Highly specific GSH-triggered bifunctional molecules to enable precise imaging and targeted therapy of cancer.

The utilization of diagnostic-integrated molecules can enable targeted delivery and controlled release to significantly enhance therapeutic effectiveness and minimize toxic effects. Herein, we developed a novel class of glutathione (GSH)-activated bifunctional molecules that respond to elevated levels of GSH in tumor microenvironment. These bifunctional molecules retained the pharmacodynamic effects of parent molecules and mitigated cytotoxicity.

Production of the siderophore lysochelin in rich media through maltose-promoted high-density growth of sp. 3655.

Siderophores are produced by bacteria in iron-restricted conditions. However, we found maltose could induce the biosynthesis of the siderophore lysochelin in sp. 3655 in rich media that are not compatible with siderophore production.

All-in-one nanotheranostic platform based on tumor microenvironment: new strategies in multimodal imaging and therapeutic protocol.

Conventional tumor diagnosis and treatment approaches have significant limitations in clinical application, whereas personalized theranostistic nanoplatforms can ensure advanced diagnosis, precise treatment, and even a good prognosis in cancer. Tumor microenvironment (TME)-targeted therapeutic strategies offer absolute advantages in all aspects compared to tumor cell-targeted therapeutic strategies. It is essential to create a TME-responsive all-in-one nanotheranostic platform to facilitate individualized tumor treatment.

Recent Advances in Signaling Pathways and Kinase Inhibitors for Leukemia Chemotherapy.

Leukemia is a malignant clonal disease of hematopoietic stem cells, which accounts for about 3% of the total incidence of tumors and is particularly prevalent among children and adolescents. It mainly includes four types of leukemia, namely ALL, AML, CLL, and CML, which are often aggressive and challenging diseases to treat. Several signaling pathways are dysregulated in almost all types of leukemia, such as JAK, PI3K, and MAPK, and others are dysregulated in specific types of leukemia, like Wnt/β-catenin, Hedgehog, FLT3, Bcr-Abl, and so on.

A bifunctional agent for efficient imaging of PD-L1 and antimelanoma activity.

Immune checkpoint inhibitors targeting PD-L1 lead to challenging patterns of efficacy and toxicity. Herein, by focusing on tracing the molecular biomarker of response to efficacy, we formulated a central hypothesis for the construction of theranostic functional monoclonal antibody incorporation with tracing ability based on fluorescence turn-on and controllable release strategies. Functional atezolizumab was constructed by in situ assembly of both biorthogonal group and controllable release group.

DPPH Radical Scavenging Activity of New Phenolics from the Fermentation Broth of Mushroom .

In recent years, wild morel mushroom species have begun to be widely cultivated in China due to their high edible and medicinal values. To parse the medicinal ingredients, we employed the technique of liquid-submerged fermentation to investigate the secondary metabolites of . Two new natural isobenzofuranone derivatives (-) and one new orsellinaldehyde derivative (), together with seven known compounds, including one -orsellinaldehyde (), phenylacetic acid (), benzoic acid (), 4-hydroxy-phenylacetic acid (), 3,5-dihydroxybenzoic acid (), ,'-pentane-1,5-diyldiacetamide (), and 1H-pyrrole-2-carboxylic acid (), were obtained from the fermented broth of .

Discovery of intracellular self-assembly protein degraders driven by tumor-specific activatable bioorthogonal reaction.

Proteolysis Targeting Chimera (PROTAC) is a type of bifunctional chimeric molecule that can directly degrade the binding proteins through the ubiquitin-proteasome pathway. PROTAC has shown great potential in overcoming drug resistance and targeting undruggable targets. However, there are still many shortcomings that need to be solved urgently, including worse membrane permeability and bioavailability induced by their large molecular weight.

Identification and Biosynthetic Study of the Siderophore Lysochelin in the Biocontrol Agent .

is a genus of bacteria emerging as new biocontrol agents in agriculture. Although iron acquisition is essential for the bacteria, no siderophore has been identified from any . Here, we report the identification of the first siderophore, 1,8-bis(2,3-dihydroxybenzoyl)spermidine (lysochelin), and its biosynthetic gene cluster from .

Discovery of novel antibody-drug conjugates bearing tissue protease specific linker with both anti-angiogenic and strong cytotoxic effects.

Bevacizumab is an FDA-approved class of monoclonal antibodies used to inhibit angiogenesis and promote normalization of blood vessels. It is usually combined with chemotherapeutic agents to treat a variety of solid tumors. However, the whole-body toxicities and toxicity associated with chemotherapy greatly limit the clinical use of this combination therapy.

Discovery of novel PROTACs based on multi-targeted angiogenesis inhibitors.

Anti-angiogenesis has been proved to be an effective strategy for the treatment of tumors. Anti-angiogenic drugs had achieved certain therapeutic effects. However, drug resistance also gradually emerged and limited the application of angiogenesis inhibitors.

Identification of the Biosynthetic Gene Cluster for the anti-MRSA Lysocins through Gene Cluster Activation Using Strong Promoters of Housekeeping Genes and Production of New Analogs in sp. 3655.

The Gram-negative gliding bacteria represent a new and rich source for bioactive natural products. In an effort to discover new antibiotics, we found a cryptic biosynthetic gene cluster (BGC) in sp. 3655 that shared a high similarity with the putative lysocin BGC identified previously from sp.

