MicroRNA-122-functionalized DNA tetrahedron stimulate hepatic differentiation of human mesenchymal stem cells for acute liver failure therapy

As the most abundant liver-specific microRNA, microRNA-122 (miR122) played a crucial role in the differentiation of stem cells into hepatocytes. However, highly efficient miR122 delivery still confronts challenges including poor cellular uptake and easy biodegradation. Herein, we for the first time demonstrated that the tetrahedral DNA (TDN) nanoplatform had great potential in inducing the differentiation of human mesenchymal stem cells (hMSCs) into functional hepatocyte-like cells (HLCs) by transferring the liver-specific miR122 to hMSCs efficiently without any extrinsic factors. As compared with miR122, miR122-functionalized TDN (TDN-miR122) could significantly up-regulate the protein expression levels of mature hepatocyte markers and hepatocyte-specific marker genes in hMSCs, indicating that TDN-miR122 could particularly activate the hepatocyte-specific properties of hMSCs for developing cell-based therapies in vitro. The transcriptomic analysis further indicated the potential mechanism that TDN-miR122 assisted hMSCs differentiated into functional HLCs. The TDN-miR122-hMSCs exhibited hepatic cell morphology phenotype, significantly up-regulated specific hepatocyte genes and hepatic biofunctions in comparison with the undifferentiated MSCs. Preclinical in vivo transplantation appeared that TDN-miR122-hMSCs in combination with or without TDN could efficiently rescue acute liver failure injury through hepatocyte function supplement, anti-apoptosis, cellular proliferation promotion, and anti-inflammatory. Collectively, our findings may provide a new and facile approach for hepatic differentiation of hMSCs for acute liver failure therapy. Further large animal model explorations are needed to study their potential in clinical translation in the future.

Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure

Reactive oxygen species(ROS)-associated oxidative stress,inflammation storm,and massive hepatocyte necrosis are the typical manifestations of acute liver failure(ALF),therefore specific therapeutic interventions are essential for the devastating disease.Here,we developed a platform consisting of versatile biomimetic copper oxide nanozymes(Cu NZs)-loaded PLGA nanofibers(Cu NZs@PLGA nanofibers)and decellularized extracellular matrix(dECM)hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells(hADMSCs-derived HLCs)(HLCs/Cu NZs@fiber/dECM).Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF,and reduce the massive accumulation of pro-inflammatory cytokines,herein efficiently preventing the deterioration of hepatocytes necrosis.Moreover,Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted HLCs.Meanwhile,HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF therapy.The dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of HLCs.In addition,the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host liver.Hence,HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF mice.This strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.

Electron Probe Microanalysis of Monazite and Its Applications to U-Th-Pb Dating of Geological Samples

Electron probe microanalysis(EPMA) dating of monazite has been developed over decades. However, limited by the detectability and analytical sensitivity of dating-related elements(Th, Pb, U and Y), the EPMA dating has been restricted to geological research. In this study, various probe currents, beam diameters and counting times have been utilized on a JEOL JXA-8230 electron microprobe to determine the optimal experimental conditions for measuring Th, Pb, U and Y in monazite. The optimal conditions are:(1) accelerating voltage is 15 k V;(2) probe current is 100 n A;(3) beam diameter is 1 μm;(4) the peak and background counting time of U and Pb are 200 and 100 s;and(5) the peak and background counting time of Th and Y are 100 and 50 s. We apply this method to monazite from garnet-bearing biotite gneiss in the Zanhuang area of the Central Orogenic Belt of the North China Craton. The Pb O-Th O2* isochron age calculated by EPMA data is 1 812±17 Ma(MSWD=2.06), which is similar to the weighted mean 207 Pb/206 Pb age(1 805±12 Ma, MSWD=1.07) obtained by LA-ICP-MS. This study suggests that EPMA dating of monazite as a powerful dating technique can be widely used in geochronological study.

