Nuclear-Targeted Nanostrategy Regulates Spatiotemporal Communication for Dual Antitumor Immunity.

Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge. In this study, a nuclear-targeted photodynamic nanostrategy is developed to establish positive spatiotemporal communication, further activating dual antitumor immunity, namely innate and adaptative immunity. The mSiO2 -Ion@Ce6-NLS nanoparticles (NPs) are designed, whose surface is modified by ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS: PKKKRKV), and their pores are loaded with the photosensitizer hydrogen chloride e6 (Ce6). Ion-modified NPs enhance intratumoral enrichment, and NLS-modified NPs exhibit nuclear-targeted characteristics to achieve nuclear-targeted photodynamic therapy (nPDT). mSiO2 -Ion@Ce6-NLS with nPDT facilitate the release of damaged double-stranded DNA from tumor cells to activate macrophages via stimulator of interferon gene signaling and induce the immunogenic cell death of tumor cells to activate dendritic cells via "eat me" signals, ultimately leading to the recruitment of CD8+ T-cells. This therapy effectively strengthens positive communication to reshape the dual antitumor immune microenvironment, further inducing long-term immune memory, and eventually inhibiting tumor growth and recurrence.

Golgi Apparatus-Targeted Photodynamic Therapy for Enhancing Tumor Immunogenicity by Eliciting NLRP3 Protein-Dependent Pyroptosis.

Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors. Previous studies proposed that NLRP3 was activated by translocation to the mitochondria. However, a recent authoritative study has challenged this model and proved that the Golgi apparatus might be a prerequisite for the activation of NLRP3. In this study, we first developed a Golgi apparatus-targeted photodynamic strategy to induce the activation of NLRP3 by precisely locating organelles. We found that Golgi apparatus-targeted photodynamic therapy could significantly upregulate NLRP3 expression to promote the subsequent release of intracellular proinflammatory contents such as IL-1ß or IL-18, creating an inflammatory storm to enhance innate immunity. Moreover, this acute NLRP3 upregulation also activated its downstream classical caspase-1-dependent pyroptosis to enhance tumor immunogenicity, triggering adaptive immunity. Pyroptosis eventually led to immunogenic cell death, promoted the maturation of dendritic cells, and effectively activated antitumor immunity and long-lived immune memory. Overall, this Golgi apparatus-targeted strategy provided molecular insights into the occurrence of immunogenic pyroptosis and offered a platform to remodel the tumor microenvironment.

Enhancement of anti-PD-1/PD-L1 immunotherapy for osteosarcoma using an intelligent autophagy-controlling metal organic framework.

Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, CUR-BMS1166@ZIF-8@PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity. After entering tumor cells, the pH-sensitive nanoparticles induced autophagy and decreased the intracellular pH, which in turn further facilitated the release of CUR to enhance autophagic activity. Transferring CBZP to orthotopic OS tumor-bearing mice showed powerful antitumor effects and established long-term immunity against tumor recurrence, accompanied by enhanced dendritic cell maturation and tumor infiltration of CD8+ T lymphocytes. Collectively, CBZP exhibited synergistic effects in treating OS by combining ICD induction with checkpoint blockade, thereby shedding light on the use of autophagy control as a potential clinical therapy for OS.

Morphological and microscopical identification of Genkwa Ramulus and its adulterants / 中国中药杂志

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.

Research on quality standards of Euonymus fortunei / 中国中药杂志

To establish quality standards of Euonymus fortunei, and supply scientific evidence for the quality control of Euonymus fortunei. Empirical and microscopic identification methods were adopted to observe morphological and histological characters. The contents of water, total ash, acid-insoluble ash and alcohol-soluble extractive were analysed according to the methods of Chinese Pharmaco- poeia (2010). Dulcitol and reference herbs were used to identify materia medica of Euonymus fortunei by TLC method. The total flavonol glycosides contents were analysed by HPLC method, using quercetin and kaempferol as reference substances. Quercetin and kaempferol were separated on a C18 column (4.6 mm x 250 mm, 5 μm) with methanol-0.1% formic acid(51:49) as the mobile phase and detected at 366 nm. The flavonoid aglycones content was then multiplied by a conversion coefficient, and the result was the total flavonol glycosides content. The macroscopical identification, microscopic features and TLC methods were proper. The average contents of water, total ash, acid-insoluble ash, alcohol-soluble extractive and total flavonol glycosides were 8.76%, 6.48%, 0.31%, 17.48% and 0.211% , respectively. The quality standards established on the basis of the research results were suitable for the quality evaluation of Euonymus fortunei.

Comparative study on identification of Clematidis Radix et Rhizoma from different origins based on microstructure and NIRS method / 中国中药杂志

Microscopic identification and NIRS methods were applied to identify Clematidis Radix et Rhizoma of two different origins. The results showed that both methods could identify the samples. NIRS could identify the two samples nondestructively, and provides a basis for establishment of a standard herbs radix clematidis NIRS fingerprint in the future.

