[Quality control of Tianwang Buxin Pills based on UPLC fingerprint and multi-component quantification].

Tianwang Buxin Pills have demonstrated therapeutic effects in clinical practice, whereas there is a serious lack of comprehensive quality control to ensure the safety and effectiveness of clinical medication. In this study, ultra-performance liquid chromatography(UPLC) was employed to establish the fingerprint and the method for simultaneously determining the content of seven components of Tianwang Buxin Pills. Furthermore, chemometrics was employed to identify the key factors for the stable quality, which provided a reference for the comprehensive quality control and evaluation of this preparation. There were 25 common peaks in the UPLC fingerprints of 15 batches of Tianwang Buxin Pills, from which thirteen compounds were identified. A quantitation method was established for seven pharmacological components(α-linolenic acid, salvianolic acid B, glycyrrhetinic acid, schisandrin A, ß-asarone, 3,6'-disinapoylsucrose, and ligustilide). The principal component analysis(PCA) and partial least square discriminate analysis(PLS-DA) were performed to determine the key pharmacological components for controlling the quality stability of Tianwang Buxin Pills, which included 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone. The established fingerprint and multi-component content determination method have strong specificity, stability, and reliability. In addition, 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone are the key pharmacological components that ensure the quality stability between batches and can be used to comprehensively control the quality of Tianwang Buxin Pills. The findings provide a scientific basis for the quality evaluation and standard establishment of Tianwang Buxin Pills.

Polyacetylenes from Saposhnikovia divaricata and their anticancer activity.

Nine polyacetylenes, including five new compounds named sadivaethynes E-I (1-5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1-5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4+ probability analysis. Among them, the absolute configuration of compound 1-2, 4-5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC50 value of 11.66 µM against HEPG2.

BATMAN-TCM 2.0: an enhanced integrative database for known and predicted interactions between traditional Chinese medicine ingredients and target proteins.

Traditional Chinese medicine (TCM) is increasingly recognized and utilized worldwide. However, the complex ingredients of TCM and their interactions with the human body make elucidating molecular mechanisms challenging, which greatly hinders the modernization of TCM. In 2016, we developed BATMAN-TCM 1.0, which is an integrated database of TCM ingredient-target protein interaction (TTI) for pharmacology research. Here, to address the growing need for a higher coverage TTI dataset, and using omics data to screen active TCM ingredients or herbs for complex disease treatment, we updated BATMAN-TCM to version 2.0 (http://bionet.ncpsb.org.cn/batman-tcm/). Using the same protocol as version 1.0, we collected 17 068 known TTIs by manual curation (with a 62.3-fold increase), and predicted ∼2.3 million high-confidence TTIs. In addition, we incorporated three new features into the updated version: (i) it enables simultaneous exploration of the target of TCM ingredient for pharmacology research and TCM ingredients binding to target proteins for drug discovery; (ii) it has significantly expanded TTI coverage; and (iii) the website was redesigned for better user experience and higher speed. We believe that BATMAN-TCM 2.0, as a discovery repository, will contribute to the study of TCM molecular mechanisms and the development of new drugs for complex diseases.

In vitro construction of cartilage organoids based on extracellular matrix microcarriers of cartilage / 中华创伤杂志

