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Ning Wang

Publications and source records attributed to Ning Wang.

At least 19 recordsLinked to original sources
PubMed2026

A De Novo 16p13.3 Triplication Underlying Early-Onset Complex Neurodegeneration.

BACKGROUND: Neurodegenerative disorders are clinically and genetically heterogeneous, characterized by progressive neuronal loss and multidomain functional decline. Despite a presumed genetic etiology, a substantial proportion of cases remain molecularly undiagnosed. OBJECTIVE: The aim was to identify the genetic cause of an early-onset neurodegenerative disorder presenting with ataxia and cognitive impairment. METHODS: Rare copy-number variants were detected via short-read whole-genome sequencing (WGS), with candidate structural models inferred using long-read WGS. We performed transcriptomic profiling of peripheral blood leukocytes by RNA sequencing, with validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: We identified a de novo copy-number gain at 16p13.3. Combined copy-number profiling and long-read WGS suggested a candidate model comprising a triplicated segment in tandem with a proximal duplication, joined to a distal duplication via an inverted junction. Transcriptomic analysis demonstrated significant upregulation of ATP6V0C, AMDHD2, and PDPK1. CONCLUSIONS: These findings support a role for structural variation in early-onset neurodegeneration and highlight the value of combining short-read copy-number profiling with long-read WGS to detect and characterize complex genomic rearrangements. © 2026 International Parkinson and Movement Disorder Society.

16p13.3↗
PubMed2026

Highly efficient base editing at PCSK9 and normal human embryo development.

Cas9-based tools enable programmable DNA lesions for studying repair outcomes, gene function, and genome correction. In human embryos, Cas9-induced DNA double-strand breaks are genotoxic, causing frequent aneuploidy and large deletions1,2. Here, we evaluate DNA repair outcomes at nicks and mismatches introduced by base editors at the PCSK9 and HBG loci in human embryos. Delivering ABE8e-V106W as a protein at fertilization achieved editing at all PCSK9 alleles, supporting development to the blastocyst stage and the derivation of homozygous edited stem cell lines. No insertions or deletions were detected, although rare on-target chromosome breakage and chromosomal abnormalities occurred. Nevertheless, editing at bystander and off-target sites was mosaic, and the introduction of the editor as mRNA caused frequent embryo arrest due to guide-independent deaminase activity. Thus, unlike Cas9-induced DNA breaks, base editor-induced lesions are efficiently repaired. However, undesirable consequences for the genome and development can occur, currently precluding clinical use in reproduction.

Journal Article↗
PubMed2026

Comparative genomics and phylogenetic analysis of three Malvaceae species on the basis of chloroplast genomes.

INTRODUCTION: The Malvaceae family shows rich species diversity and has substantial economic and medicinal value. However, the frequent interspecific hybridization among members of this family has resulted in confused phylogenetic relationships among the groups, limiting the usefulness of traditional classification methods. METHODS: This study aimed to investigate the phylogenetic relationships among selected taxa of Malvaceae by evaluating 23 chloroplast (CP) genomes, including three newly assembled CP genomes. Among these three genomes, the CP genome of Hibiscus schizopetalus L. was reported for the first time, while the CP genomes of Alcea rosea L. and Hibiscus grewiifolius L., which have been deposited in NCBI, were re-analyzed here alongside newly generated data for comparative purposes. In addition, 20 downloaded CP genomes encompassing 13 genera were analyzed using SNPs in whole CP genomes data. RESULTS: The results showed that the genomes ranged from 160,403 to 161,978 base pairs in length and consisted of small single copies (SSCs) and large single copies (LSCs) separated by two inverted repeat sequences (IRs), forming a typical quadripartite circular structure. The entire genome sequence showed relative conservation across species in terms of structure, GC content, codon usage, and gene composition. The mutation sites were mainly located in the LSC and SSC regions, and the variability in the non-coding regions was higher than that in the coding regions. The nucleotide polymorphism (Pi) analysis identified the non-coding regions such as ndhF-rpl32 and psbZ-trnG as high variable hotspots. A maximum likelihood phylogenetic tree was constructed based on SNPs in whole CP genomes data. The phylogenetic analysis divided these 23 species into five highly supported clades. It also revealed a close sister-group relationship between Abelmoschus and Hibiscus species, suggesting that Hibiscus may have a separate lineage from okra species. DISCUSSION: In conclusion, the increasing availability of CP genome resources will enhance our understanding of the classification and evolutionary patterns of the Malvaceae family. The development of molecular markers will provide important molecular evidence for precise identification and classification revision of plants in this family.

