[Overview of Chinese medicinal materials industry in 2021 and development suggestions].

This paper introduced the overview of the "eight trends" of Chinese medicinal materials(CMM) industry in 2021, analyzed the problems of CMM production, and put forward development suggestions. Specifically, "eight trends" could be summarized as follows.(1) The growing area of CMM tended to be stable, and some provinces began to release the local catalog of Dao-di herbs.(2) The protection process of new varieties accelerated, and a number of excellent varieties were bred.(3) The theory of ecological cultivation was further enriched, and the demonstration effect of ecological cultivation technology was prominent.(4) Some CMM realized complete mechanization and formed typical model cases.(5) The number of cultivation bases using the traceability platform increased, and provincial internet trading platforms were set up.(6) The construction of CMM industrial clusters accelerated, and the number of provincial-level regional brands increased rapidly.(7) Many new agricultural business entities were founded nationwide, and a variety of methods were used to drive the intensified development of CMM.(8) A number of local TCM laws were promulgated, and the management regulation of food and medicine homology substances catalogs was issued. On this basis, four suggestions for CMM production were proposed.(1) It is suggested to speed up the formulation of the national catalog of Dao-di herbs and carry out the certification of Dao-di herbs production bases.(2) Ecological planting of forest and grassland medicine should be further strengthened in terms of technical research and promotion based on the principle of ecological priority.(3) The basic work of disaster prevention should be paid more attention and technical measures for disaster mitigation should be developed.(4) The planted area of commonly used CMM should be incorporated into the national regular statistical system.

[Analysis and evaluation of paddy-upland rotation of Gastrodia elata- Oryza sativa in Dabie Mountains].

Gastrodia elata, as the valuable Chinese medicinal material, has been used for more than 2 000 years in China. With the increasing market demand for G. elata, the traditional wild resources have been unable to transform into commodities. At present, local authorities give full play to the advantages of natural resources and vigorously cultivate G. elata to form the cultivation mode and technical system with local characteristics. Huanggang Comprehensive Experimental Station of National Technical System of Chinese Medicinal Materials Industry has optimized and summarized the paddy-upland rotation of G. elata-Oryza sativa in Dabie Mountains of Hubei province through field visits and guidance for four consecutive years. Based on the ecological adaptability and planting characteristics of G. elata and O. sativa, and the actual production experience of farmers, analyzed the principle of paddy-upland rotation from production environment selection and fungus treatment, and evaluated the paddy-upland rotation of G. elata-O. sativa from production status, ecological benefits, and economic benefits. The paddy-upland rotation of G. elata-O. sativa has achieved efficient cultivation of G. elata and produced considerable economic benefits. Through the summary, analysis, and evaluation of the paddy-upland rotation mode of G. elata-O. sativa in Dabie Mountains, the present study put forward the optimization strategy of cultivation technology for G. elata in low-altitude areas, i.e., to use artificial Armillaria sticks instead of traditional cut-log for substitute cultivation of G. elata, which can effectively alleviate the "bacteria-forest contradiction" arising from the cultivation of G. elata. It can also improve the ecological environment and production status of the Dabie Mountains and even the G. elata producing areas at the same altitude.

[Contributions and strategies of eco-agriculture of Chinese medicine services for carbon dioxide peaking and carbon neutrality].

Carbon dioxide peaking and carbon neutrality have become hot issues of political and economic activities in China and abroad. The structure and development of various industries in China will be profoundly affected in the process of accomplishing "Dual Carbon" goals. Eco-agriculture of Chinese medicine(EACM) highlights the balance and sustainable development of the ecosystem while producing high-quality medicinal materials. With chemically synthesized fertilizers, pesticides, and growth regulators prohibited, EACM emphasizes the recycling of agricultural and sideline products and the reduction of waste output, which results in the minimal negative impact on the ecological environment. Therefore, it is typical agriculture with low-carbon sources and high-carbon sinks. This study reviewed the mechanism and potential of EACM in carbon dioxide peaking and carbon neutrality, analyzed the specific ways of EACM in reducing carbon sources and increasing carbon sinks based on the typical ecological planting pattern, and proposed the point of view to strengthen EACM as well as the "Dual Carbon" theory and research methods, so as to direct low-carbon and efficient deve-lopment. Furthermore, this study advocated to comprehensively promote the transformation of Chinese medicine production from chemical agriculture to eco-agriculture to improve the comprehensive benefits of contribution rate of carbon neutrality, explore and establish carbon sink compensation mechanism to ensure the sustainable and healthy development of EACM, and strengthen the training of EACM and "Dual Carbon" theory and technologies to continuously improve the capacity of EACM in sustainable development. This study is expected to provide a reference for the development of ecological functions in EACM and the development of economic functions through ecological functions.

