Biomedical subjects

Xing Zhang

Publications and source records attributed to Xing Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Cross-target and cell-preferential CRISPR-Cas9 inhibition with carbohydrate-tagged oligonucleotides.

Precise control of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) activity is important for limiting off-target effects and chromosomal rearrangements. Existing inhibitors, including anti-CRISPR proteins and spacer-targeting oligonucleotides, can be constrained by immunogenicity, target-sequence dependence, or delivery challenges. Here, we developed single-stranded DNA oligonucleotides that target conserved regions of the Streptococcus pyogenes Cas9 single-guide RNA (sgRNA) scaffold rather than the variable spacer. Screening identified single-stranded DNA 7 (ssDNA7), which targets stem-loop-1 and the adjacent linker and inhibits Cas9 activity across multiple tested spacer sequences and genomic loci without redesigning the inhibitor. Carbohydrate conjugation improved oligonucleotide stability and preferentially enhanced inhibitory activity in selected liver-derived or cancer cell models. Amplicon sequencing confirmed inhibition of endogenous editing in multiple cell models and normal liver-derived organoids, and supported cell-preferential inhibition in matched cell comparisons. These findings establish sgRNA-scaffold targeting as a strategy for cross-target inhibition of Cas9 and show that carbohydrate conjugation can tune its cellular activity.

CRISPR-Cas9↗

PubMed2026

Integrated Genomic and Immune Profiling of Early Onset Lung Cancer in East Asians Reveals a Distinct Molecular Architecture.

BACKGROUND: The age cut-off for early-onset lung cancer (EOLC) varies across studies (40-50 years). Here, we define EOLC as diagnosis at ≤ 40 years, a threshold identifying a subgroup with distinct clinical characteristics. However, whether EOLC differs fundamentally from late-onset lung cancer (LOLC) at the molecular level and represents a distinct subtype requiring different management remains unclear. METHODS: This integrated analysis included genomic and immune profiling data from 8,021 lung cancer patients, comprising 302 EOLC and 7,719 LOLC cases. Using targeted sequencing, we assessed somatic and germline alterations, mutational signatures, and immune biomarkers including tumor mutational burden (TMB), MSI status, and PD-L1 expression. RESULTS: EOLC patients were more often female, had adenocarcinoma, and earlier-stage disease. Molecular profiling revealed significant enrichment of ERBB2 mutations in EOLC, while KRAS, TP53, and MET mutations were more common in LOLC. Mutational signature analysis indicated tobacco-related signatures predominated in LOLC, whereas endogenous processes contributed more substantially in EOLC. Germline analysis showed a higher burden of pathogenic variants in EOLC (14.57% vs. 8.93%, P < .01), with TP53 and BRCA1 being particularly prominent. Immunologically, LOLC tumors exhibited higher TMB and PD-L1 positivity. CONCLUSION: Integrated profiling establishes EOLC as a distinct molecular subtype, defined by a unique triad: an ERBB2-driven somatic profile, germline susceptibility in DNA damage response pathways, and an endogenous mutagenic process within a low-TMB microenvironment. The findings are specific to the selected threshold and should be interpreted accordingly, while elucidating EOLC pathogenesis and supporting age-specific management strategies.

Humans↗

PubMed2026

IRES-like element-mediated translation of vsp1S4(-) suppresses BmCPV replication via RNAi antagonism.

Double-stranded RNA (dsRNA) viruses are thought to express proteins exclusively from their sense strand, while the antisense strand serves primarily as a replication template. Whether the antisense strand harbors hidden coding potential remains largely unexplored. Here, by integrating ribosome profiling and mass spectrometry, we identify a conserved 78-amino acid microprotein, vsp1S4(-), encoded by an antisense small open reading frame (sORFs) of the Bombyx mori cypovirus (BmCPV) genome. We demonstrate that vsp1S4(-) translation is driven by a previously unrecognized IRES-like element. Functional characterizations reveal that vsp1S4(-) localizes to the plasma membrane and acts as a negative regulator of viral replication. Mechanistically, vsp1S4(-) interacts directly with the viral RNAi suppressor NSP8, competitively disrupting the NSP8-AGO2 complex. This action restores the host's antiviral RNAi response, thereby limiting viral proliferation. Our findings challenge the conventional view of dsRNA virus coding capacity, unveil a novel viral immune evasion and replication control mechanism, and highlight antisense-encoded microproteins as potential targets for antiviral therapy.

