A Novel Zn2Cys6 Transcription Factor, TopC, Positively Regulates Trichodin A and Asperpyridone A Biosynthesis in Tolypocladium ophioglossoides.

Asperpyridone A represents an unusual class of pyridone alkaloids with demonstrated potential for hypoglycemic activity, primarily by promoting glucose consumption in HepG2 cells. Trichodin A, initially isolated from the marine fungus Trichoderma sp. strain MF106, exhibits notable antibiotic activities against Staphylococcus epidermidis. Despite their pharmacological significance, the regulatory mechanisms governing their biosynthesis have remained elusive. In this investigation, we initiated the activation of a latent gene cluster, denoted as "top", through the overexpression of the Zn2Cys6 transcription factor TopC in Tolypocladium ophioglossoides. The activation of the top cluster led to the biosynthesis of asperpyridone A, pyridoxatin, and trichodin A. Our study also elucidated that the regulator TopC exerts precise control over the biosynthesis of asperpyridone A and trichodin A through the detection of protein-nucleic acid interactions. Moreover, by complementing these findings with gene deletions involving topA and topH, we proposed a comprehensive biosynthesis pathway for asperpyridone A and trichodin A in T. ophioglossoides.

Development of a New Heteropolyoxotantalate Cluster for Multidimensional Polyoxotantalate Materials.

A unique heteropolyoxotantalate (hetero-POTa) cluster [P2O7Ta5O14]7- (P2Ta5) was first developed using pyrophosphate as a key to open the ultrastable skeleton of the classical Lindqvist-type [Ta6O19]8- precursor. The P2Ta5 cluster can serve as a general and flexible secondary building unit to create a family of brand-new multidimensional POTa architectures. This work not only promotes the limited structural diversity of hetero-POTa but also provides a practical strategy for new extended POTa architectures.

Oxalate-assisted assembly of two polyoxotantalate supramolecular frameworks with proton conduction properties.

An oxalate-assisted strategy was first developed for creating new polyoxotantalates (POTas). With this strategy, two brand-new POTa supramolecular frameworks based on uncommon dimeric POTa secondary building units (SBUs) were constructed and characterized. Interestingly, the oxalate ligand can not only serve as a coordination ligand to form unique POTa SBUs but also act as a key hydrogen bond acceptor to construct supramolecular architectures. Besides, the architectures show outstanding proton conductivity. The strategy opens up new opportunities for developing new POTa materials.

3d-4f Heterometallic cluster incorporated polyoxoniobates with magnetic properties.

A series of 3d-4f heterometallic cluster incorporated polyoxoniobates (PONbs) with different magnetic properties were first made and characterized. This work not only provides a promising strategy to make new heterometallic cluster incorporated PONbs but also demonstrates an ideal model to probe how transition-metal ions influence the magnetic property of PONbs.

Atomically Dispersed Co to an End-Adsorbing Molecule for Excellent Biomimetically and Prime Sensitively Detecting O2•- Released from Living Cells.

Single-atom catalysis efficiently exposes the catalytic sites to reactant molecules while rendering opportunity to investigate the catalysis mechanisms at atomic levels for scientific insights. Here, for the first time, atomically dispersed Co atoms are synthesized as biomimetic "enzymes" to monitor superoxide anions (O2•-), delivering ultraordinary high sensitivity (710.03 µA·µM-1·cm-2), low detection limit (1.5 nM), and rapid response time (1.2 s), ranking the best among all the reported either bioenzymatic or biomimetic O2•- biosensors. The sensor is further successfully employed to real-time monitor O2•- released from living cells. Moreover, theoretical calculation and analysis associated with experimental results discover that a mode of end adsorption of the negatively charged O2•- on the Co3+ atom rather than a bridge or/and side adsorption of the two atoms of O2•- on two Co3+ atoms, respectively, plays an important role in the single-atomic catalysis toward O2•- oxidation, which not only facilitates faster electron transfer but also offers better selectivity. This work holds great promise for an inexpensive and sensitive atomic biomimetic O2•- sensor for bioresearch and clinic diagnosis, while revealing that the adsorption mode plays a critical role in single-atom catalysis for a fundamental insight.

High-dimensional Polyoxoniobates Constructed from Lanthanide-incorporated High-nuclear {[Ln(H2 O)4 ]3 [Nb24 O69 (H2 O)3 ]2 } Secondary Building Units.

In this work, two rare high-dimensional polyoxoniobates with formulas of H9 [Cu(en)(H2 O)2 ][Cu(en)2 ]8 [Dy(H2 O)4 ]3 [Nb24 -O69 (H2 O)3 ]2 ⋅ 36H2 O (1) and H9 K[Cu(en)2 (H2 O)]5 [Cu(en)2 ]4 -[Eu(H2 O)4 ]3 [Nb24 O69 (H2 O)3 ]2 ⋅ 2en ⋅ 45H2 O (2) have been obtained under hydrothermal conditions. These extended materials are constructed from lanthanide-incorporated triangular-prism-like polyoxoniobate secondary building units (SBUs) {[Ln(H2 O)4 ]3 [Nb24 O69 (H2 O)3 ]2 } (Ln=Dy, Eu). 1 and 2 represent the first examples of high-dimensional polyoxometalate materials based on such lanthanide-incorporated triangular-prism-like polyoxoniobate SBUs. Furthermore, the proton conduction property and the luminescent emission of these materials were evaluated.

Composite cluster-organic frameworks based on polyoxometalates and copper/cobalt-oxygen clusters.

Two rare mixed-cluster-organic frameworks (CH3NH3)3[Cu4-(µ3-O)2(Lb)4][MnMo6O18(La)2]·4NMF·5H2O (1) and [(CH3)2NH2]3[Co5-(µ3-O)2(Lb)6]-[MnMo6O18(La)2]·5DMF (2) (La = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol; Lb = 4-(2-(4-pyridyl)ethenyl) benzoic acid; NMF = N-methylformamide; DMF = N,N-dimethylformamide) have been obtained, exhibiting the first two porous materials simultaneously integrating polyoxometalates and transition-metal-oxygen clusters as secondary building units (SBUs).

TRPM7 overexpression enhances the cancer stem cell-like and metastatic phenotypes of lung cancer through modulation of the Hsp90α/uPA/MMP2 signaling pathway.

BACKGROUND: Waixenicin A, a bioactive extract of soft coral Sarcothelia edmondsoni, has been shown to be anti-neoplastic. However, its mechanisms of action remain unclear. Cancer stem cells (CSCs) and associated stemness factors are implicated in lung cancer. Here, we investigated the role of Waixenicin A on CSCs-like and metastatic lung cancer cells. METHODS: We demonstrated and compared TRPM7 expression in the non-tumor lung tissues or bronchial epithelial 16-HBE cell line. TRPM7 was aberrantly expressed in the cancer tissues and SPCA-1, NCI-H520, SK-MES-1, A549 and 95D cell lines. RESULTS: Increased TRPM7 expression was associated with enhanced SOX2, KLF4, and CD133, Hsp90α, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90α/uPA/MMP2 axis. Coincidently, Waixenicin A treatment downregulated TRPM7 and oncogenic markers; Waixenicin A also attenuated the ability of lung cancer cells to form tumorspheres, in vitro. In validation, our clinicopathological analyses showed that a higher TRPM7 expression was positively correlated with the larger tumor size (p = 0.007), positive lymph node metastasis (p = 0.005) and disease grade (p = 0.003). CONCLUSIONS: Through its ability to inhibit Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer.