Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 61
1.
Chempluschem ; : e202400320, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38853751

Multifluorinated aromatics serve as supramolecular synthons in the research of organic electro-optic (EO) materials by exploiting π-π stacking interaction between the aromatic hydrocarbon and multifluorinated aromatic groups for performance improvement. However, non-classical hydrogen bonding remains largely unexplored in fluorinated EO dendrimers. In this study, three Fréchet-type generation 1 benzyl ether co-dendrons were synthesized by replacing one benzyl group with 2,3,5,6-tetrafluorobenzyl (p-HF4Bz), pentafluorobenzyl (C6F5Bz), and 2,3,4,5-tetrafluorobenzyl (o-HF4Bz) groups, to afford the benzoic acid derivatives D1, D2, and D3, which were further bonded to the donor and π-bridge moieties to afford three co-dendronized push-pull phenyltetraene chromophores EOD1, EOD2, and EOD3, respectively. The weak C-H⋅⋅⋅X (X = O, F) interactions in the crystal structure of D1 cumulatively add to the benzoic acid dimers to form an extended hydrogen-bonded network, while D2 is crystallized into a centric one-dimensional chain with strong intermolecular interactions. The poled films of EOD1 with PMMA exhibited the largest and most stable EO activity with optical homogeneity among the series. The results identify the effectiveness of weak but favorable hydrogen bonds enabled by the enhanced carbon acidity of p-HF4Bz synthon in D1, over the interactions in D2 and D3, for the rational design of supramolecular EO dendrimers.

2.
J Am Chem Soc ; 146(25): 17348-17354, 2024 Jun 26.
Article En | MEDLINE | ID: mdl-38864188

Our study unveils a novel approach to accessing boryl radicals through the spontaneous homolytic cleavage of B-B bonds. We synthesized a hexaaryl-substituted diboron(6) dianion, 1, via the reductive B-B coupling of 9-borafluorene. Intriguingly, compound 1 exhibits the ability to undergo homolytic B-B bond cleavage, leading to the formation of boryl radical anions, as confirmed by EPR studies, in the presence of the 2.2.2-cryptand at room temperature. Moreover, it directly reacts with diphenylacetylene, producing an unprecedented 1,6-diborylated allene species, where the phenyl ring is dearomatized. Density functional theory computational studies suggest that homolytic B-B bond cleavage is favored in the reaction path, and the formation of the boryl radical anion is crucial for dearomatization. Additionally, it achieves the dearomative diborylation of anthracene and the activation of elemental sulfur/selenium under mild conditions. The borylation products have been successfully characterized by NMR spectra, HRMS, and X-ray single-crystal diffraction.

3.
Natl Sci Rev ; 11(4): nwad327, 2024 Apr.
Article En | MEDLINE | ID: mdl-38487495

Iron-metal clusters are crucial in a variety of critical biological and material systems, including metalloenzymes, catalysts, and magnetic storage devices. However, a synthetic high-nuclear iron cluster has been absent due to the extreme difficulty in stabilizing species with direct iron-iron bonding. In this work, we have synthesized, crystallized, and characterized a (Tp*)4W4S12(Fe@Fe12) cluster (Tp* = tris(3,5-dimethyl-1-pyrazolyl)borate(1-)), which features a rare trideca-nuclear, icosahedral [Fe@Fe12] cluster core with direct multicenter iron-iron bonding between the interstitial iron (Fei) and peripheral irons (Fep), as well as Fep···Fep ferromagnetic coupling. Quantum chemistry studies reveal that the stability of the cluster arises from the 18-electron shell-closing of the [Fe@Fe12]16+ core, assisted by its bonding interactions with the peripheral tridentate [(Tp*)WS3]4- ligands which possess both S→Fe donation and spin-polarized Fe-W σ bonds. The ground-state electron spin is theoretically predicted to be S = 32/2 for the cluster. The existence of low oxidation-state (OS ∼ +1.23) iron in this compound may find interesting applications in magnetic storage, spintronics, redox chemistry, and cluster catalysis.