[Strategic analysis on value accounting and realization of ecological products of Chinese materia medica].

Green agriculture has become the "wind vane" of agricultural reform in the new era. The development concept of Chinese materia medica(CMM) ecological agriculture and the emergence of new technologies provide momentum for the supply of high-quality green ecological products. As special ecological products, Dao-di herbs have medicinal, economic, ecological, and cultural values. The ecological planting of CMM and the value realization of ecological products are of great significance for the high-quality development of CMM agriculture and for prospering agriculture by improving quality. Therefore, this paper reviews the development status and typical cases, and puts forward the advantages of ecological product value realization of Dao-di herbs. On this basis, a value accounting system for ecological products of CMM was constructed from three aspects: supply services, ecological services, and cultural services. Finally, the suggestions for realizing the value of CMM ecological products are put forward.(1)It is suggested to strengthen the practice of ecological planting and production of CMM, and innovate the value realization model of ecological products.(2)The ecological planting bases of Dao-di herbs should be constructed to enhance the supply capacity of high-quality ecological products.(3)The quality and safety of ecological CMM should be improved to create the ecological planting brand of Dao-di herbs.(4)The ecological product value system and mechanism should be improved for realizing the value of CMM ecological products.(5)The education and publicity should be strengthened to raise the public awareness of the value of CMM ecological products.

[Assessment of soil fertility in Artemisia argyi planting areas in Qichun county based on minimum data set].

This study aims to explore the soil fertility in the main Artemisia argyi planting areas in Qichun county.To be specific, the soil physical and chemical properties in the main planting areas of A.argyi in Qichun county were analyzed.On this basis, 12 indexes were selected for principal component analysis(PCA) which was then combined with the norm value of each index and the correlation coefficients between the indexes to establish the minimum data set(MDS).The radar map was plotted to directly demonstrate the level of each index and the comprehensive level of the sampling sites.The comprehensive index model was used to calculate the soil fertility quality index(SFQI) of the total data set(TDS) and MDS(SFQI-TDS and SFQI-MDS, respectively), and linear regression of the two was performed.The results showed that the indexes that made up the MDS for soil fertility evaluation were pH, available potas-sium, available iron, available zinc, available manganese, available copper, and available magnesium.The radar map suggested the greatest difference in soil organic matter and smallest difference in available nitrogen among the 14 sampling sites.Moreover, the overall content of available phosphorus and available iron was high, while that of available nitrogen was the lowest.The SFQI-MDS which was yielded based on the weight of each index in MDS calculated with the norm value was more sensitive and the SFQI had stronger correlation with TDS-SFQI, which can better represent TDS-SFQI.SFQI-MDS was in the range of 0.298-0.784, with the average of 0.565 and variation coefficient of 18.38%.Caohe Town had the highest average SFQI-MDS.Clustering of SFQI-MDS value suggested that the soil fertility can be classified into 4 levels: level Ⅰ(SFQI ≥ 0.677) indicated excellent soil fertility, which accounted for 11.24%(mainly in Qingshi town, Balihu, and Zhangbang town); level Ⅱ(0.571≤SFQI≤0.680) meant good fertility, which made up 43.82%(mainly in Caohe town, Hengche town, and Pengsi town); level Ⅲ(0.466≤SFQI≤0.557) indicated average fertility, which took up 32.58%(mainly in Chidong town and Zhulin town); level Ⅳ(SFQI≤0.421) suggested poor fertility, which accounted for 12.36%(mainly in Guanyao town).It is recommended that nitrogen, potassium, magnesium, and calcium fertilizers should be increased and organic ferti-lizer should be applied for the cultivation of A.argyi in Qichun county to improve soil fertility and soil physical and chemical properties.

