ENO1 contributes to the gemcitabine resistance of pancreatic cancer through the YAP1 signaling pathway.

Pancreatic cancer (PC), a leading cause of cancer-related deaths, has a 5-year survival rate of approximately 10%. α-Enolase (ENO1) is a junction channel protein involved in tumor cell apoptosis and chemoresistance. However, the role of ENO1 in PC remains unclear.

Rational Design of Covalent Kinase Inhibitors by an Integrated Computational Workflow (Kin-Cov).

Covalent kinase inhibitors (CKIs) hold great promise for drug development. However, examples of computationally guided design of CKIs are still scarce. Here, we present an integrated computational workflow (Kin-Cov) for rational design of CKIs.

Edge-oriented phosphatizing engineering of 2D Ni-MOFs with a tailored d-band center for boosting catalytic activity.

Metal-organic framework (MOF)-based heterostructures have aroused widespread interest owing to their extensive compositional tunability and interesting catalytic properties. However, the precise edge-oriented growth of transition metal compounds at the edges of 2D MOFs to construct edge mode heterostructures remains a great challenge due to their inherent thermodynamic instability. Here, edge-oriented growth of NiP at the edges of a 2D Ni-MOF was achieved for the first time by precisely tuning the phosphorus source content and phosphating temperature.

The ultrathin palladium nanosheets for sensitive and visual Hg detection in the food chain.

The detection of mercury, one of the ten most dangerous chemicals, is significant to provide helpful information for assessing mercury toxicity and health risks. However, it is a challenge to explore simple, sensitive, accurate, and cheap Hg detection methods. Noble metal nanomaterials are used for Hg detection by the colorimetric method widely.

Cyclic coupling of photocatalysis and adsorption for completely safe removal of N-nitrosamines in water.

The incomplete removal of N-nitrosamines in water through current degraded techniques and the carcinogenicity of N-nitrosamines call for alternative complete and safe removal approaches. Here, we describe a cyclic coupling process of photocatalysis and adsorption enabling N-nitrosamines in water thoroughly and safely removed. Among them, the immobilized TiO/Ti photocatalyst degraded N-nitrosamines into primary and secondary amines up to 100% by attacking on nitrosyl nitrogen via •OH originated from its nanowire film morphology.

The influence of modified molecular (D/L-serine) chirality on the theragnostics of PAMAM-based nanomedicine for acute kidney injury.

Acute kidney injury (AKI) is a severe clinical disease with extremely high morbidity and mortality. It is challenging to find a simple method for early detection of AKI and monitoring the treatment results. Renal tubular damage and inflammation are early events in AKI.

Effect of temperature on PTEs deportment and ecological risks of the biochars obtained from sewage sludge.

Sewage sludge-derived biochars (SSBCs) were obtained at temperatures of 300, 500, and 700 °C to investigate the potentially toxic elements (PTEs) behaviors and assess the environmental acceptability for the possible application in the environment. Results indicated that PTEs exhibited diversely in the distribution of chemical speciation, while all elements tended to be immobilized in biochar matrix and the total amount elevated during the pyrolysis. The risk assessment of biochars implied a low degree of environmental risk for the utilization of SSBCs prepared at high temperatures.

MEKK3 in hybrid snakehead (Channa maculate ♀ ×Channa argus ♂): Molecular characterization and immune response to infection with Nocardia seriolae and Aeromonas schubertii.

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is a serine/threonine protein kinase that acts as a key regulator and is widely involved in various innate and acquired immune signaling pathways. In this study, we first cloned the complete open reading frame (ORF) of the MEKK3 gene (named CcMEKK3) in a hybrid snakehead (Channa maculate ♀ × Channa argus ♂). The full-length ORF of CcMEKK3 is 1851 bp, and encodes a putative protein of 616 amino acids containing a serine/threonine kinase catalytic (S-TKc) domain and a Phox and Bem1p (PB1) domain.

HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones.

Upon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors to initiate DNA repair. Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. Here, we report the crystal structures of human HPF1/PARP1-CAT ΔHD complex at 1.

Immunomodulatory activity of puerarin in RAW264.7 macrophages and cyclophosphamide-induced immunosuppression mice.

Context: Puerarin, a natural isoflavone extracted from , is famous for treating various cardiovascular and cerebrovascular diseases. However, little is known about its direct immunomodulatory activity.

Objective: This study was designed to investigate the and immunomodulatory effects of by using the murine monocyte-macrophage cell line RAW264.

MgTiO spinel modified by nitrogen doping as a Visible-Light-Active photocatalyst for antibacterial activity.

Nitrogen doped MgTiO spinel, i.e. MgTiON, has been synthesized and investigated as a photocatalyst for antibacterial activity.

Two types of TNF-α and their receptors in snakehead (Channa argus): Functions in antibacterial innate immunity.

Tumor necrosis factor-α (TNF-α) is a pluripotent mediator of pro-inflammatory and antimicrobial defense mechanisms and a regulator of lymphoid organ development. Although two types of TNF-α have been identified in several teleost species, their functions in pathogen infection remain largely unexplored, especially in pathogen clearance. Herein, we cloned and characterized two types of TNF-α, termed shTNF-α1 and shTNF-α2, and their receptors, shTNFR1 and shTNFR2, from snakehead (Channa argus).

Bacteria-induced IL-1β and its receptors in snakehead (Channa argus): Evidence for their involvement in antibacterial innate immunity.

