Biomedical subjects

Jun Shen

Publications and source records attributed to Jun Shen.

At least 19 recordsLinked to original sources

PubMed2026

TECTB Variants Reveal Tectorial Membrane Vulnerability in Dominant Non-Syndromic Hearing Loss.

Identifying new genes responsible for non-syndromic hearing loss remains a critical goal as many patients still lack a molecular diagnosis despite comprehensive genetic testing. The tectorial membrane (TM) is a specialized acellular matrix of the inner ear, essential for stimulating mechanosensitive hair cell stereocilia bundles and maintaining frequency tuning and auditory sensitivity. Although mutations in genes encoding several non-collagenous proteins found in the TM (TECTA, CEACAM16, OTOG, OTOGL) have been identified as deafness genes, definitive evidence implicating β-tectorin (TECTB) has been lacking. Here, we present multiple lines of genetic and experimental evidence linking heterozygous missense variants in TECTB (NM_058222.3:c.674G>A, p.Cys225Tyr and NM_058222.3:c.853C>T, p.Arg285Cys), with hearing loss. Each variant affects highly conserved residues within or directly flanking the zona pellucida domain. Using a Tectb-C225Y knock-in mouse model, we show that homozygous animals exhibit severe hearing loss and profound disruption of TM morphology, while heterozygous animals display decreased staining density within the TM and increased susceptibility to noise-induced hearing loss, despite normal auditory thresholds. These findings identify TECTB as a novel human deafness gene, further elucidate its contribution to maintaining TM integrity and resilience against environmentally-related auditory decline.

beta‐tectorin (TECTB)↗

PubMed2026

Genome-Wide Identification and Colchicine-Responsive Expression Profiling of the Tubulins (TUA and TUB) Gene Family in Phoebe bournei.

Phoebe bournei is an economically and ecologically important woody species native to China. As a core component of colchicine-triggered polyploid breeding, the tubulin genes (TUA and TUB) have been identified and functionally analyzed in many plants, but not yet in P. bournei. Here, tubulin family members in P. bournei were identified through sequence alignment and subsequently characterized using comprehensive bioinformatic analyses. In particular, a total of six PbTUA and ten PbTUB members were identified and grouped into two and five subfamilies, respectively, according to phylogenetic relationships. Most tubulin proteins were small (414-522 aa) with predicted stability. Furthermore, 36 collinear gene pairs were identified, suggesting a possible contribution to the evolutionary expansion of this family. For different tissues, the expression levels of most tubulin genes were generally lower in leaves but higher in roots. Besides, treatment with 1.0% colchicine inhibited the expression of all 15 tubulin genes except PbTUB6. These results provide preliminary insights into tubulin genes associated with polyploid induction and supply candidate genes for future functional studies toward polyploid germplasm creation of P. bournei.

Phoebe bournei↗

PubMed2026

Plasma Proteomics Identifies Thousand-and-One-Amino Acid Kinase 3 as a Potential Biomarker of Rheumatoid Arthritis Activity and a Novel Therapeutic Target.

OBJECTIVE: Bone destruction associated with active rheumatoid arthritis (RA) remains a major therapeutic challenge, with a lack of reliable molecular markers reflecting bone injury. This study aims to identify novel biomarkers linked to bone destruction in active RA through proteomic analysis, providing new strategies for precise monitoring and targeted therapy. METHODS: Data-independent acquisition mass spectrometry was used for proteomic quantification and bioinformatic analysis on plasma samples from 160 patients with RA and 40 healthy controls. Key proteins associated with bone destruction were screened by integrating Sharp scores with synovial single-cell RNA sequencing data and subsequently validated in two independent cohorts (N1 = 50 and N2 = 10) using enzyme-linked immunosorbent assay and multiplex immunohistochemistry. Functional studies were conducted using fibroblast-like synoviocytes (FLSs) in vitro and a collagen-induced arthritis (CIA) mouse model in vivo. RESULTS: A total of 4,998 plasma proteins were identified, with 506 showing significant differential expression between active and remitted RA. Thousand-and-one-amino acid kinase 3 (TAOK3) levels were positively associated with Sharp scores and markedly elevated in patients with active RA. Combining TAOK3 with C-reactive protein improved diagnostic accuracy for active RA (area under the curve = 0.915). High TAOK3 expression was also associated with increased relapse frequency. Functional studies showed that TAOK3 knockdown suppressed the tumor-like phenotype of FLSs and down-regulated matrix metalloproteinase 1/2/3 and cathepsin K, whereas TAOK3 overexpression promoted pannus cell-mediated bone erosion, mitigated by TAOK3-targeted inhibitor. In vivo, its inhibition showed therapeutic effects in CIA mice. CONCLUSION: TAOK3 serves as a potential biomarker for bone destruction in active RA and as a therapeutic target for precision monitoring and intervention.

