[Material basis of stench of animal medicine: a review].

Despite the distinctive characteristics and remarkable efficacy, animal medicine is stenchy, which decreases the comp-liance of patients. At the moment, the research on the method for deodorizing animal medicines lags behind. To be specific, the components related to the odor and the basic properties transformation of the components are unclear and there is a lack of specific deodorizing method. This study aims to clarify the main components related to the stench of animal medicine, such as aldehydes, amines, trimethylamines and sulfur compounds, and their basic properties, and to explore their metabolism and transformation in vivo and in vitro, which is expected to serve as a reference for the research on deodorization of animal medicine and development of new techniques.

The molecular mechanism of chronic stress affecting the occurrence and development of breast cancer and potential drug therapy.

According to the 2020 data released by the International Agency for Research on Cancer, breast cancer has surpassed lung cancer as the world's most newly diagnosed first-time cancer. Compared with patients with other types of cancer, those with breast cancer experience greater mental stress and more severe psychological impacts because of the life-threatening diagnosis, physical changes, treatment side effects, and family and social life dysfunctions. These usually manifest as anxiety, depression, nervousness, and insomnia, all of which elicit stress responses. Particularly under chronic stress, the continuous release of neurotransmitters from the neuroendocrine system can have a highly profound impact on the occurrence and prognosis of breast cancer. However, because of the complex mechanisms underlying chronic stress and the variability in individual tolerance, evidence of the role of chronic stress in the occurrence and evolution of breast cancer remains unclear. This article reviewed previous research on the correlation between chronic stress and the occurrence and development of breast cancer, particularly the molecular mechanism through which chronic stress promotes breast cancer via neurotransmitters secreted by the nervous system. We also review the progress in the development of potential drugs or blockers for the treatment of breast cancer by targeting the neuroendocrine system.

Screening S protein - ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19.

The Coronavirus disease, 2019 (COVID-19) is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which poses a major threat to human life and health. Given its continued development, limiting the spread of COVID-19 in the population remains a challenging task. Currently, multiple therapies are being tried around the world to deal with SARS-CoV-2 infection, and a variety of studies have shown that natural products have a significant effect on COVID-19 patients. The combination of SARS-CoV-2 S protein with Angiotensin converting enzyme II(ACE2) of host cell to promote membrane fusion is an initial critical step for SARS-CoV-2 infection. Therefore, screening natural products that inhibit the binding of SARS-CoV-2 S protein and ACE2 also provides a feasible strategy for the treatment of COVID-19. Establishment of high throughput screening model is an important basis and key technology for screening S protein-ACE2 blockers. Based on this, the molecular structures of SARS-CoV-2 and ACE2 and their processes in the life cycle of SARS-CoV-2 and host cell infection were firstly reviewed in this paper, with emphasis on the methods and techniques of screening S protein-ACE2 blockers, including Virtual Screening (VS), Surface Plasmon Resonance (SPR), Biochromatography, Biotin-avidin with Enzyme-linked Immunosorbent assay and Gene Chip Technology. Furthermore, the technical principle, advantages and disadvantages and application scope were further elaborated. Combined with the application of the above screening technologies in S protein-ACE2 blockers, a variety of natural products, such as flavonoids, terpenoids, phenols, alkaloids, were summarized, which could be used as S protein-ACE2 blockers, in order to provide ideas for the efficient discovery of S protein-ACE2 blockers from natural sources and contribute to the development of broad-spectrum anti coronavirus drugs.

[Microbial community structure and transformation of indoles in soaking and fermentation of Indigo Naturalis].

The soaking and fermentation of Baphicacanthus cusia( Nees),the important intermediate link of Indigo Naturalis processing,facilitates the synthesis of indigo and indirubin precursors and the dissolution of endogenous enzymes and other effective components,while the role of microorganisms in the fermentation is ignored. The present study investigated the changes of microbial community structure in Indigo Naturalis processing based on 16 S amplicon sequencing and bioinformatics. Meanwhile,the contents of indigo,indirubin,isatin,tryptanthrin,indole glycoside,etc. were determined to explore the correlation between the microorganisms and the alterations of the main components. As demonstrated by the results,the microbial diversity decreased gradually with the fermentation,which bottomed out after the addition of lime. Proteobacteria,Bacteroidetes,and Firmicutes were the main dominant communities in the fermentation. The relative abundance of Proteobacteria declined gradually with the prolongation of fermentation time,and to the lowest level after the addition of lime. The relative abundance of Firmicutes increased,and that of Bacteroidetes decreased first and then increased. The contents of effective substances in Indigo Naturalis also showed different variation tendencies. As fermentation went on,indole glycoside decreased gradually; indigo first increased and then decreased; indirubin and isatin first decreased and then increased; tryptanthrin gradually increased. Those changes were presumedly related to the roles of microorganisms in the synthesis of different components. This study preliminarily clarified the important role of microorganisms in the soaking and fermentation and provided a scientific basis for the control of Indigo Naturalis processing and the preparation of high-quality Indigo Naturalis.