As a central pro-inflammatory cytokine, interleukin-1β (IL-1β) plays critical roles in the inflammatory response, pathogen infection, and immunological challenges in mammals. Although fish IL-1β has been confirmed to participate in inflammatory response to pathogen infection, few studies have been performed to characterize the antibacterial and bactericidal functions of fish IL-1β. In this study, snakehead (Channa argus) IL-1β (shIL-1β) and its receptors, shIL-1R1 and shIL-1R2, were cloned and functionally characterized.

Integrating metabolomics and physiological analysis to investigate the toxicological mechanisms of sewage sludge-derived biochars to wheat.

Effects of sewage sludge biochars (SSBCs) on the growth of wheat and the specific toxicological mechanisms were investigated from a metabolic perspective for better ecological risk assessment. We observed that conversion of sludge to biochar remarkably changed the properties, and also caused a significant (p < 0.05) reduction of the toxicity towards wheat.

Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors.

ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, binds tightly to ZAK protein ( = 8.

Biochar accelerates PAHs biodegradation in petroleum-polluted soil by biostimulation strategy.

Sawdust and wheat straw biochars prepared at 300°C and 500°C were applied to petroleum-polluted soil for an 84-day incubation to estimate their effectiveness on polycyclic aromatic hydrocarbons (PAHs) removal. Biochars alone were most effective at reducing PAHs contents. However, adding biochar to soils in company with NaN solution resulted in a decreasing trend in terms of PAHs removal, which was even lower than treatment CK without biochar.

Structural pharmacological studies on EGFR T790M/C797S.

Drug-resistance is a major challenge in targeted therapy of EGFR mutated non-small cell lung cancers (NSCLCs). The third-generation irreversible inhibitors such as AZD9291, CO-1686 and WZ4002 can overcome EGFR T790M drug-resistance mutant through covalent binding through Cys 797, but ultimately lose their efficacy upon emergence of the new mutation C797S. To develop new reversible inhibitors not relying on covalent binding through Cys 797 is therefore urgently demanded.

Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration.

Tissue repair and regenerative medicine address the important medical needs to replace damaged tissue with functional tissue. Most regenerative medicine strategies have focused on delivering biomaterials and cells, yet there is the untapped potential for drug-induced regeneration with good specificity and safety profiles. The Hippo pathway is a key regulator of organ size and regeneration by inhibiting cell proliferation and promoting apoptosis.

Discovery and characterization of a novel potent type II native and mutant BCR-ABL inhibitor (CHMFL-074) for Chronic Myeloid Leukemia (CML).

BCR gene fused ABL kinase is the critical driving force for the Philadelphia Chromosome positive (Ph+) Chronic Myeloid Leukemia (CML) and has been extensively explored as a drug target. With a structure-based drug design approach we have discovered a novel inhibitor CHMFL-074, that potently inhibits both the native and a variety of clinically emerged mutants of BCR-ABL kinase. The X-ray crystal structure of CHMFL-074 in complex with ABL1 kinase (PDB ID: 5HU9) revealed a typical type II binding mode (DFG-out) but relatively rare hinge binding.

The antitumor activity of Meconopsis horridula Hook, a traditional Tibetan medical plant, in murine leukemia L1210 cells.

Background: Meconopsis horridula Hook (M. horridula) has been used as a traditional Tibetan medicine to relieve heat and pain as well as mobilize static blood, and it is recognized as a good treatment for bruises. This study is the first trial to evaluate the tumor inhibitory activity of M.

Gypenosides Synergistically Enhances the Anti-Tumor Effect of 5-Fluorouracil on Colorectal Cancer In Vitro and In Vivo: A Role for Oxidative Stress-Mediated DNA Damage and p53 Activation.

Objective: 5-Fluorouracil (5-Fu) has been widely used as a first-line drug for colorectal cancer (CRC) treatment but limited by drug resistance and severe toxicity. The chemo-sensitizers that augment its efficiency and overcome its limitation are urgently needed. Gypenosides (Gyp), the main components from Gynostemma pentaphyllum (Thunb.

Induction of Mitochondrial Dependent Apoptosis in Human Leukemia K562 Cells by Meconopsis integrifolia: A Species from Traditional Tibetan Medicine.

Objectives: Meconopsis integrifolia (M. integrifolia) is one of the most popular members in Traditional Tibetan Medicine. This study aimed to investigate the anticancer effect of M.

Functional analysis of insect molting fluid proteins on the protection and regulation of ecdysis.

Molting fluid accumulates between the old and new cuticles during periodical ecdysis in Ecdysozoa. Natural defects in insect ecdysis are frequently associated with melanization (an immunity response) occurring primarily in molting fluids, suggesting that molting fluid may impact immunity as well as affect ecdysis. To address this hypothesis, proteomic analysis of molting fluids from Bombyx mori during three different types of ecdysis was performed.

Enhanced photocatalytic performance of N-nitrosodimethylamine on TiO2 nanotube based on the role of singlet oxygen.

N-nitrosodimethylamine (NDMA) photocatalytic degradation performance and mechanism were investigated on the TiO2 nanotube prepared from anatase TiO2 nanopowder in terms of the production of reactive oxygen species including hydroxyl radical, singlet oxygen and superoxide radical. Significantly higher NDMA degradation efficiency was obtained on anatase TiO2 nanotube rather than anatase TiO2 nanopowder. The tubular morphology may be responsible for almost 100% NDMA removal on TiO2 nanotube, presumably due to its confinement effect leading to NDMA molecules within the nanotube being attacked by reactive oxygen species such as hydroxyl radical and singlet oxygen, and initiating reaction inside the nanotube.