Human skin achieves high sensitivity and a wide range of tactile perception through its gradient structure and the synergistic function of various receptors. However, significant challenges remain in achieving multifunctional synergy enhancement for artificial skin. This study develops a soft-tough bilayer gradient hydrogel based on a salting-out and ion coordination toughening strategy, achieving high sensitivity (7.
View Article and Find Full Text PDFCovalent inhibitors are an emerging class of therapeutics, but methods to comprehensively profile their binding kinetics and selectivity across the proteome have been limited. Here we introduce COOKIE-Pro (COvalent Occupancy KInetic Enrichment via Proteomics), an unbiased method for quantifying irreversible covalent inhibitor binding kinetics on a proteome-wide scale. COOKIE-Pro uses a two-step incubation process with mass spectrometry-based proteomics to determine and values for covalent inhibitors against both on-target and off-target proteins.
View Article and Find Full Text PDFMetabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation.
View Article and Find Full Text PDFThe spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput in situ mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here we developed a tissue-expansion method compatible with matrix-assisted laser desorption/ionization mass-spectrometry imaging (TEMI).
View Article and Find Full Text PDFRecently discovered complete ammonia-oxidizing (comammox) microorganisms can completely oxidize ammonia to nitrate and play an important role in the nitrogen (N) cycle across various ecosystems. However, little is known about the vertical distribution and metabolic versatility of comammox communities in mangrove ecosystems. Here we profiled comammox communities from deep sediments (up to 5 m) in a mangrove wetland by combining metagenome sequencing and physicochemical properties analysis.
View Article and Find Full Text PDFThe spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here, we developed a Tissue Expansion method compatible with matrix-assisted laser desorption/ionization Mass spectrometry Imaging (TEMI).
View Article and Find Full Text PDFThe scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo.
View Article and Find Full Text PDFIn the process of fully mechanized top-coal caving mining, the top-coal is affected by mining-induced stress, and the stress varies along the strike direction of working face, so the boundary position of its entering the limit equilibrium state changes accordingly. The determination of the boundary along the strike direction of working face can provide scientific guidance for the stability control of support-surrounding rock in fully mechanized top-coal caving face. Using the research methods of theoretical analysis, physical similarity simulation experiment and numerical simulation experiment, the stress state analysis model of the boundary position of the top-coal limit equilibrium zone under macro-scale conditions was established, the stress state characterization method of the boundary of the top-coal limit equilibrium zone along the strike direction of working face was given, and the quantitative characterization of the boundary of the top-coal limit equilibrium zone along the strike direction of working face was realized by combining with the mining-induced stress path, and the distance relationship between the boundary of the top-coal limit equilibrium zone and the langwall face along the strike direction of working face was revealed.
View Article and Find Full Text PDFThe scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and has emerged as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain, we harnessed proteolysis targeting chimera (PROTAC) technology to develop a first-in-class RIPK1 degrader, LD4172. LD4172 exhibited potent and selective RIPK1 degradation both and .
View Article and Find Full Text PDFThe scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and has emerged as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain, we harnessed proteolysis targeting chimera (PROTAC) technology to develop a first-in-class RIPK1 degrader, LD4172. LD4172 exhibited potent and selective RIPK1 degradation both and .
View Article and Find Full Text PDFTo solve the problem that the macroscopic deformation and failure of coal-rock medium under external loads are easy to be observed while the internal stress transfer mode and path are unclear. Based on the discrete element idea, the numerical models for pure coal or rock samples and coal-rock combination samples with different lithologies and combination methods under concentrated force are established by PFC2D software. Then the influence of coal or rock strength and combination methods on the internal stress transfer law and distribution evolution characteristics of coal-rock medium are discussed from the perspectives of macroscopic stress and mesoscopic force chain, respectively.
View Article and Find Full Text PDFHealthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis.
