Discovery of Highly Potent Small-Molecule PD-1/PD-L1 Inhibitors with a Novel Scaffold for Cancer Immunotherapy.

Inhibition of the PD-1/PD-L1 interaction through small-molecule inhibitors is a promising therapeutic approach in cancer immunotherapy. Herein, we utilized as the lead compound to develop a series of novel PD-1/PD-L1 small-molecule inhibitors with a naphthyridin scaffold. Among these compounds, displayed the most potent inhibitory activity for the PD-1/PD-L1 interaction (IC = 15.

Discovery of novel dual Bruton's tyrosine kinase (BTK) and Janus kinase 3 (JAK3) inhibitors as a promising strategy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronically systemic autoimmune disorder, which is related with various cellular signal pathways. Both BTK (Bruton's Tyrosine Kinase) and JAK3 (Janus Kinase 3) play important roles in the pathogenesis of rheumatoid arthritis. Herein, we reported the discovery of dual BTK/JAK3 inhibitors through bioisosterism and computer-aided drug design based on the structure of BTK inhibitor ibrutinib.

Correlation analysis of metabolic characteristics and the risk of metabolic-associated fatty liver disease - related hepatocellular carcinoma.

Metabolic-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease worldwide and the main cause of hepatocellular carcinoma (HCC). To explore the risk factors of MAFLD-HCC, we evaluated the independent and combined effects of metabolic characteristics on the risk of MAFLD-HCC. We retrospectively analyzed 135 MAFLD-HCC patients who were treated at the Second Affiliated Hospital of Kunming Medical University from January 2015 to December 2020 and 135 MAFLD patients as the control group.

First-In-Human Study on Pharmacokinetics, Safety, and Tolerability of Single and Multiple Escalating Doses of Hepenofovir, a Novel Hepatic Targeting Prodrug of Tenofovir in Healthy Chinese Subjects.

Hepenofovir, a novel hepatic targeting prodrug of tenofovir, has been developed for the treatment of chronic hepatitis B (CHB). This is a first-in-human study to evaluate the pharmacokinetics (PK) and tolerability of single and multiple escalating doses of hepenofovir in healthy Chinese subjects. This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (25-200 mg) study under fasted conditions comprising a food-effect investigation (200 mg) and a multiple-ascending-dose (MAD) (25 mg) study under fasted conditions.

Effects of salt and heat treatment on the physicochemical properties, microstructure, secondary structure, and simulated in vitro gastrointestinal digestion of duck egg white.

Background: The texture and structure of the duck egg white (DEW) gel under salt and heat treatment are crucial to its digestibility. Specifically, the structural changes of food protein gels have been recognized for their potential to regulate in vitro digestion. In this study, the effects of gel characteristics and simulated in vitro gastrointestinal digestion of DEW under combined salt and heat treatment were investigated.

Changes in physicochemical properties, gel structure and in vitro digestion of marinated egg white gel during braising.

In this paper, changes in physicochemical properties, gel structure and in vitro digestion of marinated egg with spice or tea during braising were investigated. Results indicated that the moisture content and surface hydrophobicity of marinated egg white showed an overall decreased trend. The springiness of marinated egg white showed an increased trend, and the hardness in the late stage showed an increased trend.

Relationship between protein structure changes and in vitro digestion of preserved egg white during pickling.

In this paper, the relationship between protein structure changes and in vitro digestion of preserved egg white (PEW) during pickling was studied. Results showed that as the pickling time increased, moisture content of PEW exhibited a decreasing trend, pH value and hardness of PEW exhibited an increasing trend. Environmental Scanning Electron Microscopy (ESEM) revealed that alkali-treated duck egg white could form a more compact gel network structure during pickling.

A new species of from the Dabie Mountains in eastern China (Anura, Ranidae).

A new species is described from the Dabie Mountains in Anhui Province, China, based on morphological character differences and molecular analyses. The new species can be distinguished from its congeners by a combination of diagnostic characters. The results of phylogenetic analyses (based on 12s rRNA, 16s rRNA, ND2, Cyt , RAG1, BDNF and Tyr) and genetic distances (based on Cyt ) indicate that the new species belongs to the group, and is placed as the sister taxon to .

Molecular phylogeny of Entomobrya (Collembola: Entomobryidae) from China: Color pattern groups and multiple origins.

Highly diversified colorations among springtails (Collembola) have been widely used for species diagnosis, but their phylogenetic significance is poorly known. We addressed this issue in the largest Entomobryinae genus Entomobrya, which possesses variable color patterns among species. The relationships within the genus and to other genera have also rarely been studied.

Graphene microfiber as a scaffold for regulation of neural stem cells differentiation.

We report the cytocompatibility and regulating effects of the nanostructured reduced graphene oxide (rGO) microfibers, which are synthesized through a capillary hydrothermal method, on neural differentiation of neural stem cells (NSCs). Our findings indicate that the flexible, mechanically strong, surface nanoporous, biodegradable, and cytocompatible nanostructured rGO microfibers not only offer a more powerful substrate for NSCs adhesion and proliferation compared with 2D graphene film and tissue cluture plate but also regulate the NSCs differentiation into neurons and form a dense neural network surrounding the microfiber. These results illustrate the great potential of nanostructured rGO microfibers as an artificial neural tissue engineering (NTE) scaffold for nerve regeneration.

Static pressure-induced neural differentiation of mesenchymal stem cells.

Growing experimental evidence suggests that physical cues play an important role in regulating the fate of stem cells and stimulating their differentiation behavior. We report here that static pressure enables the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into neural-like cells within several hours in the absence of disruptive bio-factors or chemicals. The realization of such differentiation is supported by the observation of characteristic morphology of neural-like cells with neurites, and an up-regulated expression level of neural-specific markers.