Objective:To study the in vitro construction of functional and self-renewing cartilage organoids based on cartilage acellular extracellular matrix (ECM) microcarriers.Methods:Fresh porcine articular cartilage was taken. The merely crushed cartilage particles were set as natural cartilage group and ECM microcarriers of appropriate particle size, which were prepared by the acellular method of combining physical centrifugation and chemical extraction, were set as microcarrier group. Cartilage organoids were constructed by loading human umbilical cord mesenchymal stem cells (hUCMSCs) and human chondrocytes (hCho) with a ratio of 3∶1 with microcarriers through a rotating bioreactor. The organoids with different induction times were divided into 0-, 7-, 14-, and 21-day induction groups. The cell residues of the microcarrier group and natural cartilage group were evaluated by 4′, 6-diaminidine 2-phenylindole (DAPI) fluorescence staining and DNA quantitative analysis. The retention of microcarrier components was observed by Safranin O and toluidine blue stainnings, and the collagen and glycosaminoglycan (GAGs) levels in the microcarrier group and the natural cartilage group were determined by colorimetric method and dimethyl-methylene blue (DMMB) method. The microcarriers were further characterized by scanning electron microscopy and energy dispersive spectroscopy. The hUCMSCs cultured with Dulbecco′s Modified Eagle′s Medium (DMEM) supplemented with fetal bovine serum (FBS) in a volume fraction of 10% was used as the control group and the hUCMSCs cultured with the microcarrier extract was used as the experimental group. Subgroups of hUCMSCs cultured at 3 time points: 1, 3 and 5 days were set up in the two groups separately. Cell Counting Kit 8 (CCK-8) was used to detect the biocompatibility of the two groups. The cellular activity of the organoids of the 0-, 7-, 14-, and 21-day induction groups was detected by live/dead staining and the self-renewal ability of the cartilage organoids of the 14-day induced group was identified by Ki67 fluorescence staining. The organoids of the 7-, 14-, and 21-day induction groups were detected by RT-PCR in terms of the expression levels of chondrogenesis-related marker aggrecan (ACAN), type II collagen (COL2A1), SRY-related high mobility group-box gene-9 (SOX9), cartilage hypertrophy-and mineralization-related marker type I collagen (COL1A1), Runt-related transcription factor-2 (RUNX2), and osteocalcin (OCN). Colorimetric and DMMB assays were performed to determine the ability of organoids in the 0-, 7-, 14-, and 21-day induction groups to secrete collagen and GAGs.Results:The results of DAPI fluorescent staining showed that the natural cartilage group had a large number of nuclei while the microcarrier group hardly had any nuclei. The DNA content of the microcarrier group was (7.8±1.8)ng/mg, which was significantly lower than that of the natural cartilage group [(526.7±14.7)ng/mg] ( P<0.01). Saffranin O and toluidine blue staining showed that the microcarrier was dark- and uniform-colored and it kept a lot of cartilage ECM components. The collagen and GAGs contents of the microcarrier group were (252.9±1.4)μg/mg and (173.4±0.8)μg/mg, which were significantly lower than those of the natural cartilage group [(311.9±2.2)μg/mg and (241.3±0.7)μg/mg] ( P<0.01). Scanning electron microscopy showed that the surface of the microcarriers had uneven and interleaved collagen fiber network. The results of energy spectrum analysis showed that elements C, O and N were evenly distributed in the microcarriers, indicating that the composition of the microcarrier was uniform. The microcarrier had good biocompatibility and there was no statistical significance in the results of CCK-8 test between the control group and the experimental group after 1 and 3 days of culture ( P>0.05). After 5 days of culture, the A value of the experimental group was 0.53±0.02, which was better than that of the control group (0.44±0.03) ( P<0.05). In the 0-, 7-, 14-, and 21-day induction groups, hUCMSCs and hCho were attached to the surface of the microcarriers, with good cellular activity, and the live/death rates were (70.6±1.1)%, (80.5±0.6)%, (94.5±0.9)%, and (90.8±0.5)% respectively ( P<0.01). There were a large number of Ki67 positive cells in cartilage organoids. RT-PCR showed that the expression levels of ACAN, COL2A1, SOX9, COL1A1, RUNX2 and OCN were 1.00±0.09, 1.00±0.24, 1.00±0.18, 1.00±0.03, 1.00±0.06 and 1.00±0.13 respectively in the 7-day induction group; 4.16±0.28, 5.09±1.25, 5.65±1.05, 0.47±0.01, 1.68±0.02 and 0.21±0.06 respectively in the 14-day induction group; 13.42±0.92, 3.07±0.21, 1.84±1.08, 2.72±0.17, 2.91±0.18 and 3.32±1.20 respectively in the 21-day induction group. Compared with the 7-day induction group, the expression levels of ACAN, COL2A1, SOX9 and RUNX2 in the 14-day group were increased ( P<0.05), but COL1A1 expression level was decreased ( P<0.05), with no significant difference in OCN expression level ( P>0.05). Compared with the 7-day induction group, the expression levels of ACAN, COL1A1 and RUNX2 in the 21-day induction group were significantly increased ( P<0.01), with no significant differences in the expression levels of COL2A1, SOX9 and OCN ( P>0.05). Compared with the 14-day induction group, the expression levels of ACAN, COL1A1, RUNX2 and OCN in the 21-day group were increased ( P<0.05 or 0.01), with no significant difference in the expression level of COL2A1 ( P>0.05), but the expression level of SOX9 was decreased ( P<0.05). The contents of collagen in 0-, 7-, 14-and 21-day induction groups were (219.15±0.48)μg/mg, (264.07±1.58)μg/mg, (270.83±0.84)μg/mg and (280.01±0.48)μg/mg respectively. The GAGs contents were (171.18±1.09)μg/mg, (184.06±1.37)μg/mg, (241.08±0.84)μg/mg and (201.14±0.17)μg/mg respectively. Compared with the 0-day induction group, the contents of collagen and GAGs in 7-, 14-, and 21-day induction groups were significantly increased ( P<0.01), among which the content of collagen was the lowest in 7-day induction group ( P<0.01) but the highest in the 21-day induced group ( P<0.01); the content of GAGs was the lowest in the 7-day induced group ( P<0.01) but the highest in the 14-day induction group ( P<0.01). Conclusions:The microcarriers prepared by combining physical and chemical methods are decellularized successfully, with more matrix retention, uniform composition and on cytotoxicity. By loading microcarriers with hUCMSCs and hCho, cartilage organoids are successfully constructed in vitro, which are characterized by good cell activity, self-renewal ability, strong expression of genes related to chondrogenesis and secretion of collagen and GAGs. The cartilage organoids constructed at 14 days of induction have the best chondrogenic activity.

