Rationally construction of atomic-precise interfacial charge transfer channel and strong build-in electric field in nanocluster-based Zscheme heterojunctions with enhanced photocatalytic hydrogen production

The lack of effective charge transfer driving force and channel limits the electron directional migration in nanoclusters(NC)-based heterostructures,resulting in poor photocatalytic performance.Herein,a Z-scheme NC-based heterojunction(Pt1Ag28-BTT/CoP,BTT=1,3,5-benzenetrithiol)with strong internal electric field is constructed via interfacial Co-S bond,which exhibits an absolutely superiority in photocatalytic performance with 24.89 mmol·h^(−1)·g−1 H_(2)production rate,25.77%apparent quantum yield at 420 nm,and~100%activity retention in stability,compared with Pt1Ag28-BDT/CoP(BDT=1,3-benzenedithiol),Ag29-BDT/CoP,and CoP.The enhanced catalytic performance is contributed by the dual modulation strategy of inner core and outer shell of NC,wherein,the center Pt single atom doping regulates the band structure of NC to match well with CoP,builds internal electric field,and then drives photogenerated electrons steering;the accurate surface S modification promotes the formation of Co-S atomic-precise interface channel for further high-efficient Z-scheme charge directional migration.This work opens a new avenue for designing NC-based heterojunction with matchable band structure and valid interfacial charge transfer.

Spatial metabolomics highlights metabolic reprogramming in acute myeloid leukemia mice through creatine pathway

Acute myeloid leukemia(AML)is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming.Here,we applied spatial metabolomics to achieve high-throughput,in situ identification of metabolites within the liver metastases of AML mice.Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics.This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle,coupled with an upregulation of the creatine metabolism.The upregulation of creatine synthetases Gatm and Gamt,as well as the creatine transporter Slc6a8,resulted in a marked accumulation of creatine within tumor foci.This process further enhances oxidative phosphorylation and glycolysis of leukemia cells,thereby boosting ATP production to foster proliferation and infiltration.Importantly,we discovered that inhibiting Slc6a8 can counter these detrimental effects,offering a new strategy for treating AML by targeting metabolic pathways.

Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3

The TEA domain(TEAD)family proteins(TEAD1-4)are essential transcription factors that control cell differentiation and organ size in the Hippo pathway.Although the sequences and structures of TEAD family proteins are highly conserved,each TEAD isoform has unique physiological and pathological functions.Therefore,the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases.Here,we identified a novel TEAD 1/3 covalent inhibitor(DC-TEADin1072)with biochemical IC50 values of 0.61±0.02 and 0.58±0.12μmol/L against TEAD1 and TEAD3,respectively.Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DCTEAD3 in03 with the IC_(50) value of 0.16±0.03μmol/L,which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling(ABPP)assays.In cells,DC-TEAD3 in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD(1-4)reporter assays with the IC50 value of1.15μmol/L.When administered to zebrafish juveniles,experiments showed that DC-TEAD3 in03 reduced the growth rate of zebrafish caudal fins,indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages.