Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics;methods to identify dose–toxicity relationships in TCM;and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae.

A Study on The Timeliness of Credit Rating on Bond Defaults--Evidence from Chinese Bond Market

With the increase of China’s bond issuance and slowdown of the economic growth,the potential credit risks such as bond default in the bond market are gradually emerging.The frequent occurrence of bond defaults and the problem of false credit ratings make bond investors and market participants more cautious about the credit ratings issued by rating agencies.Based on the default bonds from 2016 to 2019,this paper analyzes the adjustment of rating of defaulted bonds by rating agencies before default.It also compares the impact of both the regulatory events and the entrance of international agencies on timeless of credit ratings on default bonds.At the same time,the divergence of rating timeliness between different rating agencies is compared.The research shows that after the unified supervision of regulators and the punishment of Dagong Global Credit Rating Co.Ltd in 2018,the timeliness of rating agencies'downgrading of defaulted bonds has increased significantly;Compared with other rating agencies,the timeliness of rating agencies owned by international rating agencies are better.

Spin splitting of vortex beams on the surface of natural biaxial hyperbolic materials

We investigated the spin splitting of vortex beam on the surface of biaxial natural hyperbolic materials(NHMs)rotated by an angle with respect to the incident plane. An obvious asymmetry of spatial shifts produced by the left-handed circularly(LCP) component and right-handed circularly polarized(RCP) component is exhibited. We derived the analytical expression for in-and out-of-plane spatial shifts for each spin component of the vortex beam. The orientation angle of the optical axis plays a key role in the spin splitting between the two spin components, which can be reflected in the simple expressions for spatial shifts without the rotation angle. Based on an α-MoO_(3) biaxial NHM, the spatial shifts of the two spin components with the topological charge were investigated. As the topological charge increases, the spatial shifts also increase;in addition, a tiny spatial shift close to zero can be obtained if we control the incident frequency or the polarization of the reflected beams. It can also be concluded that the maximum of the spin splitting results from the LCP component at p-incidence and the RCP component at s-incidence in the RB-Ⅱ hyperbolic frequency band. The effect of the incident angle and the thickness of the α-MoO_(3) film on spin splitting is also considered. These results can be used for manipulating infrared radiation and optical detection.

Biological basis of “depression with liver-qi stagnation and spleen deficiency syndrome”: A digital gene expression profiling study

Objective:To investigate the biological basis of“depression with liver-qi stagnation and spleen deficiency syndrome”.Methods:A digital gene expression profiling method was conducted to explore global changes in the mRNA transcriptome in a rat model of depression with liver-qi stagnation and spleen deficiency syndrome.Real-time quantitative polymerase chain reaction(q-PCR)was performed to verify the five genes most interest based on the Kyoto Encyclopedia of Genes and Genome(KEGG)analysis.Sini San,which disperses stagnated liver qi and strengthens the spleen,was administered to the model rats to observe whether it could reverse these genetic changes in the liver.Results:Forty-six differentially expressed genes were identified.Three of the five genes of most interestdHnf4a,Hnf4g and Cyp1a1dbased on KEGG analysis,were confirmed by realtime q-PCR.Sini San reduced the gene expression changes of Hnf4a,Hnf4g and Cyp1a1 in the rat model.Conclusions:Hnf4a,Hnf4g and Cyp1a1 are involved in“depression with liver-qi stagnation and spleen deficiency syndrome”.These findings indicate that depressed rats with liver-qi stagnation and spleen deficiency syndrome are at risk of liver diseases.Furthermore,our results will inform exploration of the etiology of depression and help in the development of effective therapeutic strategies.

Government Inspectors' Penalties and Charging Fee of Investment Banks--Empirical research based on data of Chinese public companies

This paper uses data of Chinese public companies from 2004-2015 to test the relationship between government inspectors'penalties and charging fee of investment bank.The test results show that after getting the penalties from government inspectors the charging fee of investment bank would decrease significantly.This negative impact of penalties on charging fee is more significant to the investment bank that has high reputation.This indicates that the penalties of government inspectors damage the reputation of investment banks.This research could help understand the effects of the government inspection on the reputation of investment banks.

