Combination of Molecule-Targeted Therapy and Photodynamic Therapy Using Nanoformulated Verteporfin for Effective Uveal Melanoma Treatment.

Uveal melanoma (UM) is the most common primary ocular malignancy in adults and has high mortality. Recurrence, metastasis, and therapeutic resistance are frequently observed in UM, but no beneficial systemic therapy is available, presenting an urgent need for developing effective therapeutic drugs. Verteporfin (VP) is a photosensitizer and a Yes-Associated Protein (YAP) inhibitor that has been used in clinical practice. However, VP's lack of tumor targetability, poor biocompatibility, and relatively low treatment efficacy hamper its application in UM management. Herein, we developed a biocompatible CD44-targeting hyaluronic acid nanoparticle (HANP) carrying VP (HANP/VP) to improve UM treatment efficacy. We found that HANP/VP showed a stronger inhibitory effect on cell proliferation than that of free VP in UM cells. Systemic delivery of HANP/VP led to targeted accumulation in the UM-tumor-bearing mouse model. Notably, HANP/VP mediated photodynamic therapy (PDT) significantly inhibited UM tumor growth after laser irradiation compared with no treatment or free VP treatment. Consistently, in HANP/VP treated tumors after laser irradiation, the tumor proliferation and YAP expression level were decreased, while the apoptotic tumor cell and CD8+ immune cell levels were elevated, contributing to effective tumor growth inhibition. Overall, the results of this preclinical study showed that HANP/VP is an effective nanomedicine for tumor treatment through PDT and inhibition of YAP in the UM tumor mouse model. Combining phototherapy and molecular-targeted therapy offers a promising approach for aggressive UM management.

Molecular radio afterglow probes for cancer radiodynamic theranostics.

X-ray-induced afterglow and radiodynamic therapy tackle the tissue penetration issue of optical imaging and phototherapy. However, inorganic nanophosphors used in this therapy have their radio afterglow dynamic function as always on, limiting the detection specificity and treatment efficacy. Here we report organic luminophores (IDPAs) with near-infrared afterglow and 1O2 production after X-ray irradiation for cancer theranostics. The in vivo radio afterglow of IDPAs is >25.0 times brighter than reported inorganic nanophosphors, whereas the radiodynamic production of 1O2 is >5.7 times higher than commercially available radio sensitizers. The modular structure of IDPAs permits the development of a smart molecular probe that only triggers its radio afterglow dynamic function in the presence of a cancer biomarker. Thus, the probe enables the ultrasensitive detection of a diminutive tumour (0.64 mm) with superb contrast (tumour-to-background ratio of 234) and tumour-specific radiotherapy for brain tumour with molecular precision at low dosage. Our work reveals the molecular guidelines towards organic radio afterglow agents and highlights new opportunities for cancer radio theranostics.

Neodymium (3+)-Coordinated Black Phosphorus Quantum Dots with Retrievable NIR/X-Ray Optoelectronic Switching Effect for Anti-Glioblastoma.

Heteroatom interaction of atomically thin nanomaterials enables the improvement of electronic transfer, band structure, and optical properties. Black phosphorus quantum dots (BP QDs) are considered to be candidate diagnostic and/or therapeutic agents due to their innate biocompatibility and exceptional photochemical effects. However, BP QDs are not competitive regarding second near-infrared (NIR-II) window medical diagnosis and X-ray induced phototherapy. Here, an Nd3+ ion coordinated BP QD (BPNd) is synthesized with the aim to sufficiently improve its performances in NIR-II fluorescence imaging and X-ray induced photodynamic therapy, benefitting from the retrievable NIR/X-ray optoelectronic switching effects between BP QD and Nd3+ ion. Given its ultrasmall size and efficient cargo loading capacity, BPNd can easily cross the blood-brain barrier to precisely monitor the growth of glioblastoma through intracranial NIR-II fluorescence imaging and impede its progression by specific X-ray induced, synergistic photodynamic chemotherapy.

Ag+ -Coupled Black Phosphorus Vesicles with Emerging NIR-II Photoacoustic Imaging Performance for Cancer Immune-Dynamic Therapy and Fast Wound Healing.

