported components in Hirudo mainly include protein polypeptides, pteridines, and lipids, which have anti-coagulant, anti-thrombotic, anti-atherosclerotic, anti-tumor, and other pharmacological effects. This study reviewed the processing history evolution, chemical consti-tuents, and pharmacological effects of Hirudo to provide a reference for the related research on Hirudo.

The interaction effect of grip strength and lung function (especially FVC) on cardiovascular diseases: a prospective cohort study in Jiangsu Province, China.

OBJECTIVE: Lung function and grip strength (GS) are associated with cardiovascular disease (CVD), but whether these risk factors interact to affect CVD is unknown. This study aimed to explore the interactions between lung function and GS with major CVD (defined as fatal/non-fatal myocardial infarction, stroke, and heart failure) incidence. METHODS: We conducted a prospective cohort study on the Chinese population in Jiangsu Province. Cox proportional hazards models were used to explore the associations between GS, lung function, and major CVD incidence. RESULTS: A total of 5967 participants were included in our study; among them, 182 participants developed major CVD. Participants with low forced vital capacity (FVC) had a higher risk of major CVD (hazard ratio (HR) = 1.45; 95% confidence interval (CI): 1.05-2.01; P < 0.05) compared with normal FVC. The risk of major CVD incidence (HR = 0.54; 95% CI: 0.35-0.83; P < 0.01) was significantly lower in participants with high GS than in individuals with low GS. The interaction between FVC and GS for major CVD incidence (P = 0.006) was statistically significant. Compared with normal FVC participants with high GS, low FVC participants with low GS had the highest risk of major CVD incidence (HR = 2.50; 95% CI: 1.43-4.36; P < 0.01). CONCLUSION: Among people with low FVC, the risk of major CVD is lower with high GS. Participants with low FVC and low GS have the highest risk of major CVD. Therefore, more attention should be paid to the incidence of major CVD in individuals with low FVC, especially those who have lower GS.

Nicotine-induced miR-21-3p promotes chemoresistance in lung cancer by negatively regulating FOXO3a.

Lung cancer is the leading cause of cancer-related mortality worldwide and cigarette smoking is reported to contribute to the lung cancer-related mortality. The present study aimed to investigate the molecular mechanism underlying nicotine-induced chemoresistance in lung cancer. The expression of microRNA (miR)-21-3p and its predicted target FOXO3a in lung cancer cells was detected via reverse transcription-quantitative PCR, in the presence or absence of nicotine. The regulatory effect of miR-21-3p and FOXO3a on lung cancer cell proliferation and apoptosis induced by docetaxel or cisplatin treatment was evaluated by performing Cell Counting Kit-8 and Annexin V/PI staining assays, respectively. The interaction between miR-21-3p and FOXO3a was analyzed by performing luciferase reporter assays and western blotting. FOXO3a overexpression rescue experiments were conducted in vitro and in vivo using a xenograft mouse model to assess the function of miR-21-3p/FOXO3a in lung cancer. Nicotine induced miR-21-3p expression in lung cancer cells in a dose-dependent manner. miR-21-3p downregulated FOXO3a expression by directly binding to the 3'-untranslated region of FOXO3a. Moreover, miR-21-3p knockdown sensitized lung cancer cells to docetaxel or cisplatin treatment. Mechanistically, FOXO3a was predicted as a direct target of miR-21-3p. FOXO3a overexpression promoted the chemosensitivity of lung cancer cells to docetaxel or cisplatin treatment. Furthermore, FOXO3a overexpression antagonized the regulatory function of miR-21-3p on docetaxel- or cisplatin-treated lung cancer cells. In the docetaxel- or cisplatin-treated lung cancer xenograft mouse model, miR-21-3p promoted chemoresistance via negatively regulating FOXO3a. Therefore, the present study demonstrated that nicotine-induced miR-21-3p promoted chemoresistance to docetaxel or cisplatin treatment via negatively regulating FOXO3a, which may serve as a novel therapeutic strategy for the treatment of patients with chemoresistant lung cancer.

[Simultaneous determination of 11 active components in Lonicera japonica flowers and leaves at different development stages by HPLC-DAD].

This study aims to develop an HPLC-DAD method for simultaneous determination of 11 components(6 phenolic acids and 5 iridoids) in Lonicera japonica flowers(LjF) and leaves(LjL), and compare the content differences of LjF at different development stages, LjL at different maturity levels, and between LjF and LjL. One-way ANOVA, principal component analysis(PCA), and orthogonal partial least-squares discriminant analysis(OPLS-DA) were employed to compare the content of the 11 components. The content of total phenolic acids, total iridoid glycosides, and total 11 components in LjF showed an overall downward trend with the development of flowers. The content of total phenolic acids, total iridoid glycosides, and total 11 components in young leaves were higher than those in mature leaves. The results of PCA showed that the samples at different flowering stages had distinguishable differences in component content. The VIP value of OPLS-DA showed that isochlorogenic acid A, chlorogenic acid, and secologanic acid were the main differential components of LjF at different development stages or LjL with different maturity levels. LjF and LjL have certain similarities in chemical composition while significant differences in component content. The content of total phenolic acids in young leaves was significantly higher than that in LjF at various development stages. The content of total iridoid glycosides in young leaves was similar to that in LjF before white flower bud stage. The total content of 11 components in young leaves was significantly higher than that in LjF at green flower bud stage, before and during completely white flower bud stage. LjL have great potential for development. Follow-up research on the pharmacodynamic equivalence of LjF and LjL(especially young leaves) should be carried out to speed up the development and application of LjL.

[Analysis of heavy metal pollution in Lonicerae Japonicae Flos and its health risk assessment].

In this study, the content of five heavy metals(Pb, Cd, As, Hg, and Cu) in 59 batches of Lonicerae Japonicae Flos(LJF) medicinal materials and pieces were determined by inductively coupled plasma mass spectrometry(ICP-MS). The health risk assessment was processed using the maximum estimated daily intake(EDI), target hazard quotients(THQ), and carcinogenic risks(CR) assessment models. With reference to the limit standard for heavy metal content in LJF specified in 2020 edition of Chinese Pharmacopoeia, five batches produced in Hebei were found to contain excessive Pb, and the remaining 54 batches met the specifications, with the unqualified rate of 8.47%. Comparative analysis of heavy metal content in LJF samples from three different producing areas, namely Shandong, Henan, and Hebei showed that the levels of Pb, As, and Hg in LJF from Hebei were significantly higher than those from Henan and Shandong. The samples produced in Shandong contained the highest content of Cd. The samples from Hebei contained the highest content of Cu while those from Shandong had the lowest content of Cu. As demonstrated by health risk assessment based on the EDI, THQ and CR models, these 59 batches of LJF samples did not cause significant health hazards for the exposed population, and there was no potential non-carcinogenic or carcinogenic risk. In conclusion, a few of LJF samples contained excessive heavy metals, so some measures, including controlling production environment, cultivating management mode, and optimizing processing methods, should be taken for ensuring the medication safety of LJF.

[Aflatoxins and fungal community distribution during harvesting and processing of Platycladi Semen].

This study aimed to analyze aflatoxins content and fungal community distribution in the harvesting and processing of Platycladi Semen, and explore the key link that affects aflatoxins contamination. The related Platycladi Semen samples of different maturity periods(cone non-rupture period, early rupture, and complete rupture period) and different processing periods(before drying, during 2-d drying, during 7-d drying, before and after seed scale removal, before and after peeling, 1 d after color sorting, and 7 d after color sorting) were collected for identifying the fungal community composition on sample surface by ITS amplicon sequencing. Then the content of aflatoxins B_1, B_2, G_1 and G_2 was determined by HPLC-MS/MS. The results showed that during the harvesting of Platycladi Semen from cone non-rupture to complete rupture, aflatoxins were only detected in the seed scale and seed coat, with aflatoxin G_2 in the seed scale and aflatoxin B_1 in the seed coat. During the drying, with the prolongation of drying time, aflatoxins B_1 and G_2 were detected simultaneously in the seed scale, aflatoxin B_1 in the seed coat, and low-content aflatoxin B_1 in the seed kernel. During subsequent processing, the aflatoxin content in seed kernel during subsequent processing was slighted increased. As demonstrated by fungal detection, Aspergillus flavus was not present during the harvesting of Platycladi Semen, but present during the drying and processing. Its content in the seed coat during the drying process was relatively higher. In short, Platycladi Semen should be harvested as soon as possible after it becomes fully mature. Drying process is the key link of preventing aflatoxin contamination. It is advised to build a sunlight room or adopt similar settings, standardize the operations in other processes, and keep the surrounding environment clean to minimize aflatoxin contamination.

Automatic Sleep Staging Algorithm Based on Time Attention Mechanism.

The most important part of sleep quality assessment is the automatic classification of sleep stages. Sleep staging is helpful in the diagnosis of sleep-related diseases. This study proposes an automatic sleep staging algorithm based on the time attention mechanism. Time-frequency and non-linear features are extracted from the physiological signals of six channels and then normalized. The time attention mechanism combined with the two-way bi-directional gated recurrent unit (GRU) was used to reduce computing resources and time costs, and the conditional random field (CRF) was used to obtain information between tags. After five-fold cross-validation on the Sleep-EDF dataset, the values of accuracy, WF1, and Kappa were 0.9218, 0.9177, and 0.8751, respectively. After five-fold cross-validation on the our own dataset, the values of accuracy, WF1, and Kappa were 0.9006, 0.8991, and 0.8664, respectively, which is better than the result of the latest algorithm. In the study of sleep staging, the recognition rate of the N1 stage was low, and the imbalance has always been a problem. Therefore, this study introduces a type of balancing strategy. By adopting the proposed strategy, SEN-N1 and ACC of 0.7 and 0.86, respectively, can be achieved. The experimental results show that compared to the latest method, the proposed model can achieve significantly better performance and significantly improve the recognition rate of the N1 period. The performance comparison of different channels shows that even when the EEG channel was not used, considerable accuracy can be obtained.

