Biomedical subjects

Xu Yang

Publications and source records attributed to Xu Yang.

5 recordsLinked to original sources

PubMed2026

Engineered Ratiometric Near-Infrared Probes Enable Dual-Organelle Visualization of G-Quadruplex in Living Cells.

G-quadruplexes (G4s) participate in nuclear genome regulation and mitochondrial metabolism, but tools for monitoring both compartments in the same living cell remain limited. Here, we report PEG-INR-Me, a ratiometric near-infrared (NIR) probe designed for simultaneous visualization of nuclear and mitochondrial G4-associated signals. G4 binding enhances the long-wavelength emission, whereas the short-wavelength channel serves as an operational normalization channel under matched acquisition conditions. Accordingly, cellular Channel640/Channel560 values are interpreted as relative readouts within a defined compartment and experiment, rather than as absolute comparisons of G4 abundance between organelles. PEG-INR-Me revealed parallel cell-cycle-associated changes in nuclear and mitochondrial signals, higher signals in cancer cells than in noncancerous cells, and concurrent decreases during cisplatin treatment followed by partial recovery after caspase inhibition. These observations establish temporal concordance between mitochondria and nucleus. Following direct local administration, the probe also distinguished 4T1 tumors from a contralateral subcutaneous control site. PEG-INR-Me therefore provides a dual-compartment imaging platform for investigating nuclear and mitochondrial G4-associated dynamics, and their mechanistic relationship deserves to be further investigated.

G‐Quadruplexes↗

PubMed2026

Genomic Profiling, Risk Stratification, and Post-Transformation Treatment Outcomes in Patients with Transformed Small-Cell Lung Cancer: A Multicenter Analysis.

BACKGROUND: Transformed small-cell lung cancer (T-SCLC) is an increasingly recognized resistance mechanism in EGFR-mutant lung adenocarcinoma. This study aimed to identify early predictors of histologic transformation and evaluate post-transformation treatment outcomes. METHODS: We retrospectively collected 163 T-SCLC patients from five Chinese centers. Next-generation sequencing was performed on 60 EGFR-mutant patients, including 47 paired primary-transformed samples. Integrated genomic and clinical analyses were conducted to delineate molecular features and survival outcomes. RESULTS: Among 150 EGFR-mutant patients, the median time to SCLC transformation was 25.8 months and median post-transformation overall survival (OS) was 14.2 months. Clinical and survival data for the 13 EGFR wild-type patients are reported descriptively given the limited sample size. Among 108 treatment-evaluable patients, first-line EGFR-TKI plus chemotherapy, chemotherapy alone, and immune checkpoint inhibitors (ICIs) plus chemotherapy yielded median progression-free survival (PFS) of 6.2, 5.30, and 4.07 months (P = 0.041) and median OS of 21.2, 27.6, and 13.6 months (P = 0.193). In later-line therapy, taxane-based regimens achieved a median PFS of 6.93 months, outperforming camptothecin-based (1.13 months) and other regimens (1.90 months; P = 0.049). High evolutionary diversity was associated with shorter post-transformation OS (6.77 vs. 11.10 months), with restricted cubic spline analysis showing a nonsignificant trend toward a nonlinear association (P = 0.055).Age, RB1/NTRK1 mutation, and secondary T790M mutation were identified as independent risk factors and integrated into a predictive model with high accuracy. CONCLUSIONS: This study establishes a clinically applicable model for early prediction and risk stratification of SCLC transformation. Taxane-based regimens emerge as a promising later-line therapeutic option for T-SCLC.

