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Wei Zhuang

Publications and source records attributed to Wei Zhuang.

At least 19 recordsLinked to original sources
PubMed2026

Metabolic-cell-death gene trio predicts survival and cuproptosis sensitivity in colorectal cancer.

BACKGROUND: Metabolic cell death (MCD) modulates colorectal cancer (CRC) progression, yet its prognostic value remains unexplored. We aimed to build an MCD-centred gene signature for outcome prediction and precision therapy. METHODS: Transcriptomes of 1,174 CRC patients were integrated. Weighted gene co-expression network analysis, differential expressions and least absolute shrinkage and selection operator (LASSO) + random survival forest were successively applied to derive a three-gene (CDKN2A/MPC1/AHCY) risk model. Functional, immune-infiltration, drug-sensitivity and genomic analyses were performed, followed by validation in fresh clinical specimens and cell lines. RESULTS: Integrative metabolic-death transcriptomics identified CDKN2A, MPC1 and AHCY as the hub drivers of CRC. Their three-gene signature robustly stratified patients into high- and low-risk subsets [3-year area under the curve (AUC) 0.83-0.85, P<0.001]. High-risk tumors were enriched for extracellular matrix (ECM)-receptor-interaction pathways, displayed abundant myeloid-derived suppressor cell (MDSC) infiltration and were more vulnerable to AZD8186, AZ960 and JAK inhibitors. Guided by these in-silico findings, we functionally confirmed that CDKN2A silencing markedly repressed proliferation, invasion and migration of SW480/HCT116 cells and potentiated cuproptosis via up-regulation of lipoylated DLAT/DLST and CTR1. CONCLUSIONS: We report the first MCD-derived prognostic platform for CRC that simultaneously predicts survival and therapeutic response. Targeting CDKN2A-enhanced cuproptosis represents a promising metabolic-precision strategy for high-risk patients.

Colorectal cancer (CRC)↗
PubMed2026

Protein isolation markedly enhances in vitro digestibility, nutritional quality, and bioactivity of fungal mycelial proteins.

Fungal mycelial proteins are promising sustainable protein sources, yet their nutritional utilization is often limited by structural constraints. This study systematically evaluated the effects of protein isolation on the proteomic composition, gastrointestinal digestion behavior, amino acid utilization, and bioactivity of Pleurotus citrinopileatus mycelial proteins. Quantitative proteomics identified 3591 proteins, of which 3374 were shared between mycelial flour (PCMF) and protein isolate (PCMPI), indicating that PCMPI primarily represents the soluble proteome fraction. In vitro digestion revealed that PCMPI exhibited significantly higher digestibility (93.98%) than PCMF (42.98%) (p&#xa0;<&#xa0;0.05), reaching levels comparable to whey protein isolate. Enhanced enzymatic accessibility in PCMPI promoted rapid peptide generation during the gastric phase and efficient amino acid release during the intestinal phase, resulting in higher peptide (634.76&#xa0;mg/g) and free amino acid levels (341.69&#xa0;mg/g) at the digestion endpoint. Consequently, PCMPI achieved a balanced amino acid profile with a PDCAAS of 1.0. Moreover, its digestion products exhibited stronger antioxidant activity (IC&#x2085;&#x2080;&#xa0;=&#xa0;8.36&#xa0;mg/mL) and ACE inhibitory activity (IC&#x2085;&#x2080;&#xa0;=&#xa0;15.65&#xa0;mg/mL) compared with PCMF. Mechanistically, protein isolation disrupted the cell wall matrix, shifting digestion from a structure-limited to an accessibility-driven regime. Collectively, these findings demonstrate that protein isolation markedly enhances the digestibility, nutritional quality, and functional potential of mycelial proteins, supporting their application as high-value sustainable protein ingredients.

Digestion↗
PubMed2006

Two-dimensional vibrational optical probes for peptide fast folding investigation.

A simulation study shows that early protein folding events may be investigated by using a recently developed family of nonlinear infrared techniques that combine the high temporal and spatial resolution of multidimensional spectroscopy with the chirality-specific sensitivity of amide vibrations to structure. We demonstrate how the structural sensitivity of cross-peaks in two-dimensional correlation plots of chiral signals of an alpha helix and a beta hairpin may be used to clearly resolve structural and dynamical details undetectable by one-dimensional techniques (e.g. circular dichroism) and identify structures indistinguishable by NMR.

