Interpretation of guidance on non-clinical safety evaluation for nanomedicines / 药学学报

With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.

Micro-computed tomography evaluation of the effects of orthodontic force on immature maxillary first molars and alveolar bone mineral density of Sprague–Dawley rats / 대한치과교정학회지

Objective@#To investigate changes in the immature teeth of Sprague–Dawley rats during orthodontic treatment and to explore the changes in the peri-radicular alveolar bone through micro-computed tomography (CT). @*Methods@#Twenty-five 26-day-old male Sprague–Dawley rats were included. The maxillary left first molar was moved mesially under a continuous force of 30 cN, and the right first molar served as the control. After orthodontic treatment for 7, 14, 21, 28, and 42 days, the root length, tooth volume, and alveolar bone mineral density (BMD) around the mesial root were measured through micro-CT. @*Results@#The immature teeth continued to elongate after application of orthodontic force. The root length on the force side was significantly smaller than that on the control side, whereas the differences in the volume change between both sides were not statistically significant. Alveolar bone in the coronal part of the compression and tension sides showed no difference in BMD between the experimental and control groups. The BMD of the experimental group decreased from day 14 to day 42 in the apical part of the compression side and increased from day 7 to day 42 in the apical part of the tension side. The BMD of the experimental group decreased in the root apex part on day 7. @*Conclusions@#The root length and volume of immature teeth showed continued development under orthodontic forces. Alveolar bone resorption was observed on the compression side, and bone formation was observed on the tension side.

Overview of Chinese medicinal materials industry in 2021 and development suggestions / 中国中药杂志

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.

The role of gut microbiota in eye diseases / 中华实验眼科杂志

In recent years, the study of symbiotic microbial community on human health and disease has gradually become a hot spot.In particular, the Human Microbiome Project and the emergence of 16S rRNA gene sequencing technology have further promoted the study of human-related microbiota.The gut microbiota is the largest microecosystem of the human body.Normal gut microbiota plays an important role in maintaining host immune balance, promoting nutrient metabolism and sustaining intestinal homeostasis.At present, there is increasing evidence that gut microbiota disorders are associated with a variety of diseases, not only having an impact on the intestinal tract but also affecting many extraintestinal tissues and organs.With the emergence of the concept of gut-brain axis, which interacts between gut microbiota and brain, some researchers suggest that there may also be gut-eye axis between gut microbiota and eye.This review summarized the recent research advances on the role of gut microbiota in ophthalmic diseases, including corneal diseases, uveitis, retinopathies, and the ophthalmic diseases associated with systemic diseases, in the hope that it could provide evidence for the existence of gut-eye axis and new idea for the treatment of ophthalmic diseases in the future.

Chinese medicinal materials industry during the 14th Five-Year Plan period: trends and development suggestions / 中国中药杂志

This study steps through the future perspectives and gives the development suggestions of Chinese medicinal materials(CMM) industry by presenting the characteristics and open problems during the 13 th Five-Year Plan period. The development of CMM industry presents the following trends:(1)the development of Dao-di herbs speeds up with the increasing demand for high-quality CMM;(2)the mismatch between supply and demand is aggravating, which presses for supply-side structural reform;(3)ecological planting will become the core mode of production and bolster rural revitalization;(4)the demand for CMM with both medical and edible values keeps growing, and the antibiotic-free feed policy brings significant opportunities;(5)the "Internet Plus CMM" wave emerges, which promotes the construction of traceability system. Finally, we put forward the following suggestions for the sustainable development of CMM industry:(1)optimizing the layout for the production of Dao-di herbs according to local conditions;(2)strengthening the commercialization of the seeds and the breeding, multiplication, and extension of CMM to accelerate the realization of specialized seed production, mechanized seed processing, localized variety layout, and county-based unified seed supply;(3)ensuring the safety of pesticide use and accelerating the registration of special pesticides;(4)promoting both theoretical and practical research on ecological production of CMM;(5)publicizing the demonstration and popularization of CMM traceability system. Overall, significant progress has been achieved in the CMM industry during the 13 th Five-Year Plan period, and this industry is in a critical stage of high-quality development, facing both challenges and opportunities.