Animals↗

PubMed2025

Structure-activity relationships study on inhibition of CRISPR-Cas9 by glycosaminoglycans.

The CRISPR-Cas9 system is a revolutionary genome editing system known for its precision, simplicity and efficiency, playing a crucial role in gene-editing. It has enabled applications ranging from biomedicine to agriculture. However, the uncontrollable activity of Cas9 has raised significant safety concerns in clinical settings, limiting its broader application. Consequently, regulating CRISPR-Cas9 activity holds substantial promise for enhancing the safety and efficacy of gene-editing technologies. In this study, we demonstrated that sulfated glycosaminoglycans (GAGs) exhibit inhibitory effects of Cas9. Specifically, both chondroitin sulfate (CS) and heparin (HP) can inhibit CRISPR/Cas9 activity, with heparin showing a stronger inhibitory effect that correlates positively with its concentration. Molecular dynamics simulations indicate that sulfated heparin residues might inhibit Cas9 function by binding to essential DNA-binding sites, which are crucial for functional interactions, potentially impairing activity. Additionally, higher molecular weight GAGs exhibit enhanced inhibitory effects under the same sulphation. Notably, the sulfation site also influenced activity. C6-sulfation of chondroitin sulfate is more favorable for Cas9 inhibition, and N-sulfation of heparin enhances its inhibitory effect on Cas9 activity. These findings provide valuable insights into the development of carbohydrate-based inhibitors for CRISPR-Cas9, offering a foundation for further exploration in this field.

CRISPR-Cas Systems↗

PubMed2006

Simple and complex spatiotemporal structures in a glycolytic allosteric enzyme model.

Pattern formation in glycolysis is studied with a classical reaction-diffusion allosteric enzyme model. It is found that, similar to recent experimental reports in the yeast extracts, a small magnitude local perturbation can induce transient target waves in a two dimensional oscillatory medium. An above threshold stimulation generates target waves which eventually evolve into spatiotemporal chaos upon collisions with the boundary or other wave activities. Detailed simulation studies show that the studied simple glycolytic reaction-diffusion model can support three types of spatiotemporal behaviors which are independent of the boundary conditions: (1) a spatially uniform stable steady state, (2) periodic global oscillations and (3) spatiotemporal chaos.

Adenosine Diphosphate↗

PubMed2006

A nearly modern amphibious bird from the Early Cretaceous of northwestern China.

Three-dimensional specimens of the volant fossil bird Gansus yumenensis from the Early Cretaceous Xiagou Formation of northwestern China demonstrate that this taxon possesses advanced anatomical features previously known only in Late Cretaceous and Cenozoic ornithuran birds. Phylogenetic analysis recovers Gansus within the Ornithurae, making it the oldest known member of the clade. The Xiagou Formation preserves the oldest known ornithuromorph-dominated avian assemblage. The anatomy of Gansus, like that of other non-neornithean (nonmodern) ornithuran birds, indicates specialization for an amphibious life-style, supporting the hypothesis that modern birds originated in aquatic or littoral niches.

Animals↗

PubMed2006

Gate-controlled rectifying behavior in C70@SWNT networks.

We report the gate-controlled rectification behavior in C(70)@SWNT networks at room temperature in air. The electrical transport characteristics can be fitted well with the conventional Schottky diode model. The origin of the rectifying behavior in fullerene peapod networks device is qualitatively discussed. This paper demonstrates a strategy for diode fabrication based on peapod networks.

Journal Article↗

PubMed2006

Recombined DNA vaccines encoding calreticulin linked to HPV6bE7 enhance immune response and inhibit angiogenic activity in B16 melanoma mouse model expressing HPV 6bE7 antigen.