Malvaceae↗
PubMed2026

ITPRIPL1: A tumor immune-associated biomarker with prognostic and therapeutic implications in gastrointestinal cancer.

Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1(ITPRIPL1) has recently been implicated in tumor-immune regulation, yet its tumor-type specificity and clinical relevance in gastrointestinal malignancies remain unclear. Here, we performed an integrative analysis of ITPRIPL1 across stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and esophageal carcinoma (ESCA) using bulk transcriptomics, immune pathway analyses, survival modeling, single-cell RNA sequencing, immunofluorescence validation, and therapeutic correlation analyses. Although ITPRIPL1 was upregulated across gastrointestinal cancers, its prognostic significance was highly tumor-specific, with elevated expression consistently predicting unfavorable survival only in STAD. In gastric cancer, ITPRIPL1 expression was closely associated with immune-related pathways and genomic instability features, and its prognostic association varied across immune contexts, particularly according to CD8⁺/CD4⁺ T-cell abundance, with an exploratory association also observed for zeta-chain-associated protein kinase 70 (ZAP70) expression. Single-cell and immunofluorescence analyses demonstrated preferential enrichment of ITPRIPL1 in T cells and tumor-adjacent immune structures. Notably, Exploratory analyses further showed that higher ITPRIPL1 expression was associated with favorable survival outcomes in selected external pretreatment immunotherapy cohorts and with lower IC50 values for several agents in cancer cell-line pharmacogenomic datasets. Collectively, these findings identify ITPRIPL1 as an immune-associated biomarker with primary clinical relevance in gastric cancer.

Humans↗
PubMed2025

Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.

BACKGROUND: Epigenetic dysregulation plays a pivotal role in cancer immune evasion by orchestrating tumour antigen silencing, immune cell dysfunction, and the formation of an immunosuppressive microenvironment. By disrupting successive phases of the cancer-immunity cycle-from antigen presentation to T cell exhaustion-these aberrations facilitate immune escape and tumour progression, highlighting the need for targeted epigenetic intervention. AIM OF REVIEW: This review systematically dissects how epigenetic alterations impair anti-tumour immunity at each stage of the CI cycle. It not only integrates fragmented mechanistic evidence but also emphasizes underexplored crosstalk between specific epigenetic regulators and immune cell types. It further highlights emerging technologies-such as single-cell epigenomics, spatial multi-omics, and CRISPR-based screens-that are driving discovery of novel therapeutic targets and refining patient stratification. Key scientific concepts of review. We discuss how epigenetic interventions, alone or in combination with immunotherapies, can reinvigorate immune responses and overcome resistance to current treatments. A particular focus is given to how integrative high-resolution platforms are mapping immunoepigenetic landscapes, enabling mechanism-informed, precision immunotherapy strategies. By bridging epigenetic regulation with translational immuno-oncology, this review outlines a future where epigenetic reprogramming becomes central to overcoming immune evasion in cancer.

Humans↗
PubMed2006

Contributions of the active and passive components of the cytoskeletal prestress to stiffening of airway smooth muscle cells.

Airway smooth muscle cells exhibit stiffening during contractile activation. This stiffening may be interpreted as a result of the stabilizing influence of the mechanical prestress stored within the cytoskeleton (CSK). However, in vivo, airway smooth muscle cells contract while simultaneously experiencing breathing-induced stretching. Excessive stretching of cells could cause actin-myosin crosslinks, and possibly other cytoskeletal filaments, to break, thereby leading to dissipation of the prestress and inhibition of further cell stiffening. The aim of this study is to investigate the stiffening behavior of individual human airway smooth muscle (HASM) cells exposed to a combination of substrate stretching, contractile activation and relaxation. We treated cultured HASM cells with either contractile (histamine) or relaxing (DBcAMP) pharmacological agonists and used magnetic cytometry technique to investigate the stiffening behavior of these cells during uniform substrate stretching (0-30%). Cells that were not treated, as well as those treated with histamine, exhibited increasing stiffening during stretching up to 20% of substrate strain, with additional stiffening becoming inhibited for substrate strains of 20-30%. In contrast, in cells treated with DBcAMP, stretching produced moderate but continuous stiffening with increasing substrate strain. These results indicate that both active and passive components of the prestress contribute to cell stiffening. We also observed that cells permeabilized with saponin exhibited stiffening at low levels (<10%) of substrate stretching, similar to non-permeabilized cells, but not at high levels (10-30%) of stretching, where stiffening was inhibited. These data suggest that at low levels of substrate strains the relative contributions of ion channel activation as well as actin and focal adhesion remodeling are less important for stiffening than passive distension of the CSK. Taken together, our results suggest that both the active and passive components of the cytoskeletal prestress contribute to the stiffening behavior of HASM cells under physiological conditions, but that at high levels of cellular distensions there is a possible tradeoff between these two components with the contribution from the passive component becoming increasingly more important.