Arthritis, Rheumatoid↗

PubMed2025

ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time.

PURPOSE: The Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen's semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years. METHODS: Thirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (www.clinicalgenome.org). RESULTS: Eight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported. CONCLUSION: Genes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.

Humans↗

PubMed2006

Relayed (13)C magnetization transfer: detection of malate dehydrogenase reaction in vivo.

Malate dehydrogenase catalyzes rapid interconversion between dilute metabolites oxaloacetate and malate. Both oxaloacetate and malate are below the detection threshold of in vivo MRS. Oxaloacetate is also in rapid exchange with aspartate catalyzed by aspartate aminotransferase, the latter metabolite is observable in vivo using (13)C MRS. We hypothesized that the rapid turnover of oxaloacetate can effectively relay perturbation of magnetization between malate and aspartate. Here, we report indirect observation of the malate dehydrogenase reaction by saturating malate C2 resonance at 71.2 ppm and detecting a reduced aspartate C2 signal at 53.2 ppm due to relayed magnetization transfer via oxaloacetate C2 at 201.3 ppm. Using this strategy the rate of the cerebral malate dehydrogenase reaction was determined to be 9+/-2 micromol/g wet weight/min (means+/-SD, n=5) at 11.7 Tesla in anesthetized adult rats infused with [1,6-(13)C(2)]glucose.

Animals↗

PubMed2006

Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

Animals↗

PubMed2006

Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-13C]GABA derived from glia-specific substrate [2-13C]acetate.

Brain [2-(13)C]gamma-aminobutyric acid (GABA) signal derived from the glia-specific substrate [2-(13)C]acetate reflects the extent of the GABA-glutamine neurotransmitter cycling between GABAergic neurons and glial cells. We report, for the first time, in vivo quantification of the GABA-glutamine cycling flux. The GABA-glutamine cycling flux rate was determined to be 1.8+/-0.4 micromol/(gh) (mean+/-S.D., n=6, approximately 6% of total tricarboxylic acid cycle rate) in the neocortex of vigabatrin-treated rats. The relatively small magnitude of glial contribution to the clearance of extracellular GABA measured in this study provided in vivo evidence to support the concept of a significant neuronal reuptake of GABA, which short-circuits the GABA-glutamine cycling pathway for repletion of released neurotransmitter GABA.

Acetates↗

PubMed2006

Structural, magnetic, and magnetoresistive properties of electrodeposited Ni5Zn21 alloy nanowires.

Ni5Zn21 alloy nanowires were fabricated through template-assisted electrochemical deposition method. The morphology and microstructures of as-deposited nanowires were determined by field-emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD), high-resolution transmission electron microscope (HRTEM), electron diffraction (ED), and electron probe microanalysis (EPMA). The accurate composition was measured via induced coupling plasma atomic emission spectroscopy. SEM results show that Ni5Zn21 nanowires are deposited in most of the nanopores of the template, and they are continuous and dense throughout the whole length. The XRD result demonstrates that the nanowires are mainly composed of a cubic gamma phase Ni5Zn21 alloy, but there also exists a trace of Zn-rich eta phase. HRTEM and ED reveal that the alloy nanowires are polycrystalline with the crystallite size of several tens of nanometers. EPMA of a single nanowire illustrates that there exist Ni-rich microzones in as-deposited nanowires. Subsequent magnetic measurements of the array also confirmed the existence of them. In addition, it can be further inferred that the shape of Ni-rich microzones is probably barlike or disklike, from the anisotropy of zero field cooling/field cooling (ZFC/FC) curves as well as the vortex magnetization behavior of the Ni5Zn21 nanowire array. The low-temperature magnetoresistance of the Ni5Zn21 nanowire array was also measured. Giant magnetoresistance instead of anisotropic magnetoresistance is suggested to be responsible for contributing to the magnetoresistance.