A silver-ion-coupled black phosphorus (BP) vesicle (BP Ve-Ag+ ) with a second near infrared (NIR-II) window photoacoustic (PA) imaging capability was firstly constructed to maximize the potential of BP quantum dot (QD) in deeper bioimaging and diversified therapy. The embedded Ag+ could improve the relatively large band gap of BP QD via intense charge coupling based on theoretical simulation results, subsequently leading to the enhanced optical absorption capability, accompanied with the occurrence of the strong NIR-II PA signal. Guiding by NIR-II PA bioimaging, the hidden Ag+ could be precisely released with the disassembly of Ve during photodynamic therapy process and captured by macrophages located in lesion region for arousing synergistic cancer photodynamic/Ag+ immunotherapy. BP Ve-Ag+ can contrapuntally kill pathogenic bacteria and accelerate wound healing monitored by NIR-II PA imaging.

[Design and implementation of information management system for Chinese materia medica resources survey].

By means of the established Information Management System for Chinese materia medica resources survey, the national, provincial and county level organization, personnel and the implementation of the program of Chinese materia medica resources survey, and the survey team of medicinal plant investigation, photos, Chinese herbal medicine market survey, the traditional Chinese materia medica resources knowledge survey, germplasm resources investigation and the data collation and summary specimen have been realised. Throughout the whole working process of the fourth national Chinese materia medica resources survey, it is ensured that all data were no missing, no repeat, and well stored and managed. The Information Management System can improve the standardization degree of Chinese materia medica resources survey, and maintain the continuity.

[Design and implementation of data reporting system for Chinese materia medica resources survey].

The collection, summary and sharing of all kinds of survey data are one of the main tasks and achievements in the national census of Chinese materia medica resources organized and implemented by the State Administration of Traditional Chinese Medicine. It is a key link in the implementation of the national census of Chinese materia medica resources. Based on the client / server architecture, the data reporting system for Chinese materia medica resources survey has been established for reporting system application model of geospatial data service based on Web implementation, through the SOA framework, to achieve the data collection summary of the seven aspects of the local data configuration, data reporting, data verification, data reporting, PDA data import and export, APP data import, track instrument data import. The system services include the general investigation, the focus of investigation, specimen information, herbs sample information, market research, germplasm survey, traditional knowledge survey of these seven aspects of the 312 indicators of the report, serving the Chinese materia medica resource survey of field survey data collection and internal data collation. The system provides the technical support for the national census of Chinese materia medica resources, improves the efficiency of the census of Chinese materia medica resources, and is conducive to the long-term preservation of the data of Chinese materia medica resources census, the transformation and sharing of the results.

[Design and implementation of mobile terminal data acquisition for Chinese materia medica resources survey].

In this paper, a data acquisition system based on mobile terminal combining GPS, offset correction, automatic speech recognition and database networking technology was designed implemented with the function of locating the latitude and elevation information fast, taking conveniently various types of Chinese herbal plant photos, photos, samples habitat photos and so on. The mobile system realizes automatic association with Chinese medicine source information, through the voice recognition function it records the information of plant characteristics and environmental characteristics, and record relevant plant specimen information. The data processing platform based on Chinese medicine resources survey data reporting client can effectively assists in indoor data processing, derives the mobile terminal data to computer terminal. The established data acquisition system provides strong technical support for the fourth national survey of the Chinese materia medica resources (CMMR).

[Design and implementation of data checking system for Chinese materia medica resources survey].

The Chinese material medica resources (CMMR) national survey information management system has collected a large amount of data. To help dealing with data recheck, reduce the work of inside, improve the recheck of survey data from provincial and county level, National Resource Center for Chinese Materia Medical has designed a data checking system for Chinese material medica resources survey based on J2EE technology, Java language, Oracle data base in accordance with the SOA framework. It includes single data check, check score, content manage, check the survey data census data with manual checking and automatic checking about census implementation plan, key research information, general survey information, cultivation of medicinal materials information, germplasm resources information the medicine information, market research information, traditional knowledge information, specimen information of this 9 aspects 20 class 175 indicators in two aspects of the quantity and quality. The established system assists in the completion of the data consistency and accuracy, pushes the county survey team timely to complete the data entry arrangement work, so as to improve the integrity, consistency and accuracy of the survey data, and ensure effective and available data, which lay a foundation for providing accurate data support for national survey of the Chinese material medica resources (CMMR) results summary, and displaying results and sharing.

[Design and implementation of Chinese materia medica resources survey results display system].