A Nanostructured Molybdenum Disulfide Film for Promoting Neural Stem Cell Neuronal Differentiation: toward a Nerve Tissue-Engineered 3D Scaffold.

Physical cues from nanostructured biomaterials have been shown to possess regulating effects on stem cell fate. In this study, nanostructured molybdenum disulfide (MoS ) thin films (MTFs) are prepared by assembling MoS nanosheets on a flat substrate. These films are used as a new biocompatible platform for promoting neural stem cell (NSC) differentiation.

A new species of Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae) from Guizhou, China.

A new species of the genus Hemiphyllodactylus is described from Huishui County, Guizhou Province, Southwest China. Hemiphyllodactylus huishuiensis sp. nov.

Sequencing of complete mitochondrial genome for Tsinling Tree Toad ().

The complete mitochondrial genome sequence of was determined in this research. The length of mitogenome is 17850 bp, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, 1 O and 1 control region. The phylogentic tree was reconstructed using the BI method based on concatenated nucleotide sequences of mtDNA genes (12S ribosomal small subunit gene/12S rRNA; NADH dehydrogenase subunit 1 gene/ND1, including adjacent transfer RNAs and the partial 16S ribosomal large subunit gene).

Localized committed differentiation of neural stem cells based on the topographical regulation effects of TiO2 nanostructured ceramics.

In this study, a porous-flat TiO2 micropattern was fabricated with flat and nanoporous TiO2 ceramics for investigating the effect of topography on neural stem cell (NSC) differentiation. This finding demonstrates that localized committed differentiation could be achieved in one system by integrating materials with different topographies.

Microenvironment-Driven Bioelimination of Magnetoplasmonic Nanoassemblies and Their Multimodal Imaging-Guided Tumor Photothermal Therapy.

Biocompatibility and bioelimination are basic requirements for systematically administered nanomaterials for biomedical purposes. Gold-based plasmonic nanomaterials have shown potential applications in photothermal cancer therapy. However, their inability to biodegrade has impeded practical biomedical application.

Self-Powered Electrical Stimulation for Enhancing Neural Differentiation of Mesenchymal Stem Cells on Graphene-Poly(3,4-ethylenedioxythiophene) Hybrid Microfibers.

Engineered conductive scaffolds toward neural regeneration should have the ability to regulate mesenchymal stems cell (MSC) differentiation into neural lineage through an electrical stimulation-assisted culture process. In this work, a self-powered electrical stimulation-assisted neural differentiation system for MSCs was realized by combining a high effective triboelectric nanogenerator (TENG) to supply pulsed electric simulation signals and a poly(3,4-ethylenedioxythiophene) (PEDOT)-reduced graphene oxide (rGO) hybrid microfiber (80 μm in diameter) as a scaffold. The conductive PEDOT endows the rGO-PEDOT hybrid microfiber with an enhanced electrical conductivity and maintains a good cytocompatibility.

Construction of titanium dioxide nanorod/graphite microfiber hybrid electrodes for a high performance electrochemical glucose biosensor.

The demand for a highly sensitive and selective glucose biosensor which can be used for implantable or on-time monitoring is constantly increasing. In this work, TiO2 nanorods were synthesized in situ on the surface of graphite microfibers to yield TiO2 nanorod/graphite microfiber hybrid electrodes. The TiO2 nanorods not only retain the high activity of the immobilized glucose molecule, but also promote the direct electron transfer process on the electrode surface.

Rutile Nanorod/Anatase Nanowire Junction Array as Both Sensor and Power Supplier for High-Performance, Self-Powered, Wireless UV Photodetector.

Self-powered UV photodetectors based on TiO2 nanotree arrays have captured much attention in recent years because of their many advantages. In this work, rutile/anatase TiO2 (R/A-TiO2 ) heterostructured nanotree arrays are fabricated by assembling anatase nanowires as branches on rutile nanorods. External quantum efficiencies as high as 90% are reached at 325 nm.

Cellular internalization of LiNbO3 nanocrystals for second harmonic imaging and the effects on stem cell differentiation.

Second harmonic generation (SHG) nanocrystals have recently been reported to label cancer cells and other functional cell lines due to their unique double-frequency property. In this paper, we report for the first time the use of lithium niobate (LiNbO3, LN) nanocrystals as SHG labels for imaging stem cells. Rat mesenchymal stem cells (rMSCs) were labeled with LN nanocrystals in order to study the cellular internalization of the nanocrystals and the influence on stem cell differentiation.

TiO2 Nanorod Array Constructed Nanotopography for Regulation of Mesenchymal Stem Cells Fate and the Realization of Location-Committed Stem Cell Differentiation.

As a physical cue for controlling the fate of stem cells, surface nanotopography has attracted much attention to improve the integration between implants and local host tissues and cells. A biocompatible surface TiO2 nanorod array is proposed to regulate the fate of bone marrow derived mesenchymal stem cells (MSCs). TiO2 substrates with different surface nanotopographies: a TiO2 nanorod array and a polished TiO2 ceramic are built by hydrothermal and sintering processes, respectively.

Effects of Graphene Quantum Dots on the Self-Renewal and Differentiation of Mesenchymal Stem Cells.

The influence of graphene quantum dots (GQDs) on key characteristics of bone marrow derived mesenchymal stem cells (MSCs) phenotype (i.e., self-renewal, differentiation potential, and pluripotency) is systematically investigated in this work.

Construction of a 3D rGO-collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells.

The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds.

Mitochondrial genome of Pachytriton feii (Urodela: Salamandridae).

In this paper, the complete mitochondrial genome of Pachytriton feii is sequenced and reported for the first time. In our result, the complete mitochondrial genome of P. feii is 16 293 bp in length.