Calreticulin (CRT) has been reported to have an effect of upregulating MHC class I presentation as well as inhibiting angiogenesis in vitro and in vivo. Combination of dual mechanisms of enhanced immunogenicity of human papillomavirus (HPV) 6bE7 antigen and antiangiogenesis may be introduced in the strategy of vaccines against condyloma acuminatum (CA) resulting from HPV infection. Therefore, we constructed DNA vaccines by employing different lengths of CRT chimerically linked to a model antigen HPV6bE7 and investigated the immunological and antiangiogenic effects of these vaccines in a B16 melanoma model that express HPV6bE7 antigen. Our results showed that vaccination with CRT180/HPV6bE7 or CRT120/HPV6bE7 enhanced the presence of CD8(+) T cells and TCRgammadelta T cells in vivo, increased the specific lysis activity against E7-expressing cells and secretion levels of IL-2 and IFN-gamma by activating T cells in vitro significantly. Moreover, recombined CRT180 or CRT120 with HPV6bE7 vaccines could elicit a more efficient E7-specific immune response than HPV6bE7 alone. The similarity of immunological enhancement of CRT180/HPV6bE7 and CRT120/HPV6bE7 implies that the immunologically active region mainly exist in fragment 1-120 aa. Furthermore, CRT180/HPV6bE7 and CRT180 displayed remarkable superiority over CRT120/HPV6bE7 in vivo angiogenesis assay, suggesting that the antiangiogenic activity of CRT resides in a domain between aa 120 and 180. Vaccination with CRT180/HPV6bE7 generated the best protective effect of delaying tumor formation and reduction of tumor size in tumor growth inhibition experiment among all DNA constructs. Therefore, CRT180/HPV6bE7 vaccine may enhance the immunological response to HPV6bE7 and inhibit angiogenesis. This construct may be useful in preventing HPV-associated dermatosis and may be developed as a promising strategy to control CA.

Animals↗

PubMed2006

DNA nicking by HinP1I endonuclease: bending, base flipping and minor groove expansion.

HinP1I recognizes and cleaves the palindromic tetranucleotide sequence G downward arrowCGC in DNA. We report three structures of HinP1I-DNA complexes: in the presence of Ca(2+) (pre-reactive complex), in the absence of metal ion (binary complex) and in the presence of Mg(2+) (post-reactive complex). HinP1I forms a back-to-back dimer with two active sites and two DNA duplexes bound on the outer surfaces of the dimer facing away from each other. The 10 bp DNA duplexes undergo protein-induced distortions exhibiting features of A-, B- and Z-conformations: bending on one side (by intercalation of a phenylalanine side chain into the major groove), base flipping on the other side of the recognition site (by expanding the step rise distance of the local base pair to Z-form) and a local A-form conformation between the two central C:G base pairs of the recognition site (by binding of the N-terminal helix in the minor groove). In the pre- and post-reactive complexes, two metals (Ca(2+) or Mg(2+)) are found in the active site. The enzyme appears to cleave DNA sequentially, hydrolyzing first one DNA strand, as seen in the post-reactive complex in the crystalline state, and then the other, as supported by the observation that, in solution, a nicked DNA intermediate accumulates before linearization.

Binding Sites↗

PubMed2006

Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions.

AIM: To explore whether bone marrow mesenchymal stem cells (MSC) can differentiate into myocardial-like cells induced by myocardial medium, especially the hypoxia/reoxygenation-conditioned medium of cardiomyocytes. METHODS: Myocardial cells obtained from neonatal Sprague-Dawley rat ventricles were isolated and cultured in vitro and a hypoxia reoxygenation model was established. The MSC isolated from adult Sprague-Dawley rats were purified and then incubated with 3 different mediums: medium A- the conditioned medium of normal cardiomyocytes; medium B - the conditioned medium of cardiomyocytes after hypoxia reoxygenation; and the control medium - ordinary medium. The expressions of the cardiac myosin heavy chain (MHC), troponin T (TnT) and connexin 43 were investigated in the MSC after 24 h, 48 h and 72 h cultivation, respectively. RESULTS: The MSC expressed MHC and TnT when incubated with the conditioned medium of cardiomyocytes after hypoxia reoxygenation, but did not express connexin 43. None of MHC, TnT and connexin 43 was detected in the MSC incubated with the conditioned medium of normal cardiomyocytes. CONCLUSION: The results indicate for the first time that myocardial medium for hypoxic preconditioning can induce MSC differentiation into myocardial-like cells.

Animals↗

PubMed2006

Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction.

OBJECTIVE: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. METHODS: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson's trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. RESULTS: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups. CONCLUSION: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Lung disorders of workers exposed to rush smear dust in China.

