The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects.

Background: Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa).

Research Design & Methods: This randomized, double-blind, dose-escalation, placebo-controlled study evaluated SHR-2004 administered either intravenously (i.

High-Selectivity Laminated Gas Sensor Based on Characteristic Peak under Temperature Modulation.

Aiming at the bottleneck problem of insufficient selectivity of metal oxide gas sensors, a reliable scheme to improve selectivity is proposed, that is, a laminated sensor structure of a gas-sensitive membrane plus catalytic membrane combined with the temperature modulation technology. It is presented as a highly selective ethanol sensor as an example for verification. The laminated gas sensor is made of Sr@SnO as the gas-sensing membrane and ZSM-5 as the catalytic membrane by the microelectro mechanical system.

Use of lignin-based crude carbon dots as effective antioxidant for natural rubber.

Rubber is widely recognized as an important material, whose irreplaceable applications range from damping materials to tires. Generally, rubber is vulnerable to oxidative degradation, leading to a deterioration in the material's performance. Therefore, antioxidants are often added to extend the service life of rubber.

Enhancing the Sound and Thermal Insulation Properties of Polypropylene Foam by Preparing High Melt Strength Polypropylene.

High-performance polypropylene (PP) foam is a vital polymer product in industrial areas. However, the poor melt strength of ordinary PP homopolymer limits its foaming molding. In this work, high melt strength polypropylene (HMSPP) is prepared by using styrene (St) and tripropylene glycol diacrylate (TPGDA) as comonomers, and then PP foams are prepared by mold foaming method.

BJTJ-1837, a novel FXI activation-blocking antibody.

Background: Factor (F)XI contributes to thrombosis development while it plays a limited role in normal hemostasis. FXI targeting has the potential for preventing and treating thrombosis with little bleeding risk.

Objectives: The aim of this study was to develop novel antibody therapeutics against FXI for the treatment of thrombosis-related diseases.

Development, Characterization and Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2.

The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs.

RvD1 accelerates the resolution of inflammation by promoting apoptosis of the recruited macrophages via the ALX/FasL-FasR/caspase-3 signaling pathway.

The uncontrolled inflammatory response caused by a disorder in inflammation resolution is one of the reasons for acute respiratory distress syndrome (ARDS). The macrophage pool markedly expands when inflammatory monocytes, known as recruited macrophages, migrate from the circulation to the lung. The persistent presence of recruited macrophages leads to chronic inflammation in the resolution phase of inflammation.

Resolvin Conjugates in Tissue Regeneration 1 Promote Alveolar Fluid Clearance by Activating Alveolar Epithelial Sodium Channels and Na, K-ATPase in Lipopolysaccharide-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model.

Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway.

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects.

Methods: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration.

Elucidating the Importance of DOT1L Recruitment in MLL-AF9 Leukemia and Hematopoiesis.

gene rearrangements underlie the pathogenesis of aggressive MLL-driven acute leukemia. AF9, one of the most common MLL-fusion partners, recruits the histone H3K79 methyltransferase DOT1L to MLL target genes, constitutively activating transcription of pro-leukemic targets. DOT1L has emerged as a therapeutic target in patients with MLL-driven leukemia.

Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract.

Ziziphi Spinosae Semen (ZSS), a traditional Chinese medicine, is used in clinics for the treatment of insomnia in China and other Asian countries. Herein, we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control (NC) and -chlorophenylalanine (PCPA)-induced insomnia model (IM) rats that were orally administered the aqueous extract of ZSS. An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass (UHPLC-Q-Orbitrap-MS) method was developed and validated for the simultaneous determination of coclaurine, magnoflorine, spinosin, 6-feruloylspinosin, jujuboside A (JuA), and jujuboside B (JuB) in ZSS in rat plasma.

Human salivary histatin-1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)-induced osteogenesis and angiogenesis.

Large-volume bone defects can result from congenital malformation, trauma, infection, inflammation and cancer. At present, it remains challenging to treat these bone defects with clinically available interventions. Allografts, xenografts and most synthetic materials have no intrinsic osteoinductivity, and so an alternative approach is to functionalize the biomaterial with osteoinductive agents, such as bone morphogenetic protein 2 (BMP2).