[Characterization and phylogenetic analysis of complete chloroplast genome of cultivated Qinan agarwood].

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.

Structural characteristics of mixed pectin from ginseng berry and its anti-obesity effects by regulating the intestinal flora.

Ginseng berry is the mature berry of ginseng and its polysaccharide has hypolipidaemic effect, but its mechanism remains unclear. A pectin (GBPA) with a molecular weight of 3.53 × 104 Da was isolated from ginseng berry, it was mainly composed of Rha (25.54 %), GalA (34.21 %), Gal (14.09 %) and Ara (16.25 %). Structural analysis showed that GBPA is a mixed pectin containing rhamnogalacturonan-I and homogalacturonan domains and has a triple helix structure. GBPA distinctly improved lipid disorders in obese rats, and changed intestinal flora with enrichments of Akkermansia, Bifidobacterium, Bacteroides and Prevotella, improved the levels of acetic acid, propionic acid, butyric acid and valeric acid. Serum metabolites which involved in the lipid regulation-related pathway, including cinnzeylanine, 10-Hydroxy-8-nor-2-fenchanone glucoside, armillaribin, 24-Propylcholestan-3-ol, were also greatly changed after GBPA treatment. GBPA activated AMP-activated protein kinase, phosphorylated acetyl-CoA carboxylase, and reduced the expression of lipid synthesis-related genes sterol regulatory element-binding protein-1c and fatty acid synthases. The regulatory effects of GBPA on lipid disorders in obese rats are related to the regulation of intestinal flora and activation of AMP-activated protein kinase pathway. Ginseng berry pectin could be considered in the future as a health food or medicine to prevent obesity.

Geniposidic acid attenuates DSS-induced colitis through inhibiting inflammation and regulating gut microbiota.

Geniposidic acid (GPA) is a bioactive compound isolated from Gardenia jasminoides Ellis (Rubiaceae) that has long been used to treat arthritis, jaundice, and hypertension. However, the therapeutic effects of GPA against colitis remain underexplored. This study aimed to investigate the effect of GPA on the remission of colitis and the underlying mechanisms. A DSS-induced colitis mouse model was used to evaluate the influence of GPA on the modulation of gut microbiota and intestinal epithelial barrier function. Our results indicated that GPA improved DSS-induced mouse colitis, including loss of body weight, disease activity index (DAI), colon length, and colonic pathological damage. DSS-induced destruction of the intestinal barrier was also significantly repaired by GPA treatment. In addition, the relative levels of pro-inflammatory cytokines, such as IL-1ß and TNF-α, were markedly alleviated by GPA. Furthermore, western blot analysis revealed that GPA downregulated the protein expression of the nuclear transcription factor NF-κB. Finally, we first demonstrated that GPA could alleviate gut microbiota dysbiosis in mice with colitis by bacterial 16S rRNA sequencing. In conclusion, our study demonstrates the therapeutic and protective effects of GPA on IBD and provides novel insights into the prevention of colitis by targeting gut microbiota metabolism using natural products.

New chromones from the roots of Saposhnikovia divaricata (Turcz.) Schischk with anti-inflammatory activity.

Fifteen new chromones, sadivamones A-E (1-5), cimifugin monoacetate (6), sadivamones F-N (7-15), together with fifteen known chromones (16-30), were isolated from the ethyl acetate portions of 70% ethanol extract of Saposhnikovia divaricata (Turcz.) Schischk roots. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. Meanwhile, LPS induced RAW264.7 inflammatory cell model was used to determine the potential anti-inflammatory activity of all the isolated compounds in vitro. The results showed that compounds 2, 8, 12-13, 18, 20-22, 24, and 27 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. To determine the signaling pathways involved in the suppression of NO production by compounds 8, 12 and 13, we investigated ERK and c-Jun N-terminal protein kinase (JNK) expression by western blot analysis. Further mechanistic studies demonstrated that compounds 12 and 13 inhibited the phosphorylation of ERK and the activation of ERK and JNK signaling in RAW264.7 cells via MAPK signaling pathways. Taken together, compounds 12 and 13 may be valuable candidates for the treatment of inflammatory diseases.

Long-distance control of potato storage organ formation by SELF PRUNING 3D and FLOWERING LOCUS T-like 1.

Plants program their meristem-associated developmental switches for timely adaptation to a changing environment. Potato (Solanum tuberosum L.) tubers differentiate from specialized belowground branches or stolons through radial expansion of their terminal ends. During this process, the stolon apex and closest axillary buds enter a dormancy state that leads to tuber eyes, which are reactivated the following spring and generate a clonally identical plant. The potato FLOWERING LOCUS T homolog SELF-PRUNING 6A (StSP6A) was previously identified as the major tuber-inducing signal that integrates day-length cues to control the storage switch. However, whether some other long-range signals also act as tuber organogenesis stimuli remains unknown. Here, we show that the florigen SELF PRUNING 3D (StSP3D) and FLOWERING LOCUS T-like 1 (StFTL1) genes are activated by short days, analogously to StSP6A. Overexpression of StSP3D or StFTL1 promotes tuber formation under non-inductive long days, and the tuber-inducing activity of these proteins is graft transmissible. Using the non-tuber-bearing wild species Solanum etuberosum, a natural SP6A null mutant, we show that leaf-expressed SP6A is dispensable for StSP3D long-range activity. StSP3D and StFTL1 mediate secondary activation of StSP6A in stolon tips, leading to amplification of this tuberigen signal. StSP3D and StFTL1 were observed to bind the same protein partners as StSP6A, suggesting that they can also form transcriptionally active complexes. Together, our findings show that additional mobile tuber-inducing signals are regulated by the photoperiodic pathway.