Computer Simulation↗
PubMed2006

Synthesis of an anionically chargeable, high-molar-mass, second-generation dendronized polymer and the observation of branching by scanning force microscopy.

An efficient synthesis of a methacrylate-based, second-generation (G2) dendronized macromonomer and its free radical polymerization to the corresponding high-molar-mass G2 dendronized polymer are described. The molar mass is determined by gel permeation chromatography (GPC), light-scattering, and analytical ultracentrifugation and compared with values estimated from a scanning force microscopy (SFM) contour lengths analysis of individualized polymer strands on mica. The polymer carries terminal tert-butyl-protected carboxyl groups, the degree of deprotection of which with trifluoroacetic acid is quantified by NMR spectroscopy using the highest molar mass sample. SFM imaging of both protected (noncharged) and unprotected (charged) dendronized polymers on solid substrates reveals mostly linear chains but also some with main-chain branches. The nature of these branches is investigated and the degree roughly estimated to which they are formed. Finally, a synthetic model experiment is described which sheds some light on the aspect of whether chain transfer, a process that could lead to covalent branching, is of importance in the synthesis of the present dendronized polymers.

Journal Article↗
PubMed2006

A simple tagging system for protein encapsulation.

Molecular containers that encapsulate specific cargo can be useful for many natural and non-natural processes. We report a simple system, based on charge complementarity, for the encapsulation of appropriately tagged proteins within an engineered, proteinaceous capsid. Four negative charges per monomer were added to the lumazine synthase from Aquifex aeolicus (AaLS). The capsids formed by the engineered AaLS associate with green fluorescent protein bearing a positively charged deca-arginine tag upon coproduction in Escherichia coli. Analytical ultracentrifugation and scanning force microscopy studies indicated that the engineered AaLS retains the ability to form capsids, but that their average size was substantially increased. The success of this strategy demonstrates that both the container and guest components of protein-based encapsulation systems can be convergently designed in a straightforward manner, which may help to extend their versatility.

Amino Acid Substitution↗
PubMed2006

Simulation protocols for coherent femtosecond vibrational spectra of peptides.

Two algorithms for simulating the response of peptides to sequences of IR pulses are developed and applied to N-methyl acetamide (NMA) and a 17 residue alpha-helical peptide (YKKKH17) in D(2)O. A fluctuating vibrational-exciton Hamiltonian for the amide I mode is constructed from molecular dynamics trajectories. Coupling with the environment is described using a density functional theory electrostatic map. The cumulant expansion of Gaussian fluctuation incorporates motional narrowing due to fast frequency fluctuations and is adequate for NMA and for isotopically labeled bands in large peptides. Real-space truncation of the scattering matrix of the nonlinear exciton equations significantly reduces the computational cost, making it particularly attractive for slow fluctuations in large globular proteins.

Chemistry, Physical↗
PubMed2005

Electrostatic DFT map for the complete vibrational amide band of NMA.

An anharmonic vibrational Hamiltonian for the amide I, II, III, and A modes of N-methyl acetamide (NMA), recast in terms of the 19 components of an external electric field and its first and second derivative tensors (electrostatic DFT map), is calculated at the DFT(BPW91/6-31G(d,p)) level. Strong correlations are found between NMA geometry and the amide frequency fluctuations calculated using this Hamiltonian together with the fluctuating solvent electric field obtained from the MD simulations in TIP3 water. The amide I and A frequencies are strongly positively correlated with the C=O and N-H bond lengths. The C=O and C-N amide bond lengths are negatively correlated, suggesting the solvent-induced fluctuations of the contribution of zwitterionic resonance form. Sampling the global electric field in the entire region of the transition charge densities (TCDs) is required for accurate infrared line shape simulations. Collective electrostatic solvent coordinates which represent the fluctuations of the 10 lowest amide fundamental and overtone states are reported. Normal-mode analysis of an NMA-3H(2)O cluster shows that the 660 cm(-1) to 1100 cm(-1) oscillation found in the frequency autocorrelation functions of the amide modes may be ascribed to the two bending vibrations of intermolecular hydrogen bonds with the amide oxygen of NMA.