Zinc and cadmium 2-pyrazinephosphonates: syntheses, structures and luminescent properties.

Three new metal(II) 2-pyrazinephosphonates have been synthesized by hydrothermal reactions based on 2-pyrazinephosphonic acid (C(4)H(3)N(2)PO(3)H(2)1) as ligand, namely, Zn(C(4)H(3)N(2)PO(3)) (2), Cd[(C(4)H(3)N(2)PO(3))(H(2)O)] (3) and Cd[(C(4)H(3)N(2)PO(3)H)Cl]·H(2)O (4). In compound 2, the O-P-O bridged inorganic layers are pillared by pyrazinyl groups into a three-dimensional network. In compound 3, the {CdO(5)N} and {CPO(3)} polyhedra are interconnected via edge and corner-sharing into a metal phosphonate layer. In compound 4, the {Cd(2)Cl(2)} dimers are linked by O-P-O bridges into a one-dimensional double chain, and the chains are joined into a layer by pyrazinyl groups. Here we employ pyrazinephosphonic acids as structure directing motifs to form extended structures and materials with interesting luminescent properties. The luminescent properties studied have also been described.

Comparative study on chemcial composition between cultivated and wild Scutellariae radix / 中国中药杂志

<p><b>OBJECTIVE</b>To do some comparative study on chemical composition between the cultivated and wild samples of Radix Scutellariae.</p><p><b>METHOD</b>Thirty three samples of Radix Scutellariae were collected from different habitats. An HPLC method for fingerprint identification and simultaneous determination of baicalin, baicalein and wogonin was established, and the content of ethanolic extractive was measured according to the method in Chinese Pharmacopoeia.</p><p><b>RESULT</b>The number of chromatographic peaks in fingerprint of wild sample was more than that of cultivated sample in Hebei and Inner Mongolia. In 95% confidence intervals, the contents of baicalin, baicalein and wogonin were (15.89 +/- 1.52)%, (1.04 +/- 0.26)% and (0.27 +/- 0.07)%, respectively in the cultivated samples and (11.93 +/- 1.62)%, (1.03 +/- 0.26)% and (0.27 +/- 0.06)%, respectively in wild samples. The content of ethanolic extractive was 52.07 +/- 3.05% in the cultivated and (41.21 +/- 2.86)% in the wild within 95% confidence interval.</p><p><b>CONCLUSION</b>Slight difference between the fingerprint of the cultivated and wild samples was found, and the contents of baicalin and ethanolic extraction in the cultivated were higher than those in the wild.</p>

Dynamic change of paeoniflorin content in root of Paeonia lactiflora growing at Duolun County, Inner Mongolia / 中国中药杂志

<p><b>UNLABELLED</b>To explore the dynamic change of paeoniflorin content in root of Paeonia lactiflora.</p><p><b>METHOD</b>The samples were collected and paeoniflorin content was determined by HPLC.</p><p><b>RESULT</b>The results showed that the average content of paeoniflorin was the lowest at 3.05% in the roots collected in May, and during the fruit time it was rather high in August at 4.72%, and in September at 4.58%. The average content showed no significant differences during June to October.</p><p><b>CONCLUSION</b>Wild plant of P. lactiflora might be collected for medical use during blooming stage until wilting stage.</p>

Textual research on origin and development of genuine medicinal herbs of Shanyao / 中国中药杂志

Making textual research on Bencao and documents, this article inquires to the origin and development of genuine medicinal herbs of Shanyao (Rhizoma Dioscoreae) on the points of change of the growing areas and the development of cultivating and processing techniques and clinical uses. The study indicates that the medicinal use of Dioscorea oposita went through several periods: the period of the use of wild D. oposita before Tang dynasty, the period of the mixed use of wild and cultivating D. oposita from Song to the middle of Qing dynasty, and the period of the main use of cultivating D. oposita after the latter stage of Qing dynasty (18th century). It considers that the growing area of genuine medicinal herbs of Shanyao appeared in Ming dynasty and finally formed "Huaishanyao" on the early of 20th century. The acknowledgement of Huaishanyao as genuine medicinal herbs is related closely to its cultivating and processing techniques and clinical uses. The development of cultivating techniques provided the resource of Shanyao, the invention of processing techniques improved its appearance and quality, and the clinical uses and practices by modern and contemporary famous medical men played an important role to the social approval and development of Huaishanyao.