From the beginning of the fourth national census of traditional Chinese medicine resources in 2011, a large amount of data have been collected and compiled, including wild medicinal plant resource data, cultivation of medicinal plant information, traditional knowledge, and specimen information. The traditional paper-based recording method is inconvenient for query and application. The B/S architecture, JavaWeb framework and SOA are used to design and develop the fourth national census results display platform. Through the data integration and sorting, the users are to provide with integrated data services and data query display solutions. The platform realizes the fine data classification, and has the simple data retrieval and the university statistical analysis function. The platform uses Echarts components, Geo Server, Open Layers and other technologies to provide a variety of data display forms such as charts, maps and other visualization forms, intuitive reflects the number, distribution and type of Chinese material medica resources. It meets the data mapping requirements of different levels of users, and provides support for management decision-making.

[Application of image recognition technology in census of national traditional Chinese medicine resources].

With the development of computer and image processing technology, image recognition technology has been applied to the national medicine resources census work at all stages.Among them: ①In the preparatory work, in order to establish a unified library of traditional Chinese medicine resources, using text recognition technology based on paper materials, be the assistant in the digitalization of various categories related to Chinese medicine resources; to determine the representative area and plots of the survey from each census team, based on the satellite remote sensing image and vegetation map and other basic data, using remote sensing image classification and other technical methods to assist in determining the key investigation area. ②In the process of field investigation, to obtain the planting area of Chinese herbal medicine was accurately, we use the decision tree model, spectral feature and object-oriented method were used to assist the regional identification and area estimation of Chinese medicinal materials.③In the process of finishing in the industry, in order to be able to relatively accurately determine the type of Chinese medicine resources in the region, based on the individual photos of the plant, the specimens and the name of the use of image recognition techniques, to assist the statistical summary of the types of traditional Chinese medicine resources. ④In the application of the results of transformation, based on the pharmaceutical resources and individual samples of medicinal herbs, the development of Chinese medicine resources to identify APP and authentic herbs 3D display system, assisted the identification of Chinese medicine resources and herbs identification characteristics. The introduction of image recognition technology in the census of Chinese medicine resources, assisting census personnel to carry out related work, not only can reduce the workload of the artificial, improve work efficiency, but also improve the census results of information technology and sharing application ability. With the deepening of the work of Chinese medicine resources census, image recognition technology in the relevant work will also play its unique role.

[Morphological and microscopical identification of Genkwa Ramulus and its adulterants].

The purpose of this article is to identify Daphne genkwa and its adulterants, Wikstroemia chamaedaphne, according to the morphological and microstructure characteristics of their stem and foliage. The root of D.genkwa was studied simultaneously. The results indicated that the crude drug and processed pieces of Genkwa Ramulus were mainly composed of stems and branches where obvious opposite petiole scars and branch marks were able to be seen on their nodes. Otherwise, foliage or peduncles generally couldn't be found. Moreover, the fine silver flocculent fibers could be observed in the bark of fracture surface. The adulterants were the plant segments which were composed of stems, foliage and peduncles with spikelet-pedicel scars. There existed microstructures differences between Genkwa Ramulus and its adulterants. In the former, single thick lignified phloem fibers were interspersed in the stem phloem of the transverse section with very thick wall and unicellular non-glandular hairs could be observed on the lower epidermis of foliage. Nevertheless, in the latter, there was no thick lignified phloem fibers in cross section of stem phloem, the outer wall of epidermal cells of foliage hadthick cuticles and no non-glandular hairs in lower epidermis of foliage. The results can be used for the identification and the quality standard of the crude drug and processed pieces of D.genkwa.The characteristics of the microstructures and the transverse section can be used to identify the radix D.genkwa.

[Investigation Report of Tripterygium wilfordii and Tripterygium hypoglaucum].

OBJECTIVE: To get the information of resources, cultivation, commodity circulation and other aspects of Tripterygium wilfordii and Tripterygium hypoglaucum. METHODS: Collect samples in 13 locations of Tripterygium wilfordii and Tripterygium hypoglaucum, compare their plant morphological characteristics and growth habit, and investigate their wild resources conditions, planting information, easy-confused varieties and different commodity features. RESULTS: (1) Tripterygium wilfordii and Tripterygium hypoglaucum were mainly collected under woods or on the edge of woods,and light and moisture attributed to their distribution to some extent. (2) Wild resources of Tripterygium wilfordii and Tripterygium hypoglaucum were shrinking, and both of their cultivation history were relatively short and their cultivation technique were still in a low level. (3) Due to lack of harvesting and processing standards, decoction pieces, varying from roots, rhizomes to stems of plants, were all sold as commercial medicines. CONCLUSION: Wild resources of Tripterygium wilfordii and Tripterygium hypoglaucum are shrinking,and the standardized research on cultivation-harvest processing and commercial medicines remains to be further carried out.