Journal Article↗

PubMed2006

An efficient implementation of the "cluster-in-molecule" approach for local electron correlation calculations.

An efficient implementation of the "cluster-in-molecule" (CIM) approach is presented for performing local electron correlation calculations in a basis of orthogonal occupied and virtual localized molecular orbitals (LMOs). The main idea of this approach is that significant excitation amplitudes can be approximately obtained by solving the coupled cluster (or Moller-Plesset perturbation theory) equations of a series of "clusters," each of which contains a subset of occupied and virtual LMOs. In the present implementation, we have proposed a simple approach for constructing virtual LMOs of clusters, and new ways of constructing clusters and extracting the correlation contributions from calculations on clusters, which are more efficient than those suggested in the original work. More importantly, linear scaling of computational time of the CIM approach is achieved by evaluating the transformed two-electron integrals over LMOs using simple truncation techniques in limited operations (independent of the molecular size). With typical thresholds, for a variety of molecules our test calculations demonstrate that more than 99% of the conventional MP2 or coupled cluster with doubles correlation energies can be recovered in the present CIM approach.

Journal Article↗

PubMed2006

In vivo detection of gray and white matter differences in GABA concentration in the human brain.

A novel selective multiple quantum filtering-based chemical shift imaging method was developed for acquiring GABA images in the human brain at 3 T. This method allows a concomitant acquisition of an interleaved total creatine image with the same spatial resolution. Using T(1)-based image segmentation and a nonlinear least square regression analysis of GABA-to-total creatine concentration ratios in frontal and parietal lobes of healthy adult volunteers as a function of the tissue gray matter fraction, the mean GABA concentration in gray and white matter was determined to be 1.30+/-0.36 micromol/g and 0.16+/-0.16 micromol/g (mean+/-SD, n=13), respectively. It is expected that this method will become a useful tool for studying GABAergic function in the human brain in vivo.

Adult↗

PubMed2006

In vivo dynamic turnover of cerebral 13C isotopomers from [U-13C]glucose.

An INEPT-based (13)C MRS method and a cost-effective and widely available 11.7 Tesla 89-mm bore vertical magnet were used to detect dynamic (13)C isotopomer turnover from intravenously infused [U-(13)C]glucose in a 211 microL voxel located in the adult rat brain. The INEPT-based (1)H-->(13)C polarization transfer method is mostly adiabatic and therefore minimizes signal loss due to B(1) inhomogeneity of the surface coils used. High quality and reproducible data were acquired as a result of combined use of outer volume suppression, ISIS, and the single-shot three-dimensional localization scheme built in the INEPT pulse sequence. Isotopomer patterns of both glutamate C4 at 34.00 ppm and glutamine C4 at 31.38 ppm are dominated first by a doublet originated from labeling at C4 and C5 but not at C3 (with (1)J(C4C5) = 51 Hz) and then by a quartet originated from labeling at C3, C4, and C5 (with (1)J(C3C4) = 35 Hz). A lag in the transition of glutamine C4 pattern from doublet-dominance to quartet dominance as compared to glutamate C4 was observed, which provides an independent verification of the precursor-product relationship between neuronal glutamate and glial glutamine and a significant intercompartmental cerebral glutamate-glutamine cycle between neurons and glial cells.

Animals↗

PubMed2006

Increased oxygen consumption in the somatosensory cortex of alpha-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla.

