Spatiotemporally controlled AuNPs@ZIF-8 based nanocarriers for synergistic photothermal/chemodynamic therapy.

High efficiency and spatio-temporal control remains a challenge for multi-modal synergistic cancer therapy. Herein, based on gold nanoparticles (AuNPs) and zeolite-like imidazole skeleton material (ZIF-8), a spatio-temporal controllable photothermal/ chemical dynamic/ chemotherapy three modal synergistic anti-tumor nano-carrier (HAZD) was developed. HAZD has a size of 128.75 ± 11.86 nm, a drug loading ratio of 21.5 ± 2.2 % and an encapsulation efficiency of 71.8 ± 1.7 %. Stability, acid responsive release character, outstanding catalytic ability to generate ROS, relatively high thermal conversion efficiency up to 62.38 % and spatio-temporal controllable abilities are also found within this nano-carrier. Furthermore, HAZD performed good antitumor ability in vivo with the comprehensive effects of photothermal/ chemical dynamic/ chemotherapy. The tumor growth inhibition value is 97.1 % within 12 days, indicating its great potential in multi-modal synergistic cancer therapy. STATEMENT OF SIGNIFICANCE: Cancer remains one of the major culprits that seriously harm human health currently. With the development of materials and nanotechnology, great improvements have been made in multimodal anti-tumor strategies. However, temporal- and spatial-controllable multi-modal synergistic nanocarriers are urgently awaited for efficient and low-toxicity tumor therapy. This article proposes a spatio-temporally controllable three-modal anti-tumor strategy and designs an anti-tumor drug delivery system based on gold nanoparticles (AuNPs) and zeolite-like imidazole skeleton material (ZIF-8), which shows acid-responsive release characteristics, catalytic ability to generate ROS, relatively high thermal conversion efficiency up to 62.38 %, as well as spatio-temporal controllable abilities. Moreover, it demonstrates outstanding anti-tumor ability, with a tumor growth inhibition value of 97.1 % within 12 days, revealing its significant potential for future personalized and precise anti-tumor treatments.

Transcriptome and metabolome profiling of the medicinal plant Veratrum mengtzeanum reveal key components of the alkaloid biosynthesis.

Veratrum mengtzeanum is the main ingredient for Chinese folk medicine known as "Pimacao" due to its unique alkaloids. A diverse class of plant-specific metabolites having key pharmacological activities. There are limited studies on alkaloid synthesis and its metabolic pathways in plants. To elucidate the alkaloid pathway and identify novel biosynthetic enzymes and compounds in V. mengtzeanum, transcriptome and metabolome profiling has been conducted in leaves and roots. The transcriptome of V. mengtzeanum leaves and roots yielded 190,161 unigenes, of which 33,942 genes expressed differentially (DEGs) in both tissues. Three enriched regulatory pathways (isoquinoline alkaloid biosynthesis, indole alkaloid biosynthesis and tropane, piperidine and pyridine alkaloid biosynthesis) and a considerable number of genes such as AED3-like, A4U43, 21 kDa protein-like, 3-O-glycotransferase 2-like, AtDIR19, MST4, CASP-like protein 1D1 were discovered in association with the biosynthesis of alkaloids in leaves and roots. Some transcription factor families, i.e., AP2/ERF, GRAS, NAC, bHLH, MYB-related, C3H, FARI, WRKY, HB-HD-ZIP, C2H2, and bZIP were also found to have a prominent role in regulating the synthesis of alkaloids and steroidal alkaloids in the leaves and roots of V. mengtzeanum. The metabolome analysis revealed 74 significantly accumulated metabolites, with 55 differentially accumulated in leaves compared to root tissues. Out of 74 metabolites, 18 alkaloids were highly accumulated in the roots. A novel alkaloid compound viz; 3-Vanilloylygadenine was discovered in root samples. Conjoint analysis of transcriptome and metabolome studies has also highlighted potential genes involved in regulation and transport of alkaloid compounds. Here, we have presented a comprehensive metabolic and transcriptome profiling of V. mengtzeanum tissues. In earlier reports, only the roots were reported as a rich source of alkaloid biosynthesis, but the current findings revealed both leaves and roots as significant manufacturing factories for alkaloid biosynthesis.

Comparative chloroplast genome analysis of medicinally important Veratrum (Melanthiaceae) in China: Insights into genomic characterization and phylogenetic relationships.

