A5073165804- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Nanomaterials for catalytic reactions
- Sulfur-Based Synthesis Techniques
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Reactions
- DNA and Nucleic Acid Chemistry
- Analytical Chemistry and Chromatography
- Antibiotic Resistance in Bacteria
- Drug Transport and Resistance Mechanisms
- Advanced Photocatalysis Techniques
- Transgenic Plants and Applications
- Insect symbiosis and bacterial influences
- Foot and Ankle Surgery
- Thermal properties of materials
- Coal and Coke Industries Research
- Ion channel regulation and function
- Graphene research and applications
- Photosynthetic Processes and Mechanisms
- Advanced Breast Cancer Therapies
- Veterinary medicine and infectious diseases
- MXene and MAX Phase Materials
Shanghai University of Engineering Science
2019-2024
Shanghai University
2022-2024
Beijing National Laboratory for Molecular Sciences
2023
Peking University
2023
University of North Texas
2016-2022
University of North Texas System
2016-2022
University of North Texas Health Science Center
2016-2022
Medical College of Wisconsin
2022
Nanjing University of Chinese Medicine
2021
Fudan University
2016-2018
The practical applications for aqueous Zn ion batteries (ZIBs) are promising yet still impeded by the severe side reactions on metal. Here, a lysozyme protective layer (LPL) is prepared metal surface simple and facile self-adsorption strategy. LPL exhibits extremely strong adhesion to provide stable interface during long-term cycling. In addition, strategy triggered hydrophobicity-induced aggregation effect endows with gap-free compacted morphology which can reject free water effective...
Abstract The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how catalytic Mg 2+ ions induce conformation changes toward active state. It also remains controversial whether generates blunt-ended or staggered-ended breaks overhangs...
TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 emerged as promising target for antibody–drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy cancer treatment, their application solid tumors is hindered by high molecular weight, poor tumor penetration, and release cytotoxic molecules. Therefore, recombinant immunotoxin was developed on shark-derived...
The bacterial CRISPR-Cas9 immune system has been harnessed as a powerful and versatile genome-editing tool holds immense promise for future therapeutic applications. Despite recent advances in understanding Cas9 structures its functional mechanism, little is known about the catalytic state of HNH nuclease domain, identifying how divalent metal ions affect domain conformational transition remains elusive. A deeper activation cleavage mechanism can enable further optimization Cas9-based...
The resistance-nodulation-cell division transporter AcrB is responsible for energy transduction and substrate recognition in the tripartite AcrAB-TolC efflux system Escherichia coli. Despite a broad specificity, only few compounds have been cocrystallized with inside distal binding pocket (DBP), including doxorubicin (DOX) D13-9001. D13-9001 promising pump inhibitor that potentiates efficacy of wide variety antibiotics. To understand its inhibition effect under framework functional rotating...
The RNA-guided Cas9 nuclease from Streptococcus pyogenes has become an important gene-editing tool. However, its intrinsic off-target activity is a major challenge for biomedical applications. Distinct some reported engineering strategies that specifically target single domain, we rationally introduced multiple amino acid substitutions across domains in the enzyme to create potential high-fidelity variants, considering specificity synergistically determined by various domains. We also...
Abstract Acid-sensing ion channels (ASICs) evolved to sense changes in extracellular acidity with the divalent cation calcium (Ca 2+ ) as an allosteric modulator and channel blocker. The channel-blocking activity is most apparent ASIC3, removing Ca results opening, site’s location remaining unresolved. Here we show that a ring of rat ASIC3 (rASIC3) glutamates (Glu435), located above gate, modulates proton sensitivity contributes formation elusive block site. Mutation this residue glycine,...
The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (SpyCas9), along with a programmable single-guide RNA (sgRNA), has been exploited as significant genome-editing tool. Despite the recent advances in determining SpyCas9 structures and DNA cleavage mechanism, cleavage-competent conformation of catalytic HNH nuclease domain remains largely elusive debatable. By integrating computational experimental approaches, we unveiled validated activated Cas9-sgRNA-DNA ternary complex...