The aim of this study was to evaluate the lung disorders of the workers exposed to rush smear dust. A cross sectional study was carried out on 1,709 current workers (788 male, 921 female) in 80 factories. All subjects were asked by questionnaire, and health examination including chest X-ray was conducted for 661 workers in 35 factories. Lung function test was also examined for 119 non-smoking males among 661 subjects. Dust samplings were collected and total and respirable dust concentrations at 127 spots in 35 factories were measured. The geometric mean dust concentration in the workshops was up to 20.00 mg/m(3), and the geometric mean respirable dust concentration reached 8.22 mg/m(3). The mean quartz concentration of accumulated dust was 29.2%. The prevalence of radiographic small opacities profusion category > or = 1/0, according to the ILO 1980 Classification System, was 2.6% among 661 employees. One worker was found to have pneumoconiotic findings of 2/2 profusion accompanied with large opacity. The prevalence of pneumoconiosis (1/0 or more) correlated with cumulative dust exposure (r=0.192, p<0.0001). The similar relationship was found between the prevalence rate of cough or sputa and worksite dust concentration. In non-smokers, a positive association was found between the prevalence of cough and occupational exposure duration (r=0.080, p=0.004). Approximately 19.3% and 34.5% of employees suffered from respiratory impairment for FVC and FEV1.0, respectively. This is the first report of "rush" pneumoconiosis in China. Rush mat workers were found to be at high risk for pneumoconiosis, a preventable disease. Our results showed a dose-response relationship between rush-mat dust level and the prevalence of pneumoconiosis. Similar relationship between the prevalence of cough and sputum and the work duration was found for non-smoking workers but not for smoking workers.

Adult↗

PubMed2006

[Exercises at different intensities and sequential changes of rat skeletal muscle cell apoptosis].

OBJECTIVE: To study the effect of exercises of different intensities on rat skeletal muscle cell apoptosis. METHODS: Rat models of exhaustive exercise-induced skeletal muscle injury was established using tread mill exercises at different speeds, and the skeletal muscle cell apoptosis was detected using propidium iodide (PI) staining and flow cytometry. RESULT: No obvious gastrocnemius cell apoptosis was observed in rats with normal exercise (P>0.05), but the cell apoptosis index was statistically significant in moderate and exhaustive exercise groups (P<0.05), reaching the highest level in exhaustive exercise group after exercising. The gastrocnemius cell apoptosis index increased obviously on days 1 and 3 of exercise, and stabilized in moderate and exhaustive exercise groups. CONCLUSION: Exercises can evoke cell apoptosis and accelerate apoptotic cell clearance, and the imbalance between the two events during exercises may contribute to skeletal muscle injury.

Animals↗

PubMed2006

[Discussion on reinforcing-reducing method by lifting and thrusting the needle and slow-rapid reinforcing-reducing method from the point of view of energy].

OBJECTIVE: To resolve the contradictory in expounding of reinforcing and reducing by lifting and thrustion the needle and slow-rapid reinforcing and reducing method. METHODS: In a certain condition,the relationship between the external force (the joint force of both the pressing on the force pressing on the needle and the force arresting the needle's moving) and the speed of needle's moving is deduced by means of kinetic energy theorem, so, when the needle is heavily thrust or lifted, the speed of its moving will be increased. CONCLUSION: In the reinforcing and reducing method by lifting and thrusting the needle, "heavily"and "gently" of heavily thrustiing and gently lifting or gently thrusting and heavily lifting should be considered as differences of the amplitudes of lifting and thrusting the needle; "slow-rapid" of slow-rapid reinforcing and reducing method should be considered as difference of the speeds.

Acupuncture Therapy↗

PubMed2006

[FTIR research on the modification of plant oil pitch binders by polyester waste].

Various plant oil pitchs (cottonseed pitch, bean oil pitch, and mixed plant oil pitch) were used to prepare the plant oil pitch binders for casting. They were treated by polyester waste and processed by several technics such as esterifying. In the mean time, FTIR and TG were adopted to learn the structure, property, and sclerous mechanism of the binders. From the comparison with synthetic fat binder, the authors can see that the treated binders have similar components. They also have many excellent properties such as higher dry tensile strength and slower deflation velocity, which equal to or even exceed the properties of synthetic fat binder. Therefore, the treated binders, which were cheaper, can be used to make class I mold and core binders.