Members of Veratrum are perennial herbs widely used in traditional Chinese medicine to induce vomiting, resolve blood stasis and relieve pain. However, the intrageneric classification and phylogenetic relationships within Veratrum have long been controversial due to the complexity of morphological variations and lack of high-resolution molecular markers. In this study, we reevaluated the infrageneric relationships with the genus Veratrum using complete chloroplast genome sequence data. Herein, the complete cp genomes of ten species of Veratrum were newly sequenced and characterized. The complete cp genomes of ten species of Veratrum had the typical quadripartite structure, ranging from 151,597 bp to 153,711 bp in size and comprising a total of 135 genes. The structure of Veratrum cp genomes (i.e., gene order, content, and genome components) was highly similar across species. The number of simple sequence repeats (SSRs) ranged from 63 to 78, and of long repeats ranged from 31 to 35. Eight highly divergent regions (ndhF, psbC-psbZ, psbK-psbI, rpoB-trnC_GCA, trnK_UUU-trnQ_UUG, trnS_GCU-trnG_UCC, trnT_UGU-trnL_UAA and ycf1) were identified and are potentially useful for the DNA barcoding of Veratrum. Phylogenetic analysis among 29 taxa based on cp genomes, total genes, protein-coding genes and intergenic regions strongly supported the monophyly of Veratrum. The circumscription and relationships of the infrageneric taxa of Veratrum were well-presented with great resolution. These results will facilitate the identification, taxonomy, and utilization of Veratrum plants as well as the evolutionary studies of Melanthiaceae.

Bulk sedimentary phosphorus in relation to organic carbon, sediment textural properties and hydrodynamics in the northern Beibu Gulf, South China Sea.

Bulk sedimentary phosphorus (P) is studied to evaluate its source, distribution, preservation and enrichment in relation with organic carbon (OC), sediment textures and moisture contents in the northern Beibu Gulf. Approximately 80% of surface sediments in the investigated sites were composed of coarse sandy texture (>63 µm). Total P (TP), inorganic P (IP) and organic P (OP) contents were lower to medium range compared to the levels reported for other marginal seas. Sedimentary OC and P were derived from mixed sources, with high terrestrial influence in the coastal areas (molar OC/OP ratios >250:1). The distribution of P corroborated with the variation tendency of fine-grained sediments, moisture contents and OC. Both IP and OP may significantly influence the trophic state of seawater if released from surface sediments. Influenced by hydrodynamics, frequent resuspension and high abundance of sand, TP is less preserved, and shows low to moderate enrichment in surface sediments.

The complete chloroplast genome and phylogenetic analysis of Veratrum mengtzeanum Loes. F. (Liliaceae).

Veratrum mengtzeanum Loes. F. is a medicinal plant belonging to the genus Veratrum (Liliaceae). In the present study, we assembled and characterized the complete chloroplast (cp) genome of this species. The chloroplast genome is 152,051 bp in length, with one large single copy (LSC) region and one small single copy (SSC) region of 82,112 bp and 17,544 bp, respectively; two inverted repeat (IR) regions of 26,198 bp. It contains 131 annotated genes, including 85 protein-coding genes (PCGs), 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis indicated that V. mengtzeanum was closely related to Veratrum japonicum with 100% bootstrap value.

Efficacy and safety evaluation of intravenous infusion of cervus and cucumis polypeptides for treatment of avascular necrosis of the femoral head: a randomized clinical trial.

