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Biomedical subjects

Zhiqiang Zhang

Publications and source records attributed to Zhiqiang Zhang.

17 recordsLinked to original sources

[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].

OBJECTIVE: To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM). METHODS: A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210). RESULTS: G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10. CONCLUSION: The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.

Humans↗

The circadian clock proteins PRR modulate root hair development via the RHD6/RSL module in Arabidopsis.

Root hairs, derived from trichoblasts, are critical for plant growth and environmental adaptation. Although environmental cues are known to influence root hair development, how endogenous timing systems such as the circadian clock integrate into the core transcriptional network governing root hair formation remains unclear. Here, we show that the circadian clock-associated protein PSEUDO-RESPONSE REGULATOR5 (PRR5) physically interacts with ROOT HAIR DEFECTIVE6 (RHD6) and RHD6 LIKE1 (RSL1), two basic helix-loop-helix transcription factors essential for root hair initiation. Genetic analyses suggest that PRR proteins contribute to root hair development under long-day conditions in Arabidopsis thaliana. Simultaneous disruption of PRR5, PRR7, and PRR9 results in defective root hairs, whereas PRR5 overexpression markedly increases root hair density and length. Transcriptomic and RT-qPCR analyses reveal that PRRs enhance the expression of RHD6, RSL1, and multiple downstream root hair-responsive genes, while modulating their temporal expression patterns. Furthermore, PRR5-mediated root hair promotion requires RHD6/RSL1, and PRR proteins enhance RHD6-dependent activation of the RSL4 promoter. PRRs also contribute to root hair development under phosphate-deficient and salt-stress conditions. Together, these findings establish a molecular framework in which PRR proteins regulate the RHD6/RSL network to coordinate root hair development and environmental responses.

Arabidopsis↗

Multiomics Analysis Reveals Therapeutic Targets for Chronic Kidney Disease With Sarcopenia.

BACKGROUND: The presence of sarcopenia in patients with chronic kidney disease (CKD) is associated with poor prognosis. The mechanism underlying CKD-induced muscle wasting has not yet been fully explored. This study investigates the influence of renal secretions on muscles using multiomics sequencing. METHODS: The kidney transcriptome analysis by RNA-seq and protein profiling by tandem mass tag (TMT), serum TMT and muscle TMT were performed in CKD established using 0.2% adenine and control mice. Spp1 recombinant protein was used to study its effect on myotube atrophy in&#xa0;vitro. In animal experiments on CKD, pharmacological inhibition of Spp1 was used to explore the role of Spp1 in skeletal muscle wasting. Transcriptome analysis was performed to identify differentially expressed genes (DEGs) in the gastrocnemius muscle following Spp1 pharmacological inhibition. RESULTS: In the renal transcriptome and TMT, 503 and 377 proteins/genes respectively were co-upregulated and co-downregulated. In the serum TMT of CKD and normal control (NC) mice, 22 upregulated and 7 downregulated differentially expressed proteins (DEPs) showed the same expression patterns as those in the kidney transcriptome and TMT analysis. Based on bioinformatics analysis and reported studies, we selected Spp1 for further validation. Spp1 recombinant protein was added to C2C12 myotubes in&#xa0;vitro, and the results indicated that Spp1 significantly increased the protein levels of the muscle atrophy marker (Murf-1) and promoted the smaller myotubes (all p&#x2009;<&#x2009;0.05). Compared with NC mice, Spp1 mRNA and protein levels were significantly upregulated in the kidneys of CKD mice, and the serum concentration of Spp1 was also markedly increased (all p&#x2009;<&#x2009;0.05). In animal experiments, pharmacological inhibition of Spp1 increased the weights of gastrocnemius and tibialis anterior muscles (p&#x2009;<&#x2009;0.05) and improved muscle atrophy phenotype. Transcriptome analysis showed that DEGs in the gastrocnemius muscle following Spp1 pharmacological inhibition were enriched in protein digestion and absorption, glucagon signalling pathway, apelin signalling pathway and ECM-receptor interaction pathway. CONCLUSIONS: Our study is the first to establish a regulatory network of kidney-muscle crosstalk to explore the potential mechanism of CKD-related sarcopenia. Employing multiomics analysis, cellular assessment and animal experiments, we have identified that Spp1 could potentialy serve as a promising therapeutic target for CKD patients with sarcopenia.