Cells, Cultured↗
PubMed2006

Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat.

The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulation of breathing with intermittent hypoxia (IH) elicits long-term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anaesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH-induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA) because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic nerve activities (PNA) in equithesin-anaesthetized rats. Animals were exposed to 10 45 s episodes of 8% O(2)-92% N(2), separated by 5 min intervals of 100% O(2), and recordings were continued for 60 min following the last hypoxic exposure. Cycle-triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg kg(-1), i.v.) 20 min before the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60 min after IH, indicating a role of serotonergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 and 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympathorespiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnoea.

Acute Disease↗
PubMed2006

Eosinophilic esophagitis: pathogenesis, genetics, and therapy.

Eosinophilic esophagitis (EE) is a recently recognized disorder characterized by the accumulation of eosinophils in the esophagus. Symptoms of EE frequently mimic those of gastroesophageal reflux disease, but the 2 diseases are quite distinct in terms of the histopathology and response to therapy. We demonstrate that EE involves the interplay of numerous genes, especially the eosinophil chemoattractant eotaxin-3, allowing molecular distinction from other forms of esophagitis and consideration of targeted therapeutic intervention.

Diagnosis, Differential↗
PubMed2006

The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal terminal differentiation and interacts functionally with LMO4.

Defective permeability barrier is an important feature of many skin diseases and causes mortality in premature infants. To investigate the control of barrier formation, we characterized the epidermally expressed Grainyhead-like epithelial transactivator (Get-1)/Grhl3, a conserved mammalian homologue of Grainyhead, which plays important roles in cuticle development in Drosophila. Get-1 interacts with the LIM-only protein LMO4, which is co-expressed in the developing mammalian epidermis. The epidermis of Get-1(-/-) mice showed a severe barrier function defect associated with impaired differentiation of the epidermis, including defects of the stratum corneum, extracellular lipid composition and cell adhesion in the granular layer. The Get-1 mutation affects multiple genes linked to terminal differentiation and barrier function, including most genes of the epidermal differentiation complex. Get-1 therefore directly or indirectly regulates a broad array of epidermal differentiation genes encoding structural proteins, lipid metabolizing enzymes and cell adhesion molecules. Although deletion of the LMO4 gene had no overt consequences for epidermal development, the epidermal terminal differentiation defect in mice deleted for both Get-1 and LMO4 is much more severe than in Get-1(-/-) mice with striking impairment of stratum corneum formation. These findings indicate that the Get-1 and LMO4 genes interact functionally to regulate epidermal terminal differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Histological alternation and vitellogenin induction in adult rare minnow (Gobiocypris rarus) after exposure to ethynylestradiol and nonylphenol.

Adult rare minnow (Gobiocypris rarus) were exposed to 0, 1, 5, and 25 ng/l (nominal concentrations) of 17alpha-ethynylestradiol (EE2) and 3, 10, and 30 microg/l (nominal concentrations) of 4-nonylphenol (NP) under flow-through conditions for a period of 28 d. Low mortality was observed at 5 and 25 ng/l EE2 and the growth of fish reduced significantly at 25 ng/l EE2 compared to controls. However, the gonadosomatic indices (GSI) of male fish were significantly higher in 1 ng/l EE(2) treatments and in 10 and 30 microg/l NP treatments (p<0.05). Renal somatic indices (RSI) of male fish in EE2 treatments were significantly higher than those in controls (p<0.05). In contrast, significantly decreased GSI and RSI of female fish could only be observed in 5 and 25 ng/l EE(2) treatments (p<0.05). Hepatosomatic indices (HSI) of male fish were significantly higher in 25 ng/l EE(2) treatments. However, significantly increased of HSI of female fish could only be observed in 1 ng/l EE(2) treatments. Plasma vitellogenin (VTG) induction could be observed in males after exposed to different concentrations of EE2 and NP, and plasma VTG concentrations in females exposed to 5 and 25 ng/l EE(2) were also significantly higher than in controls (p<0.05). At level higher than 5 ng/l EE2 or 30 microg/l NP, hepatic tissue and renal tissue impairment of males could be observed. The pathological male liver was associated with a hypertrophy of hepatocytes and damages to cellar structure and accumulated eosinophilic material. Renal tissue showed different pathological effects which was reflected by accumulated eosinophilic material, hemorrhages within the kidney tubules and hypertrophy of the tubular epithelia. Also at these levels of exposure, feminization of male fish could be noticed and parts of males manifested the testis-ova phenomenon. Ovaries of female rare minnow in 25 ng/l EE2 treatment group were degenerated. Therefore when exposed to EE2 and NP even at environmental observed concentrations, adverse effects could occur in the reproductive system of adult fishes. The observed hepatic tissue and renal tissue impairment should be due to the induction and accumulation of VTG in organs, especially in males.