[Changes in forms of Indigo Naturalis slices in ancient and modern times: a systematic study on quality of purified Indigo Naturalis and crude Indigo Naturalis].

Indigo Naturalis has a long history of medicinal use with particularity and complexity in its processing. Before the Ming dynasty,Indigo Naturalis was extracted from the top layer of zymotic fluid,called " purified Indigo Naturalis". In modern processing,the precipitate " crude Indigo Naturalis" is dried to produce Indigo Naturalis after impurity removal. The form of Indigo Naturalis slices has undergone significant changes in ancient and modern times. In view of this,the quality comparison between crude Indigo Naturalis and purified Indigo Naturalis was conducted in this study with modern analytical techniques. Firstly,chemical composition was analyzed with UPLC-Q-TOF-MS,and the chemical composition of scent with HS-SPME/GC-MS/MS. The content of indigo,indirubin,total ash,and water-soluble extract was determined as well as the inorganic composition in crude Indigo Naturalis and purified Indigo Naturalis. Then,their microscopic morphology was observed and the surface element composition was investigated. Finally,the antipyretic activities of crude Indigo Naturalis and purified Indigo Naturalis were compared in the fever rat model induced by lipopolysaccharide and 2,4-dinitrophenol. The results demonstrated that the purified Indigo Naturalis had a faster and more lasting antipyretic effect,while the crude Indigo Naturalis had almost no antipyretic effect. This study is of great significance to the research on processing technology of Indigo Naturalis and provides reference for the formulation of its quality standards,production specifications and calibration procedures.

Exploring the Mechanism of Indigo Naturalis in the Treatment of Ulcerative Colitis Based on TLR4/MyD88/NF-κB Signaling Pathway and Gut Microbiota.

Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC. Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing. Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1ß,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics. Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction.

Fever and Antipyretic Supported by Traditional Chinese Medicine: A Multi-Pathway Regulation.

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19.

[Correlation between internal damage due to seven emotions in traditional Chinese medicine and pathogenesis of breast cancer from perspective of psychological stress].

Breast cancer is a major chronic disease threatening women's health. It has topped the global cancers as the diagnosed cases outnumbered lung cancer patients in 2020. Internal damage due to the seven emotions is an important cause of breast cancer and the disorders of hypothalamic-pituitary-adrenal(HPA) axis and endocrine system and the abnormal immune defense mechanism in response to psychological stress all affect the occurrence and development of breast cancer. It is noteworthy that the theory of seven emotions in traditional Chinese medicine and the psychological stress theory of modern medicine have something in common in some aspects. Therefore, this study explored the correlation between internal damage due to the seven emotions and psychological stress and analyzed the molecular biological mechanisms of psychological stress influencing breast cancer from the perspective of modern medicine, which is helpful to reasonably prevent breast cancer and other related tumors and improve the prognosis of breast cancer patients through emotion regulation.

Progress in research into the role of abnormal glycosylation modification in tumor immunity.

In abnormal glycosylation, molecules of glucose or other carbohydrates in living organisms are inappropriately attached to proteins, which causes protein denaturation. Abnormal glycosylation modification is known to directly or indirectly affect the tumor escape process, but very few studies have been performed on whether protein glycosylation changes the structure and function of immune cells and immune molecules and thereby regulates the occurrence and development of tumor escape. Therefore, this article summarizes the effect of the immune system on tumor escape in association with the abnormal glycosylation process from an immunological perspective.

Research Progress on Main Symptoms of Novel Coronavirus Pneumonia Improved by Traditional Chinese Medicine.