UV-B irradiation enhances the accumulation of beneficial glucosinolates induced by melatonin in Chinese kale sprout

Cruciferous sprout is a new form of vegetable product rich in bioactive compounds,especially glucosinolates.Previous studies have focused on increasing the accumulation of glucosinolates in cruciferous sprouts by applying different chemical regulators,with a particular focus on their contribution to nutritional quality and health benefits.Nevertheless,the effects of melatonin and UV-B irradiation on glucosinolate biosynthesis remain unclear.In this study,it was found that changes in melatonin concentrations significantly affected the contents of individual as well as total aliphatic and indolic glucosinolates.The 5μmol·L^(-1)melatonin was decided as the optimum concentration that could increase the content of beneficial glucosinolates including glucoraphanin and 4-methoxy glucobrassicin in Chinese kale sprouts.Notably,the enhancement of glucosinolate accumulation by melatonin treatment could be further amplified by UV-B irradiation.Furthermore,our results showed that R2R3-MYB transcription factor BoaMYB28 and BoaMYB51,which are central regulators of aliphatic and indolic glucosinolate biosynthesis respectively,were both involved in the regulation of glucosinolate biosynthesis by melatonin and UV-B irradiation.Additionally,the expression of glucosinolate biosynthetic genes,including BoaCYP79F1,BoaCYP83A1,BoaSUR1,BoaUGT74B1,BoaCYP79B2,BoaCYP79B3,and BoaCYP83B1 participated in the formation of core structures and BoaFMOGS-OX5,BoaAOP2,BoaCYP81F2,and BoaIGMT1 involved in the sidechain modification of aliphatic and indolic glucosinolate,was regulated by melatonin or UV-B irradiation.Taken together,these findings provide a potential strategy for improving the nutritional quality and resistance of Chinese kale sprouts.

Effect of Propofol on Colorectal Cancer Angiogenesis and Metastasis

Background: Vascular Endothelial Growth Factor (VEGF) is one of the most critical factors that stimulate angiogenesis in colorectal cancer patients. The Matrix Metalloproteinases (MMPs) are involved in the degeneration of the extracellular matrix and regulation of cell-matrix interactions. MMP-3 plays an important role in metastasis of colorectal cancer. Our aim was to investigate the effect of propofol on VEGF and MMP-3 plasma levels in colorectal cancer patients. Methods: Colorectal cancer patients were included. Blood samples were collected at before and after propofol infusion. VEGF and MMP-3 plasma levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: A total of 40 colorectal cancer patients were included. The median age of patients was 53 years. Nineteen patients were male and 21 were female. Twenty-five patients were diagnosed with colon cancer and 15 were rectal cancer. The mean propofol infusion dose was 2.02 mg/kg. There were no significant variations in VEGF and MMP-3 plasma levels after propofol infusion compared with before. No side effects occurred in all the patients. Conclusion: Propofol might have no significant effect on VEGF and MMP-3 levels in colorectal cancer patients and further studies need to be investigated.

The Impact of New Standard of Financial Instruments on Commercial Banks- A Case Study of Industrial and Commercial Bank of China

In July 2014,《International Financial Reporting Standard 9:Financial Instruments》(Referred to IFRS 9)was formally published. Compared to the former standard,《International Accounting Standard 39: Financial Instruments》(Referred to IAS 39), rules of two main aspects, the classification and measurement of financial assets and the impairment model of financial assets have been changed in IFRS 9. Taking ICBC as an example, this paper studies the impact of changes in financial instruments on commercial banks. The study shows three impacts on commercial banks’ financial report. Firstly, the changes of the classification and measurement of financial assets will have limited impacts on commercial banks. Secondly, the expected-loss model will significantly increase the loan loss reserves under the new standard, thus reducing the net asset and net profit. Thirdly, the change in the measurement way of the equity instruments of available-for-sale securities will increase the fluctuation of the net profit. This study shows investors and regulators the impact of the new standard of financial instruments on commercial banks.