HYOU1 facilitates proliferation, invasion and glycolysis of papillary thyroid cancer via stabilizing LDHB mRNA.

HYOU1 is upregulated in many kinds of cancer cells, and its high expression is associated with tumour invasiveness and poor prognosis. However, the role of HYOU1 in papillary thyroid cancer (PTC) development and progression remains to be elucidated. Here, we reported that HYOU1 was highly expressed in human PTC and associated with poor prognosis. HYOU1 silencing suppressed the proliferation, migration and invasion of PTC cells. Mechanistic analyses showed that HYOU1 silencing promoted oxidative phosphorylation while inhibited aerobic glycolysis via downregulating LDHB at the posttranscriptional level. We further confirmed that the 3'UTR of LDHB mRNA is the indirect target of HYOU1 silencing and HYOU1 silencing increased miR-375-3p levels. While LDHB overexpression significantly suppressed the inhibitory effects of HYOU1 silencing on aerobic glycolysis, proliferation, migration and invasion in PTC cells. Taken together, our findings suggest that HYOU1 promotes glycolysis and malignant progression in PTC cells via upregulating LDHB expression, providing a potential target for developing novel anticancer agents.

[Progress in studies and control strategies for diseases of Coptis chinensis].

Coptis chinensis is one of bulk traditional herbal medicines in China. In recent years, the occurrence of various diseases has caused great yield loss and quality reduction of C. chinensis, which has become an important threat of herbal medicine industry. Here we reviewed the symptoms, pathogens, epidemiology and control methods of 6 common diseases of C. chinensis including root rot, southern blight, violet root rot, leaf spot, powdery mildew, and anthracnose. This review aims at providing guidance for the disease diagnostic, pathogen identification, and control strategies of the diseases on C. chinensis, and facilitate the growth of traditional medicine industry.

[Analysis of economic benefits of Chinese medicine eco-agriculture based on multiple stakeholders].

As the most advanced environment-friendly production model in the international society, ecological agriculture of Chinese materia medica(CMM) is the only way for the development of modern agriculture. With the proposal of the declaration on ecolo-gical agriculture of CMM, "Don't grab land from farmland, don't be enemies of grass and insects, don't be afraid of barren slopes and forests, and live up to the green and green mountains", the ecological planting of CMM has blossomed all over the country, and formed a scientific theory, technology and model. Based on the theory and method of economics, this paper expounds the comprehensive benefits and development advantages of ecological agriculture of CMM from the perspectives of farmers(producers), patients(consumers) and the country. From the perspective of medicinal farmers, the input and output income of conventional agriculture and ecological agriculture of CMM such as Panax ginseng, Astragalus propinquus, Atractylodes lancea, and Bupleurum chinense were compared, and it was found that ecological agriculture of CMM had obvious advantages in net income, average annual income and input-output ratio, which could better promote farmers' income. From the perspective of patients, according to the same dose, the content of active ingredients in ecologically planted CMMs is significantly higher than that in conventionally-planted herbs, and the amount of effective substances taken by patients is also higher, so as to achieve better therapeutic effect. At the national level, ecological planting of CMM is the key to ensuring the high-quality development of CMM industry, increasing farmers' income, ensuring the safety of people's drug use and promoting the sustainable development of agriculture. It is also an important part of realizing the harmonious development of economy, society and environment and promoting ecological civilization. In general, the declaration on ecological agriculture of CMM embo-dies the core characteristics and goals of ecological agriculture, and also points of the path and vision of ecological agriculture of CMM in the future. The declaration will guide production practice, promote the benefit of farmers, and lay the foundation for the sustainable development of CMM industry.

p53-dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation.

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.