English Abstract↗

PubMed2006

[PCBs concentrations in human milk collected from a polluted area--exposure risk for feeding infants].

OBJECTIVE: To determine the concentration of PCBs and the distribution of dioxin-like compounds in human milk collected from a polluted area where discarded electronic equipment is dismantled, and to evaluate the risk for feeding infants. METHODS: The authors collected 20 and 12 milk samples from the polluted area and nearby town, respectively. Milk samples were analyzed for total PCBs (t-PCBs) by gas chromatography, and two mixed milk samples from the two areas were detected the distribution of dioxin-like compounds. RESULTS: t-PCBs in human milks of polluted area and control area were 0.39 - 3.92 microg/g fat and 0.46 microg/g (only one sample was detectable), respectively. The TEQ of PCB126 contribute to total TEQ of dioxin-like compounds was similar to other countries and regions. The TEQs of PCBs of the polluted and control area were 59 pg/g fat and 6 pg/g fat, respectively. CONCLUSION: The TEQ of PCBs of polluted area was much higher than other countries and regions, and the dioxin-like compounds intake of infants was much higher than the Tolerable Daily Intake (TDI) for dioxin recommended by WHO.

Adult↗

PubMed2006

Infection of Epstein-Barr virus in colorectal cancer in Chinese.

BACKGROUND & OBJECTIVE: Except for the tight correlation to nasopharyngeal carcinoma, accumulating evidences show that Epstein-Barr virus (EBV) is correlated to other carcinomas. This study was to investigate the correlation of EBV to colorectal carcinoma in Chinese. METHODS: EBV DNA was detected by polymerase chain reaction (PCR) in 90 specimens of primary colorectal carcinoma and 25 specimens of corresponding adjacent non-cancerous tissue, with the primers covering 2 different regions of EBV genome, BamH I W fragment and latent membrane protein 1 (LMP1) exon 3. The expression of EBV nuclear antigen 1 (EBNA1) and LMP1 were determined by immunohistochemistry, and the expression of EBV-encoded RNAs (EBERs) was detected by in situ hybridization. RESULTS: EBV LMP1 exon 3 and W fragment were detected in 27.7% and 32.2% of the 90 colorectal carcinoma specimens, which were significantly higher than the positive rate of EBV gene in the 25 adjacent non-cancerous tissues (4.0%, P<0.001). Of the 29 W fragment-positive tumors, 23 (79.3%) were EBNA1-positive, 1 (3.4%) was EBERs-positive; most EBNA1-positive cells were tumor cells with positive signals gathered in the nuclei. No expression of EBNA1 and EBERs were detected in the 8 W fragment-negative tumors. No expression of LMP1 was detected in all tumor specimens. CONCLUSION: EBV infection might be associated with colorectal carcinoma in Chinese.

Asian People↗

PubMed2006

[Quantitative analysis of epidermal growth factor receptor mRNA in laryngeal carcinoma by reverse transcription-real time polymerase chain reaction with TagMan probe].

OBJECTIVE: To establish a method of quantitative analysis of epidermal growth factor receptor(EGFR) mRNA in laryngeal carcinoma by reverse transcription-real time polymerase chain reaction with TagMan probe and evaluate its applicable value. METHODS: The technique of reverse transcription-real time polymerase chain reaction with highly specific primers and probe was applied. And with GAPDH as internal standard, EGFR mRNA in 32 laryngeal carcinoma tissues, compared with their own macroscopically normal laryngeal mucosa tissues adjacent to the tumors, were quantitatively examined. The recombinant plasmid of EGFR was constructed, and then sequenced. RESULTS: The recombinant plasmid of EGFR was successfully constructed. And the mRNA index of EGFR in 32 laryngeal carcinoma tissues in terms of M (QR) was 0.025 (0.076), which was higher than 0.008 (0.027) in their own macroscopically normal laryngeal mucosa tissues adjacent to the tumors, P value is 0. 007. CONCLUSIONS: The method of reverse transcription-real time polymerase chain reaction with TagMan probe is quite objective, precise and high throughput in the application for the mensuration of EGFR mRNA in laryngeal carcinoma.

Adult↗