The significance of changes in cerebral oxygen consumption in focally activated brain tissue is still controversial. Since the rate of cerebral oxygen consumption is tightly coupled to that of tricarboxylic acid cycle which can be measured from the turnover kinetics of [4-(13)C]glutamate using in vivo (1)H{(13)C} magnetic resonance spectroscopy, changes in tricarboxylic acid cycle flux rate were assessed in primary somatosensory cortex of alpha-chloralose anesthetized rats during electrical forepaw stimulation. With markedly improved (1)H{(13)C} magnetic resonance spectroscopy technique and the use of high magnetic field strength of 11.7 T accessible to the current study, [4-(13)C]glutamate at 2.35 ppm was spectrally resolved from overlapping resonances of [4-(13)C]glutamine at 2.46 ppm and [2-(13)C]GABA at 2.28 ppm as well as the more distal [3-(13)C]glutamate and [3-(13)C]glutamine. The results showed a significantly increased V(TCA) in focally activated primary somatosensory cortex during forepaw stimulation, corresponding to approximately 51 +/- 27% (n = 6, mean +/- SD) increase in cerebral oxygen consumption rate. Considering the high efficiency in producing adenosine triphosphate by oxidative metabolism of glucose, the results demonstrate that aerobic oxidative metabolism provides the majority of energy required for cerebral focal activation in alpha-chloralose anesthetized rats subjected to forepaw stimulation.

Adenosine Triphosphate↗

PubMed2006

Probe beam size effect on the measurement of the distance between the probe beam and the sample in photothermal deflection.

A distance-scan method to determine the distance between the probe beam and sample, which is not easily measured exactly, in photothermal deflection (PD) was reported, with which the distance and thermal diffusivity of the deflecting medium can be simultaneously measured. Probe beam size effect (PBSE) on PD phase signal was quantitatively analyzed to clearly show its physical meaning. The measured distance was experimentally verified as correct and reliable, and the measured thermal diffusivities of N2 and CO2 are in good agreement with the literature values. They could not be precisely measured by phase signal without considering the PBSE.

Journal Article↗

PubMed2006

Theoretical analysis of carbon-13 magnetization transfer for in vivo exchange between alpha-ketoglutarate and glutamate.

Many enzymes catalyze fast exchange between a small pool and a large pool in vivo. For example, aspartate aminotransferase catalyzes fast exchanges between alpha-ketoglutarate and glutamate and between oxaloacetate and aspartate, which can be detected using in vivo(13)C MRS while saturating alpha-carbons of the keto acids. Unlike in the traditional saturation transfer experiments studied using (31)P MRS, the tricarboxylic acid cycle intermediates alpha-ketoglutarate and oxaloacetate are below the detection limit of in vivo NMR. In this work, a theoretical analysis of the saturation transfer between alpha-ketoglutarate and glutamate catalyzed by aspartate aminotransferase was presented to examine the requirements for complete saturation of the rapidly turning over alpha-ketoglutarate pool without affecting the longitudinal magnetization of glutamate. The fast turnover of the small alpha-ketoglutarate pool also allows a quasi-steady-state approximation of its dynamic longitudinal relaxation. The theoretical analysis provides a useful guide for designing experimental methods to characterize saturation transfer processes associated with fast turning over small pools in vivo.

Carbon Isotopes↗

PubMed2006

Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure.

Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed > 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.

Animals↗

PubMed2006

Fuzzy neural network for flow estimation in sewer systems during wet weather.

Estimation of the water flow from rainfall intensity during storm events is important in hydrology, sewer system control, and environmental protection. The runoff-producing behavior of a sewer system changes from one storm event to another because rainfall loss depends not only on rainfall intensities, but also on the state of the soil and vegetation, the general condition of the climate, and so on. As such, it would be difficult to obtain a precise flowrate estimation without sufficient a priori knowledge of these factors. To establish a model for flow estimation, one can also use statistical methods, such as the neural network STORMNET, software developed at Lyonnaise des Eaux, France, analyzing the relation between rainfall intensity and flowrate data of the known storm events registered in the past for a given sewer system. In this study, the authors propose a fuzzy neural network to estimate the flowrate from rainfall intensity. The fuzzy neural network combines four STORMNETs and fuzzy deduction to better estimate the flowrates. This study's system for flow estimation can be calibrated automatically by using known storm events; no data regarding the physical characteristics of the drainage basins are required. Compared with the neural network STORMNET, this method reduces the mean square error of the flow estimates by approximately 20%. Experimental results are reported herein.