Exosomal Circular RNAs Mediates Chemotherapy Resistance in Tumors / 中国生物化学与分子生物学报

As an important member of the non-coding RNA family, circRNA is a kind of single-stranded RNA with a covalently closed loop structure without a polyadenylated acid tail and 5'-3' end, showing high stability, abundance and conservation across species characteristics. Recent studies have shown that circRNA plays an important role in many biological processes, including chemotherapy resistance and malignant progression. Exosomes are small extracellular phospholipid bilayer vesicles with a diameter of30-150 nm that are secreted by living cells. They can be used as carriers to encapsulate and transfer functional molecules. Exosomes are important mediators of communication between tumor cells and stromal cells. They can play a role in the transmission of chemoresistance by transferring circRNA. Aschemotherapy resistance is still a huge obstacle to the prognosis of cancer, the research of exosomalcircRNA-mediated tumor chemotherapy resistance is at the forefront of academic research, which is a blueocean with important significance. In this paper, we summarized the latest research progress in the aspects of exosome delivery of circRNA, the mechanism of exosome sorting non-coding RNA cargo, circRNA-mediated tumor chemotherapy resistance, exosome delivery of circRNA-mediated tumor chemotherapy resistance and its potential clinical application, which may provide a reference for the research of tumor chemotherapy resistance.

Research progress and prospect of endophytes from medicinal plant Atractylodes lancea / 中国中药杂志

The endophytes of medicinal plants play an important role in promoting the quality formation of the host. Therefore, this paper made a review of endophytes of medicinal plant Atractylodes lancea. According to previous studies, A. lancea boasts endophytes, such as fungi, bacteria, and actinomycetes, among which the beneficial microorganisms help the growth and development of A. lancea. There is a close interaction between the volatile oil of A. lancea and endophytes. Different endophytes vary in regulating the composition and content of the volatile oil of A. lancea, which might contribute to the quality formation of A. lancea. However, the information of the endophytic flora of A. lancea obtained by traditional culture and isolation is not enough to reflect the real situation of the endophytes of A. lancea. Little is known about the endophytes of A. lancea from different chemical types and different habitats, which is not conducive to the study of the ecological relationship between A. lancea and endophytes and limits the development and utilization of the endophytes. Therefore, at the end of this paper, the authors put forward suggestions for future research on endophytes in A. lancea, including:(1)mining the core endophyte resources of A. lancea by combining high-throughput sequencing with traditional culture and isolation;(2)exploring the relationship between the diversity of endophytes and chemical types of A. lancea;(3)strengthening the application of endophytes in A. lancea cultivation, in order to facilitate the cultivation efficiency and quality of A. lancea.

Expression of lncRNA Tsix in a mouse model of N-methyl-D-aspartic acid-induced retinal excitotoxicity and its significance / 中华实验眼科杂志