AUF1 modulates TGF-ß signal in renal tubular epithelial cells via post-transcriptional regulation of Nedd4L expression.

Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models. While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion mediated by TGF-ß was significantly compromised. Mechanically, AUF1 downregulation decreased phosphorylated Smad2/3 via increasing their E3 ligase Nedd4L at the posttranscriptional level. In addition, the current study identified Nedd4L as a previously unreported target of AUF1. AUF1 regulates Nedd4L expression at the posttranscriptional level by interaction with AREs in the 3'UTR of the Nedd4L mRNA. Collectively, the current study indicates that AUF1 might be a potential player in renal tubulointerstitial fibrosis through modulation of TGF-ß signal transduction via posttranscriptional regulation of Nedd4L.

[Influence and mechanism of stress combination on medicinal plants secondary metabolism].

Numerous studies showed that the growth of medicinal plants in their native areas was simultaneously affected by abiotic stress combinations. Compared with single stress, plants have unique responses to a combination of different abiotic stresses and cannot be inferred directly from plants' responses to each individual stress. The effect of combined stresses on plants usually has three types of synergistic antagonism or independence. The secondary metabolism in the process of medicinal plant stress combination response also played a vital role, and environmental stresses can spur the accumulation of secondary metabolites, but under the stress combination, plants induce specific gene expression of key enzymes on secondary metabolic pathways, in turn, the accumulation of secondary metabolites against stress is formed. When plants are subjected to stress combination, the interaction of multiple signaling pathways makes it highly complex for plants to respond to stress combination. This paper summarized the effects of stress combination on physiological and secondary metabolism of medicinal plants, and discussed the related physiological, biochemical and molecular mechanisms. It provides theoretical basis for improving the adaptability of medicinal plants to adversity, improving the quality of Chinese medicinal materials, and further optimizing the cultivation of medicinal plants.

BAG3-positive pancreatic stellate cells promote migration and invasion of pancreatic ductal adenocarcinoma.

BAG3 is constitutively expressed in multiple types of cancer cells and its high expression is associated with tumour progression and poor prognosis of PDAC. However, little is known about the role of BAG3 in the regulation of stromal microenvironment of PDAC. The current study demonstrated that beside PDAC tumour cells, BAG3 was also expressed in some activated stroma cells in PDAC tissue, as well as in activated PSCs. In addition, the current study demonstrated that BAG3 expression in PSCs was involved in maintenance of PSCs activation and promotion of PDACs invasion via releasing multiple cytokines. The current study demonstrated that BAG3-positive PSCs promoted invasion of PDACs via IL-8, MCP1, TGF-ß2 and IGFBP2 in a paracrine manner. Furthermore, BAG3 sustained PSCs activation through IL-6, TGF-ß2 and IGFBP2 in an autocrine manner. Thereby, the current study provides a new insight into the involvement of BAG3 in remodelling of stromal microenvironment favourable for malignant progression of PDAC, indicating that BAG3 might serve as a potential target for anti-fibrosis of PDAC.

Sestrin 2 protects against metabolic stress in a p53-independent manner.

Glucose limitation activates p53, which functions as an adaptive response to maintain cell survival. However, p53 is frequently deleted or mutated in a variety of tumors, while most cancer cells can acclimatize themselves to metabolically unfavorable surrounding, indicating that alternative mechanisms other than p53 transactivation underly adaptive response of cancer cells with p53 deletion or mutation to metabolically hostile environment. Sestrin 2 (SESN2) is a p53 downstream target, which plays a protective role against various stressful stimuli, such as genotoxic, energetic, and oxidative stress. In the current study, we demonstrated that SESN2 transcript was stabilized by glucose limitation at the posttranscriptional level irrespective of p53 status. Importantly, SESN2 also protected cells from metabolic stress triggered by glucose limitation in a p53-independent manner. Our data indicated that stabilization of SESN2 transcript might be an alternative adaptive response to metabolic stress other than p53 activation. Thereby, the current study highlights the significance of stabilization of SESN2 transcript in adaptation of cells with p53 deletion or mutation to metabolic stress.