OBJECTIVE: To investigate the efficacy and safety of intravenous cervus and cucumis polypeptides for treating avascular necrosis of the femoral head (ANFH) in regard to pain and hip function in a randomized clinical trial. METHODS: A total of 96 subjects with ANFH who were recruited at the Orthopaedic Hospital Affiliated with Hebei United University and Qian Hai Femoral Head Hospital of Beijing were assigned by lottery to an intervention group (n = 48) or a control group (n = 48). All subjects underwent physical therapy and rehabilitation exercises. In addition, subjects in the intervention group were given intravenous infusions of cervus and cucumis polypeptides. Visual analogue scale (VAS), Harris hip score, and radiography or magnetic resonance imaging were applied to assess all subjects at the beginning of treatment and 3, 6, and 9 months afterward. All the subjects were followed up for 2 years. RESULTS: At the beginning of treatment, there were no statistically significant differences between the two groups in terms of the general condition of patients or the VAS and Harris hip scores (all P > 0.05). At 3, 6, and 9 months after treatment, however, the VAS score decreased and the Harris hip score increased in all patients, with the improvement of intervention group significantly greater than that of the control group (P < 0.05). The total effectiveness rates for the intervention and control groups were 89.58% and 70.83%, respectively, with the difference being statistically significant (P < 0.05). There was no statistically significant difference between the two groups in terms of the safety of the injections (P> 0.05). CONCLUSION: Intravenous infusion of cervus and cucumis polypeptides relieved pain and improved hip function of subjects with ANFH. Thus, the intravenous infusion of cervus and cucumis polypeptides was a safe, effective treatment for ANFH.

[Synthesis of (2'-bromo-4', 5'-dimethoxy-phenyl)-(2,3-dibromo-4,5-dimethoxy-phenyl)-methane as PTP1B inhibitor].

OBJECTIVE: To synthesize (2'-bromo-4',5'-dimethoxy-phenyl)-( 2,3- dibromo-4,5-dimethoxy-phenyl)-methane (6) as protein tyrosine phosphatase 1B (PTP1B) inhibitor. METHOD: Compound 6 was synthesized by Friedel-Crafts reaction, bromination and decarbonylation and screened inhibitory activity against PTP1B by the colorimetric assay. The structure of synthetic intermediates and target product were identified on the basis of spectral analysis. RESULT: Compound 6 was synthesized successfully in four steps and evaluated for its PTP1B inhibitory activity, the screening result shown that compound 6 displayed good inhibitory activity against PTP1B. CONCLUSION: The target compound 6 was synthesized with the overall yield of 20%, which was a new compound and shown good inhibitory activity against PTP1B (inhibition 40.16% at 5 mg x L(-1)).

[Studies on chemical constituents of Laurencia saitoi].

In order to search for bioactive natural products from marine algae, the chemical constituents of red alga Laurencia saitoi was separated by the combination of normal phase silica gel, Sephadex LH-20 column chromatography and recrystallization. Seven compounds: aplysistatin (1), 5-acetoxypalisadin B (2), palisadin B (3), palisadin A (4), pacifigorgiol (5), stigmast4-en-3alpha, 6beta-diol (6), 2, 3, 5, 6-Tetrabromoindole (7), were isolated and their structures were elucidated by spectroscopic methods including 1H-NMR, 13C-NMR and MS techniques. All compounds were isolated from L. saitoi for the first time. Cytotoxicities of purified compounds were evaluated by MTT method, however, all of them were found inactive (IC50 >10 mg x L(-1).

[Bioactive sterols from red alga Acanthophora spicifera boergesen].

OBJECTIVE: To study the chemical constituents of the red alga Acanthophora spicifera boergesen aiming at searching for bioactive leading compounds. METHOD: Compounds were isolated by various chromatographic techniques including column chromatography over normal phase silica gel and Sephadex LH-20 gel and reverse phase HPLC as well as recrystallization. Their structures were determined by spectroscopic methods including IR, MS, 1D and 2D NMR techniques. MTT method was used for testing cytotoxicity of compounds against human cancer cell lines HCT-8, Bel-7402, BGC-823, A549 and HELA. Their inhibition against proliferation of dog vascular smooth muscle cells was also screened by MTT assay. RESULT: Six sterols were isolated from the ethanolic extract of the red alga Acanthophora spicifera. Their structures were identified as 6-hydroxycholest-4-ene-3-one (1), cholest-4-ene-3, 6-dione (2), cholest-5-ene-3 beta-ol (3), 5 alpha-cholestane-3, 6-dione (4), beta-sitosterol (5) and saringosterol (6). CONCLUSION: Compounds 1-3 and 5 were obtained from this genus for the first time. Compounds 1, 2 and 4 showed moderate cytotoxic activity against human cancer cell lines.

[PTP1B inhibitory activities of bromophenol derivatives from algae].