Objective:To investigate the damage effect of different concentrations of N-methyl-D-aspartic acid (NMDA) to retinal ganglion cells (RGCs) in mice and explore the expression of long noncoding RNA (lncRNA) Tsix in the retina of mice with excitotoxicity as well as the protective effect of lncRNA Tsix on retina and RGCs.Methods:A total of 105 C57B6/J mice at 7-8 weeks of age were selected and randomly divided into the normal control group, 2 mmol/L NMDA group, 10 mmol/L NMDA group, 20 mmol/L NMDA group and 40 mmol/L NMDA group using a random number table method, with 21 mice in each group.In the normal control group, the mice were intravitreally injected with 1 μl of sodium chloride solution in the right eye, and mice were given intravitreal injection of 1 μl of different doses of NMDA according to grouping.At one week after the injection, the thickness of each retinal layer, the number of ganglion cell layer (GCL) cells and the number of RGCs were analysed and compared among different groups through optical coherence tomography (OCT), hematoxylin-eosin staining, retinal whole mount staining and immunofluorescence staining.RNAscope in situ hybridization was used to verify the expression of lncRNA Tsix in the GCL of different groups.The quantitative real-time PCR was used to detect the transcript levels of Tsix in different groups.This study was approved by an Ethics Committee of Tianjin Medical University (No.SYXK2018-0004), and the use of experimental animals was in accordance with the regulations of Tianjin Medical University and ARVO statement. Results:The OCT results showed that the total retinal thickness of mice in the 2, 10, 20 and 40 mmol/L NMDA groups were (255.00±6.63), (252.40±6.41), (248.67±6.20) and (229.11±10.37)μm, respectively, which were thinner than (269.60±20.01)μm in the normal control group, and the differences were statistically significant (all at P<0.05). Hematoxylin-eosin staining showed that the cells in the GCL of the normal control group were uniform and compact, and arranged in a single layer with large and round nuclei.In the NMDA groups, the cells were uneven in volume with vacuoles and nuclear pyknosis.The cell density in the GCL was decreased significantly with the increasing NMDA doses in NMDA groups in comparison with the normal control group, and the differences were statistically significant (all at P<0.05). In the 20 mmol/L NMDA group, the cell density in the GCL was reduced to half of the normal control group.The results of retinal whole mount staining showed that the density of β3-tubulin-positive RGCs was decreased significantly as the dose of NMDA increased in NMDA groups, and the differences were statistically significant compared with the normal control group (all at P<0.05). The number of RGCs in the 10 mmol/L NMDA group was reduced to half of that in the normal control group.RNAscope results showed that lncRNA Tsix was mainly expressed in the cytoplasm of the GCL cells.The proportion of lncRNA Tsix-positive cells was significantly reduced with the increase of the NMDA dose ( F=13.670, P<0.01). The quantitative real-time PCR results verified that the trend of Tsix expression was consistent with the RNAscope result. Conclusions:NMDA exerts a dose-dependent damage to the layer thickness of mouse retina and RGCs.The expression of lncRNA Tsix in mouse retina is mainly enriched in the cytoplasm of the cells in the GCL, and the transcript level of Tsix is reduced with the increase of NMDA concentration and have a protective effect on RGCs.

Cloning and characterization of two rhamnose synthases from Sorbus aucuparia / 药学学报

Rhamnose synthase (RHM) is a key enzyme in the biosynthesis of uridine diphosphate rhamnose (UDP-Rha), reversibly converting uridine diphosphate-glucose (UDP-Glc) into UDP-Rha in the presence of NADH or NADPH. In this research, yeast extract (YE) was used to stimulate Sorbus aucuparia suspension cells. Based on a previous study of the transcriptome database of S. aucuparia suspension cells, two RHMs were cloned from S. aucuparia and named SaRHM1 (GenBank No.: MK213340) and SaRHM2 (GenBank No.: MK213341). The SaRHM1 gene contained a 2 007 bp open reading frame (ORF) encoding a polypeptide of 668 amino acids with a molecular weight of 75.25 kD, and a theoretical isoelectric point (pI) of 7.24. The SaRHM2 gene contained a 2 040 bp ORF encoding a polypeptide of 679 amino acids with a molecular weight of 76.26 kD and pI of 6.41. Bioinformatic analysis indicated that SaRHM1 and SaRHM2 contained two special sequences of GxxGxxG/A and YxxxK. Multiple sequence alignments and phylogenetic trees show that SaRHM1 and SaRHM2 have high sequence similarity with other plant species of RHMs. The results of enzyme activity assays in vitro revealed that both recombinant SaRHM1 and SaRHM2 are able to convert UDP-Glc into UDP-Rha. SaRHMs displayed maximum activity at 40 ℃ and a pH of 8 and 9, respectively. The Km values of SaRHM1 and SaRHM2 for UDP-Glc were 212.4 ± 56.70 and 361.0 ± 63.74 μmol·L-1, respectively, with Vmax values of 235.5 ± 18.98 and 516.5 ± 22.30 nmol·min-1·μg-1, respectively. This study reports the cloning and sequencing of RHMs from S. aucuparia and verifies their function, which likely provide rhamnose donors for the subsequent biosynthesis of rhamnosides.