4.
Nat Commun ; 15(1): 2590, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38519505

Group 1 elements exhibit the lowest electronegativity values in the Periodic Table. The chemical reduction of Group 1 metal cations M+ to M(0) is extremely challenging. Common tetraaryl borates demonstrate limited redox properties and are prone to decomposition upon oxidation. In this study, by employing simple yet versatile bipyridines as ligands, we synthesized a series of redox-active borate anions characterized by NMR and X-ray single-crystal diffraction. Notably, the borate anion can realize the reduction of Li+, generating elemental lithium metal and boron radical, thereby demonstrating its potent reducing ability. Furthermore, it can serve as a powerful two-electron-reducing reagent and be readily applied in various reductive homo-coupling reactions and Birch reduction of acridine. Additionally, this borate anion demonstrates its catalytic ability in the selective two-electron reduction of CO2 into CO.

5.
Int J Hyperthermia ; 40(1): 2250936, 2023.
Article En | MEDLINE | ID: mdl-37666493

OBJECTIVE: To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients. METHODS: This retrospective study recruited 57 patients aged 20-40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023. RESULTS: During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46-6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed. CONCLUSION: FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.


Papillomavirus Infections , Premature Birth , Female , Humans , Infant, Newborn , Pregnancy , Kinetics , Papillomavirus Infections/complications , Papillomavirus Infections/diagnostic imaging , Pregnancy Outcome , Retrospective Studies
6.
Chem Rec ; 23(12): e202300238, 2023 Dec.
Article En | MEDLINE | ID: mdl-37698286

Electron-precise B-B bonded compounds are valuable reagents in organic syntheses, which can be used as key starting material for the synthesis of functionalized organoboranes. Bis(pinacolato)diborane(4) B2 pin2 and its derivatives are among the most studied diboron species. However, their B-B bonds usually need to be activated by transition metal catalysts or bases for further transformations. Recently, many well-designed/reactive electron-precise B-B bonded compounds have been developed, which could facilitate direct reactions with small molecules, unsaturated substrates, and electrophiles. This review highlights the synthesis, structure, and reactivity of neutral and anionic B-B bonded compounds.

7.
Colloids Surf B Biointerfaces ; 227: 113354, 2023 Jul.
Article En | MEDLINE | ID: mdl-37201448

The clinical treatment of infected skin injuries caused by exogenous bacteria faces great challenges. Conventional therapeutic approaches are difficult to achieve synergistic effects of infection control and induction of skin regeneration. In this study, a novel tannic acid-based physically cross-linked double network hydrogel (PDH gel) was prepared on demand by covalent cross-linking of tannic acid (TA) with polyvinyl alcohol (PVA) and chelating ligand of TA with Fe3+. The homogeneity of the hydrogel was achieved by the action of glycol dispersant. With the anti-inflammatory and antioxidant properties of Fe3+ and TA, this hydrogel exhibited excellent antibacterial properties by achieving 99.69% and 99.36% bacterial inhibition against E.coli and S. aureus, respectively. Moreover, the PDH gel exhibits good biocompatibility, stretchability (up to 200%) and skin-friendliness. After 14 days of PDH-1 gel implantation in a rat model infected by S. aureus, the wound healing rate was as high as 95.21%. PDH gel-1 showed more granulation tissue, more pronounced blood vessels, higher collagen fiber density and good collagen deposition, and its recovery effect was better than that of PSH gel and PDH gel-2 in vivo. Hence, this study provides a novel avenue for the design of future clinical infected wound healing dressings.