BAG3 promotes proliferation of ovarian cancer cells via post-transcriptional regulation of Skp2 expression.

Bcl-2 associated athanogene 3 (BAG3) contains a modular structure, through which BAG3 interacts with a wide range of proteins, thereby affording its capacity to regulate multifaceted biological processes. BAG3 is often highly expressed and functions as a pro-survival factor in many cancers. However, the oncogenic potential of BAG3 remains not fully understood. The cell cycle regulator, S-phase kinase associated protein 2 (Skp2) is increased in various cancers and plays an important role in tumorigenesis. The current study demonstrated that BAG3 promoted proliferation of ovarian cancer cells via upregulation of Skp2. BAG3 stabilized Skp2 mRNA via its 3'-untranslated region (UTR). The current study demonstrated that BAG3 interacted with Skp2 mRNA. In addition, miR-21-5p suppressed Skp2 expression, which was compromised by forced BAG3 expression. These results indicated that at least some oncogenic functions of BAG3 were mediated through posttranscriptional regulation of Skp2 via antagonizing suppressive action of miR-21-5p in ovarian cancer cells.

[Community structure and diversity of soil bacteria in rhizosphere of Salvia miltiorrhiza and Salvia miltiorrhiza f. alba based on pyrosequencing].

Rhizosphere bacteria play a vital role in plant nutrition absorption,growth and disease resistance. In this study,high-throughput sequencing technology was used to analyze the rhizosphere bacterial communities of Salvia miltiorrhiza and S. miltiorrhiza f. alba. Moreover,the function of dominant rhizosphere bacterial communities was analyzed. We found that Sphingobacteriales,Sphingomonadales and Nitrosomonadaceae were both dominant and specific bacteria in the rhizosphere of S. miltiorrhiza. The main functions of dominant rhizosphere bacteria communities in both species include promoting transformation of soil nutrients,improving plant immunity and ability of stress tolerance. This study was the first to compare rhizobacterial communities structure and function of S. miltiorrhiza and S. miltiorrhiza f. alba,which provided a new theoretical reference for studing the rhizosphere mechanism of healthy S. miltiorrhiza planting in the future.

[Status and further development of regulation for pesticide registration for Chinese medicinal materials].

Nowadays, the cultivation of traditional Chinese medicinal materials is faced with the problems of pesticides illegal uses and pesticides residues. In the early period of eco-agriculture of Chinese materia medica, the uses of pesticides in special time is still inevitable. However, the registration of pesticides for Chinese medicinal materials now is far from enough to meet demand. So it is necessary to publish policies to expand the pesticides registration for Chinese medicinal materials. We collected and analyzed the data of pesticide registration for Chinese medicinal materials, the results showed that till March 2018, there were 10 kinds of Chinese medicinal materials, 91 pesticide products and 46 kinds of pesticide ingredients registered. Based on the current status of the pesticide management in China and the experience of the registration pesticide for minor crops in countries around the world, we point out that the pesticide registration for Chinese medicinal materials should be carried out in the form of minor crops and some specific methods are also provided in this paper.

[Sulfur dioxide limit standard and residues in Chinese medicinal materials].

The traditional sulfur fumigation processing method has been widely used in the initial processing and storage of traditional Chinese medicinal materials due to its economy, efficiency, convenience, high operability and effect on mold and insect prevention. However, excessive sulfur fumigation of traditional Chinese medicinal materials would lead to the changes in chemical compositions, and even endanger human health. This study showed that traditional Chinese medicinal materials were sulfur fumigated directly after being harvested for quick drying, or fumigated after being weted in the storage process for preventing mold and insects. We found that the sulfur dioxide limits for traditional Chinese medicinal materials were stricter than those for foods. Based on the existing limit standards, we obtained the data of sulfur dioxide residues for 35 types of traditional Chinese medicinal materials in a total of 862 batches. According to the limit standard in the Chinese Pharmacopoeia (150， 400 mg·kg⁻¹), the average over-standard rate of sulfur dioxide was as high as 52.43%, but it was reduced to 29.47% if calculated based on the limit for vegetable additive standard (500 mg·kg⁻¹). Sulfur fumigation issue shall be considered correctly: sulfur dioxide is a type of low toxic substance and less dangerous than aflatoxin and other highly toxic substances, and a small amount of residue would not increase the toxicity of traditional Chinese medicinal materials. However, sulfur fumigation might change the content of chemical substances and affect the quality of traditional Chinese medicinal materials. Furthermore, the exposure hazards of toxic substances are comprehensively correlated with exposure cycle, exposure frequency, and application method. In conclusion, it is suggested to strengthen the studies on the limit standard of traditional Chinese medicinal materials, formulate practical and feasible limit standard for sulfur dioxide residues in traditional Chinese medicinal materials that are consistent with the medication characteristics of traditional Chinese medicinal materials and can guarantee people's demand for safe medication.

