Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.

Owing to the diversity of composition and excellent transport properties, the ternary I−III−VI 2 type diamond-like chalcopyrite compounds are attractive functional semiconductors, including as thermoelectric materials. In this family, CuInTe 2 and CuGaTe 2 are well investigated and achieve maximum ZT values of ∼1.4 at 950 K and an average ZT of 0.43. However, both compounds have poor electrical conductivity at low temperature, resulting in low ZT below 450 K. In this work, we have greatly improved the thermoelectric performance in the quinary diamondoid compound (Cu 0.8 Ag 0.2 )(In 0.2 Ga 0.8 )Te 2 by understanding and controlling the effects of different constituent elements on the thermoelectric transport properties. Our combined theoretical and experimental effort indicates that Ga in the In site of the lattice decreases the carrier effective mass and improves the electrical conductivity and power factor of Cu 0.8 Ag 0.2 In 1−x Ga x Te 2 . Furthermore, Ag in the Cu site strongly suppresses the heat transport via the enhanced acoustic phonon−optical phonon coupling effects, leading to the ultralow thermal conductivity of ∼0.49 W m −1 K −1 at 850 K in Cu 0.8 Ag 0.2 In 0.2 Ga 0.8 Te 2 . Defect formation energy calculations suggest intrinsic Cu vacancies introduce defect levels that are important to the temperature-dependent hole density and electrical conductivity. Therefore, we introduced extra Cu vacancies to optimize the hole carrier density and improve the power factor of Cu 0.8 Ag 0.2 In 0.2 Ga 0.8 Te 2 . As a result, a maximum ZT of ∼1.5 at 850 K and an average ZT of 0.78 in the temperature range of 400−850 K are obtained, which is among the highest in the diamond-like compound family.

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The understanding of thermoelectric properties of ternary I− III−VI 2 type (I = Cu, Ag; III = Ga, In; and VI = Te) chalcopyrites is less well developed. Although their thermal transport properties are relatively well studied, the relationship between the electronic band structure and charge transport properties of chalcopyrites has been rarely discussed. In this study, we reveal the unusual electronic band structure and the dynamic doping effect that could underpin the promising thermoelectric properties of Cu 1−x Ag x GaTe 2 compounds. Density functional theory (DFT) calculations and electronic transport measurements suggest that the Cu 1−x Ag x GaTe 2 compounds possess an unusual non-parabolic band structure, which is important for obtaining a high Seebeck coefficient. Moreover, a mid-gap impurity level was also observed in Cu 1−x Ag x GaTe 2 , which leads to a strong temperature-dependent carrier concentration and is able to regulate the carrier density at the optimized value for a wide temperature region and thus is beneficial to obtaining the high power factor and high average ZT of Cu 1−x Ag x GaTe 2 compounds. We also demonstrate a great improvement in the thermoelectric performance of Cu 1−x Ag x GaTe 2 by introducing Cu vacancies and ZnTe alloying. The Cu vacancies are effective in increasing the hole density and the electrical conductivity, while ZnTe alloying reduces the thermal conductivity. As a result, a maximum ZT of 1.43 at 850 K and a record-high average ZT of 0.81 for the Cu 0.68 Ag 0.3 GaTe 2 −0.5%ZnTe compound are achieved.

The class I−III−VI 2 diamondoid compounds with tetrahedral bonding are important semiconductors widely applied in optoelectronics. Understanding their heat transport properties and developing an effective method to predict the diamondoid solid solutions' thermal conductivity will help assess their impact as thermoelectrics. In this work, we investigated in detail the heat transport properties of CuGa 1−x In x Te 2 and Cu 1−x Ag x GaTe 2 and found that in the Ag-alloyed solid solutions, the Ag atom off-centering effect results in crystallographic distortion and extra strong acoustic−optical phonon scattering and an extremely low lattice thermal conductivity. Moreover, we integrate the alloy scattering and the off-centering effect with the crystallographic distortion parameter to develop a modified Klemens model that predicts the thermal conductivity of diamondoid solid solutions. Finally, we demonstrate that Cu 1−x Ag x GaTe 2 solid solutions are promising p-type thermoelectric materials, with a maximum ZT of 1.23 at 850 K for Cu 0.58 Ag 0.4 GaTe 2 .

AimWe designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy.MethodsA dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff’s base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR).ResultsThe prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs.ConclusionThe smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy.

This study investigates Ga‐doped n‐type PbTe thermoelectric materials and the dynamic phase conversion process of the second phases via Cu2Se alloying. Introducing Cu2Se enhances its electrical transport properties while reducing its lattice thermal conductivity (κlat) via weak electron–phonon coupling. Cu2Te and CuGa(Te/Se)2 (tetragonal phase) nanocrystals precipitate during the alloying process, resulting in Te vacancies and interstitial Cu in the PbTe matrix. At room temperature, Te vacancies and interstitial Cu atoms serve as n‐type dopants, increasing the carrier concentration and electrical conductivity from ≈1.18 × 1019 cm−3 and ≈1870 S cm−1 to ≈2.26 × 1019 cm−3 and ≈3029 S cm−1, respectively. With increasing temperature, the sample exhibits a dynamic change in Cu2Te content and the generation of a new phase of CuGa(Te/Se)2 (cubic phase), strengthening the phonon scattering and obtaining an ultralow κlat. Pb0.975Ga0.025Te‐3%CuSe exhibits a maximum figure of merit of ≈1.63 at 823 K, making it promising for intermediate‐temperature device applications.

Tumor-targeting combination chemotherapy is an important way to improve the therapeutic index and reduce the side effects as compared to traditional cancer treatments. However, one of the major challenges in surface functionalization of nanoparticle (NP) is accomplishing multiple purposes through one single ligand. Upon such consideration, methotrexate (MTX), an anticancer drug with a targeting moiety inspired by the similar structure of folate, could be used to covalently link with lipid-polymer conjugate (DSPE-PEG) via a pH-sensitive dynamic covalent imine (CH═N) bond to synthesize the acid-induced function "targeting-anticancer" switching DSPE-PEG-CH═N-MTX. We hypothesize that using this kind of MTX prodrug to functionalize NP's surface would be conductive to combine the early phase active targeting function and the late-phase anticancer function in one nanosystem. Herein, a nanococktail is programmed for codelivery of epirubicin (EPI) and MTX by co-self-assembly of acid-dissociated EPI-phospholipid (PC) complex and acid-cleavable DSPE-PEG-CH═N-MTX conjugate. The obtained nanococktail (MTX-PEG-EPI-PC NPs) could not only actively target folate receptors-overexpressing tumor cells but also respond to acidic endo/lysosomes for triggering the on-demand release of pharmaceutically active EPI/MTX. The intracellular drug distribution also demonstrated that the system could codeliver two drugs to individual target sites of action, inducing the significant synergistic anticancer efficiency based on different anticancer mechanisms. More importantly, the in vivo tumor accumulation and anticancer efficacy of MTX-PEG-EPI-PC NPs (via cleavable imine bond) were significantly enhanced as compared to the individual free drug, both free drugs, PEG-EPI-PC NPs, and MTX-PEG-EPI-PC NPs (via the uncleavable amide bond). This self-synergistic tumor-targeting therapy might represent a promising strategy for cancer treatment.