Novel coronavirus (COVID-19) pneumonia has become a major threat to worldwide public health, having rapidly spread to more than 180 countries and infecting over 1.6 billion people. Fever, cough, and fatigue are the most common initial symptoms of COVID-19, while some patients experience diarrhea rather than fever in the early stage. Many herbal medicine and Chinese patent medicine can significantly improve these symptoms, cure the patients experiencing a mild 22form of the illness, reduce the rate of transition from mild to severe disease, and reduce mortality. Therefore, this paper summarizes the physiopathological mechanisms of fever, cough, fatigue and diarrhea, and introduces Chinese herbal medicines (Ephedrae Herba, Gypsum Fibrosum, Glycyrrhizae Radix et Rhizoma, Asteris Radix et Rhizoma, Ginseng Radix et Rhizoma, Codonopsis Radix, Atractylodis Rhizoma, etc.) and Chinese patent medicines (Shuang-huang-lian, Ma-xing-gan-shi-tang, etc.) with their corresponding therapeutic effects. Emphasis was placed on their material basis, mechanism of action, and clinical research. Most of these medicines possess the pharmacological activities of anti-inflammatory, antioxidant, antiviral, and immunity-enhancement, and may be promising medicines for the treatment or adjuvant treatment of COVID-19 patients.

[Accurate positioning and analysis on health function of high frequency anti-fatigue herbal medicines].

Fatigue is a widespread and complex physiological phenomenon. Chronic fatigue can lead to cardiovascular dysfunction, mental disorders and other serious pathological reactions. Therefore, how to relieve fatigue accurately and effectively is an important proposition to implement the concept of "Healthy China" in the new era. As an important part of Chinese medicine health industry, Chinese medicine health food has been developing rapidly in recent years. At present, there are 1 157 kinds of anti-fatigue health food on the market in China, most of which are single Chinese medicine and its compound. However, their functions are generally labeled as "anti-fatigue", and their function positioning is too extensive and unclear. With the deepened understanding of fatigue classification and its physiological and pathological basis, it is urgent to be combined with the progress of modern chemical and pharmacological stu-dies to differentiate and precisely position the anti-fatigue health effects of traditional Chinese medicine. For this purpose, the classifications of fatigue were summarized in this paper, and the mechanism of fatigue was explained from the aspects of energy metabolism, accumulation of metabolites, oxidative stress, inflammation, hypothalamus pituitary adrenal axis and so on. We selected 10 traditional Chinese medicines which are most frequently used in health food, analyzed their anti-fatigue effect mechanisms, and summarized the best types of anti-fatigue food, so as to promote the scientific development of anti-fatigue health food industry, expand the market application scope of anti-fatigue health food, better respond to the construction of a healthy China and serve for people's health.

[12]aneN3-Based Gemini-Type Amphiphiles with Two-Photon Absorption Properties for Enhanced Nonviral Gene Delivery and Bioimaging.

Although a plethora of nonviral gene vectors have been developed for potential gene therapy, imageable gemini surfactants with stimuli-responsiveness and high transfection efficiency are still scarce for gene delivery. Herein, three gemini amphiphiles (DEDPP-4/8/12) consisting of an aggregation-induced emission (AIE) central fluorophore: 5,6-diphenylpyrazine-2,3-diester (DEDPP), decorated with triazole-[12]aneN3 as the hydrophilic moiety and alkyl chains of various lengths as the hydrophobic moiety, were designed and synthesized for trackable gene delivery via optical imaging. All three amphiphiles exhibited ultralow critical micelle concentrations (CMCs) (up to 3.40 × 10-6 M), prominent two-photon absorption properties, and solvatochromic fluorescence. Gel electrophoresis assays demonstrated that the migration of plasmid DNA was completely retarded after condensation with these gemini amphiphiles at low concentrations (up to 10 µM). In addition, the ester bond in these amphiphiles may facilitate vector degradation and DNA release, in response to esterase and the acidic environment inside cells. Upon self-assembly with DOPE to form liposomes, DEDPP-8/DOPE achieved the best transfection efficiency in four cell lines, and the transfection efficiency of DEDPP-8/DOPE in HeLa cell lines was 23.5-fold higher than that of Lipo2000, which is unusually high for small organic molecule-based nonviral vectors. Furthermore, excellent transfection efficiency of DEDPP-8/DOPE was obtained in the presence of serum, and the red fluorescence protein (RFP) gene was successfully transfected in zebrafish embryos. Both one- and two-photon fluorescence imaging clearly demonstrated the delivery process of plasmid DNA. This study demonstrated that gemini-type amphiphiles composed of a two-photon fluorophore core conjugated with triazole-[12]aneN3 via an ester bond afforded an unprecedentedly high transfection efficiency with excellent biocompatibility, which may provide new insights for the design and development of multifunctional nonviral gene vectors for imageable gene delivery.

