STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Interconnected 1D Co3O4 nanowires on reduced graphene oxide for enzymeless H2O2 detection

Enzymeless hydrogen peroxide （H2O2） detection with high sensitivity and excellent selectivity is desirable for clinical diagnosis. Herein, one-dimensional Co3O4 nanowires have been successfully constructed on reduced graphene oxide （rGO） via a simple hydrothermal procedure and subsequent thermal treatment. These Co3O4 nanowires, assembled by small nanoparticles, are interlaced with one another and make a spider web-like structure on rGO. The formation of Co3O4-rGO hybrids is attributed to the structure-directing and anchoring roles of DDA and GO, respectively. The resulting structure possesses abundant active sites, the oriented transmission of electrons, and unimpeded pathways for matter diffusion, which endows the Co3O4-rGO hybrids with excellent electrocatalytic performance. As a result, the obtained Co3O4-rGO hybrids can serve as an efficient electrochemical catalyst for H2O2 oxidation and high sensitivity detection. Under physiological conditions, the oxidation current of H2O2 varies linearly with respect to its concentration from 0.015 to 0.675 mM with a sensitivity of 1.14 mA.mM^-1.cm^-2 and a low detection limit of 2.4 μM. Furthermore, the low potential （-0.19 V） and the good selectivity make Co3O4-rGO hybrids suitable for monitoring H2O2 generated by liver cancer HepG2 cells. Therefore, it is promising as a non-enzymatic sensor to achieve real-time quantitative detection of H2O2 in biological applications.

Boosting image-guiding radiation therapy through W_(18)O_(49) nanospheres and the second near-infrared light irradiation

More than 60%of cancer patients receive radiation therapy(RT)during their anticancer treatment.However,there is a huge challenge to improve the therapeutic efficacy of RT in less radioresponsive tumors and decrease damages dealt to the surrounding healthy tissues.Herein,we have reported the development of an efficacious RT treatment of relatively radio-resistant breast cancer using W_(18)O_(49)nanospheres and the second near-infrared(NIR)light irradiation.Featuring the X-ray attenuation ability and photothermal effect,together with ability to generate intracellular singlet oxygen and·OH,W_(18)O_(49)nanospheres can significantly increase radiation-induced DNA damage and decrease the mitochondrial membrane potential of cancer cells during RT,causing in nearby three-times improvement in inhibiting the proliferation of 4T1 cells.The in vivo evaluations verify that a rather effective therapeutic outcome is achieved by treatment of 4T1 tumor xenograft with NIR-enhanced RT using W_(18)O_(49)nanospheres.Moreover,the X-ray attenuation ability and the strong near-infrared absorption of W_(18)O_(49)nanospheres have enabled highly resolved in vivo computer tomography(CT)/photoacoustic(PA)imaging.This work presents an“all-in-one”synergistic platform to improve the therapeutic efficacy of RT in less radioresponsive tumors,therefore opening a new door for multimodal cancer therapy.

The effect of end-capping groups in A-D-A type non-fullerene acceptors on device performance of organic solar cells

A series of novel wide bandgap small molecules(IFT-ECA, IFT-M, IFT-TH and IFT-IC) based on the A-D-A structure with indenofluorene core, thiophene bridge, and different electron-deficient end-capping groups, were synthesized and used as non-fullerene acceptors in organic solar cells. The influences of end-capping groups on the device performance were studied.The four materials exhibited different physical and chemical properties due to the variation of end-capping groups, which further affect the exciton dissociation, charge transport, morphology of the bulk-heterojunction films and device performance. Among them, IFT-IC-based device delivered the best power conversion efficiency of 7.16% due to proper nano-scale phase separation morphology and high electron mobility, while the devices based on the other acceptors achieved lower device performance(4.14% for IFT-TH, <1% for IFT-ECA and IFT-M). Our results indicate the importance of choosing suitable electron-withdrawing groups to construct high-performance non-fullerene acceptors based on A-D-A motif.

Self-doped n-type small molecular electron transport materials for high-performance organic solar cells

Two naphthalene diimide （NDI） and perylene diimide （PDI） based n-type water/alcohol soluble small molecules （NFN and PFP） are designed and utilized as electron transport layers （ETLs） for organic solar cells （OSCs）. NFN and PFP are synthesized by using Sonogashira coupling from alkynyl modified fluorene with mono-bromo substituted NDI and PDI. Density functional theory study results of NFN and PFP show that they possess excellent planarity due to the employment of triple bonds as connection units. Moreover, it was shown by electron paramagnetic resonance study that both NFN and PFP possess obvious self-doping behaviors, which may effectively enhance their charge transporting capability as ETLs in OSCs. Power conversion efficiencies of 8.59% and 9.80% can be achieved for OSCs with NFN and PFP as ETLs, respectively. The higher power conversion efficiency （PCE） of PFP based photovoltaic device is originated from the stronger doping property and higher mobility of PFR