Calibration↗

PubMed2006

[Significance of dynamic enhanced MRI in differential diagnosis of radiofibrosis and recurrent nasopharyngeal carcinoma at the basilar clivus].

BACKGROUND & OBJECTIVE: Basilar clivus is a common site of recurrent nasopharyngeal carcinoma (RNPC). Biopsy of the basilar clivus is seldom done because of its deep location and complex anatomic structure, therefore, early differential diagnosis of radiofibrosis (RF) and RNPC at the basilar clivus is very difficult. This study was designed to investigate the characteristics of radiofibrosis and RNPC at the basilar clivus on dynamic enhanced magnetic resonance imaging (DMRI) for differential diagnosis. METHODS: A total of 38 NPC patients, treated in Cancer Center and the Second Affiliated Hospital of Sun Yat-sen University with follow-up of 1-5 years, were divided into 2 groups: 22 in RF group and 16 in RNPC (RNPC at the basilar clivus) group. After conventional plain MRI scan of nasopharynx, DMRI and conventional contrast enhanced T(1)-weighted imaging (T1WI) were performed. Maximal contrast enhancement ratio (MCER), time to MCER (Tmax), and contrast enhancement ratio at the 40th second of DMRI (CER(40s)) of basilar clivus, condylar process, and nasal concha were measured. RESULTS: The MCER and CER(40s) of RF at the basilar clivus were lower, and the Tmax was longer than those of RNPC at the basilar clivus. When CER40s > or =150%, CER40s of basilar clivus > or = CER(40s) of nasal concha, and the combination of these 2 indexes were respectively set as the DMRI diagnostic criteria of RNPC at the basilar clivus, the diagnostic sensitivity of the second criterion was the highest (81.3%), and the diagnostic specificity of the third criterion was also the highest (86.4%). CONCLUSIONS: DMRI is helpful for differential diagnosis of radiofibrosis and RNPC at the basilar clivus. RNPC at the basilar clivus is highly suggested when it meet the criteria of both CER(40s) > or =150% and CER(40s) of basilar clivus > or = CER(40s) of nasal concha. When the 2 criteria are conflictive, the latter is more accurate, MCER and Tmax of the basilar clivus should be took into consideration.

Adult↗

PubMed2006

[Application and estimation of subjective criterion for judging immune status of recurrent aphthous ulceration patients].

OBJECTIVE: To adopt a criterion summarized in long-term practice to judge the immune status of recurrent aphthous ulceration (RAU) patients, and to analyze its rationality and feasibility. METHODS: 60 cases were included, whose clinical information, such as age, sex, constitution status, history of system diseases and severity of ulceration were collected. The subjective judgement results of the immune status were obtained according to the criterion summarized in clinical practice. At the same time, peripheral blood parameters about immune function were examined in order to obtain the objective examination results of the immune status. With the examination result as the gold standard, the rationality of the criterion was estimated through its sensitivity and specificity. RESULTS: According to subjective judgment, there were 86.67% cases with abnormal immune status (28.33% cases with elevated immune status, and 58.33% cases with reduced immune status). According to objective examination, there were 93.33% cases with abnormal immune status (23.33% cases with elevated immune status, and 70.00% cases with reduced immune status. Sensitivity and specificity were 89.29% and 50.00% when the criterion was used to judge immune abnormality, 42.86% and 76.09% when the criterion was used to judge immune elevation, and 64.29% and 55.56% when the criterion was used to judge immune reduction. CONCLUSION: It is of some rationality and feasibility to judge the immune status according to the criterion based on clinical information, and the criterion can be used in small clinics.

Adult↗