Macrocyclic polyamine [12]aneN3 modified triphenylamine-pyrazine derivatives as efficient non-viral gene vectors with AIE and two-photon imaging properties.

With the aim to develop a novel multifunctional gene delivery system that may overcome the common barriers of gene transfection, near-infrared fluorescent triphenylamine-pyrazine was modified with a DNA condensing triazole-[12]aneN3 moiety through different length alkyl ester linkages to afford three new non-viral gene vectors, TDM-A/B/C. All compounds showed prominent solvatochromic fluorescence (Stokes shift of up to 383 nm) and two-photon absorption properties (σ2P to 101 GM), and exhibited strong aggregation-induced emission (AIE). Gel electrophoresis demonstrated that plasmid DNA was completely condensed at a concentration of 10 µM (TDM-A), 14 µM (TDM-B) and 16 µM (TDM-C), and released in esterase and acidic environment. SEM demonstrated that the three compounds were able to self-assemble and co-aggregate with DNA to form regular nanoparticles. Experiments demonstrated that TDM-A/B/C was able to integrate with DNA through electrostatic interactions and supramolecular stacking, and the short alkyl linkage favored the strong interaction with DNA. Among the three compounds, TDM-B showed the best luciferase and GFP transfection activities in the presence of DOPE, which were 156% and 310% higher than those of Lipo2000, respectively. The transfection process of DNA was clearly traced through one- and two-photon fluorescence microscopy imaging. Cellular uptake inhibition assay indicated that the DNA complex entered the cell mainly via clathrin-independent endocytosis. Furthermore, the in vivo transfection experiments of TDM-B/DOPE were successfully implemented in zebra fish embryos, and the GFP gene expression level was superior to that of Lipo2000 (200%). Finally, this study clearly unraveled that the length of the alkyl linkage affected the DNA condensation and transfection activity, which can serve as a base for the future rational design of non-viral gene vectors.

Tumor Targeting Gene Vector for Visual Tracking of Bcl-2 siRNA Transfection and Anti-Tumor Therapy.

Tumor targeting provided more effective gene therapy. Bcl-2 is an oncogene, and Bcl-2 small interfering RNA (Bcl-2 siRNA) can inhibit its expression. Here, a fluorescent and gene-loading capacity vector DPL, derived from diketopyrrolopyrrole (DPP), was developed for Bcl-2 siRNA-targeted delivery and tumor imaging in vitro and in vivo. The vector DPL showed a significant emission enhancement after interacting with siRNA, which was used to track the gene transfer process. Compared to commercial transfection reagent Lipo 2000, DPL obviously downregulated the Bcl-2 protein expression and exhibited excellent antitumor efficacy with less Bcl-2 siRNA. Importantly, DPL can target tumors to transport Bcl-2 siRNA to tumor sites in vivo based on the enhanced permeability and retention (EPR) effect for effective in vivo tumor therapy. This work inspired us to design and synthesize a multifunctional gene vector for tumor targeting and gene therapy.

Combination of [12]aneN3 and Triphenylamine-Benzylideneimidazolone as Nonviral Gene Vectors with Two-Photon and AIE Properties.

Three nonviral gene vectors, TPA-BI-A/B/C, have been designed and synthesized by the combination of one or two hydrophilic [12]aneN3 moieties and two-photon fluorescent triphenylamine-benzylideneimidazolone (TPA-BI) units through different ester linkage. Spectroscopic characterization demonstrated that TPA-BI-A/B/C had strong aggregation-induced emissions (AIE), large Stokes shifts (230, 284, and 263 nm), and large two-photon absorption cross sections (δ2PA) (67, 592, and 80 GM). Gel electrophoresis indicated that the three compounds completely condensed DNA at 15 µM in the presence of DOPE, and showed the lipase- and pH-triggered reversible release of DNA and the fluorescent recognition of the different lengths of ssDNA and dsDNA. The optimal TPA-BI-C/DOPE-mediated luciferase and GFP activity was 146% and 290% higher than those of Lipo2000. The transfection process of DNA could be traced clearly through one- and two-photon fluorescence spectra, and displayed in a 3D-video. TPA-BI-C/DOPE successfully transfected the GFP gene into zebrafish, which was superior to Lipo2000 (192%). In conclusion, TPA-BI-C/DOPE is the first nonviral gene vector with the abilities of pH/lipase enzyme responsiveness, one/two-photon fluorescent tracking of intracellular delivery of DNA, and successful transfection in vivo and in vitro, even better than Lipo2000.