OBJECTIVE: To study the protein tyrosine phosphatase-1B (PTP1B) inhibitory activity of natural products from algae aiming at searching for new way for the treatment of type 2 diabetes mellitus (T2DM) and obesity. METHOD: Bromophenols derivatives from algae were screened against the PTP1B by the colorimetric assay with GST/PTP1B fusion protein. The Me2SO was distributed as the full enzyme activity, and Na3VO4 (IC50 2 micromol L(-1)) was distributed as the positive control. Inhibition rate was assayed and IC50 were calculated by LOGIT method. RESULT: Three bromophenols from Rhodomela confervoides and Leathesia nana, 3, 4-dibromo-5-(methoxymethyl)-1, 2-benzenediol (1), 2-methyl-3-(2, 3-dibromo4, 5-dihydroxy)-propylaldehyde (2) and 3-(2, 3-dibromo-4, 5-dihydroxy-phenyl)-4-bromo-5, 6-dihydroxy-1, 3-dihydroiso-benzofuran (3) showed significant inhibitory activity against PTP1B. IC50 values were 3.4 +/- micromol L(-1), 4.5 micromol L(-1) and 2.8 micromol L(-1), respectively. CONCLUSION: The results prove that three bromophenol derivatives from algae with significant inhibitory activity against PTP1B were potential and effective therapeutic agents for treatment of T2DM and obesity.

[Studies on chemical constitutes of Acantophora spicifera].

OBJECTIVE: To study the chemical constitutes of Acantophora spicifera. METHOD: Compounds were isolated by normal phase silica gel and Sephadex LH-20 gel column chromatography, and reverse-phase HPLC, as well as recrystallization. Their structures were elucidated by spectroscopic methods. RESULT: Seven compounds were isolated from A. spicifera and their structures were identified as aplysin (1), loloilide (2), (R)-(-)-dehydrovomifoliol (3), uracil (4), thymine (5), 1-methoxy-4-(1-propenyl) benzene (6). CONCLUSION: The compounds were obtained from this genus for the first time. Compound 6 was firstly obtained from marine organisms.

[Studies on chemical constituents of Laurencia tristicha ( II )].

OBJECTIVE: To search for chemical constituents with structural diversity from Laurencia tristicha to supply for biological assay. METHOD: Compounds were isolated by means of column chromatography over normal phase silica gel and Sephadex LH-20, recrystallization and HPLC. Structures were identified by spectroscopic methods including 1D NMR, IR and MS. Cytotoxicities of the purified compounds were evaluated by MTT method. RESULT: Seven compounds were isolated from L. tristicha. Their structures were elucidated as cholesterol (1), cholesta- 5-en-3beta, 7alpha-diol (2), beta-stigmasterol (3), phytol (4), zeaxanthin (5), 4 -hydroxybenzaldehyde (6), indolyl-3-carbaldehyde (7). In the cytotoxic assay compound 2 was active against human cancer cell lines HCT-8, Bel-7402, BGc-823, A549 and HELA with IC50 values of 1.90, 2.02, 1.99, 6.52 and 1.20 microg x mL(-1), respectively. Compound 4 showed cytotoxicity against HCT-8 and HELA with IC50 value of 3.51 and 2.04 microg x mL(-1), and other compounds were inactive ( IC50 > 10 microg x mL(-1)). CONCLUSION: Compounds 1-7 were isolated from L. tristicha for the first time. In additon, compounds 2 and 4 were cytotoxic against several human cancer cell lines.

[Norisoprenoids from red alga Gymnogongrus flabelliformis].

OBJECTIVE: To investigate the chemical constituents of the red alga Gymnogongrus flabelliformis Harv. METHOD: Compounds were isolated by normal phase silica gel and Sephadex LH - 20 gel column chromatography and reverse phase HPLC. Their structures were elucidated by spectroscopic methods including MS, 1H-NMR, 13C-NMR. Cytotoxicity of the compounds was screened by using standard MIT method. RESULT: Five compounds were isolated from G. flabelliforrmis, their structures were identified as(3S, 6R, 7E)-( + )-3-hydroxyl-4, 7-mega-stigmadien-9-one (1), (3S, 5R, 6S, 7E)-(-)-3-hydroxy-5, 6-epoxy-7-megastigmene-9-one (2), (3S, 5S, 6R, 7E)-(+)3-hydroxy-5, 6-epoxy-7-megastigmene-9-one (3), dehydrovomifoliol (4), (3R)-(-)4-[(2R, 4S)-4-acetoxy-2-hydroxy-2, 6, 6-trimethylcyclohexylidene] -3-buten-2-one (5). CONCLUSION: All of the compounds were obtained from this species for the first time and compound 1 was a new natural product. These compounds were inactive (IC50 > 10 microg x mL(-1)) in the MTT assay against several human cancer cell lines.