[Diversity of arbuscular mycorrhizal fungi of Panax quinquefolius cultivated in Shandong province].

In this study, the colonization, diversity and relative abundance of arbuscular mycorrhizal fungi(AMF) in the roots of Panax quinquefolius in different habitats of Shandong province were analyzed by staining-microscopy and high-throughput sequencing. The data were analyzed by bioinformatics tools and statistical software. The results showed that the roots of P. quinquefolius in different habitats were colonized by AMF with different rates and intensities. The AMF in roots of P. quinquefolius belong to three genera, three families, three orders, one class and one phylum. At the level of order, the AMF mainly included Paraglomerales(52.48%), Glomerales(25.60%) and Archaeosporales(3.08%). At the level of family, the AMF were dominated by Paraglomeraceae(52.48%), Glomeraceae(18.94%) and Claroideoglomeraceae(3.05%). At the level of genus, Paraglomus(51.46%), Glomus(20.01%) and Claroideoglomus(3.52%) accounted for a large proportion, of which Paraglomus and Glomus were dominant. Cluster analysis showed that the AMF in roots of P. quinquefolius with close geographical locations could be clustered together. In this study, the diversity and dominant germplasm resources of AMF in roots of P. quinquefolius cultivated in the main producing areas were identified, which provi-ded basic data for revealing the quality formation mechanism of P. quinquefolius medicinal materials from the perspective of environment.

[Research progress on chemical constituents and pharmacological activities of iridoid glycosides in Lonicera japonica].

As a traditional Chinese medicinal material, Lonicera japonica has a long medicinal history. The chemical constituents of Lonicera japonica are complex, mainly including iridoid glycosides, flavonoids, triterpenes, organic acids and volatile oil. Iridoid glycosides account for a higher proportion. In addition, modern pharmacological studies have shown that the iridoid glycosides have many pharmacological activities such as antivirus, anti-inflammation, anti-tumor, liver protection and lowering blood sugar. This review intends to systematically summarize the iridoid glycosides identified from Lonicera japonica and their pharmacological activities by searc-hing Chinese and English databases, in order to provide a reference for the further development and utilization of Lonicera japonica and for the improvement of quality standards of medicinal materials.

Toad venom: A comprehensive review of chemical constituents, anticancer activities, and mechanisms.

Toad venom, a traditional natural medicine, has been used for hundreds of years in China for treating different diseases. Many studies have been performed to elucidate the cardiotonic and analgesic activities of toad venom. Until the last decade, an increasing number of studies have documented that toad venom is a source of lead compound(s) for the development of potential cancer treatment drugs. Research has shown that toad venom contains 96 types of bufadienolide monomers and 23 types of indole alkaloids, such as bufalin, cinobufagin, arenobufagin, and resibufogenin, which exhibit a wide range of anticancer activities in vitro and, in particular, in vivo for a range of cancers. The main antitumor mechanisms are likely to be apoptosis or/and autophagy induction, cell cycle arrest, cell metastasis suppression, reversal of drug resistance, or growth inhibition of cancer cells. This review summarizes the chemical constituents of toad venom, analyzing their anticancer activities and molecular mechanisms for cancer treatments. We also outline the importance of further studies regarding the material basis and anticancer mechanisms of toad venom.

[Investigation and research on fungal diversity of Platycladi Semen on Chinese market].

In the process of harvesting, production and processing, storage, and transportation, the traditional Chinese medicine Platycladi Semen is prone to mildew due to its own and environmental factors, which can nourish the production of toxic or pathogenic fungi, and even produce mycotoxins, which affects the safety of clinical medication. The 2020 edition of Chinese Pharmacopoeia limits the highest standard of aflatoxin content in Platycladi Semen. However, there are few studies on the fungal contamination of Platycladi Semen, and it is difficult to prevent and control it in a targeted manner. Therefore, based on the Illumina NovaSeq6000 platform, this article uses ITS sequence amplicon technology to analyze the distribution and diversity of fungi in 27 batches of commercially available Platycladi Semen in the Chinese market. A total of 10 phyla, 35 classes, 93 orders, 193 families, 336 genera, and 372 species of fungi were identified in China. Among them, Aspergillus, Alternaria spp. were dominant, 20 batches of samples were detected for A. flavus, 10 batches of samples were detected for A. nidulans, and all samples were detected for potential pathogenic fungi such as A. fumigatus and A. niger. According to diversity analysis, the diversity of the fungal communities in the samples from Gansu province was high, the samples in Shandong province contain the largest number of fungal species, and the samples in Guangxi province had the lo-west diversity and the least number of species. In most samples, pathogenic fungi such as A. fumigatus, A. niger, A. flavus, A. parasiticus were detected in varying degrees. This study systematically investigated the fungal contamination of Platycladi Semen from the markets in the last link of the its industrial chain, and clarified the distribution of Platycladi Semen fungi, especially toxin-producing fungi, and provided theoretical basis for the targeted prevention and control of fungal contamination in Platycladi Semen.