Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

Rare earth complexes chemiluminescence catalyzed by gold nanoparticles for fast sensing of Tb^(3+)and Eu^(3+)

Developing multiplex sensing technique is of great significance for fast sample analysis.However,the broad emissions of most chemiluminescence(CL)luminophores make the multiplex CL analysis be difficult.In this work,a simple and sensitive CL analytical method has been developed for the simultaneous determination of Tb^(3+)and Eu^(3+)thanking to their narrow band emission.The technique was based on a mixed CL system of periodate(IO4-)-hydrogen peroxide(H_(2)O_(2))-rare earth complexes,in which the reactive oxygen species(ROSs)especially singlet oxygen(^(1)O_(2))can transfer its energy to the complex of Tb^(3+)/Eu^(3+)-ethylenediaminetetraacetic acid disodium salt(EDTA)and then produce the characteristic emissions of Tb^(3+)and Eu^(3+)without cross-interference.The further experiment found that the CL emissions of Tb^(3+)and Eu^(3+)could be catalyzed by the gold nanoparticles(AuNPs)via enhancing the yield of^(1)O_(2).The CL intensities of Tb^(3+)(at 490 nm)and Eu^(3+)(at 620 nm)increased linearly with concentration of Tb^(3+)and Eu^(3+).After the optimization of the CL sensing conditions,the limits of detection(LOD)were 5.0×10^(-9)mol/L and 8.0×10^(-7)mol/L for Tb^(3+)and Eu^(3+),respectively.Finally,the method has been applied for measuring the contents of Tb^(3+)and Eu^(3+)in leaching solution of mine sample and Tb^(3+)/Eu^(3+)-contained nanomaterials with satisfactory results.The present system provides a new CL technique for multiplex sensing with simplicity and high sensitivity.

PanGu Drug Model: learn a molecule like a human

Dear Editor,Recent achievements in large-scale pre-trained models like GPT-3 and PanGu-α have demonstrated astounding performances in many downstream tasks of natural language processing (NLP),confirming AI to be user-oriented for even industrial applications.Deep learning has been recognized as the most promising technology for pharmaceuticals,a powerful molecule pre-trained model that could economize researchers’tons of time.For the strategic application of AI capabilities to the drug discovery field,we pre-trained a model called PanGu Drug Model with 1.7 billion small molecules from ZINC20 (Irwin et al.,2020),DrugSpaceX(Yang et al.,2021),and UniChem (Chambers et al.,2013).

Research on Multi-Modal Time Series Data Prediction Method Based on Dual-Stage Attention Mechanism

The production data in the industrialfield have the characteristics of multimodality,high dimensionality and large correlation differences between attributes.Existing data prediction methods cannot effectively capture time series and modal features,which leads to prediction hysteresis and poor prediction stabil-ity.Aiming at the above problems,this paper proposes a time-series and modal fea-tureenhancementmethodbasedonadual-stageself-attentionmechanism(DATT),and a time series prediction method based on a gated feedforward recurrent unit(GFRU).On this basis,the DATT-GFRU neural network with a gated feedforward recurrent neural network and dual-stage self-attention mechanism is designed and implemented.Experiments show that the prediction effect of the neural network prediction model based on DATT is significantly improved.Compared with the traditional prediction model,the DATT-GFRU neural network has a smaller aver-age error of model prediction results,stable prediction performance,and strong generalization ability on the three datasets with different numbers of attributes and different training sample sizes.

Surface molecular imprinting on g-C3N4 photooxidative nanozyme for improved colorimetric biosensing

Graphitic carbon nitride(g-C3 N4),as a visible-light-active organic semiconductor,has attracted growing attentions in photocatalysis and photoluminescence-based biosensing.Here,we demonstrated the intrinsic photooxidase activity of g-C3 N4 and then surface molecular imprinting on g-C3 N4 nanozymes was achieved for improved biosensing.Upon blue LED irradiation,the g-C3 N4 exhibited superior enzymatic activity for oxidation of chromogenic substrate like 3,3’,5,5’-tetramethylbenzidine(TMB)without destructive H2 O2.The oxidation was mainly ascribed to ·O2^-that was generated during light irradiation.The surface molecular imprinting on g-C3 N4 can lead to an over 1000-fold alleviation in matrix-interference from serum samples,4-fold improved enzymatic activity as well as enhanced substrate specificity comparing with bare g-C3 N4 during colorimetric sensing.Also,the MIP-g-C3 N4 possesses a high affinity to TMB with a Km value of only 22 μmol/L,much lower than other comment nanozymes like AuNPs,Fe3 O4 NPs,etc.It was successfully applied for detection of cysteine in serum sample with satisfactory recoveries.