Determination of carvacrol and thymol in Mosla chinensis by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a quantitative method of determination of carvacrol and thymol in Mosla chinensis.</p><p><b>METHOD</b>The sample was extracted with 95% ethanol, ODS column was used with methanol-water-acetic acid (60:40:2) as mobile phase. The detection wavelength was set at 274 nm.</p><p><b>RESULT</b>The linearities of carvacrol and thymol were respectively in the range of 0.23-2.15 microg (r = 0.9999) and 0.39-2.36 microg (r = 0.9999); the average recoveries were 99.9% (RSD 1.4%) and 98.6% (RSD 1.3%); the RSD of repeatability were 1.1% and 1.6%.</p><p><b>CONCLUSION</b>The method is reliable, and can be used for quality control of M. chinensis.</p>

Study of stinging crystals in tian nanxing / 中国中药杂志

<p><b>OBJECTIVE</b>To test whether the raphides in Tian Nanxing (Pinellia pedatisecta Schott) caused irritation.</p><p><b>METHOD</b>Scan Electron Microscope and Microscope Oberservation; Animal experimental study.</p><p><b>RESULT</b>Through the comparision of unprocessed Tian Nanxing to processed ones which included 36 h, 72 h, 120 h processed samples, the great modifications in the structure of raphides, especially for the ones with barbs in the processed samples was observed with time course study. A further animal experimental study went to show that the rate of change for raphides with barbs existed a dose-reponse relationship to irritation.</p><p><b>CONCLUSION</b>Investigations of the causes of these reactions showed that raphides of calcium oxalate are, at least in part, responsible for the Tian Nanxing's irritation.</p>

Determination of flavone for Scutellaria baicalensis from different areas by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To describe the difference between native and nonative herbs by determining contents of seven kinds of flavone for twenty-five samples from seventeen areas.</p><p><b>METHODS</b>HPLC. Fluid phase: MEOH-H2O-CH3COOH(ICE) (41:59:0.2) and (50:50:0.2). Detection wavelength: 275.</p><p><b>RESULTS</b>The contents of baicalin are 6%-9%, wogenin are 2%-8%, baicalein are 0.1%-1.6%, neobaicalein are 0.01%-0.2%, wogonin are 0.01%-0.3%, visidulin and oroxylin are trace amounts or undetected.</p><p><b>CONCLUSION</b>The native and nonative herbs have no distinct differce in absolute component ratio. The ratio of baicalin and wogenin is under three. The ratio of baicalin and baicalein, baicalin and wogonin is between twenty and fifty.</p>

A study on genetic variation between wild and cultivated populations of Paeonia lactiflora Pall / 药学学报

<p><b>AIM</b>To discuss the genetic differentiation between wild and cultivated populations of Paeonia lactiflora Pall., and to find the reason for forming the genuineness of Radix Paeoniae rubra (Chishao) and Radix Paeoniae alba (Baishao).</p><p><b>METHODS</b>Forty three representative samples of P. lactiflora from 11 localities were analyzed by RAPD method with 21 random primers. According to RAPD results, the genetic diversity and genetic differentiation of P. lactiflora were detected by the percentage of polymorphic sites (PPB), the coefficient of gene differentiation (GST) and analysis of molecular variance (AMOVA).</p><p><b>RESULTS</b>(1) At species level, the PPB of P. lactiflora was 85.26%, the Nei's gene diversity (Ht) was 0.166. The PPB in wild population (WP) was 77.61%, which was more than that (54.96%) in cultivated population for medicine (MP), and that (61.76%) in cultivated population for ornament (OP). (2) AMOVA showed that 29.50% of the genetic diversity resulted from differentiation among populations. Pairwise Phist distance (0.3632) between WP and MP was furthest, while that (0.0973) between MP and OP was closest, indicating population differentiation was significant (P < 0.001). (3) In general, cluster analysis revealed that the samples of P. lactiflora were divided in wild and cultivated groups (except for 39). In WP, individuals of Duolun were separated from those of other localities. In MP, the clusters of samples corresponded well with their own habitats.</p><p><b>CONCLUSION</b>In addition to environmental factor, genetic differentiation should be the main cause for the genuineness of "Chishao" and "Baishao". Because of over collection and worse habitat, P. lactiflora in Duolun, whose root is the famous Chinese Geo-herbal--"Duolun Chishao", is progresively rare. So, it should become the endangered germplasm resource to protect.</p>

Study on the physicochemical properties of cultivated soil of genuine crude and no-enuine crude Chinese Angelica / 中国中药杂志

<p><b>OBJECTIVE</b>To provide basis for environmental factors of genuine crude Chinese angelica.</p><p><b>METHOD</b>On-the-spot investigation and indoor chemical analysis were made to study the physicochemical properties of cultivated soil of Chinese angelica.</p><p><b>RESULT AND CONCLUSION</b>The physical properties and the organic matte and mineral nutrition of cultivated soil of Chinese angelica are best in Min County, Gansu Province. The ecological environment is the leading factor in forming genuine crude Chinese angelica.</p>