Determination of five neurotransmitters in the rat brain for the study of the hypnotic effects of Ziziphi Spinosae Semen aqueous extract on insomnia rat model by UPLC-MS/MS.

Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), glutamic acid (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile.

D-Serine Contributes to Seizure Development via ERK Signaling.

A seizure is one of the leading neurological disorders. NMDA receptor-mediated neuronal excitation has been thought to be essential for epileptogenesis. As an endogenous co-agonist of the NMDA receptor, D-serine has been suggested to play a role in epileptogenesis.

Waterlogging-induced adventitious root formation in cucumber is regulated by ethylene and auxin through reactive oxygen species signalling.

Development of adventitious roots (ARs) at the base of the shoot is an important adaptation of plants to waterlogging stress; however, its physiological mechanisms remain unclear. Here, we investigated the regulation of AR formation under waterlogged conditions by hormones and reactive oxygen species (ROS) in Cucumis sativus L., an agriculturally and economically important crop in China.

The electroclinical features of idiopathic generalized epilepsy patients presenting with fixation-off sensitivity.

To determine the electroclinical features of fixation-off sensitivity (FOS) in patients with idiopathic generalized epilepsy (IGE). We searched the EEG database using the terms "fixation-off sensitivity" and "idiopathic generalized epilepsy" over a four-year period from March 2014 to April 2018 in the Xijing Hospital, Xi'an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos.

Construction of a versatile expression library for all human single-pass transmembrane proteins for receptor pairings by high throughput screening.

Interactions between protein ligands and receptors play crucial roles in cell-cell signalling. Most of the human cell surface receptors have been identified in the post-Human Genome Project era but many of their corresponding ligands remain unknown. To facilitate the pairing of orphan receptors, 2762 sequences encoding all human single-pass transmembrane proteins were selected for inclusion into a mammalian-cell expression library.

3-Substituted-N-(4-hydroxynaphthalen-1-yl)arylsulfonamides as a novel class of selective Mcl-1 inhibitors: structure-based design, synthesis, SAR, and biological evaluation.

Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins, is a validated and attractive target for cancer therapy. Overexpression of Mcl-1 in many cancers results in disease progression and resistance to current chemotherapeutics. Utilizing high-throughput screening, compound 1 was identified as a selective Mcl-1 inhibitor and its binding to the BH3 binding groove of Mcl-1 was confirmed by several different, but complementary, biochemical and biophysical assays.

Targeting recruitment of disruptor of telomeric silencing 1-like (DOT1L): characterizing the interactions between DOT1L and mixed lineage leukemia (MLL) fusion proteins.

The MLL fusion proteins, AF9 and ENL, activate target genes in part via recruitment of the histone methyltransferase DOT1L (disruptor of telomeric silencing 1-like). Here we report biochemical, biophysical, and functional characterization of the interaction between DOT1L and MLL fusion proteins, AF9/ENL. The AF9/ENL-binding site in human DOT1L was mapped, and the interaction site was identified to a 10-amino acid region (DOT1L865-874).

In silico discovery of acylated flavonol monorhamnosides from Eriobotrya japonica as natural, small-molecular weight inhibitors of XIAP BIR3.

Targeting the baculoviral inhibitor of apoptosis proteins repeat (BIR) 3 of X-linked inhibitor of apoptosis proteins (XIAP) represents an innovative strategy for the design of chemosensitizers. Acylated flavonol monorhamnosides (AFMR) from Eriobotrya japonica Lindl. (Rosaceae) were virtually predicted as ligands of the XIAP BIR3 domain by using a previously generated pharmacophore model.

La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells.

The effects of La3+ on the unfolded protein response signaling pathways were investigated in human hepatoblastoma HepG2 cells. Our data showed that La3+ could induce unfolded protein response in HepG2 cells, including a significant increase of BiP/GRP78 level, which is an important ER residential chaperone and an ER stress hallmark, in a concentration and time-dependent manner, UPR transducer IRE1 phosphorylation and splicing activation IRE1 downstream substrate XBP1 mRNA. By using La3+-affinity chromatography, the possible cellular target of La3+ leading to UPR events was shown to be the ER residential chaperone BiP/GRP78.