Rhamnogalacturonan-I enriched pectin from steamed ginseng ameliorates lipid metabolism in type 2 diabetic rats via gut microbiota and AMPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Meyer (Ginseng) has traditionally been used to treat diabetes. Polysaccharide is the main active component of ginseng, and has been proved to have hypoglycaemic and hypolipidaemic effects, but its mechanism remains unclear. AIM OF THE STUDY: This study aimed to evaluate the effect and the potential mechanism of rhamnogalacturonan-I enriched pectin (GPS-1) from steamed ginseng on lipid metabolism in type 2 diabetes mellitus (T2DM) rats. MATERIALS AND METHODS: GPS-1 was prepared by water extraction, ion-exchange and gel chromatography. High-glucose/high-fat diet combined with streptozotocin was used to establish T2DM rat models, and lipid levels in serum and liver were tested. 16S rRNA sequencing and gas chromatography-mass spectrometry were used to detect the changes of gut microbiota and metabolites. The protein and mRNA levels of lipid synthesis-related genes were detected by Western blot and quantitative real-time polymerase chain reaction. RESULTS: The polyphagia, polydipsia, weight loss, hyperglycaemia, hyperlipidaemia and hepatic lipid accumulation in T2DM rats were alleviated after GPS-1 intervention. GPS-1 modulated the gut microbiota composition of T2DM rats, increased the levels of short-chain fatty acids, and promoted the secretion of glucagon-like peptide-1 and peptide tyrosine tyrosine. Further, GPS-1 activated AMP-activated protein kinases, phosphorylated acetyl-CoA carboxylase, reduced the expression of sterol regulatory element-binding protein-1c and fatty acid synthases in T2DM rats. CONCLUSIONS: The regulation effects of GPS-1 on lipid metabolism in T2DM rats are related to the regulation of gut microbiota and activation of AMP-activated protein kinase pathway.

Thermodynamics, Conformation, and Biocatalytic Performance of Glucose Oxidase Combined with Black Phosphorus Quantum Dots.

Glucose oxidase (GOD) has a wide range of applications in biosensing and cancer treatment as a result of its unique biocatalytic properties. More importantly, GOD could synergistically enhance the cancer therapeutic effect when combined with other cancer therapeutic strategies. However, the interaction of GOD with a cancer therapeutic agent has not been well-studied. Herein, the thermodynamic properties of the interaction between black phosphorus quantum dots (BPQDs) and GOD were systematically elucidated, and the dose-dependent conformational and enzymatic activity changes of BPQDs on GOD were quantitatively and qualitatively analyzed. The results indicated that the stoichiometric ratio of BPQDs to GOD was approximately 1:1. In particular, fluorescence spectroscopy, circular dichroism spectra, and Fourier transform infrared spectra have synergistically studied the changes in secondary and tertiary conformations of GOD induced by BPQDs. Higher doses of BPQDs resulted in a loose structure of GOD but still maintained the native conformation and preserved effective enzymatic activity, effectively catalyzing the production of H2O2 from glucose in a cell. The interaction mechanism between BPQDs and GOD provides a theoretical basis for the design of GOD-based multimodal synergistic cancer therapy and its clinical translation analysis.

[Effect of origin species, body weight, and gender on quality of Bufonis Venenum].