Anti-Infective Agents , Hydrogels , Animals , Rats , Hydrogels/pharmacology , Staphylococcus aureus , Wound Healing , Anti-Bacterial Agents/pharmacology , Escherichia coli
8.
Bioorg Chem ; 130: 106220, 2023 01.
Article En | MEDLINE | ID: mdl-36347088

Photothermal therapy (PTT) has gained extensive interest in tumor treatments due to its non-invasive and low-toxic nature. However, the currently available photothermal agents (PTAs) mostly show unsatisfactory photothermal conversion efficiency (PCE). Besides, as a local cancer treatment modality, PTT fails to inhibit metastasis of tumors. To address these issues, in this study, two aza-boron-dipyrromethene (aza-BODIPY)-based organic photothermal agents (OPTAs), Fc-aza-BODIPY and TPA-aza-BODIPY, were rationally coined by introducing two strong electron-donating ferrocene (Fc) moieties and two triphenylamine (TPA) rotors, which could boost intramolecular photo-induced electron transfer (PET) and molecular rotation respectively, thereby improving the PCE of aza-BODIPY dyes. After encapsulation of hydrophobic Fc-aza-BODIPY (or TPA-aza-BODIPY) and quercetin with biodegradable PLGA and DSPE-mPEG2000, the resulting nanoparticles (FAQ NPs and TAQ NPs) showed excellent optical properties with PCE of ∼72.0% and ∼79.7% and specific tumor accumulations through enhanced permeability and retention (EPR) effects. Consequently, these two NPs possessed prominent antitumor effects under 880 nm laser irradiation. Moreover, both FAQ NPs and TAQ NPs loaded with quercetin could inhibit tumor metastasis efficiently. These two multifunctional nanomaterials integrating OPTAs and anti-metastasis agents constructed a cooperative treatment program, which may provide a potential opportunity for future clinical cancer treatment.


Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Quercetin , HeLa Cells , Nanoparticles/chemistry , Neoplasms/drug therapy
9.
Int J Mol Sci ; 23(24)2022 Dec 10.
Article En | MEDLINE | ID: mdl-36555298

Herein, we developed a dual-activated prodrug, BTC, that contains three functional components: a glutathione (GSH)-responsive BODIPY-based photosensitizer with a photoinduced electron transfer (PET) effect between BODIPY and the 2,4-dinitrobenzenesulfonate (DNBS) group, and an ROS-responsive thioketal linker connecting BODIPY and the chemotherapeutic agent camptothecin (CPT). Interestingly, CPT displayed low toxicity because the active site of CPT was modified by the BODIPY-based macrocycle. Additionally, BTC was encapsulated with the amphiphilic polymer DSPE-mPEG2000 to improve drug solubility and tumor selectivity. The resulting nano-prodrug passively targeted tumor cells through enhanced permeability and retention (EPR) effects, and then the photosensitizing ability of the BODIPY dye was restored by removing the DNBS group with the high concentration of GSH in tumor cells. Light-triggered ROS from activated BODIPY can not only induce apoptosis or necrosis of tumor cells but also sever the thioketal linker to release CPT, achieving the combination treatment of selective photodynamic therapy and chemotherapy. The antitumor activity of the prodrug has been demonstrated in mouse mammary carcinoma 4T1 and human breast cancer MCF-7 cell lines and 4T1 tumor-bearing mice.


Breast Neoplasms , Nanoparticles , Photochemotherapy , Prodrugs , Humans , Mice , Animals , Female , Prodrugs/pharmacology , Prodrugs/therapeutic use , Breast Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Nanoparticles/chemistry , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Cell Line, Tumor
11.
Int J Biol Macromol ; 215: 377-386, 2022 Aug 31.
Article En | MEDLINE | ID: mdl-35728636