Animals↗
PubMed2006

Evaluation of the thermal stability of Gardasil.

The thermostability of GARDASIL (Merck & Co., Inc, Whitehouse Station, NJ, USA), a developmental vaccine against human papillomavirus (HPV), was evaluated using an enzyme immunoassay, referred to as the in vitro relative potency (IVRP) assay and differential scanning calorimetry (DSC). Gardasil samples were stored at temperatures ranging from 4 to 42 degrees C and tested for IVRP at various time points. Extrapolation of the IVRP results indicates GARDASIL is extremely stable. The half-life of the vaccine is estimated to be 130 months or longer at temperatures up to 25 degrees C. At 37 degrees C, the half-life is predicted to be 18 months and at 42 degrees C, the half-life is predicted to be approximately three months. Differential scanning calorimetry (DSC) analysis was used to evaluate the process of protein denaturation during a rapid temperature increase (as opposed to long-term storage at a specific temperature). Differences were seen among the DSC profiles of the four HPV types tested. This indicates that small differences in the amino acid structure can have a significant effect on the intermolecular contacts that stabilize the L1 proteins and the VLP assembly. For the Gardasil samples evaluated here, DSC results demonstrated the relative overall structural stability of the VLPs, but were not predictive of the excellent long-term stability observed with the IVRP assay.

Calorimetry, Differential Scanning↗
PubMed2006

Co-infection with HIV and hepatitis C virus in former plasma/blood donors: challenge for patient care in rural China.

BACKGROUND: Illegal commercial plasma donation in the late 1980s and early 1990s caused blood-borne infections in China. OBJECTIVES: To estimate the prevalence of HIV and hepatitis C virus (HCV) infections and to identify associated risk factors in central China with a history of illegal plasma collection activities. DESIGN AND METHODS: A cross-sectional study was carried out in 2004, in which all adult residents in four villages in rural Shanxi Province were invited for a questionnaire interview and testing of HIV and HCV antibodies. RESULTS: Of 3062 participating villagers, 29.5% reported a history of selling whole blood or plasma. HIV seropositivity was confirmed in 1.3% of subjects and 12.7% were HCV positive. Their co-infection rates were 1.1% among all study subjects, 85% among HIV-positive subjects, and 8.7% among HCV-positive subjects. Selling plasma [odds ratio (OR), 22.5; 95% confidence interval (CI), 16.1-31.7; P < 0.001] or blood (OR, 3.1; 95% CI, 2.3-4.2; P < 0.001) were independently associated with HIV and/or HCV infections. Although a spouse's history of selling plasma/blood was not associated with either infection, the HIV or HCV seropositivity of a spouse was significantly associated with HIV and/or HCV infections (both OR, 3.2; 95% CI, 2.0-5.2 in men, 2.0-4.9 in women; P < 0.001). For men, residence in the village with a prior illegal plasma collection center (OR, 2.5; 95% CI, 1.7-3.7; P < 0.001) and for women, older age (OR, 3.4; 95% CI, 1.2-14.0; P = 0.04) were associated with HIV and/or HCV infections. CONCLUSIONS: HIV and HCV infections are now prevalent in these Chinese communities. HIV projects should consider screening and care for HCV co-infection.

Adolescent↗
PubMed2006

Antagonism or synergism. Role of tyrosine phosphatases SHP-1 and SHP-2 in growth factor signaling.

SHP-1 and SHP-2 are two Src homology 2 domain-containing tyrosine phosphatases with major pathological implications in cell growth regulating signaling. They share significant overall sequence identity, but their biological functions are often opposite. SHP-1 is generally considered as a negative signal transducer and SHP-2 as a positive one. However, the precise role of each enzyme in shared signaling pathways is not well defined. In this study, we investigated the interaction of these two enzymes in a single cell system by knocking down their expressions with small interfering RNAs and analyzing the effects on epidermal growth factor signaling. Interestingly, knockdown of either SHP-1 or SHP-2 caused significant reduction in the activation of ERK1/2 but not Akt. Furthermore, SHP-1, SHP-2, and Gab1 formed a signaling complex, and SHP-1 and SHP-2 interact with each other. The interaction of SHP-1 with Gab1 is mediated by SHP-2 because it was abrogated by knockdown of SHP-2, and SHP-2, but not SHP-1, binds directly to tyrosine-phosphorylated Gab1. Together, the data revealed that both SHP-1 and SHP-2 have a positive role in epidermal growth factor-induced ERK1/2 activation and that they act cooperatively rather than antagonistically. The interaction of SHP-1 and SHP-2 may be responsible for previously unexpected novel regulatory mechanism of cell signaling by tyrosine phosphatases.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Ischemia impairs the association between connexin 43 and M3 subtype of acetylcholine muscarinic receptor (M3-mAChR) in ventricular myocytes.