Based on standard sampling for Bufonis Venenum, this study analyzed the effect of the origin, and body weight and gender of Bufo bufo gargarizans on the quality of Bufonis Venenum. To be specific, mass spectrometry(MS) and the content determination methods in Chinese Pharmacopoeia(2020) were adopted. First, MS was performed on 76 Bufonis Venenum samples collected from 40 cities/counties in 17 provinces/autonomous regions which were derived from B. bufo gargarizans and B. melanostictus. Based on content determination, the body weight and gender of B. bufo gargarizans, which influenced the quality of Bufonis Venenum, were evaluated. Multivariate statistical analysis suggested huge difference in the material basis of the medicinal material derived from B. bufo gargarizans and B. melanostictus, and 9 differential compounds were identified. The content of components specified in Chinese Pharmacopoeia was higher in the medicinal material derived from B. bufo gargarizans than in the medicinal material derived from B. melanostictus. The content of the components specified in Chinese Pharmacopoeia was low in Bufonis Venenum derived from heavy B. bufo gargarizans, and higher in the Bufonis Venenum produced by male B. bufo gargarizans than in that produced by female B. bufo gargarizans irrespective of time and geographic location. In summary, this study provide new ideas and reference for the quality control of Bufonis Venenum, collection and processing of Bufonis Venenum, artificial breeding of B. bufo gargarizans, and biosynthesis mechanism of Bufonis Venenum.

Dexmedetomidine Combined with Low-Dose Propofol Declines Learning and Memory Impairment and Neural Cell Injury in Developing Rats.

Background: General anesthesia in early childhood may affect all aspects of neurodevelopment, resulting in learning and behavior defects. Therefore, there is an urgent need to find safe anesthetics or put forward more comprehensive anesthesia schemes to solve the negative effects caused by existing anesthetics. The objective of this study is to explore the impact of dexmedetomidine (Dex) incorporated with low-dose propofol (PRO) on learning and memory ability and neural cells in developing rats. Methods: Eighty SD rats were randomly divided into 4 groups including the Sham group, Lipid group, L-PRO group, and Dex + L-PRO group. After treatment, the spatial learning and memory ability of rats in each group were assessed by the water maze test and the passive avoidance test. The damage of hippocampal tissues was assessed by Nissl staining; the apoptosis, the levels of inflammatory factors, and the level of oxidative stress were measured by Tunel staining, ELISA, and biochemical assays, respectively. Besides, qRT-PCR and Western Blot determined the expression of apoptosis-related proteins, neurotrophic factors, and MAPK signaling pathway-related proteins in the hippocampus. Results: Compared with the L-PRO group, the Dex + L-PRO group had better spatial learning and memory ability. Administration of Dex and L-PRO greatly alleviated neural cell damage in the hippocampus and decreased the levels of IL-6, IL-1ß, and TNF-α. Besides, it significantly decreased the content of ROS and malondialdehyde (MDA), glutathione (GSH), when up-regulating the levels of IL-10, antioxidant superoxide dismutase (SOD) and BDNF, receptor tyrosine kinase B (TrkB), and neurotrophin-3 (NT-3) related to hearing function and significantly lower activity of MAPK signaling pathway. Conclusion: Dex combined with low-dose PRO can significantly inhibit inflammation, oxidative stress response, neuronal apoptosis, MAPK signaling pathway activity and promote the secretion of neurokines in hippocampus to reduce neural cell damage and avoid the learning and memory impairment caused by anesthetics in developing rats.

Nanoarchitectured Graphene Organic Framework for Drug Delivery and Chemo-photothermal Synergistic Therapy.

The combination of phototherapy and chemotherapy has received extensive attention in the field of cancer therapy. Hence, graphene organic framework (GOF) with a large d-spacing was prepared by solvothermal method, and a novel nanocomposite based on bovine serum albumin (BSA) and the anticancer drug doxorubicin (DOX) was developed, which effectively achieved a photothermal-chemotherapy synergistic treatment. When the feeding ratio was 1:1.6, the DOX loading capacity was 18.51%, and the GOF-BSA/DOX nanocomposite possessed unobvious pH response characteristic, as well as the cumulative release of DOX reached 54.17% at 42°C in the acidic environment (pH = 5.0). The nanocarriers also showed excellent photothermal property and photothermal stability in vitro. In addition, under 808 nm near-infrared laser (NIR) irradiation, the GOF-BSA/DOX nanocomposites generated a large amount of heat, which significantly enhanced the synergistic antitumor effect of in vitro photothermal-chemotherapy. Furthermore, the GOF-BSA/DOX nanocomposites exhibited significantly increased cytotoxicity in the NIR compared with chemotherapy or photothermal therapy alone, suggesting that the combination of chemotherapy and photothermal therapy has excellent antitumor capacity. Therefore, porous GOF nanocarriers may have great potential in combined anti-tumour therapy.