Humans↗

PubMed2026

Constipation and Psychiatric Disorders: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies have shown a link between constipation (CN) and psychiatric disorders, including Schizophrenia (SP), Bipolar disorder (BD), Schizoaffective disorder (SD), and Parkinson's disease (PD). However, it is still unknown whether CN affects the occurrence and development of psychiatric disorders or whether psychiatric disorders cause the occurrence and development of CN. Therefore, this study used Mendelian randomization (MR) analysis to evaluate the relationship between CN and psychiatric disorders. METHOD: We used genome-wide association studies (GWAS) to assess the relationship between constipation (N = 411, 623) and four psychiatric disorders, including SP ( N = 77, 096), BD (N = 51, 710), SD ( N = 210, 962), PD (N = 482, 730 ), using bidirectional MR analysis. Inverse variance weighting (IVW), MR Egger (ME) and Weighted median (WM) were used as causal analysis methods. Cochran's Q test, funnel plot, MR Egger intercept test and Leave.one.out analysis were used to detect sensitivity. Confounding factors were analyzed and eliminated by LDtrait to avoid influencing the final MR Analysis result. RESULTS: The results of positive MR analysis indicated that there was no evidence of influence of constipation on SP (OR 1.043, 95%CI 0.946 - 1.149, P value = 0.398), BD (OR 1.114, 95%CI 0.995 - 1.248, P value = 0.062), SD (OR 0.934, 95%CI 0.674 - 1.294, P value = 0.682) and PD (OR 1.118, 95%CI 0.918 - 1.361, P value = 0.269) under gene prediction. Reverse MR analysis suggested that SP (OR 1.030, 95% CI 1.001-1.060, P value = 0.042) had a causal relationship with constipation. BD (OR 0.993, 95% CI 0.962-1.025, P value = 0.664), SD (OR 1.021, 95% CI 0.984-1.059, P value = 0.265) and PD (OR 1.004, 95% CI 0.974-1.035, P value = 0.790) were not associated with CN. CONCLUSION: There was a positive association between SP and CN. CN may have no exact causal relationship with BD, SD and PD, and the interaction mechanism between these diseases needs to be further explored.

Constipation↗

PubMed2025

Identification of a novel phage depolymerase against ST11 K64 carbapenem-resistant Klebsiella pneumoniae and its therapeutic potential.

UNLABELLED: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinical pathogen with a high mortality rate, and its clinical management and infection control have become a serious challenge. Phage-encoded depolymerase cleaves the capsular polysaccharide, a major virulence factor of K. pneumoniae. This study aimed to identify a phage depolymerase targeting ST11 K64 CRKP, evaluate its antimicrobial activity and therapeutic efficacy, and provide new alternative therapeutic strategies for K64 CRKP. Phages were screened from untreated hospital sewage using clinically isolated CRKP as the host bacterium. The host range, efficiency of plaque formation, optimal multiplicity of infection, adsorption efficiency, and one-step growth curve of phage vB_KpnP_IME1309 were determined by the double-layer agar plate culture method. The morphology of the phage was observed by transmission electron microscopy. Phage nucleic acids were extracted for whole-genome sequencing, and the phage-encoded depolymerase gene ORF37 was amplified by polymerase chain reaction. Next, a recombinant plasmid was constructed to induce depolymerase expression, which was verified using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In vitro bactericidal activity was determined using a combined serum assay, and the anti-K. pneumoniae biofilm effect of depolymerase was determined by crystal violet staining. Finally, a Galleria mellonella larvae infection model was established to investigate the therapeutic effect of depolymerase on larvae in vivo. Here, we isolated and characterized a phage vB_KpnP_IME1309 targeting ST11 K64 CRKP, which featured a latent period of 20 min and a burst size of approximately 290 plaque-forming units/cell. It contained 41 predicted open reading frames, of which ORF37 encoded depolymerase. The expressed and purified depolymerase Dep37 cleaved only ST11 K64 CRKP and formed a translucent halo on the agar plate. Dep37 increased the susceptibility of K. pneumoniae B1 to serum killing, inhibited CRKP biofilm formation, and degraded mature biofilms. The combination of Dep37 and kanamycin was significantly more effective in treating CRKP biofilms compared to either Dep37 or kanamycin alone. An injection of Dep37 at 5 min and 2 h after the CRKP infection of Galleria mellonella larvae increased their survival rates by up to 73% and 53%, respectively. Depolymerase Dep37 may be used as a potential method for capsule typing of K. pneumoniae, showing great promise for the development of novel alternative therapeutic strategies against ST11 K64 CRKP. IMPORTANCE: A novel phage vB_KpnP_IME1309 targeting ST11 K64 carbapenem-resistant Klebsiella pneumoniae (CRKP) was isolated and characterized. The ORF37 encoding depolymerase gene of phage vB_KpnP_IME1309 was successfully expressed and purified. Depolymerase increases the susceptibility of CRKP to serum killing, inhibits CRKP biofilm formation, and degrades mature biofilms. The combination of depolymerase and kanamycin is significantly more effective than either depolymerase or kanamycin alone in the treatment of CRKP biofilm. Depolymerase injection at 5 min and 2 h after CRKP infection of Galleria mellonella larvae increased the survival rate of larvae by up to 73% and 53%, respectively. Depolymerase Dep37 may be used as a method for the development of novel alternative therapeutic strategies against ST11 K64 CRKP.

Klebsiella pneumoniae↗

PubMed2021

RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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