Effect of combined application of inorganic and organic fertilizers on growth and quality of Salvia miltiorrhiza / 中国中药杂志

The study is aimed through field experiments to study the effect of combined application of organic and chemical fertilizers on the growth and quality of Salvia miltiorrhiza, provide ideas for reducing fertilization while increasing the efficiency as well as improving the quality of produces. The experiment included 6 treatments viz., no fertilization(CK), full application of chemical fertilizer(F), 25% orga-nic fertilizer with 75% chemical fertilizer(M25), 50% organic fertilizer with 50% chemical fertilizer(M50), 75% organic fertilizer with 25% chemical fertilizer(M75), and fully apply organic fertilizer(M100). The results showed that:(1)from the perspective of yield and economic benefits, M75 was the best and M100 second;(2)for effective components, the combined application of organic and chemical fertilizers increased the content of main water-soluble components and the total content of effective components, among which M25 and M50 were better.

Effects and mechanisms of nitrogen application on stress resistance of Chinese materia medica / 中国中药杂志

Nitrogen fertilizers play an important role in the regulation of plant stress resistance. Impacts of nitrogen fertilizers on abiotic stress resistance and biotic stress resistance of Chinese materia medica(CMM) were summarized in this study. Adequate nitrogen application improves the abiotic stress resistance and weed resistance of CMM, however adverse effect appears when excess nitrogen is used. Generally, pest resistance decreases along with nitrogen deposition, while effects of nitrogen application on disease resistance vary with different diseases. Mechanisms underlying the impact of nitrogen fertilizers on plant stress resistance were also elucidated in this study from three aspects including physical defense mechanisms, biochemistry mechanisms and molecular defense mechanisms. Nitrogen availability modulates physical barrier of CMM like plant growth, formation of lignin and wax cuticle, and density of stomata. Growth of CMM promoted by nitrogen fertilizer may cause some decrease in pest resistance of CMM due to an increase in hiding places for pest along with plant growth. High ambient humidity caused by excessive plant growth facilitates the growth and development of CMM pathogen. Nitrogen application can also interfere with the accumulation of lignin in CMM which makes CMM more vulnerable to pest and pathogen attack. Stomatal closing delays due to nitrogen application is also a causal factor of increasing pathogen infection after nitrogen deposition. Biochemical defenses of plants are mainly achieved through nutrient elements, secondary metabolites, defense-related enzymes and proteins. Nutritional level of CMM and various antioxidant enzymes and resistance-related protein activities are elevated along with nitrogen deposition. These antioxidant enzymes can reduce the damage of reactive oxygen species content produced by plant in response to adversity and therefore enhance stress resistance of CMM. Researches showed that nitrogen application could also cause an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. Nitrogen-mediated molecular defense mechanisms includes multiple plant hormones and nitric oxide signals. Plant hormones related to plant defense like salicylic acid, jasmonic acid and abscisic acid can be modulated by nitrogen application. Negative effect of nitrogen deposition was found on salicylic acid accumulation and the expression of related plant disease resistance genes. However, jasmonic acid level can be elevated by nitrogen. Nitric oxide signals constitute an important part of nitrogen mediated defense mechanisms. Nitric oxide signaling is related to many aspects of plant immunity. The roles of nitrogen fertilizers in CMM stress resistance are complex and may vary with different CMM varieties and environments. Further studies are urgently needed to provide a comprehensive understanding of how to improve stress resistance of CMM by using fertilizers.

Effects and mechanisms of nitrogen fertilizers on soil and tritrophic interactions in Chinese medicinal plants ecosystem / 中国中药杂志