[Distribution characteristics of Bufo bufo gargarizans resources in China based on quality evaluation of Bufonis Venenum].

On the premise of strictly controlling the harvesting conditions of Bufonis Venenum, we studied the relationship between the quality and resource distribution of Bufonis Venenum in China, aiming to provide the data for comprehensively understanding the geographical distribution and characteristics of Bufonis Venenum in China. In this study, 105 samples of Bufonis Venenum were collected from 42 counties and cities in 19 provinces in China, and the material basis and index components were determined by mass spectrometry and high performance liquid chromatography. The obtained data formed the quality database of Bufonis Venenum from different producing areas in China. The analysis of the material basis showed that Bufonis Venenum was mainly produced in two characteristic regions(north area and south area) divided by Qinling Mountains, northern edge of Huaiyang hills and the connecting area of Huang-Huai Plain, Huangshan Mountains, and Tianmu Mountains. Eight differential components were identified in the Bufonis Venenum samples from the south area and the north area. All the Bufonis Venenum samples from the north area showed the content of index components above the requirements of Chinese Pharmacopoeia(2020 edition), while those from the south area had the content of index components lower than the standards of Chinese Pharmacopoeia(2020 edition). The quality evaluation showed uneven distribution of Bufonis Venenum quality, which was high in the north and low in the south. The results provided a research basis for the breeding base selection of Bufo bufo gargarizans.

Reshuffling of the ancestral core-eudicot genome shaped chromatin topology and epigenetic modification in Panax.

All extant core-eudicot plants share a common ancestral genome that has experienced cyclic polyploidizations and (re)diploidizations. Reshuffling of the ancestral core-eudicot genome generates abundant genomic diversity, but the role of this diversity in shaping the hierarchical genome architecture, such as chromatin topology and gene expression, remains poorly understood. Here, we assemble chromosome-level genomes of one diploid and three tetraploid Panax species and conduct in-depth comparative genomic and epigenomic analyses. We show that chromosomal interactions within each duplicated ancestral chromosome largely maintain in extant Panax species, albeit experiencing ca. 100-150 million years of evolution from a shared ancestor. Biased genetic fractionation and epigenetic regulation divergence during polyploidization/(re)diploidization processes generate remarkable biochemical diversity of secondary metabolites in the Panax genus. Our study provides a paleo-polyploidization perspective of how reshuffling of the ancestral core-eudicot genome leads to a highly dynamic genome and to the metabolic diversification of extant eudicot plants.

Transcription factor StABI5-like 1 binding to the FLOWERING LOCUS T homologs promotes early maturity in potato.

Potato (Solanum tuberosum L.) maturity involves several important traits, including the onset of tuberization, flowering, leaf senescence, and the length of the plant life cycle. The timing of flowering and tuberization in potato is mediated by seasonal fluctuations in photoperiod and is thought to be separately controlled by the FLOWERING LOCUS T-like (FT-like) genes SELF-PRUNING 3D (StSP3D) and SELF-PRUNING 6A (StSP6A). However, the biological relationship between these morphological transitions that occur almost synchronously remains unknown. Here, we show that StABI5-like 1 (StABL1), a transcription factor central to abscisic acid (ABA) signaling, is a binding partner of StSP3D and StSP6A, forming an alternative florigen activation complex and alternative tuberigen activation complex in a 14-3-3-dependent manner. Overexpression of StABL1 results in the early initiation of flowering and tuberization as well as a short life cycle. Using genome-wide chromatin immunoprecipitation sequencing and RNA-sequencing, we demonstrate that AGAMOUS-like and GA 2-oxidase 1 genes are regulated by StABL1. Phytohormone profiling indicates an altered gibberellic acid (GA) metabolism and that StABL1-overexpressing plants are insensitive to the inhibitory effect of GA with respect to tuberization. Collectively, our results suggest that StABL1 functions with FT-like genes to promote flowering and tuberization and consequently life cycle length in potato, providing insight into the pleiotropic functioning of the FT gene.