SpyCas9 and its engineered variants can recognize NYGG PAMs, affecting their use for genome editing off-target predictions.
The off-target effects of Streptococcus pyogenes Cas9 (SpCas9) pose a significant challenge to harness it as therapeutical approach. Two major factors can result in SpCas9 off-targeting: tolerance target DNA–guide RNA (gRNA) mismatch and less stringent recognition protospacer adjacent motif (PAM) flanking the DNA. Despite abundance engineered SpCas9-gRNA variants with improved sensitivity DNA–gRNA mismatch, studies focusing on enhancing PAM stringency are quite few. A recent pioneering study...
A hybrid nanomaterial composed of ZnO nanoparticles (NPs) and CuTCNQ (copper 7,7,8,8-tetracyanoquinodimethane) nanowires (NWs) was successfully fabricated in a simple solution method. The electron field emission properties the NWs were dramatically improved over those raw NWs. maximum current density ZnO-CuTCNQ six times that array. Importantly for NWs, no obvious degradation observed fluctuation less than 10% during period 4000 seconds. It is significance coating layer NPs produced by our...
Abstract AcrB is the inner membrane transporter of tripartite multidrug efflux pump AcrAB-TolC in E. coli , which poses a major obstacle to treatment bacterial infections. X-ray structures have identified two types substrate-binding pockets porter domains trimer: proximal binding pocket (PBP) and distal (DBP) suggest functional rotating mechanism each protomer cycles consecutively through three distinct conformational states (access, extrusion). However, details substrate translocation...
The need for precision control of CRISPR-Cas9 genome editing has created a demand anti-CRISPR molecules. Recently, the first class small-molecule Cas9 inhibitors been identified, verifying feasibility regulating activity using direct-acting small However, it remains enigmatic as to location ligand binding site(s) on and how leads functional inhibition. Here, we established an integrative computational protocol, including massive site mapping, molecular docking, dynamics simulations, free...
Diatom bloom is characterized by a rapid increase of population density. Perception density and physiological responses can significantly influence their survival strategies, subsequently impacting fate. The itself serve as signal, which perceived through chemical signals or chlorophyll fluorescence triggered high cell density, intracellular signaling mechanisms remain to be elucidated. In this study, we focused on the model diatom, Phaeodactylum tricornutum, designed an orthogonal...
A specific checkpoint between target DNA binding and cleavage primarily governs the precision of Cas9 gene editing. Although various CRISPR-Cas9 variants have been developed to improve accuracy, we still lack a comprehensive understanding how they work at molecular level. Herein, focused on studying late-stage conformational transitions an evolved mutant (evoCas9) that start from precleavage state. Our submilliseconds dynamic simulations reveal presence base mismatches leads HNH nuclease...
A hydroamination of unactivated alkynes and lithium bis(fluorosulfonyl)imide (LiN(SO2F)2) is described under mild conditions, affording a single regioisomer the sulfonyl fluorides. This method features broad functional group compatibility delivers target vinyl fluorosulfonimides in good to excellent yields. Moreover, gram-scale terminal internal achieved. Further transformations exploiting reactivity fluorosulfonimide are subsequently developed for synthesis fluorosulfates diphenyl sulfate.
Magnesium ions (Mg2+), abundant in living cells, are essential for biomolecular structure, dynamics, and function. The biological importance of Mg2+ has motivated continuous development improvement various models molecular dynamics (MD) simulations during the last decades. There four types nonbonded models: point charge based on a 12–6 or 12–6–4 type Lennard-Jones (LJ) potential, multisite LJ potential. Here, we systematically assessed performance these (21 total) terms maintaining...
Cycloartenyl ferulate (CF) is abundant in brown rice with multiple biologic functions. It has been reported to possess antitumor activity; however, the related mechanism of action CF not clarified. Herein, we unexpectedly uncover immunological regulation effects and its molecular mechanism. We discovered that directly enhanced killing capacity natural killer (NK) cells for various cancer vitro. In vivo, also improved surveillance mouse models lymphoma clearance metastatic melanoma dependent...