New Sesquiterpenoids from the Fermented Broth of and their Anti-Acetylcholinesterase Activity.

is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids-teucdiol C (), D (), E (), and F (), together with two known sesquiterpenoids teucdiol B () and epi-guaidiol A ()-were obtained from its fermented broth of . Their structures were elucidated by the analysis of NMR data, HR Q-TOF MS spectral data, CD, IR, UV, and single crystal X-ray diffraction.

Anti-Inflammatory Effect of a Polyphenol-Enriched Fraction from on Lipopolysaccharide-Stimulated RAW 264.7 Macrophages and Acetaminophen-Induced Liver Injury in Mice.

A polyphenol-enriched fraction (PEF) from , whose leaves have been traditionally utilized for the treatment of diverse medical ailments, was investigated for the anti-inflammatory effect and molecular mechanisms by using lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages and acetaminophen- (APAP-) induced liver injury mouse model. Results showed that PEF significantly attenuated LPS-induced nitric oxide (NO) and prostaglandin E (PGE) production and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in RAW 264.

Gunnilactams A-C, Macrocyclic Tetralactams from the Mycelial Culture of the Entomogenous Fungus Paecilomyces gunnii.

Three novel macrocyclic tetralactams, gunnilactam A (1), gunnilactam B (2), and gunnilactam C (3), were isolated from the submerged fermentation broth of Paecilomyces gunnii, an entomogenous fungus identified as the anamorph of Cordyceps gunnii. Their structures were determined using NMR data, HREIMS, and single-crystal X-ray crystallography. Gunnilactam A exhibited selective cytotoxic activity against human prostate cancer C42B cells with an IC value of 5.

A Sphingosine-type cerebroside in Clavicorona pyxidata induce fruit body formation.

Clavicorona pyxidata is a wild edible and medicinal mushroom that is rich in bioactive natural products and has thus been extensively used as traditional medicine in China. The present study has determined that the organic crude extract prepared from a fermented culture of C. pyxidata imparted auto-inhibitory effects on mycelial growth and then induced the formation of fruiting bodies.

Inhibitory activities against rice pathogens of 8-hydroxy-2,4,6-octatriynamide from Agrocybe sp.

8-Hydroxy-2,4,6-octatriynamide, a natural polyacetylene with inhibitory activities against rice pathogens, was isolated from the liquid fermentation broth of strain Agrocybe sp. YB2005 during screening for new natural chemical agents to control rice pathogens. 8-hydroxy-2,4,6-octatriynamide was purified by consecutive chromatography over a Cl8 reversed phase silica gel, sephadex LH-20 and silica gel.

New apoptosis-inducing sesquiterpenoids from the mycelial culture of Chinese edible fungus Pleurotus cystidiosus.

Two new bisabolane-type sesquiterpenoids, pleuroton A (1) and pleuroton B (2), and three clitocybulol derivatives, clitocybulol D (3), clitocybulol E (4), and clitocybulol F (5), were obtained from the mycelial culture of edible fungus Pleurotus cystidiosus O. K. Mill by repeated column chromatography over RP-18, Sephadex LH-20, and silica gel.

New abscisic acid-related metabolites from Phellinus vaninii.

Two new and three known abscisic acid-related metabolites were obtained from the potato dextrose agar culture of Phellinus vaninii YB2005. Their structures were established on the basis of detailed spectroscopic analyses, including 1D NMR, 2D NMR, and HR-Q-TOF-MS techniques. The putative biosynthesis pathway of these secondary metabolites would decipher the mechanism of the symbiosis between plant and fungi from the view of chemistry.

[Construction of Saccharomyces cerevisiae mutant with knockout of SNF4 gene].

Construction and ethanol production effects of SNF4 gene knockout in Saccharomyces cerevisiae were described in this paper. For knockout of SNF4 gene in S. cerevisiae YS2, a PCR-amplified disruption cassette was used, encoding the short flanking homologous regions to the SNF4 gene and Kan(r) as selectable marker.

Isolation, structure elucidation and apoptosis-inducing activity of new compounds from the edible fungus Lentinus striguellus.

Three new natural compounds, striguellolide A (1), striguellol A (2) and striguellone A (6), together with three known ones, 3,4-trans-dihydroxy-6-methoxy-2,2-dimethylchroman (3), 3-hydroxy-6- methoxy-2,2-dimethylchroman-4-one (4) and 3-hydroxy-6- methoxy-2,2-dimethylchroman (5), were isolated from the agar cultures of the edible fungal strain Lentinus striguellus. Their structures were elucidated by spectroscopic and mass spectrometric analyses, including 1D-, 2D-NMR and HR-ESI-Q-TOF-MS, and chemical reactions. Striguellone A showed cytotoxicity against HeLa cells by MTT assay and was found to be an activator of apoptosis, assessed by morphological observation and cell cycle analysis using the flow cytometer.

Clavicorolides A and B, sesquiterpenoids from the fermentation products of edible fungus Clavicorona pyxidata.

Clavicorolides A (1) and B (2), two sesquiterpenoids possessing a novel backbone named as Clavicoronane-type, together with one new and two known Protoilludane-type sesquiterpenoids, namely, Tsugicolines M (3), A (4), and C (5), and Sterpurane (6), and Lactarane-type sesquiterpenoid Lactarorufin A (7), were isolated from the fermentation products of Clavicorona pyxidata YB2005. Their structures including relative and absolute configurations were elucidated on the basis of NMR data and analysis of X-ray single crystal diffraction.