Selenium-enriched Candida utilis: Efficient preparation with l-methionine and antioxidant capacity in rats.

Selenium-enriched Candida utilis has attracted much attention due to its expanding application in food and feed additives. The objective of this study was to efficiently prepare selenium-enriched C. utilis and to investigate the effects of the prepared yeast on antioxidant capacity in rats. A batch culture of selenium-enriched C. utilis was first carried out, and the addition of sodium selenite (Na(2)SeO(3)) after all glucose had been consumed was found to favor higher intracellular glutathione and organic selenium content. Moreover, l-methionine boosted yeast cell growth and glutathione biosynthesis, and prevented glutathione from leaking to the extracellular space that can be caused by Na(2)SeO(3). We therefore developed a two-stage culture strategy involving supplementation with l-methionine and Na(2)SeO(3) at separate culture phases to improve the performance of selenized C. utilis. Using this two-stage culture strategy, intracellular glutathione content reached 18.6 mg/g and 15.5mg/g, respectively, in batch and fed-batch systems, and organic selenium content reached 905.2 µg/g and 984.7 µg/g, respectively. The effects of selenium-enriched C. utilis on the activities of antioxidant related enzymes in rats were investigated, and the prepared selenium-enriched C. utilis was shown to be an optimal dietary supplement for enhancing antioxidant capacity in rats.

[Locality identification of Chinese medicinal plant Scutellaria baicalensis (Lamiaceae) population-level DNA barcoding].

Scutellaria baicalensis is an important traditional Chinese medicine and Scutellaria flavonoids have received worldwide attention in recent years. It is the basis of controlling quality of S. baicalensis to develop a reliable genetic marker system used to identify locality of origin. Because of the characteristics of maternal inherited and high-rate of evolution, the cpDNA intergenic spacer can effectively elucidate the degree of genetic variation in different areas of the same species (populations), which can be used as the population-level DNA barcoding to locality identify. In this study, we have used the molecular phylogeography analysis for the three cpDNA intergenic spacers atpB-rbcL, trnL-trnF and psbA-trnH of 17 wild populations from different localities, which reveals the 20 haplotypes, including 13 polymorphic sites and constitutes a shallow gene tree. The authers have divided the haplotypes of S. baicalensis into three grades of population-level DNA barcoding according to the frequence and geographic distribution: 3 highest-frequency haplotypes as area-population-level DNA barcoding, 3 haplotypes were mainly shared by 2-3 adjacent populations as region-population-level DNA barcoding, and there are also 8 unique-population haplotypes as unique-population-level DNA barcoding. The result of this study reveals that population-level DNA barcoding is a reliable genetic marker used to locality identify of S. baicalensis.

[Construction of medicinal plant core collection based on molecular phylogeography].

The paper introduces the current situation and the characteristics of the medicinal plant core collection. It expounds the significance and research methods for the medicinal plant core collection based on molecular phylogeography. Guided by molecular phylogeography, the essay explores the feasibility and methods of medicinal plant core collection for the medicinal plants with rich wild resources and without wild resources. It further forecasts the application of medicinal plant core collection methods on the basis of molecular phylogegraphy.

[GC-MS analysis on volatile components of wild Trogopterus faeces from Laishui county of Hebei province].

OBJECTIVE: To analysis the volatile components of Trogopterus faeces. METHOD: The volatile components of Trogopterus faeces was extracted by steam distillation and analyzed by GC-MS. RESULT: Eighty-five volatile components were identified and the main components are cedrol (12.31%) and caryophyllene (7.5%). CONCLUSION: The volatile components of the samples are originated from the ingredients or other chemical compositions with similar basic structure of the fodders.

[Comparative research on pharmacognostic characteristics and microscopic characteristics of Radix Paeoniae Rubra from different areas].

OBJECTIVE: To compare pharmacognostic characteristics and microscopic characteristics of Radix Paeoniae Rubra (chishao) from different areas. METHOD: Pharmacognostic characteristics and microscopic characteristics of Radix Paeoniae Rubra were compared by microscope count methods. RESULT: Chishao in duolun was more straighter and longer, cortex with a set of closely spaced rill, peel off easily, pink section, etc. The wild chishao were different from the cultivated chishao on pharmacognostic characteristics and microscopic characteristics, such as appearance shape, smell, vessel arrangement, and number of crystal and starch in unit area. CONCLUSION: Chishao in duolun were different form others, appearance shape, wood fiber, difference of appearance shape, vessel arrangement, and number of crystal and starch in unit area can be used as identificatin feature of the wild chishao and the cultivated chishao.