Nitrogen is one of the most frequently used fertilizers in growth of Chinese medicinal plants(CMP). As in many other ecosystems, CMP ecosystem is also composed of plant-herbivore-natural enemy(tritrophic) interactions. Nitrogen fertilizer influences the growth and reproduction of CMP, and it is also able to heavily shape the ecosystem functions of CMP ecosystem through bottom-up forces. Understanding the specific effects of nitrogen fertilizer towards each trophic level will be beneficial to improve the resistance of CMP to herbivore and enhance the control efficiency of nature enemies to herbivore, and eventually, maximize the yield and quality of CMP. Most papers published on nitrogen use in plants focused mainly on the impact of nitrogen fertilization on CMP yield and quality. Influences of nitrogen application on CMP ecosystem get little attention at present. Therefore, this review summed up the potential effects of nitrogen fertilization on CMP ecosystem from perspectives of soil and tritrophic interactions. First of all, nitrogen fertilizer might decrease soil microbial biomass and altered the community structures of soil bacteria, fungi and protozoa. Negative effects of nitrogen fertilizer were found on biodiversity of soil bacteria and protozoa. Different fungi species respond differently to nitrogen fertili-zers. Nitrogen deposition can also decrease the soil pH. Decreases in soil microbial diversity and soil acidification can cause negative effects on CMP growth. In addition, nitrogen fertilizer could regulate the pest resistance of CMP including constitutive and inducible resistance. Both positive and negative effects of nitrogen application were found on pest resistance of CMP. Moreover, the development and predation of natural enemies were influenced by nitrogen deposition. Nitrogen influences natural enemies in many ways including plant volatiles, plant nutrient and structure and the supplementary food quality. Nectar and honeydew of plants and preys serve as important food source for natural enemies especially in early season when preys are still not available. Finally, the interactions between herbivores and their natural enemies were also shaped by nitrogen fertilizer in many aspects like increasing the nutritional content of prey and changing control efficiency of natural enemies. Some herbivores have evolved a strategy to sequester secondary metabolites which they absorbed from plant during their feeding. Studies showed that sequestration efficiency of secondary metabolites in prey could also be regulated by nitrogen. Parasitic, emergence, reproduction rate and longevity of parasites were found positively correlated with nitrogen deposition. Hopefully this study will shed light on practicable and economical application of nitrogen in cultivation of CMP.

Current situation of nitrogen application and its effects on yield and quality of Chinese materia medica / 中国中药杂志

Nitrogen fertilizer has been the long-lasting crucial component in cultivation of Chinese materia medica(CMM) and crops for its profound effects on enhancing the productivity. In consideration of its role in better production, intensive and excessive application of N fertilizer is often found in CMM cultivation. Therefore, firstly, this review summarized various concentrations of N application with regards to different CMM and districts from the literatures published in the last two decades. The recommended concentration of nitrogen application of forty seven CMM species were covered in this review. We found that the optimum rates of nitrogen fertili-zer for different medicinal plants species were varied in the range between 0-1 035.55 kg·hm~(-2). Most of the optimum rates of nitrogen fertilizer for CMM in published researches fell between 100-199 kg·hm~(-2). The optimum rate of nitrogen fertilizer is not only related to amount of nitrogen required for different medicinal plants but also to soil fertilities of different fields. In addition, we outlined the diffe-rent effects of proper and excessive nitrogen deposition on yield of CMM. Proper nitrogen deposition benefits the yield of CMM, howe-ver, excessive nitrogen use accounts for a decrease in CMM yield. We elucidated that nutritional content, water use efficiencies, and photosynthesis capacity were major influencing factors. Researches showed that proper nitrogen fertilizer could promote the water use efficiencies of plants and boost photosynthesis. Consequently, the yield of CMM can be enhanced after nitrogen deposition. However, negative effects of nitrogen fertilizer were also found on plant including producing toxic substances to the soil and causing severe pest damages. Lastly we analyzed the impact of N fertilizer application on secondary metabolites which accounts for a large part of active pharmaceutical ingredients of CMM. It usually caused an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. The potential underlying mechanisms are the different synthetic pathways of these metabolites and the plant nutritional status. Synthesis of non-nitrogen-containing secondary metabolites like phenols can be inhibited after nitrogen application because of the competition of the same precursor substances between metabolites synthesis and plant growth. To sum up, impacts and mechanisms of nitrogen fertilizer on yield and quality enhancement of CMM were discussed in this review. Negative effects of excessive nitrogen application on CMM should be paid special attention in CMM cultivation and prescription fertilization based on the field soil quality is strongly recommended. Overall, this review aims to provides insights on improving the proper application of N fertilizer in the cultivation of CMM.