We used Western blot analysis to examine the expression of connexin 43 and M2/M3 acetylcholine muscarinic receptors (mAChR) and their interaction in ventricular myocytes from control and the ischemic heart. We confirmed that the connexin 43 and M2/ M3-mAChR were expressed in ventricular myocytes. Moreover, we showed that M3-mAChR was expressed in non-glycosylated (72 kDa) and glycosylated forms (115 kDa). Immunostaining showed that connexin 43 is closely associated with M3-mAChR in parts of cell membranes of myocytes. Immunoprecipitation of lysate of cardiac myocytes with M2/M3-mAChR antibody pulled down a 44 kDa protein recognized by connexin 43 antibody. Ischemia increased the expression of M3-mAChR in myocytes. The ischemiainduced increase in the M3-mAChR expression was specific because ischemia did not affect the expression of M1, M2, M4 and M5- mAChR in the heart. On the other hand, ischemia decreased the expression of connexin 43 in myocardium. We also examined the effect of ischemia on the interaction between M2/M3-mAChR and connexin 43. Ischemia suppressed the association of M3-mAChR with connexin 43 but did not affect the association of connexin 43 with M2-mAChR. Administration of choline before ischemia not only partially restored the expression of connexin 43 but also attenuated the ischemia-induced suppression of the association between connexin 43 and M3-mAChR. We conclude that connexin 43 interacts with M2/M3-mAChR and that ischemia specifically impairs the association between M3-mAChR and connexin 43.

Animals↗
PubMed2006

TGFbeta/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability.

Homeobox (Hox) gene mutations and their altered expressions are frequently linked to human leukemia. Here, we report that transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP) inhibits the bone marrow transformation capability of Hoxa9 and Nup98-Hoxa9, the chimeric fusion form of Hoxa9 identified in human acute myeloid leukemia (AML), through Smad4, the common Smad (Co-Smad) in the TGFbeta/BMP signaling pathway. Smad4 interacts directly with the homeodomain of Hoxa9 and blocks the ability of Nup98-Hoxa9 to bind DNA, thereby suppressing its ability to regulate downstream gene transcription. Mapping data revealed that the amino-terminus of Smad4 mediates this interaction and overexpression of the Hoxa9 interaction domain of Smad4 was sufficient to inhibit the enhanced serial replating ability of primary bone marrow cells induced by Nup98-Hoxa9. These studies establish a novel mechanism by which TGFbeta/BMP regulates hematopoiesis and suggest that modification of Hox DNA-binding activity may serve as a novel therapeutic intervention for those leukemias that involve deregulation of Hox.

Animals↗
PubMed2006

Matrix-bound phosphine in Antarctic biosphere.

Phosphine (PH(3)) is a natural gaseous carrier of phosphorus in its geochemical cycles, and it might be of importance to the phosphorus balance of natural ecosystem. For the first time phosphine levels were investigated in the Earth's coldest, driest, and most southerly Antarctic biosphere. Matrix-bound phosphine (MBP) was found in sea animal guanos, ornithogenic sediments and soils. Phosphine concentrations varied with different sea animal guanos. Average phosphine concentrations in empire penguin, gentoo penguin, sea lion, skua and gull guanos were 2.54+/-1.28 ng kg(-1), 6.21+/-2.15 ng kg(-1), 9.12+/-4.66 ng kg(-1), 11.90+/-1.29 ng kg(-1) and 14.55+/-6.74 ng kg(-1), respectively. The contents of phosphorus in these various matrixes have an important effect on MBP concentrations. The levels of phosphine appeared an increasing tendency with the content of TP, IP and OP in sea animal guanos, ornithogenic sediments or soils. The correlation between PH(3) and Fe, Mn, Al in these matrixes was also analyzed and discussed. Phosphine showed an obviously positive correlation with Fe in sea animal guanos. However, excessively high Fe, Al and Mn may inhibit the formation of PH(3) in the ornithogenic soils or sediments in the Antarctic biosphere.

Animals↗