Enhanced optical imaging and fluorescent labeling for visualizing drug molecules within living organisms

The visualization of drugs in living systems has become key techniques in modern therapeutics.Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization.At the subcellular level,super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs.Moving beyond subcellular imaging,researchers have integrated multiple modes,like optical near-infrared II imaging,to study the complex spatiotemporal interactions between drugs and their surroundings.By combining these visualization approaches,researchers gain supplementary information on physiological parameters,metabolic activity,and tissue composition,leading to a comprehensive understanding of drug behavior.This review focuses on cutting-edge technologies in drug visualization,particularly fluorescence imaging,and the main types of fluorescent molecules used.Additionally,we discuss current challenges and prospects in targeted drug research,emphasizing the importance of multidisciplinary cooperation in advancing drug visualization.With the integration of advanced imaging technology and molecular design,drug visualization has the potential to redefine our understanding of pharmacology,enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.

Fully self-powered instantaneous wireless liquid level sensor system based on triboelectric nanogenerator

Self-powered sensors are highly sought for wireless sensing applications in space exploration,industries,and environmental monitoring,etc.However,most current self-powered sensor technologies are based on the multiple energy conversion routine:energy collection,rectification,energy storage,and power management before it can be used for sensor systems,leading to exceptionally low energy utilization efficiency and very short periods of wireless sensing operation with majority of information lost.Here,we propose a triboelectric nanogenerator(TENG)based fully self-powered instantaneous and real-time wireless sensor system which does not contain electronic devices and microchips,but the passive components only.An innovative cylindrical capacitive-type liquid level sensor is also proposed and is then integrated into the wireless sensor system for monitoring liquid levels or identifying substance of the liquids.This sensor system can convert pulsed voltage output of the TENG into sinusoidal signal with a resonant frequency containing the sensing information and is transmitted to the receiver in distance in real-time.The maximum transmission distance of the sensor system could reach 1.5 m for a 10 cm diameter magnetic-core coil pair.The wireless sensor system exhibited excellent stability and excellent linearity with a sensitivity of 4.63 kHz/cm,and demonstrated its great application potential for the self-powered liquid level monitoring.

Brassinosteroids fine-tune secondary and primary sulfur metabolism through BZR1-mediated transcriptional regulation

For adaptation to ever-changing environments,plants have evolved elaborate metabolic systems coupled to a regulatory network for optimal growth and defense. Regulation of plant secondary metabolic pathways such as glucosinolates(GSLs) by defense phytohormones in response to different stresses and nutrient deficiency has been intensively investigated, while how growth-promoting hormone balances plant secondary and primary metabolism has been largely unexplored. Here, we found that growth-promoting hormone brassinosteroid(BR) inhibits GSLs accumulation while enhancing biosynthesis of primary sulfur metabolites, including cysteine(Cys) and glutathione(GSH) both in Arabidopsis and Brassica crops, fine-tuning secondary and primary sulfur metabolism to promote plant growth. Furthermore, we demonstrate that of BRASSINAZOLE RESISTANT 1(BZR1), the central component of BR signaling, exerts distinct transcriptional inhibition regulation on indolic and aliphatic GSL via direct MYB51 dependent repression of indolic GSL biosynthesis, while exerting partial MYB29 dependent repression of aliphatic GSL biosynthesis. Additionally, BZR1 directly activates the transcription of APR1 and APR2 which encodes rate-limiting enzyme adenosine 5′-phosphosulfate reductases in the primary sulfur metabolic pathway.In summary, our findings indicate that BR inhibits the biosynthesis of GSLs to prioritize sulfur usage for primary metabolites under normal growth conditions.These findings expand our understanding of BR promoting plant growth from a metabolism perspective.

Efficient Synthesis of Isoquinolines by AgNO3-Catalyzed Sequential Imination-Annulation of 2-Alkynyl Aldehydes with Ammonium Bicarbonate

An operationally simple approach for the tandem synthesis of isoquinolines by the reaction of o-alkynylalde- hydes with ammonium bicarbonate via Ag-catalyzed 6-endo-dig ring closure is described. The reaction conditions and the scope of the reaction are examined, and a variety of substituted isoquinolines are prepared in moderate to excellent yields.