Advances in Mechanism of Traditional Chinese Medicines and Its Active Ingredients Treating Dyslipidemia / 中国实验方剂学杂志

Dyslipidemia is a disease of lipid metabolism. At present, the prevalence of dyslipidemia in adults in China is as high as 40.40%. In the United States, there are more than 100 million individuals with abnormal low-density lipoprotein cholesterol (LDL-C), and the incidence rate is increasing year by year and showing a trend of becoming younger. Dyslipidemia is closely related to a variety of diseases such as fatty liver, atherosclerosis , hypertension, coronary heart disease, diabetes, and stroke. It has now developed into a global public health problem that seriously threatens human life and health. Modern medicine believes that its pathogenesis is complicated and is related to abnormal glucose and lipid metabolism, insulin resistance (IR) and other factors. Chinese medicine ascribes it to primary asthenia-secondary sthenia syndrome, which is closely related to the liver, spleen, and kidney. It is believed that excessive fat and grease can cause phlegm and cause many diseases. In terms of its treatment, western medicine mainly uses statin chemical synthesis preparations, with stable therapeutic effect, but many adverse reactions such as myalgia, myositis, rhabdomyolysis and acute renal injury are the main factors restricting its clinical application. Traditional Chinese medicine (TCM) has a long history, and multi-pathway, multi-target, multi-level regulation of dyslipidemia, few adverse reactions and low drug dependence are the principal advantages of TCM in treating dyslipidemia. At present, there are more and more researches on the prevention and treatment of dyslipidemia by TCM, but they are mainly focused on the observation of curative effect and the summary of prescription, and there are relatively few in-depth discussion and summary of the mechanism of TCM. Through comprehensively retrieving and collating the relevant domestic and foreign literatures in the past five years, we reviews from the perspective of effective ingredients, therapeutic pathways, and targets of action, and comprehensively introduces the latest research progress of TCM on the mechanism of regulating dyslipidemia, and put forward some suggestions for the possible research direction in the future, in order to provide new ideas and theoretical basis for TCM in clinical prevention and treatment of this disease.

Changes in DNA methylation of retinal gene promoter regions and their significance in type 1 diabetic rats / 中华实验眼科杂志

Objective:To study the methylation level of retinal gene promoter region in a rat model of type 1 diabetes (T1D) and investigate the correlation between DNA methylation level and retinal damage caused by T1D.Methods:Twenty male SD rats aged 8-10 weeks were randomly divided into a control group and a T1D group using a random number table.T1D model was established via a rat tail vein injection of streptozotocin (STZ). The same volume of sodium citrate buffer was injected in the same way in the control group.Body mass of the rats was monitored before and after the injection of STZ.Blood glucose concentration of the rats was detected three days and five weeks following the injection.Methylated DNA immunoprecipitation-chip (MeDIP-chip) technology was employed to analyze the DNA methylation in the CpG islands of retinal gene promoter regions of the rats.Methylation data were compared between the two groups and subjected to Gene Ontology (GO) and pathway enrichment analyses.This study protocol was evaluated and approved by the Institutional Animal Care and Use Committee of Tianjin Medical University, and the use and care of the animals were in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.Results:Compared to the normal control group, typical deregulated metabolic syndromes were found in the T1D group.including hyperphagia, polydipsia, polyuria, and loss of body weight.According to the results of MeDIP-chip analysis, 1 478 differentially methylated gene loci were detected in the T1D group compared to the normal control group, of which 689 were hypermethylated and 789 hypomethylated.Of these differentially methylated loci 768, 365 and 345 were located in high, intermediate, and low CpG-density promoters, respectively.GO analysis showed that the differentially methylated genes were involved in some molecular functions such as protein binding.The pathway analysis revealed that the hypermethylated genes in the rats of the T1D group were associated with mitogen-activated protein kinase (MAPK) and calcium signaling pathways; whereas the hypomethylated genes were associated with MAPK, Notch, and glutamatergic synapse signaling pathways.Conclusions:Methylation level of the majority of genes was altered in T1D rats.A differential methylation in the retinal gene promoter regions provides a preliminary theoretical basis for elucidating the molecular mechanism underpinning diabetic retinopathy and searching for novel therapeutic targets.

Porcine circovirus 3 capsid protein induces autophagy in HEK293T cells by inhibiting phosphorylation of the mammalian target of rapamycin / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin-proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.