Cu-Doped black phosphorus quantum dots as multifunctional Fenton nanocatalyst for boosting synergistically enhanced H2O2-guided and photothermal chemodynamic cancer therapy.

Chemodynamic therapy (CDT) is a cancer treatment that converts endogenous H2O2 into hydroxyl radicals (˙OH) through Fenton reaction to destroy cancer cells. However, there are still some challenges in accelerating the Fenton reaction of CDT and improving the biodegradability of nanocatalysts. Herein, a multifunctional biomimetic BPQDs-Cu@GOD (BCG) Fenton nanocatalyst for boosting synergistically enhanced H2O2-guided and photothermal CDT of cancer is reported. Cu2+ in BCG can be reduced to Cu+ by black phosphorus quantum dots (BPQDs), triggering a Cu+-mediated Fenton-like reaction to degrade H2O2 and generate abundant ˙OH for cancer CDT. The loaded glucose oxidase (GOD) can consume the glucose in the tumor to produce abundant H2O2 for Fenton-like reaction. In addition, Cu2+ in BCG can react with GSH in tumor cells to alleviate the antioxidant capacity of tumor tissues, further improving the CDT efficacy. Furthermore, the photothermal performance of BPQDs can be enhanced by capturing Cu2+, improving the photoacoustic imaging and photothermal therapy (PTT) functions. More importantly, the enhanced photothermal performance can rapidly accelerate the Fenton-like reaction under NIR irradiation. Finally, Cu2+ can accelerate the degradation of BPQDs, which can reduce the retention of reagents. As a novel multifunctional biocompatible Fenton nanocatalyst, BCG have great potential in cancer therapy.

pH-Sensitive Bioprobe for Multichannel Mitochondrial Imaging and Photodynamic Therapy.

Tumor targeting therapy and photodynamic therapy are effective anti-cancer therapies. Their research progress has attracted wide attention and is one of the focuses of anti-cancer drug research and development. The design and synthesis of multifunctional organic phototheranostic agents for superior image-guided diagnosis and phototherapy play an increasingly positive role in cancer diagnosis and treatment. Herein, F16M and CyM were obtained through functional design from cyanine and F16. Physicochemical characterization and biological application results showed that CyM is a multifunctional organic biological probe, which can realize intracellular multichannel (green, yellow, red, and NIR) imaging, pH detection, and mitochondrial-targeted photodynamic therapy. As an organic phototheranostic agent, it could not only realize near-infrared imaging and photodynamic therapy in vivo and in vitro but also has excellent biocompatibility and good guiding significance for the development of multichannel imaging and mitochondrial-targeting photodynamic therapy.

Multifunctional Probes with High Utilization Rates: Self-Assembled Merocyanine Nanoparticles in Water as Acid-Base Indicators and Mitochondrion-Targeting Chemotherapeutic Agents.

Multifunctional probes with high utilization rates have great value in practical applications in various fields such as cancer diagnosis and therapy. Here we have synthesized two organic molecules based on merocyanine. They can self-assemble in water to form ∼1.5 nm nanoparticles. Both of them have good application potential in fluorescent anticounterfeit printing ink and pH detection. More importantly, they have excellent mitochondrial targeting ability, intracellular red light and near-infrared dual-channel imaging ability, strong antiphotobleaching ability, and in vivo and in vitro near-infrared imaging capabilities, showing superior chemotherapy capabilities and biocompatibility in the 4T1 tumor-bearing mouse model.