[Quantitative analysis and stability of p-hydroxybenzyl hydrogen sulfite in sulfur-fumigated Gastrodiae Rhizoma].

Studies on the characteristic chemical markers of sulfur fumigation have become an effective auxiliary way for quality control of traditional Chinese medicine. This study established a quantitative analysis method for the determination of p-hydroxybenzyl hydrogen sulfite (p-HS) in Gastrodiae Rhizoma (GR) based on UPLC-MS/MS. Then, 37 batches of GR were screened, and the results showed that 27 batches of them were sulfur-fumigated. Especially, the GR samples in Yunnan producing areas were sulfur-fumigated more seriously. Based on the stability of p-HS after different storage time and heat treatment methods, it was found that the content of p-HS was stable and reliable in the storage period of 8 months and under normal heat treatment (50, 60, 70, 80 °C) conditions. In conclusion, this study shows a high sensitivity, good selectivity and good stability of p-HS, which can provide reference for the quality control and sulfur fumigation screening of GR.

[Changes of chemical compositions and sulfur dioxide residues of Gastrodiae Rhizoma with different storage times].

To study the effect of different storage time on the chemical compositions and sulfur dioxide residues of sulfur-fumigated Gastrodiae Rhizoma (GR), and provide scientific basis for solving the quality and safety issues of sulfur-fumigated traditional Chinese medicinal materials. GR, sulfur-fumigated GR and its medicinal slices were stored under the same conditions, and then 8 active ingredients and sulfur dioxide residues were measured respectively. The results showed that the content of gastrodins in sulfur-fumigated GR and its medicinal slices was significantly lower than that in the non-fumigated GR. Moreover, the content of sulfur dioxide residue in sulfur-fumigated GR was significantly higher than that in its medicinal slices. That is to say, sulfur fumigation degree had significantly higher effect on GR quality as compared with its medicinal slices. During the whole storage time (8 months), the content of the eight chemical components in GR was not changed greatly in general. However, after the storage for 4 months, the content of 8 components and sulfur dioxide residues in all of GR samples were significantly changed. In particular, the content of sulfur dioxide residue in GR medicinal materials decreased up to 50% or more.

[Quality changes in Gastrodia Rhizoma of different origins and forms before and after sulfur fumigation].

As Gastrodiae Rhizoma (GR) is one of the herbs more seriously affected by sulfur fumigation, so its quality has been always of a great concern. In this paper, GR samples collected from eight main producing areas and in three forms were fumigated with sulfur and quantitatively and qualitatively analyzed based on UPLC-Q-TOF-MS/MS. The results showed that the contents of gastrodin, parishin, parishin B and parishin C were decreased, while the content of parishin E was increased after sulfur fumigation treatment. Besides, a new sulfur marker named p-hydroxybenzyl hydrogen sulfite was produced in sulfur-fumigated GR samples. As compared with producing origins, forms had a greater impact on the quality of GR, especially in Hongtianma and Wutianma. Besides, the contents of gastrodins and parishins in Hongtianma from Jilin were lowest as compared with those in other producing areas. This might be correlated with planting patterns and environmental factors. In conclusion, sulfur fumigation has a more obvious impact on the quality of GR than origins and forms, which is attributed to the generation of new sulfur fumigated markers.