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Wenhui Li

Publications and source records attributed to Wenhui Li.

At least 19 recordsLinked to original sources
PubMed2025

Noninvasive detection and differentiation of gastric malignancy using cell-free DNA biomarkers.

INTRODUCTION: Gastric cancer remains a major global health burden, with high mortality driven by late-stage diagnoses that limit treatment options and reduce survival. Current diagnostic methods such as endoscopy and biopsy are invasive, resource-intensive, and impractical for large-scale early detection. OBJECTIVES: This study aimed to develop and validate an ensemble machine learning model integrating four cell-free DNA (cfDNA) fragmentomic feature classes derived from 5 × whole genome sequencing (WGS) data to non-invasively differentiate malignant gastric cancer from benign gastric lesions in high-risk or symptomatic patients. METHODS: A total of 681 plasma samples were prospectively collected, comprising 329 from patients with gastric cancer or high-grade intraepithelial neoplasia (HGIN) and 352 from individuals with benign gastric conditions. The dataset was divided into a training cohort (n = 333) and a temporally independent validation cohort (n = 348). An external validation cohort of 305 participants was also included. RESULTS: The ensemble model achieved an AUROC of 0.920 in cross-validation testing on the training cohort, 0.912 in the independent validation cohort, and 0.896 (95% CI 0.860-0.932) in the external cohort. At a pre-specified prediction threshold of 0.402, the model demonstrated 93.3% sensitivity and 71.9% specificity in the validation cohort, yielding a PPV of 71.3% and an NPV of 93.5%. In the external cohort, sensitivity and specificity were 91.7% and 69.1%, respectively (PPV 75.7%, NPV 88.8%). Model scores correlated with clinical stage, tumor grade, and histopathological subtype. Approximately 71% of non-cancer patients could have been spared unnecessary endoscopy. CONCLUSIONS: The cfDNA fragmentomics-based ensemble model enables accurate, non-invasive differentiation between gastric cancer and benign gastric lesions in high-risk or symptomatic patients. This approach demonstrates strong potential as a pre-endoscopy triage tool, supporting earlier detection and more efficient use of diagnostic resources.

Humans↗
PubMed2025

Malonate promotes CD8+ T cell memory formation via protein malonylation.

Protein malonylation represents a recently identified posttranslational modification whose role in CD8+ T cell differentiation and functionality remains incompletely understood. In this study, we demonstrate that enhancing protein malonylation through sodium malonate (SM) treatment promotes CD8+ T cell memory formation in response to bacterial infection, subsequently potentiating recall responses. Comparative metabolomic analysis between SM-treated and control CD8+ T cells revealed significant metabolic alterations associated with protein malonylation. We present the first comprehensive proteomic analysis of lysine malonylation in murine CD8+ T cells, identifying 77 malonylation sites across 64 proteins involved in diverse cellular processes, particularly metabolic pathways. Malonylation of STAT6 was confirmed via the use of a specific chemical probe. Notably, we established that malonylation at the lysine 374 site of STAT6 results in increased TCF1 expression, due to alleviated transcriptional repression of TCF1 by STAT6. Collectively, our findings provide compelling evidence that protein malonylation plays a significant role in regulating CD8+ T cell memory formation.

Animals↗
PubMed2006

Deformation of a trapped Fermi gas with unequal spin populations.

The real-space densities of a polarized strongly interacting two-component Fermi gas of 6Li atoms reveal two low-temperature regimes, both with a fully paired core. At the lowest temperatures, the unpolarized core deforms with increasing polarization. Sharp boundaries between the core and the excess unpaired atoms are consistent with a phase separation driven by a first-order phase transition. In contrast, at higher temperatures the core does not deform but remains unpolarized up to a critical polarization. The boundaries are not sharp in this case, indicating a partially polarized shell between the core and the unpaired atoms. The temperature dependence is consistent with a tricritical point in the phase diagram.

Journal Article↗
PubMed2006

Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein.

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a protective Ag for vaccine design. We previously demonstrated that the receptor-binding domain (RBD) of S protein contains multiple conformational epitopes (Conf I-VI) that confer the major target of neutralizing Abs. Here we show that the recombinant RBDs derived from the S protein sequences of Tor2, GD03, and SZ3, the representative strains of human 2002-2003 and 2003-2004 SARS-CoV and palm civet SARS-CoV, respectively, induce in the immunized mice and rabbits high titers of cross-neutralizing Abs against pseudoviruses expressing S proteins of Tor2, GD03, and SZ3. We also demonstrate that the Tor2-RBD induced-Conf I-VI mAbs can potently neutralize both human SARS-CoV strains, Tor2 and GD03. However, only the Conf IV-VI, but not Conf I-III mAbs, neutralize civet SARS-CoV strain SZ3. All these mAbs reacted significantly with each of the three RBD variants (Tor2-RBD, GD03-RBD, and SZ3-RBD) that differ at several amino acids. Regardless, the Conf I-IV and VI epitopes were completely disrupted by single-point mutation of the conserved residues in the RBD (e.g., D429A, R441A, or D454A) and the Conf III epitope was significantly affected by E452A or D463A substitution. Interestingly, the Conf V epitope, which may overlap the receptor-binding motif and induce most potent neutralizing Abs, was conserved in these mutants. These data suggest that the major neutralizing epitopes of SARS-CoV have been apparently maintained during cross-species transmission, and that RBD-based vaccines may induce broad protection against both human and animal SARS-CoV variants.