Carbon dots-peroxyoxalate micelle as a highly luminous chemiluminescence system under physiological conditions

Chemiluminescence(CL) has been widely used for bioanalysis owing to its high sensitivity, low background and simplicity. However, most of the CL systems need acidic/alkaline conditions or organic solvent to enhance their luminescent efficiency, and the non-physiological conditions can usually lead to the misfunction of biomolecules during biosensing. Herein, we report a highly luminous CL system under physiological conditions based on carbon dots-bis(2-carbopentyloxy-3,5,6-trichlorophenyl) oxalate(CDsCPPO) micelles, and further used it in biosensing application. In the CL system, the amphiphilic surfactant packed CPPO and hydrophobic CDs together to form CDs-CPPO micelles. Such micelles solution not only isolated the CPPO from water to prevent its hydrolysis but also made the close proximity between CPPO and CDs, thus significantly enhancing the CDs quantum yield. The CL quantum yield was calculated to be 5.26 × 10^(-4) einsteins/mol, about 200-fold higher than that of the most commonly used luminol CL system. The oxidases(e.g., glucose oxidase) were tested to be susceptible to the organic solvent and non-physiological p H. Hence, the CL system was used for the detection of oxidase substrates(exemplified by glucose) in serum samples, and the limit of detection was as low as 8.4 nmol/L. The highly luminous CL system that can work under physiological conditions is promising for biosensing applications.

G-quadruplex-assisted enzyme strand recycling for amplified label-free fluorescent detection of UO_2^(2+)

DNAzyme that can catalytically cleave of substrate DNA has shown to be attractive for amplified detection in biosensing events. During the catalytic process, the recycling of enzyme strand of DNAzyme is critically important. In this work, a G-quadruplex-assisted enzyme strand recycling strategy was developed for amplified label-free fluorescent detection of uranyl ion(UO_2^(+2)). The DNAzyme was activated by the target UO_2^(+2) and further cleaved the substrate strand that contained the G-quadruplex sequence. The following formation of G-quadruplex helps the separation between the enzyme strand and the cleaved substrate strand, thus improving the recycle use of the enzyme strand. Such strategy allowed lablel-free detection of 0.2–200 ng/mL UO_2^(+2)via SYBR green I(SG)-based fluorescence. The detection limit(3 d) is as low as0.06 ng/mL(about 0.2 nmol/L), comparable to those obtained by ICP-MS and labeled DNAzyme. It was applied for detection of UO_2^(+2) in spiked environmental water samples with recoveries in the range of96%–103%. This biosensor, with the advantages of simplicity and high sensitivity, is an appealing tool for fast detection of UO_2(+2) in environmental water samples.

NiCe bimetallic nanoparticles embedded in hexagonal mesoporous silica (HMS) for reverse water gas shift reaction

Reverse water gas shift(RWGS)reaction is a crucial process in CO_(2)utilization.Herein,Ni-and NiCe-containing hexagonal mesoporous silica(Ni-HMS and NiCe-HMS)catalysts were synthesized using an insitu one-pot method and applied for RWGS reaction.At certain reaction temperatures 500-750℃,Ni-HMS samples displayed a higher selectivity to the preferable CO than that of conventionally impregnated Ni/HMS catalyst.This could be originated from the smaller NiO nanoparticles over Ni-HMS catalyst.NiCe-HMS exhibited higher activity compared to Ni-HMS.The catalysts were characterized by means of TEM,XPS,XRD,H_(2)-TPR,CO_(2)-TPD,EPR and N_(2) adsorption-desortion technology.It was found that introduction of Ce created high concentration of oxygen vacancies,served as the active site for activating CO_(2).Also,this work analyzed the effect of the H_(2)/CO_(2)molar ratio on the best NiCe-HMS.When reaction gas H_(2)/CO_(2)molar ratio was 4 significantly decreased the selectivity to CO at low temperature,but triggered a higher CO_(2)conversion which is close to the equilibrium.

Double-Stranded DNA Matrix for Photosensitization Switching

Photosensitization,originated from the activation of triplet states,is the basis of many photodynamic applications,but often competes with a series of nonradiative processes.Herein,we communicate a new function of double-stranded DNA(dsDNA)for label-free photosensitization switching.Up to∼70-fold singlet oxygen generation boosting was observed for SYBR Green I(SG)upon binding with dsDNA.Detailed photophysical and theoretical studies have revealed the role of dsDNA as a matrix,which could efficiently suppress the nonradiative transitions of SG.