Oxidative stress damage caused by free radicals around the moist microenvironment of wound has been a clinical challenge in skin tissue healing. Here, a novel chitosan-based bioinspired asymmetric wound repair composite (BAWRC) film was designed by facilitated endogenous tissue engineering strategy through layer-by-layer self-assembly technology for accelerated wound healing. The asymmetric characteristics were skillfully reflected by two different functional layers: hydrophilic chitosan (CS)/silk fibroin (SF) repair layer, and a hydrophobic bacteriostatic tea tree oil (TTO) layer with a rough surface. Simultaneously, sodium ascorbate (SA)-entrapped poly (lactic-co-glycolic acid) (PLGA) microspheres are distributed homogeneously in the hydrophilic layer to induce antioxidant response for skin repair. The distinctive asymmetric structure of BAWRC film endows it with synergistic effects, i.e., protects against the risk of infection from the external environment and facilitates deep skin wound healing. Results show that the minimum inhibition and bactericidal concentration of the BAWRC film were 1.25 and 6.25 mg/mL, respectively, demonstrating good antibacterial properties. The content of biofilm formation was significantly reduced when the concentration of TTO exceeds 5 mg/mL, indicating TTO shows a positive effect on bacteriostasis. In addition, the DPPH rates of BAWRC film were up to 64.7 % after incubation for 12 h, which was ascribed to that the release of SA and TTO as a natural product could accelerate free radical scavenging. The BAWRC film exhibited excellent biocompatibility, and good antibacterial capacity, enhancing adhesion and proliferation of the NIH3T3 cell in vitro, further facilitating the healing of a rat full-thickness skin wounds model. Herein, this versatile asymmetric film possesses great potential for clinical management of wound healing and related soft tissue regeneration.


Chitosan , Acceleration , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Mice , NIH 3T3 Cells , Rats , Wound Healing
12.
Int J Biol Macromol ; 208: 760-771, 2022 May 31.
Article En | MEDLINE | ID: mdl-35364198

Wound dressing is a kind of significant artificial materials for protecting injured tissues and promoting wound healing. However, fabrication of antibacterial wound dressing usually involves tedious procedures and toxic components. Herein, we demonstrate a multifunctional chitosan/silver/tannic acid (CS/Ag/TA) cryogel based on an economic method to block acute hemorrhage and promote wound healing. The prepared CS/Ag/TA cryogel not only performs steady stability and compressibility, but also shows good antibacterial ability for both S. aureus and E. coli. Attributing to TA molecules, the CS/Ag/TA cryogel can effectively scavenge more than 95% of free radicals, showing effective oxidation resistance. Due to the porous structure and positive charge of CS, the prepared cryogel exhibits good hemostatic capability with a hemostasis time less than 20 s. Benefitting from the good biocompatibility and cell proliferation, the CS/Ag/TA cryogel can significantly promote wound repair in the skin incision model. All the results indicated that the greenly fabricated cryogel can be widely applied in clinic for hemostasis and wound healing.


Chitosan , Silver , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Cryogels/chemistry , Escherichia coli , Hemostasis , Silver/pharmacology , Staphylococcus aureus , Tannins/pharmacology , Wound Healing
13.
Inorg Chem ; 61(9): 4150-4158, 2022 Mar 07.
Article En | MEDLINE | ID: mdl-35200007

The rational synthesis of iron-sulfur clusters with excellent control of the core ligands has been a significant challenge in biomimetic chemistry. In this work, the rational construction of versatile Mo-Fe-S cubane clusters was realized using a LEGO strategy. (LEGO is a line of plastic construction toys consisting of various interlocking plastic bricks which can be assembled and connected in different ways to construct versatile objects. Herein we use "LEGO strategy" as an analogy for the stepwise synthetic methodology, and we use "brick" to represent a corner atom of the cubane structure.) Through careful synthetic control, the ⟨Fe⟩, ⟨S⟩, and ⟨Cl⟩ bricks were mounted piece-by-piece onto the basic ⟨MoS3⟩ frame to stepwise construct the incomplete cubane core ⟨MoFe2S3Cl⟩ and the complete cubane core ⟨MoFe3S3Cl⟩. The significantly elongated Fe-Cl bonds for the bridging chlorides in the ⟨MoFe2S3Cl⟩ and ⟨MoFe3S3Cl⟩ cores permit ligand metatheses to introduce 2p donors at the bridging sites, which used to be a challenge in traditional iron-sulfur chemistry. Therefore, in subsequent controlled reactions, the bridging ⟨Cl⟩ bricks of the ⟨MoFe2S3Cl⟩ and ⟨MoFe3S3Cl⟩ frames could be easily replaced by ⟨N⟩ , ⟨O⟩, or ⟨S⟩ bricks to generate the ⟨MoFe2S3N⟩, ⟨MoFe2S3O⟩, ⟨MoFe3S3N⟩, and ⟨MoFe3S4⟩ cluster cores, demonstrating more choices for the LEGO synthetic strategy. The series of Mo-Fe-S clusters and their derivatives, together with related synthetic strategies, offers a good platform and methodology for biomimetic chemistry in relation to nitrogenase, especially the FeMo cofactor.

14.
Colloids Surf B Biointerfaces ; 208: 112116, 2021 Dec.
Article En | MEDLINE | ID: mdl-34564039

Osteoarthritis disease can easily lead to articular cartilage degeneration and subchondral bone damage, so the demand for suitable articular substitutes is gradually increasing. In order to simulate the complex environment of different layers in natural joint, we fabricate the continuous one-phase gradient scaffold. In the study, CS (chitosan) was modified with SH (sodium hyaluronate) and GO (graphene oxide) to form the whole scaffold. nHAP (Nano-hydroxyapatite) was in situ generated with gradient distribution in the scaffold. Continuous interface can better imitate the combination style of cartilage and subchondral bone at joint. The diverseness of scaffold's different layer in water absorption/retention rate and mechanical property is similar to the difference of articular cartilage and subchondral bone. Meanwhile, the cell experiments demonstrated that the bionic scaffold can well promote the proliferation of bone marrow mesenchymal stem cell. Articular defect model further confirmed that the scaffold can better induce articular regeneration. Herein, the prepared scaffold might be an excellent candidate for endogenous articular repair.


Cartilage, Articular , Mesenchymal Stem Cells , Durapatite , Tissue Engineering , Tissue Scaffolds
15.
Article En | MEDLINE | ID: mdl-34333232

Ovarian development is a complex physiological process for crustacean reproduction that is divided into the oogonium proliferation stage, endogenous vitellogenic stage, exogenous vitellogenic stage, and oocyte maturation stage. Proteomics analysis offers a feasible approach to reveal the proteins involved in the complex physiological processes of any organism. Therefore, this study performed a comparative proteomics analysis of the ovary and hepatopancreas at three key ovarian stages, including stages I (oogonium proliferation), II (endogenous vitellogenesis) and IV (exogenous vitellogenesis), of the Chinese mitten crab Eriocheir sinensis using a label-free quantitative approach. The results showed that a total of 2,224 proteins were identified, and some key proteins related to ovarian development and nutrition metabolism were differentially expressed. The 26 key proteins were mainly involved in the ubiquitin/proteasome pathway (UPP), cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway during oogenesis. Fifteen differentially abundant proteins (DAPs) were found to participate in vitellogenesis and oocyte development, such as vitelline membrane outer layer protein 1 homolog, vitellogenin, vitellogenin receptor, heat shock 70 kDa protein cognate 3 and farnesyl pyrophosphate synthase. Forty-seven DAPs related to nutrition metabolism were identified, including the protein digestion, fatty acid metabolism, prostaglandin metabolism, lipid digestion and transportation, i.e. short-chain specific acyl-CoA dehydrogenase, acyl-CoA desaturase, fatty acid-binding protein, long-chain fatty acid CoA ligase 4, and hematopoietic prostaglandin D synthase. These results not only indicate proteins involved in ovarian development and nutrient deposition but also enhance the understanding of the regulatory pathways and physiological processes of crustacean ovarian development.


Brachyura , Proteomics , Animals , China , Female , Hepatopancreas , Ovary , Vitellogenesis
16.
Cell Death Dis ; 12(4): 340, 2021 04 01.
Article En | MEDLINE | ID: mdl-33795657

Osteoporosis is the most prevailing primary bone disease and a growing health care burden. The aim of this study was to clarify the functional roles and mechanisms of the circ-ITCH regulating osteogenic differentiation of osteoporosis. Circ-ITCH and yes-associated protein 1 (YAP1) levels were downregulated, but the miR-214 level was upregulated in osteoporotic mice and patients. Knockdown of circ-ITCH inhibited the alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) during osteogenic induction. Furthermore, miR-214 was a target of circ-ITCH, knockdown of miR-214 could impede the regulatory effects of sh-circ-ITCH on osteogenic differentiation. Moreover, miR-214 suppressed hBMSCs osteogenic differentiation by downregulating YAP1. Finally, in vivo experiments indicated that overexpression of circ-ITCH could improve osteogenesis in ovariectomized mice. In conclusion, circ-ITCH upregulated YAP1 expression to promote osteogenic differentiation in osteoporosis via sponging miR-214. Circ-ITCH could act as a novel therapeutic target for osteoporosis.


Adaptor Proteins, Signal Transducing/metabolism , Cell Differentiation/physiology , MicroRNAs/metabolism , Osteoporosis/metabolism , Transcription Factors/metabolism , Animals , Cells, Cultured , Humans , Mesenchymal Stem Cells/metabolism , Mice , MicroRNAs/genetics , Osteoblasts/metabolism , Osteogenesis/genetics , Osteogenesis/physiology , YAP-Signaling Proteins
17.
Dalton Trans ; 50(20): 6840-6847, 2021 May 28.
Article En | MEDLINE | ID: mdl-33912872

Structural mimicking of the nitrogenase FeMo cofactor has long been a challenge in synthetic inorganic chemistry and bioinorganic chemistry. This already very tough task had become even harder after the discovery of an interstitial light atom, which was later evidenced to be carbide. From a synthetic point of view, to introduce such a 2p atom into the core of a Fe-S cluster would have to overcome the coordination competition from overwhelming sulfide ligands. Recently, we have reported a controlled synthetic strategy named redox metathesis based on template-assisted structure design, and have successfully synthesized a couple of nitride-incorporated edge-bridged double cubane (N-EBDC) W-Fe-S clusters. In this work, we have systematically studied the terminal ligand substitutions of heteroleptic N-EBDC clusters, utilizing ethanethiolate, thiophenolate, p-thiocresolate, azide, and methoxide to replace the terminally bound chloride ligands. Structural analysis of this family of N-EBDC clusters reveals that different terminal ligands affect the fine structures of the cluster cores at different levels. Further studies by cyclic voltammetry indicate that these N-EBDC clusters with distinct terminal ligands exhibit different redox behaviors, furnishing in-depth information on the electronic structure of these clusters potentially related to their reactivity. This study provided useful information for the investigation of nitrogenase related Fe-S clusters toward structural and functional mimicking of the nitrogenase FeMo cofactor.

18.
Eur J Med Chem ; 215: 113251, 2021 Apr 05.
Article En | MEDLINE | ID: mdl-33611187

Development of the drug with high therapeutic efficacy and low toxicity is crucial to cancer ablation. In this study, we have demonstrated a red light-responsive prodrug BDP-TK-CPT by connecting the chemotherapeutic agent camptothecin with a boron dipyrromethene (BDP)-based photosensitizer via a reactive oxygen species (ROS)-labile thioketal chain. Since camptothecin is modified by a BDP-based macrocycle at the active site, the formed prodrug displays an extremely low toxicity in dark. However, upon illumination by red light, it can efficiently generate ROS leading to cell death by photodynamic therapy. Meanwhile, the ROS generated can destroy thioketal group to release free camptothecin which further results in local cell death by chemotherapy. The combined antitumor effects of the prodrug have been verified in HepG2, EC109, and HeLa cancer cells and mice bearing H22 tumors. This study may provide an alternative strategy for stimuli-responsive combination treatment of tumors by conjugation of ROS-activatable prodrugs with photosensitizing agents.


Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Prodrugs/therapeutic use , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/radiation effects , Apoptosis/drug effects , Cell Line, Tumor , Combined Modality Therapy , Drug Therapy , Female , Humans , Light , Mice , Necrosis/chemically induced , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/radiation effects , Prodrugs/chemical synthesis , Prodrugs/radiation effects , Reactive Oxygen Species/metabolism
19.
Plant Biotechnol J ; 19(3): 517-531, 2021 03.
Article En | MEDLINE | ID: mdl-32946650

The Chinese jujube (Ziziphus jujuba Mill.), a member of the Rhamnaceae family, is an important perennial fruit tree crop of substantial economic, ecological and nutritional value, and is also used as a traditional herbal medicine. Here, we report the resequencing of 493 jujube accessions, including 202 wild and 291 cultivated accessions at >16× depth. Our population genomic analyses revealed that the Shanxi-Shaanxi area of China was jujube's primary domestication centre and that jujube was then disseminated into East China before finally extending into South China. Divergence events analysis indicated that Ziziphus acidojujuba and Ziziphus jujuba diverged around 2.7 Mya, suggesting the interesting possibility that a long pre-domestication period may have occurred prior to human intervention. Using the large genetic polymorphism data set, we identified a 15-bp tandem insertion in the promoter of the jujube ortholog of the POLLEN DEFECTIVE IN GUIDANCE 1 (POD1) gene, which was strongly associated with seed-setting rate. Integrating genome-wide association study (GWAS), transcriptome data, expression analysis and transgenic validation in tomato, we identified a DA3/UBIQUITIN-SPECIFIC PROTEASE 14 (UBP14) ortholog, which negatively regulate fruit weight in jujube. We also identified candidate genes, which have likely influenced the selection of fruit sweetness and crispness texture traits among fresh and dry jujubes. Our study not only illuminates the genetic basis of jujube evolution and domestication and provides a deep and rich genomic resource to facilitate both crop improvement and hypothesis-driven basic research, but also identifies multiple agriculturally important genes for this unique perennial tree fruit species.


Ziziphus , China , Fruit/genetics , Genome-Wide Association Study , Genomics , Ziziphus/genetics
20.
Hortic Res ; 7(1): 89, 2020.
Article En | MEDLINE | ID: mdl-32528701

Jujube (Ziziphus jujuba Mill.) is an important perennial fruit tree with a range of interesting horticultural traits. It was domesticated from wild jujube (Ziziphus acidojujuba), but the genomic variation dynamics and genetic changes underlying its horticultural traits during domestication are poorly understood. Here, we report a comprehensive genome variation map based on the resequencing of 350 accessions, including wild, semi-wild and cultivated jujube plants, at a >15× depth. Using the combination of a genome-wide association study (GWAS) and selective sweep analysis, we identified several candidate genes potentially involved in regulating seven domestication traits in jujube. For fruit shape and kernel shape, we integrated the GWAS approach with transcriptome profiling data, expression analysis and the transgenic validation of a candidate gene to identify a causal gene, ZjFS3, which encodes an ethylene-responsive transcription factor. Similarly, we identified a candidate gene for bearing-shoot length and the number of leaves per bearing shoot and two candidate genes for the seed-setting rate using GWAS. In the selective sweep analysis, we also discovered several putative genes for the presence of prickles on bearing shoots and the postharvest shelf life of fleshy fruits. This study outlines the genetic basis of jujube domestication and evolution and provides a rich genomic resource for mining other horticulturally important genes in jujube.

...