[Shapes, properties and microstructures of gadfly].

OBJECTIVE: To search and identify the microstructure of medicinal properties of six kinds of gadfly. METHOD: The medicinal properties, different body parts and bristles microscopic characteristics were compared. RESULT: The two-spotted yellow gadfly had a smaller size. Its length no more than 14 mm, body wall debris was yellow brown or pale yellow, the seta was smaller than that of the other gadflies; while the other five varieties' body lengths all exceeded 15 mm, and their body wall debris mostly were brown black or gray and black. CONCLUSION: The authentication between the two-spotted yellow gadfly and the other five varieties can be made by the microscopic characteristics of their medicinal properties, body wall debris colors, bristle lengths, and basal diameters.

[Determination of prim-O-glucosylcimifugin and 5-O-methylvisammisoide in Saposhnikovia divaricata and HPLC fingerprint analysis].

OBJECTIVE: To develop HPLC methods for the determination of prim-O-glucosylcimifugin and 5-O-methylvisammisoide in Saposhnicovia divaricata and of HPLC fingerprint to compare the wild and culture varieties. METHOD: Conditions of determination: Shimadzu C18 column (4.6 mm x 150 mm, 5 microm), methanol-water (40:60) as mobile phase with the flow rate of 1 mL x min(-1). The detection wavelength was 254 nm. Conditions of HPLC fingerprint: MG II C18 column (4.6 mm x 250 mm, 5 microm), the mobile phase was acetonitrile-water with the flow rate of 1 mL x min(-1), using linear gradient elution, the column temperature was 30 degrees C. RESULT: The average recovery of prim-O-glucosylcimifugin was 99.6% (RSD 0.72%, n=6). The average recovery of 5-O-methylvisammisoide was 102.6% (RSD 0.88%, n=6). The contents of prim-o-glucosylcimifugin in wild and culture varieties were (4.96 +/- 2.59) and (3.61 +/- 1.82) mg x g(-1) respectively. The contents of 5-O-methylvisammisoide were (3.91 +/- 2.09) and (4.37 +/- 2.02) mg x g(-1) respectively. The compositions of S. divaricata were effective separated under the conditions of HPLC fingerprint. CONCLUSION: The HPLC determination method of prim-O-glucosylcimifugin and 5-O-methylvisammisoide is convenient and accurate. The HPLC fingerprint analysis method could be a basis for quality control and classification evaluate of S. divaricata.

[Differences in shapes and properties and microscopic frameworks of wild and cultivated Radix Salviae Miltiorrhizae from different regions].

OBJECTIVE: To compare the differences in shapes and properties and the microscopic frameworks of the wild and cultivated Radix Salviae Miltiorrhizae from different regions. METHOD: The differences in the shapes and properties, the characters of transverse sections, the powder and disintegrated tissue of roots were compared using microscopic measurement and statistics analysis. RESULT: The wild Radix Salviae Miltiorrhizae had several long cylinder roots with rough flaky squama skin and brown red or wine culour, the cultivated had root of many branch with cling skin and brick-red or chestnut culour. The difference of microscopic histological structure was that the xylem vessel of wild Radix Salviae Miltiorrhizae had bunched vessel with the rank form of big diameter alternating with small diameter, and had stone cell on samples from some producing region, the xylem vessel of the cultivated had no bunched vessel and no stone cell with the rank form of tangential radial. Radix Salviae Miltiorrhizae cultivated in Sichuan Province is called original-region medicinal materials and named Chuandanshen. Chuandanshen had the differences with the Salviae Miltiorrhizae Radix cultivated in other region. The root of Chuandanshen had 1.2 cm diameter, and was bulky and fat with solid fabric and the fracture with brownish yellow color and cutin-alikeness, its xylem vessel of transverse section of root was thin with the rank form of tangential radial, and 19-24 vascular bundle and a few wood fiber. CONCLUSION: Salviae Miltiorrhizae Radix of the wild and the cultivated, of the original-region (Chuandanshen) and the other-region, have the differences in the shapes and properties, and the microscopic frameworks. The character can be identified by the differences in the shapes of medicinal materials, and the rank form of vascular bundle of transverse section of root.