监管处罚与投资银行声誉

本文研究了监管处罚对投资银行声誉的影响。研究表明,投资银行受监管处罚会使其声誉受损、市场竞争力下降。受处罚后,投资银行在首次公开发行承销领域的市场份额和承销收费均会显著下降,客户上市后再融资时会更容易变更承销商。我们进一步讨论了监管声誉损失影响投资银行的传导路径,即受监管处罚后新股保荐项目审核的通过率显著下降,从而影响投资银行新股发行的市场份额和承销收费。我们也发现,在受处罚后,为了恢复声誉,投资银行选择客户时更谨慎,更倾向于选择低风险、高质量的发行人。

TCMSTD 1.0: a systematic analysis of the traditional Chinese medicine system toxicology database

Dear Editor,The safety and modernization of traditional Chinese medicine (TCM) are significant concerns for users’ lives and health. Recently, the adverse effects caused by TCM and traditional nontoxic TCM have been frequently reported (Joo et al., 2020;Liu et al., 2021). As the safety of TCM continues to attract widespread attention, many researchers have been investigating the toxicity of TCM in regard to the toxic ingredients, effects, mechanisms, and detoxification strategies in TCM (Figure S1 in Supporting Information). Although some TCMs cause toxic reactions, they also play key roles in treating certain unignorable diseases (Fang et al., 2022).Therefore, toxicity research is crucial and urgently needed to develop and safely use TCM.

Effects of Sini San used alone and in combination with fluoxetine on central and peripheral 5-HT levels in a rat model of depression

OBJECTIVE: To investigate the effects of Sini San and fluoxetine on the levels of central and peripheral 5-HT in a rat model of depression, and provide new insight into the treatment of depression with integrated Chinese-Western Medicine.METHODS: A rat model of depression was established by chronic mild stress(CMS). Model rats received either Sini San, fluoxetine, a combination of the two drugs, or no drug treatment. Healthy naive rats were used as controls. Open field and sucrose preference tests were used to assess depression-like behavior. ELISA and immunohistochemistry were used to determine central and peripheral levels of 5-HT.RESULTS: In the group with no drug treatment,central 5-HT expression decreased while peripheral5-HT concentrations increased as CMS continued.Four weeks after CMS, Sini San alone was less effective in reducing depression-like behavior than fluoxetine alone or in combination with Sini San,but combined use was more effective than fluoxetine alone. Eight weeks after CMS, Sini San alone or in combination with fluoxetine was more effective in reducing depression-like behavior than fluoxetine alone. Furthermore Sini San and fluoxetine used alone or in combination notably increased central 5-HT expression and decreased peripheral 5-HT levels in the rat model.CONCLUSION:The results of the present study indicate that there is a synergistic action between the two medicines in the treatment of depression. Sini San exhibited a relatively long lag before its effects were observed; however, by eight weeks the Traditional Chinese Medicine appeared at least as effective as fluoxetine. We suggest that Sini San can replace fluoxetine in the later stages of depression treatment to minimize side effects observed with long-term fluoxetine administration.

Investigation on thermo-mechanical behavior of reinforced concrete energy pile with large cross-section in saturated sandy soil by model experiments

Energy piles are a new type of heat exchange systems with buried pipes in a pile foundation,which optimize a ground source heat pump system for the utilization of shallow geothermal energy.In this study,based on the principle of similarity,the thermo-mechanical behavior of the model energy pile with a large cross-section in saturated sandy soil was experimentally evaluated.The pre-cast model concrete pile with a diameter of 0.2 m and length of 1.5 m was buried in saturated sand in a steel box with dimensions of 2.5 m×2.5 m×2.0 m(length×width×height).The pile was heated using water in the polyethylene(PE)pipe,which was connected to a water cycle temperature controller.At a constant inlet water temperature of 55℃,three thermal cycles were carried out with the same heating and cooling periods and different water flow rates.The temperature distributions in the pile and soil,in addition to the pore pressure,soil pressure,and displacement of the pile,were monitored to clarify the thermo-mechanical behavior of the pile and soil.The heat transfer efficiency was analyzed based on the temperature difference and water flow rates.The measured strain at different locations in the pile under cyclic thermal loading revealed that the uneven strain that developed in a pile body should be considered for its long-term application.Furthermore,focus should be directed toward the long-term unrecoverable displacement of the energy pile due to the thermal plastic strain and thermal consolidation of the soil.