Amides↗
PubMed2005

Organocatalytic asymmetric epoxidation reactions in water-alcohol solutions.

The diastereo- and enantioselective organocatalytic epoxidation of alpha,beta-unsaturated aldehydes in aqueous solutions is presented. By the screening of the reaction conditions for the epoxidation of cinnamic aldehyde applying hydrogen peroxide as the oxidant and 2-[bis-(3,5-bis-trifluoromethyl-phenyl)-trimethylsilanyloxy-methyl]-pyrrolidine as the catalyst, a highly stereoselective reaction has been developed. The scope of the diastereo- and enantioselective organocatalytic epoxidation in aqueous solutions is documented by the asymmetric epoxidation of alpha,beta-unsaturated aldehydes with enantioselectivities up to 96% ee.

Journal Article↗
PubMed2005

Stochastic Liouville equations for hydrogen-bonding fluctuations and their signatures in two-dimensional vibrational spectroscopy of water.

The effects of hydrogen-bond forming and breaking kinetics on the linear and coherent third-order infrared spectra of the OH stretch of HOD in D2O are described by Markovian, not necessarily Gaussian, fluctuations and simulated using the stochastic Liouville equations. Slow (0.5 ps) fluctuations are represented by a collective electrostatic coordinate, whereas fast (<100 fs) frequency fluctuations are described using either a second collective electrostatic coordinate or a four-state jump (FSJ) model for hydrogen-bonding configurations. Parameters for both models were obtained using a 1-ns molecular-dynamics trajectory calculated using the TIP4P force field combined with an electrostatic ab initio map. The asymmetry of the photon-echo spectra (larger linewidth on the blue side than on the red side) predicted by the FSJ is in better agreement with recent experiments.

Algorithms↗
PubMed2005

A versatile catalyst for asymmetric reactions of carbonyl groups working purely by activation through hydrogen bonding: Mukaiyama-aldol, hetero Diels-Alder and Friedel-Crafts reactions.

Bis-sulfonamides are demonstrated to be promising candidates for the efficient activation of carbonyl compounds through hydrogen bonding. Exemplified by three carbonyl addition reactions: Mukaiyama-aldol, hetero Diels-Alder and Friedel-Crafts reactions we show that bis-triflamides or bis-nonaflamides of commercially available chiral diamines act as chiral Brønsted-acid catalysts, leading to the optically active products in moderate to excellent yields and with enantioselectivities up to 73% ee.

Journal Article↗
PubMed2005

Enantioselective Friedel-Crafts type addition of indoles to nitro-olefins using a chiral hydrogen-bonding catalyst--synthesis of optically active tetrahydro-beta-carbolines.

The enantioselective Friedel-Crafts addition of indoles to nitro-olefins using chiral hydrogen-bonding bis-sulfonamides as the catalysts has been developed. The reactions, in the presence of only 2 mol% catalyst, generally proceed in high yields and with enantioselectivities up to 64% ee, and the enantiomeric excess can be improved to >98% ee by recrystallization. Various synthetic transformations of the Friedel-Crafts adducts are demonstrated: the nitro group can easily be reduced to the corresponding amine and the product obtained can undergo a stereocontrolled Pictet-Spengler cyclization to give, for example, enantiopure tetrahydro-beta-carbolines. The X-ray structure of the chiral bis-sulfonamides has been determined and based on these structures the mechanism for the stereoselectivity in the reaction is discussed.

Journal Article↗
PubMed2005

Catalytic and enantioselective aza-ene and hetero-Diels-Alder reactions of alkenes and dienes with azodicarboxylates.

Lewis acids such as Cu(OTf)(2), Zn(OTf)(2), Yb(OTf)(3) and Nd(OTf)(3) catalyze the aza-ene reaction of alkenes with azodicarboxylates, giving the allylic amination adducts. The use of bis(2,2,2-trichloroethyl)azodicarboxylate as the amination reagent and Cu(OTf)(2) and Yb(OTf)(3) as the catalysts gave the aza-ene reaction of different alkenes, leading to the corresponding allyl amines in high yields. Chiral copper complexes prepared from Cu(OTf)(2) and chiral bisoxazoline ligands were found to catalyze the enantioselective aza-ene reaction of azodicarboxylates with alkenes and the hetero-Diels-Alder reaction with cyclopentadiene, giving the corresponding aza-ene- and hetero-Diels-Alder adducts, respectively, in good yields and moderate enantioselectivities.

Journal Article↗
PubMed2005

Asymmetric organocatalytic epoxidation of alpha,beta-unsaturated aldehydes with hydrogen peroxide.

The first asymmetric organocatalytic epoxidation of alpha,beta-unsaturated aldehydes is presented. A chiral bisaryl-silyl-protected pyrrolidine acts as a very selective epoxidation organocatalyst using simple oxidation agents, such as hydrogen peroxide and tert-butyl hydroperoxide. The asymmetric epoxidation reactions proceed under environmental friendly reaction condition in, for example, water mixtures of alcohols, and the scope of the reaction is demonstrated by the formation of optically active alpha,beta-epoxy aldehydes in high yields and enantioselectivities >94% ee. Furthermore, the direct synthesis of the sex pheromone from an acaric mite by asymmetric epoxidation of citral is presented.

Journal Article↗
PubMed2005

Dissecting coherent vibrational spectra of small proteins into secondary structural elements by sensitivity analysis.

The response of proteins to sequences of femtosecond infrared pulses provides a multidimensional view into their equilibrium distribution of structures and snapshot pictures of fast-triggered dynamical events. Analyzing these experiments requires advanced computational tools for assigning regions in the resulting multi-dimensional correlation plots to specific secondary-structure elements and their couplings. A differential sensitivity analysis technique based on a perturbation of the local (real space) Hamiltonian is developed to achieve that goal. Application to the amide I region of a small globular protein reveals regions associated with the alpha-helix, beta-sheet, and their coupling. Comparison of signals generated in different directions shows that the double-quantum-coherence signal has a higher sensitivity to the couplings compared with the single-quantum-coherence (photon echo) technique.

Infrared Rays↗
PubMed2005

An easy approach to optically active alpha-amino phosphonic acid derivatives by chiral Zn(II)-catalyzed enantioselective amination of phosphonates.

A catalytic direct enantioselective electrophilic amination of beta-keto phosphonates has been developed applying chiral bisoxazoline-zinc(II) complexes as the catalyst. The reaction proceeds well for both acyclic and cyclic substrates in high yields and with up to 98% ee using azodicarboxylates as the nitrogen source. The scope of the reaction is, for example, the further transformation to optically active beta-hydroxy-alpha-amino phosphonates with very high stereoselection.

Amination↗
PubMed2005

Collective solvent coordinates for the infrared spectrum of HOD in D2O based on an ab initio electrostatic map.

An ab initio MP2 vibrational Hamiltonian of HOD in an external electrostatic potential parametrized by the electric field and its gradient-tensor is constructed. By combining it with the fluctuating electric field induced by the D(2)O solvent obtained from molecular dynamics simulations, we calculate the infrared absorption of the O-H stretch. The resulting solvent shift and infrared line shape for three force fields (TIP4P, SPC/E, and SW) are in good agreement with the experiment. A collective coordinate response for the solvent effect is constructed by identifying the main electrostatic field and gradient components contributing to the line shape. This allows a realistic stochastic Liouville equation simulation of the line shapes which is not restricted to Gaussian frequency fluctuations.

Computer Simulation↗
PubMed2005

Low-dose anticoagulation in Chinese patients with mechanical heart valves.

The aim of this study was to provide guidelines for optimal anticoagulation in Chinese patients after mechanical heart valve replacement. A Carbomedics valve was implanted in 178 patients between July 2000 and July 2003. During follow-up, 22 bleeding events and 1 thromboembolic complication occurred. The linearized rates of bleeding and thromboembolism were 5.83% and 0.26% per patient-year, respectively. The linearized mortality rate was 0.79% per patient-year. The final mean international normalized ratio (INR) was 1.68+/-0.38, however there was a significant variation between the early and late periods of follow-up. For Chinese patients with mechanical heart valves, bleeding was the major complication rather than thromboembolism. Low-dose anticoagulation (international normalized ratio 1.4-2.0) could markedly decrease bleeding and effectively prevent thromboembolism. As the INR was most unstable in the first postoperative month, re-examination of patients in this period is critical.

Adolescent↗