Distinct enhancer-promoter modes determine Sox2 regulation in mouse pluripotent cells

Sox2 is a key transfer factor for maintaining pluripotency and self-renewal in embryonic stem cells(ESCs),1 though the mechanism of its transcriptional regulation in ESCs has not been fully addressed.Distal enhancer-promoter interactions are vital for Sox2 transcription activity in mammals.However,how these diverse interactions individually influence Sox2 gene regulation in mouse ESCs remains unclear.Previous studies found that three distal enhancers(termed E1,E2,and E3)interact with Sox2 promoter?(Fig.1A;Fig.S1A,and Table S1).

Magnetic beads-based multicolor colorimetric immunoassay for ultrasensitive detection of aflatoxin B_(1)

Aflatoxin B_(1)(AFB_(1))is one of the most toxic,mutagenic and carcinogenic mycotoxin,widely exists in contaminated food,grains and feedstuff products.In this study,a novel magnetic beads multicolor colorimetric immunoassay(MBMCIA)based on Au@Ag nanorods(Au@Ag NRs)is proposed to visual detect ultralow concentration of AFB_(1)with high-resolution by the naked-eye.To design the MBMCIA system,AFB_(1)-BSA conjugates were first coated on the surface of magnetic beads(MBs),then alkaline phosphatase(ALP)as a bridge between immunoassay a nd color reaction was used for catalytic hydrolysis of ascorbic acid-phosphate to generate reductive ascorbic acid.Finally,the yielded ascorbic acid could reduce silver ions to grow a silver coating on the surface of gold nanorods to generate Au@Ag NRs,which leads to the bule-shifted longitudinal absorption peak of Au NRs,accompanying with a series of perceptible color change.Under the optimal conditions,the proposed MBMCIA exhibited go od sensitivity and specificity for the detection of AFB_(1)with the detection limit as low as 5.7 pg/mL Meanwhile,the MBMCIA was also applied for the analysis of AFB_(1)in spiked wheat samples,the obtained recoveries range from 99.1%to 104.3%with relative standard deviation(RSD)less than 7.05%were acceptable.The proposed MBMCIA integrates separated,enriched,anti-interfe rence and signal read-out into one,which opens up a new avenue for an on-site visual food safety inspection or environmental monitoring.

A step-by-step multiple stimuli-responsive metal-phenolic network prodrug nanoparticles for chemotherapy

Currently,chemotherapy is the main clinical therapy of tumors.Depressingly,most chemotherapeutic drugs such as doxorubicin and paclitaxel(PTX)have poor water solubility,leading to low bioavailability and serious side effects.Till now,although a variety of nanoparticulate drug delivery systems have been designed to ameliorate the above disadvantage of chemotherapy drugs,their application is still severely limited due to the complex preparation,poor stability,low drug loading,and premature drug release.Herein,a metal phenolic network-based drug delivery system with superior stability,satisfactory drug loading capacity,good biocompatibility,reduced undesired premature release,and excellent anti-tumor ability has been established for achieving step-by-step multiple stimuli-responsive drug delivery.Firstly,the redox-responsive dimeric paclitaxel(diPTX)prodrug was synthesized.Then diPTX@Fe&tannic acid(diPTX@Fe&TA)complex nanoparticles with satisfactory PTX loading capacity were obtained by deposition of Fe&TA network complex on the nanocore of diPTX rapidly with a simple method.The diPTX@Fe&TA nanoparticles have a hydrodynamic diameter of 152.6±1.2 nm,long-term colloidal stability,and high PTX loading content of 24.7%.Besides,diPTX@Fe&TA could expose to the acidic lysosomal environment and the reduction cytoplasmic environment continuously,resulting in the sequential release of diPTX and PTX when it was phagocytosed by tumor cells.Meanwhile,PTX showed almost no release under physiological condition(pH 7.4),which effectively inhibited the undesirable premature release of PTX.More importantly,diPTX@Fe&TA could suppress the growth of tumor effectively in vivo,along with negligible toxicity for organs.This work developed a simple and novel approach for the construction of a stepwise multiple stimuli-responsive drug delivery system with superior stability and satisfactory drug loading capacity to inhibit tumor growth effectively.