Animals↗
PubMed2006

Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor.

The GP(1,2) envelope glycoproteins (GP) of filoviruses (marburg- and ebolaviruses) mediate cell-surface attachment, membrane fusion, and entry into permissive cells. Here we show that a 151-amino acid fragment of the Lake Victoria marburgvirus GP1 subunit bound filovirus-permissive cell lines more efficiently than full-length GP1. An homologous 148-amino acid fragment of the Zaire ebolavirus GP1 subunit similarly bound the same cell lines more efficiently than a series of longer GP1 truncation variants. Neither the marburgvirus GP1 fragment nor that of ebolavirus bound a nonpermissive lymphocyte cell line. Both fragments specifically inhibited replication of infectious Zaire ebolavirus, as well as entry of retroviruses pseudotyped with either Lake Victoria marburgvirus or Zaire ebolavirus GP(1,2). These studies identify the receptor-binding domains of both viruses, indicate that these viruses utilize a common receptor, and suggest that a single small molecule or vaccine can be developed to inhibit infection of all filoviruses.

Amino Acid Sequence↗
PubMed2006

Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals.

Most of the SARS-CoV-infected patients spontaneously recovered without clinical intervention while a small percentage succumbed to the disease. Here, we characterized temporal changes in N protein-specific and S glycoprotein-specific neutralizing antibody (Nab) responses in infected patients who have either recovered from or succumbed to SARS-CoV infection. Recovered patients were found to have higher and sustainable levels of both N protein-specific and S glycoprotein-specific Nab responses, suggesting that antibody responses likely play an important role in determining the ultimate disease outcome of SARS-CoV-infected patients.

Antibodies, Viral↗
PubMed2006

Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain.

The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.

Angiotensin-Converting Enzyme 2↗
PubMed2005

Pairing and phase separation in a polarized Fermi gas.

We report the observation of pairing in a gas of atomic fermions with unequal numbers of two components. Beyond a critical polarization, the gas separates into a phase that is consistent with a superfluid paired core surrounded by a shell of normal unpaired fermions. The critical polarization diminishes with decreasing attractive interaction. For near-zero polarization, we measured the parameter beta = -0.54 +/- 0.05, describing the universal energy of a strongly interacting paired Fermi gas, and found good agreement with recent theory. These results are relevant to predictions of exotic new phases of quark matter and of strongly magnetized superconductors.

Journal Article↗
PubMed2005

SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.

Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.

Angiotensin-Converting Enzyme 2↗
PubMed2005

Structure of SARS coronavirus spike receptor-binding domain complexed with receptor.

The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.

Amino Acid Sequence↗
PubMed2005

Androgen receptor mutations identified in prostate cancer and androgen insensitivity syndrome display aberrant ART-27 coactivator function.

The transcriptional activity of the androgen receptor (AR) is modulated by interactions with coregulatory molecules. It has been proposed that aberrant interactions between AR and its coregulators may contribute to diseases related to AR activity, such as prostate cancer and androgen insensitivity syndrome (AIS); however, evidence linking abnormal receptor-cofactor interactions to disease is scant. ART-27 is a recently identified AR N-terminal coactivator that is associated with AR-mediated growth inhibition. Here we analyze a number of naturally occurring AR mutations identified in prostate cancer and AIS for their ability to affect AR response to ART-27. Although the vast majority of AR mutations appeared capable of increased activation in response to ART-27, an AR mutation identified in prostate cancer (AR P340L) and AIS (AR E2K) show reduced transcriptional responses to ART-27, whereas their response to the p160 class of coactivators was not diminished. Relative to the wild-type receptor, less ART-27 protein associated with the AR E2K substitution, consistent with reduced transcriptional response. Surprisingly, more ART-27 associated with AR P340L, despite the fact that the mutation decreased transcriptional activation in response to ART-27. Our findings suggest that aberrant AR-coactivator association interferes with normal ART-27 coactivator function, resulting in suppression of AR activity, and may contribute to the pathogenesis of diseases related to alterations in AR activity, such as prostate cancer and AIS.

Amino Acid Substitution↗
PubMed2005

Reorganization of ErbB family and cell survival signaling after Knock-down of ErbB2 in colon cancer cells.

The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.

Cell Line, Tumor↗
PubMed2005

Dipole-dipole excitation and ionization in an ultracold gas of Rydberg atoms.

In cold dense Rydberg atom samples, the dipole-dipole interaction strength is effectively resonant at the typical interatomic spacing in the sample, and the interaction has a 1/R3 dependence on interatomic spacing R. The dipole-dipole attraction leads to ionizing collisions of initially stationary atoms, which produces hot atoms and ions and initiates the evolution of initially cold samples of neutral Rydberg atoms into plasmas. More generally, the strong dipole-dipole forces lead to motion, which must be considered in proposed applications.

Journal Article↗
PubMed2005

Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2.

Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002-2003 SARS outbreak and during the much less severe 2003-2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002-2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002-2003 SARS epidemic.

Amino Acid Sequence↗