[Chemical constituents from red alga Corallina pilulifera].

OBJECTIVE: To investigate the chemical constituents of red alga Corallina pilulifera. METHOD: Compounds were isolated by normal phase silica gel and Sephadex LH - 20 gel column chromatography, reverse phase HPLC and recrystallization. Their structures were elucidated by spectroscopic methods including MS, 1H-NMR, 13C-NMR, HSQC, HMBC. Cytotoxicity of the compounds was screened by using standard MTT method. RESULT: Seven compounds were isolated from red alga C. pilulifera, their structures were identified as (E) -phytol epoxide (1), phytenal (2), phytol (3), dehydrovomifoliol (4), loliolide (5), 3beta-hydroxy-5alpha, 6alpha-epoxy-7-megastigmene-9-one (6), 4-hydroxybenzaldehyde (7). CONCLUSION: All of the compounds were obtained from this species for the first time. These compounds were inactive (IC50 > 10 microg x mL(-1)) in the MTT assay.

[Studies on chemical constitutes of green alga Chaetomorpha basiretorsa and their bioactivity].

OBJECTIVE: To study the chemical constituents of Chaetomorpha basiretorsa and screen for bioactive leading compounds. METHOD: Compounds were isolated by normal phase silica gel and Sephadex LH-20 gel column chromatography, reverse phase MPLC and reverse phase HPLC. Their structures were elucidated by spectroscopic methods including MS, IR and 1D, 2D NMR. Cytotoxicity of the compounds was screened by using standard MTT method. The purified compounds' inhibition against proliferation of dog vascular smooth muscle cells was also screened by MTT assay. RESULT: Five compounds were isolated from C. basiretorsa and their structures were identified as euphol (I), loloilide (II), 4-cumylphenol (III), zeaxanthin (IV) and lactucaxanthin (V). CONCLUSION: All these compounds were obtained from this genus for the first time. Compound (III), 4-cumylphenol, was a new nature product. All compounds were inactive (IC50 > 10 microg x mL(-1)) in cytotoxicity screening. In inhibition against proliferation of dog vascular smooth muscle cells test, the cell survival ratio to compound I was (0.32 +/- 0.056)% which indicate its potential anti-atherosclerotic bioactivity.

[Chemical constituents from marine alga Chaetomorpha basiretorsa].

OBJECTIVE: To investigate the chemical constituents of marine alga Chaetomorpha basiretorsa. METHOD: Compounds were isolated by normal phase silica gel and Sephadex LH-20 gel colum chromatography, reverse phase MPLC, reverse phase HPLC and recrystallization. Their structures were elucidated by spectroscopic methods including MS, IR, NMR, and X-ray crystalography. Cytotoxicity of the compounds were screened by using standard MTT method. RESULT: Nine compounds were isolated from C. basiretorsa and their structures were identified as N-phenyl-2-naphthalenamine( I ), dibutyl phthalate( II ), diisobutyl phthalate( III ), 1-phenyl-ethane-1, 2-diol( IV ), 2-hydrox-gamma-benzaldehyde( V ), diethyleneglycol monobenzoate( VI ), uracil( VII ), thymine( VIII ) and thymidine( IX ). CONCLUSION: All these compounds were obtained from this genus for the first time, N-phenyl-2-naphthalenamine and diethyleneglycol monobenzoate were first reported from the marine organisms. Compound I and VII showed moderate activity against KB cell(IC50 10.15 microg x mL(-1) for I and 3.79 microg x mL(-1) for VII ) and MCF-7 cell(IC50 3.24 microg x mL(-1) for VII).

Bromophenols from the brown alga Leathesia nana.

Two new bromophenols, (E)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-2-methylpropenal (1) and 3-(2,3-dibromo-4,5-dihydroxyphenyl)-2-methyl-1-propanol (2), together with 11 known bromophenols (3-13), were isolated from the ethanolic extract of the brown alga Leathesia nana S. et G. Their structures have been elucidated by spectroscopic methods, including IR, MS, HRMS, 1D and 2D NMR techniques.