[Effects of irrigation frequency of organic nutrient solution and irrigation amount on yield, quality, fertilizer and water use efficiency of melon in facility]. / æœ‰æœºè¥å »æ¶²çŒæº‰é¢‘æ¬¡å’ŒçŒæ°´é‡å¯¹è®¾æ–½ç”œç“œäº§é‡ã€å“è´¨åŠè‚¥æ°´åˆ©ç”¨æ•ˆçŽ‡çš„å½±å“.

To investigate the organic cultivation mode for high-yield and high-quality melon, we measured the growth of melon that grown in pots with different conditions of organic nutrient solution and irrigation. There were three irrigation frequencies of organic nutrient solution (8-time application, each time 750 mL per plant, F1; 12-time application, each time 500 mL per plant, F2; 16-time application, each time 375 mL per plant, F3) and two different irrigation amount per single plant (irrigating by 120% daily evapotranspiration (ET) before fruit enlargement, by 140%ET after fruit enlargement, W1; irrigating by 140%ET before fruit enlargement, by 160%ET after fruit enlargement, W2), following a randomized block trial design. The effects of those treatments on photosynthetic characteristics, yield, quality, fertilizer and water use efficiency of melon were investigated. The results showed that photosynthetic rate of melon leaves was significantly increased by more frequent and less amount of organic nutrient solution application. Fruit yield and water use efficiency were significantly improved under low irrigation condition. Fertilizer utilization was optimal under the treatments of high irrigation and medium organic nutrient solution frequency. Fruit quality was improved under less organic nutrient solution and relatively suitable water supply. A mathematical model of exponential function y=0.214e0.18x (R2=0.851) could be used to quantify the relationship between the vitamin C content of melon fruit and frequency of organic nutrient solution application. Considering the variables, such as yield, quality and water use efficiency, F3W1 treatment was recommended with the aim to improve fruit quality and optimal water use efficiency under promising yield, which could achieve high-yield and high-quality cultivation of organic melon in facilities.

Imaging nucleus viscosity and G-quadruplex DNA in living cells using a nucleus-targeting two-photon fluorescent probe.

A two-photon fluorescent probe, TP-2Bz, was designed and synthesized and it exhibited good targeting capabilities toward cell nuclei. In particular, TP-2Bz demonstrated a high selectivity to both G-quadruplex DNA and viscosity inside the nucleus with significant ratiometric enhancement in fluorescence, providing a specific, versatile imaging tool for analyzing the viscosity and G-quadruplex DNA in living cells.

Growth differentiation factor-15 (GDF-15), novel biomarker for assessing atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease.

OBJECTIVE: Growth differentiation factor-15 (GDF-15) has been identified as a strong biomarker of cardiovascular diseases; however, no evidence are available concerning the relationship of GDF-15 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). METHODS: Twenty patients with rheumatic heart disease were divided into two groups, 10 cases with AF and 10 cases with sinus rhythm (SR). Clinical data and blood samples were collected; left atrial appendage was taken by the surgeon in the process of valve replacement. Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to determine the level of cardiac fibrosis, the expression level of GDF-15 was evaluated via immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). RESULTS: Compared with SR group, more collagen deposited in the atrial tissue of AF group. The distribution of GDF-15 in the AF group was significantly higher than SR group (P<0.05). In addition, plasma GDF-15 level and mRNA level of GDF-15 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. After linear correlation analysis, the expression level of GDF-15 was found to be positively related to the degree of cardiac fibrosis. CONCLUSION: GDF-15 might involve in the development and maintenance of atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease, and GDF-15 could be used as a novel biomarker to evaluate myocardial fibrosis in the future.