Mineral Chemistry of Biotite and Its Petrogenesis Implications in ca.2.5 Ga Wangjiazhuang Granitic Pluton,North China Craton

The Wangjiazhuang granitic pluton is located in the central Zanhuang Domain,the central part of the North China Craton,which is mainly composed of biotite monzogranite with few mafic microgranular enclaves.Biotite is an important ferromagnesian mineral in most of the intermediatefelsic igneous rocks,and its mineral chemistry can record the properties of magma and the petrogenetic physicochemical conditions.In this study,we carried out a detailed petrographic study by electric probe microanalysis on biotite for the biotite monzogranite and mafic microgranular enclaves,to discuss the source,physicochemical conditions,and the magma mingling/mixing processes of the Wangjiazhuang granite.The results show significantly different chemical compositions from the biotite monzogranite and mafic microgranular enclaves.The crystallization of these biotite grains from the biotite monzogranite and mafic microgranular enclaves all occurred in low oxygen fugacity.The biotite grains in biotite monzogranite are rich in Fe,poor in Mg,which belong to siderophyllite.The ratios of[(Fe^(3+)+Fe^(2+))/(Fe^(3+)+Fe^(2+)+Mg2+)]are between 0.78 and 0.86.The average of FeOT(total FeO)/MgO of biotite grains in biotite monzogranite is 9.02.The MF values[2×Mg/(Fe^(2+)+Mg+Mn)]of biotite monzogranite are between 0.31 and 0.47,suggesting biotite monzogranite derived from crustal source rocks(metasedimentary rocks).The formation of granitic rocks including the Wangjiazhuang granite was related to the subduction event at ca.2.5 Ga which resulted in the melting event,and then induced the early partial melting of TTGs and metasedimentary rocks.The biotite in mafic microgranular enclaves varies from siderophyllite to ferrobiotite,and MF values range from 0.63 to 1.06,suggesting that magma of mafic microgranular enclaves had experienced magma mixing/mingling in various degrees.Biotite monzogranite and parts of mafic microgranular enclaves have a similar crystallized condition,while other mafic microgranular enclaves are different from biotite monzogranite.The differences between biotite monzogranite and mafic microgranular enclaves may be a consequence of continuous interaction between granitic and mafic magmas.

Low-molecular-weight supramolecular adhesive with resistance to low temperatures

The design of adhesive materials with strong adhesion capacity at low temperatures is a great challenge.Herein,we report a low-molecular-weight supramolecular adhesive that exhibits good adhesion performance to various surfaces at low temperatures(from-18℃ to-80℃).Moreover,this supramolecular adhesive has good adhesion ability in the presence of water.

A Tibetan Sentence Boundary Disambiguation Model Considering the Components on Information on Both Sides of Shad

Sentence Boundary Disambiguation(SBD)is a preprocessing step for natural language processing.Segmenting text into sentences is essential for Deep Learning(DL)and pretraining language models.Tibetan punctuation marks may involve ambiguity about the sentences’beginnings and endings.Hence,the ambiguous punctuation marks must be distinguished,and the sentence structure must be correctly encoded in language models.This study proposed a component-level Tibetan SBD approach based on the DL model.The models can reduce the error amplification caused by word segmentation and part-of-speech tagging.Although most SBD methods have only considered text on the left side of punctuation marks,this study considers the text on both sides.In this study,465669 Tibetan sentences are adopted,and a Bidirectional Long Short-Term Memory(Bi-LSTM)model is used to perform SBD.The experimental results show that the F1-score of the Bi-LSTM model reached 96%,the most efficient among the six models.Experiments are performed on low-resource languages such as Turkish and Romanian,and high-resource languages such as English and German,to verify the models’generalization.

Supramolecular Adhesive Materials from Natural Acids and Sugars with Tough and Organic Solvent-Resistant Adhesion

Natural adhesives have been widely replaced by industrial adhesives made from petroleum-based products.Compared with that of traditional natural adhesives,modern industrial adhesives show improved adhesion performance.However,the drawbacks of modern adhesives,including toxicity and nonbiodegradability,drive the need for new and high-performance adhesive materials from renewable and biocompatible natural feedstock.In this study,a new family of acid-sugar adhesive materials exhibiting excellent and long-term adhesion effects was developed inspired by the concept of deep eutectic solvents(DESs).The supramolecular polymerization between natural sugars and acids gave rise to both strong cohesion and adhesion properties.Moreover,high resistance to organic solvents is an advantage of acid-sugar supramolecular adhesive materials.This study not only dramatically expands the applications of DESs but also sheds light on the development of supramolecular adhesive materials as promising alternatives to polymeric adhesives.