View Article and Find Full Text PDFAs a public infrastructure service, remote sensing data provided by smart cities will go deep into the safety field and realize the comprehensive improvement of urban management and services. However, it is challenging to detect criminal individuals with abnormal features from massive sensing data and identify groups composed of criminal individuals with similar behavioral characteristics. To address this issue, we study two research aspects: pickpocketing individual detection and pickpocketing group identification.
View Article and Find Full Text PDFCustomizable structures and patterns are becoming powerful tools for biomimetic design and application of soft materials. The construction of long-range ordered self-wrinkled structures on multi-dimensional and complex-shaped surfaces with facile, fast and efficient strategies still faces serious challenges. During the stretch-recovery process, the carboxyl groups in the polyacrylamide/sodium alginate dual network gel form robust coordination with Fe to achieve a hard shell layer, resulting in a modulus mismatch between the inner soft layer and the outer hard layer, thereby forming a wrinkled surface.
View Article and Find Full Text PDFThe recognition of traffic signs is of great significance to intelligent driving and traffic systems. Most current traffic sign recognition algorithms do not consider the impact of rainy weather. The rain marks will obscure the recognition target in the image, which will lead to the performance degradation of the algorithm, a problem that has yet to be solved.
View Article and Find Full Text PDFSparse mobile crowd sensing saves perception cost by recruiting a small number of users to perceive data from a small number of sub-regions, and then inferring data from the remaining sub-regions. The data collected by different people on their respective trajectories have different values, and we can select participants who can collect high-value data based on their trajectory predictions. In this paper, we study two aspects of user trajectory prediction and user recruitment.
View Article and Find Full Text PDFHealthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis.
View Article and Find Full Text PDFCurr Res Chem Biol
May 2022
Building on our previous work on ibrutinib-based reversible covalent Bruton's tyrosine kinase (BTK) PROTACs, we explored a different irreversible BTK inhibitor poseltinib as the BTK binder for PROTAC development. Different from ibrutinib, converting the irreversible cysteine reacting acrylamide group of poseltinib to a reversible covalent cyano-acrylamide group dramatically decreases the binding affinity to BTK by over 700 folds. Interestingly, one of the reversible covalent BTK PROTACs based on poseltinib with a rigid linker, dubbed as PS-RC-1, is highly potent (IC = ~10 nM) in Mino cells but not in other mantle cell lymphoma (MCL) cell lines, such as Jeko-1 and Rec-R cells.
View Article and Find Full Text PDFPrecise assignment of sialylation linkages at the glycopeptide level is of importance in bottom-up glycoproteomics and an indispensable step to understand the function of glycoproteins in pathogen-host interactions and cancer progression. Even though some efforts have been dedicated to the discrimination of α2,3/α2,6-sialylated isomers, unambiguous identification of sialoglycopeptide isomers is still needed. Herein, we developed an innovative glycosyltransferase labeling assisted mass spectrometry (GLAMS) strategy.
View Article and Find Full Text PDFAnal Bioanal Chem
March 2019
Rheumatoid arthritis (RA) is an autoimmune disease in which certain immune cells are dysfunctional and attack their own healthy tissues. There has been great difficulty in finding an accurate and efficient method for the diagnosis of early-stage RA. The present shortage of diagnostic methods leads to the rough treatments of the patients in the late stages, such as joint removing.
View Article and Find Full Text PDFThe purpose of this study was to develop a promising wound dressing. Though chitosan cross-linked with genipin has been widely used as biomaterials, with the addition of partially oxidized Bletilla striata polysaccharide, the newly developed material in this study (coded as CSGB) showed less gelling time, more uniform aperture distribution, higher water retention, demanded mechanical strength and more L929 cell proliferation compared to the chitosan cross-linked only with genipin. Owning to partial blocking of free amino groups of chitosan, CSGB revealed almost no antibacterial activities, thus the bilayer composite of chitosan-silver nanoparticles (CS-AgG) on CSGB was designed to inhibit microbial invasion.
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