Pattern and matching technology of ecological planting for Chinese materia medica based on system level / 中国中药杂志

The ecological agriculture of Chinese materia medica(CMM) has become the most dynamic and promising new field in the global ecological agriculture. The development of ecological planting of CMM has become the national strategy of Chinese traditional medicine agriculture. It has been highly valued and has flourished throughout the country, and has formed some more mature ecological planting models of CMM. Based on the system level, this paper sorts out the common ecological cultivation patterns of CMM, and obtains five basic patterns: landscape pattern at the ecological landscape level, circulation pattern at the ecosystem level, stereo model at the bio-community level, biodiversity patterns at the level of biological populations and well-established models at the level of biological individuals. On this basis, eight common ecological planting techniques of CMM were obtained, includingwild tending techniques, fine agricultural farming techniques, directional cultivation techniques, soil improvement techniques, soil testing and fertilization techniques, mycorrhizal cultivation techniques, green control technology for pests and diseases and facility cultivation techniques.This paper aims to provide theoretical basis for scientific research and popularization and application of CMM ecological planting.

Pattern of ecological planting for Chinese materia medica based on regional distribution / 中国中药杂志

As an environment-friendly agriculture, ecological agriculture of Chinese materia medica(CMM) is being implemented in all parts of the country. Due to the stronger dependence on natural environmental conditions, ecological agriculture of CMM shows obvious regional differences in production practice. More mature CMM ecological planting patterns representative of each region were collected. It was found that common types of patterns in various regions of the country mainly included intercropping,intercropping,rotation planting mode, undergrowth planting mode, wild tending planting mode and landscape ecological planting mode. Based on the Construction Plan of National Dao-di Herbs Production Base(2018-2025) and Chinese Medicine Division, this paper systematically sorts out the pattern of ecological planting of CMM in the 8-avenue medicinal materials production areas according to the varieties and regions. The specific pattern of ecological planting of CMM included the ginseng undergrowth planting pattern in northeastern China, the bionics wild ecological planting of the Forsythia suspensa in northern China, the Fritillaria thunbergii-rice rotation in eastern China, the imitation wild planting pattern under the Polygonatum cyrtonema in central China, the planting pattern of the Fructus amomi under forest in southern China, the Ligusticum chuanxiong-rice rotation pattern in the Southwest, wild tending of Glycyrrhiza uralensis in the Northwest, and rhubarb imitation wild planting pattern in Qinghai-Tibet area. Finally, it is expected to provide reference for the screening and popularization of ecological planting patterns of other CMMs in various distribution areas.

Land use strategy of ecological agriculture of Chinese materia medica in future development / 中国中药杂志

With the rapid development of comprehensive health industry, the demand for Chinese medicinal materials is increasing. There is also a growing demand for land for the cultivation of Chinese medicinal materials.Based on the analysis of the demand characteristics of planting habitats for Chinese medicinal herbs, this paper finds that compared with the cultivated environment, the wild environment is more conducive to the improvement of the quality and stress resistance of medicinal plants. The eco-planting for Chinese medicinal materials is the only way to achieve high quality, efficient and sustainable production of traditional Chinese medicine. Therefore, according to the habitat distribution characteristics of wild medicinal plants, combined with the current situation of land resource utilization in China and the increasing demand for land for Chinese herbal medicine cultivation, the land use strategy of Chinese herbal medicine ecological agriculture was proposed. ① To vigorously develop underwood planting and change the existing field cultivation mode. ② To make full use of mountainous areas and barren slopes to carry out wild planta tending or planting imitates wild condition. ③ According to the development law and biological characteristics of medicinal plants, the land resources should be developed and used rationally according to local conditions.This can not only meet the requirements of the specific growth environment of Chinese medicinal materials, realize the sustainable development of the Chinese medicinal materials industry, but also increase the economic income of people in mountainous areas, provide scientific and effective solutions for the land use of Chinese medicinal materials, and also have important significance for the protection of wild Chinese medicinal materials.

Porcine circovirus 3 capsid protein induces autophagy in HEK293T cells by inhibiting phosphorylation of the mammalian target of rapamycin / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin-proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.