Sarcopenia↗

Pcf11 is a termination factor in Drosophila that dismantles the elongation complex by bridging the CTD of RNA polymerase II to the nascent transcript.

The mechanism by which Pol II terminates transcription in metazoans is not understood. We show that Pcf11 is directly involved in termination in Drosophila. dPcf11 is concentrated at the 3' end of the hsp70 gene in cells, and depletion of dPcf11 with RNAi causes Pol II to readthrough the normal region of termination. dPcf11 also localizes to most transcribed loci on polytene chromosomes. Biochemical analysis reveals that dPcf11 dismantles elongation complexes by a CTD-dependent but nucleotide-independent mechanism and that dPcf11 forms a bridge between the CTD and RNA. This bridge appears to be crucial because an anti-CTD antibody, which also dismantles the elongation complex, is found to bridge the CTD to RNA. dPcf11 was observed to inhibit transcription at low, but not high, nucleotide levels, suggesting that dPcf11 dismantles paused elongation complexes. These results provide a biochemical basis for the dependency of termination on pausing and the CTD in metazoans.

Adenosine Triphosphate↗

Localization of latent epileptic activities using spatio-temporal independent component analysis of FMRI data.

Localizing interictal epileptic activities is a difficult problem in clinical practice. We report a novel noninvasive technique, resting functional magnetic resonance imaging (fMRI) with spatio-temporal independent component analysis (ICA), for localizing interictal epileptic activities. First, the fMRI data is separated into independent spatial patterns by spatial-ICA, and the patterns with Z-values larger than a threshold are selected as the potential spatial patterns of the epileptic activities. Second, the temporal series of the active points in the selected patterns are separated by temporal-ICA, and the component with the biggest Gaussian deviation (kurtosis) is selected as the representative of the epileptic discharge activity in a sub-region. Finally, those spatial sub-regions, which have distinct epileptic discharge activities confirmed by temporal-ICA are considered as the epileptic foci. This method was applied to fMRI data of six epileptic patients, and the results are consistent with the clinical assessment. Though more studies are required to validate this technique, the above preliminary results demonstrate the potential of using the resting fMRI with spatio-temporal ICA to detect and localize latent epileptic activities.

Adult↗

Mechanism of neurophysiological treatment of amblyopia using functional magnetic resonance imaging.

PURPOSE: To research the mechanism of neurophysiological treatment of amblyopia by observing the visual cortex activation under rotating grating stimulus with functional magnetic resonance imaging (MRI), and identify the components of the activation. METHODS: Nine healthy volunteers were examined using gradient-recalled echo and echo-planar imaging (GRE-EPI) pulse sequence performed at the 1.5 Tesla MRI scanner. In the block designing, rotating grating, stationary grating and luminance were plotted as task states, stationary grating, luminance and darkness as control states, respectively. The tasks of stimuli included 6 steps. Imaging processing and statistical analysis were carried out off-line using statistical parametric mapping (SPM99) software in single-subject. RESULTS: Some individual areas of visual cortex were activated by various stimuli information supplied by rotating grating. The strong activation in the middle of occipital lobe related to the stimuli of luminance, bilateral activation of Brodmann's 19th area related to visual motion perception, and the mild activation in the middle of occipital lobe related to form perception. CONCLUSION: The plotting of control state is important in bock design. The effective visual information of rotating grating includes components of luminance, visual motion perception and form perception. Functional MRI has potential as a tool for studying the physiological mechanism of visual cortex.

Adult↗

CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3'-end processing factor, Pcf11.

Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and transcription termination. Using elongation complexes (ECs) formed from purified yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on the C-terminal domain (CTD) of the largest subunit of Pol II and the CTD-interaction domain (CID) of Pcf11. Our experiments reveal a novel termination mechanism whereby Pcf11 bridges the CTD to the nascent transcript and causes dissociation of both Pol II and the nascent transcript from the DNA in the absence of nucleotide hydrolysis. We posit that conformational changes in the CTD are transduced through Pcf11 to the nascent transcript to cause termination.

Base Sequence↗

Protection of rhesus monkeys against infection with minimally pathogenic simian-human immunodeficiency virus: correlations with neutralizing antibodies and cytotoxic T cells.

We studied the capacity of active immunization of rhesus monkeys with HIV-1 envelope protein (Env) to induce primary virus cross-reactive neutralizing antibodies to prevent infection following intravenous challenge with simian-human immunodeficiency virus (SHIV). Monkeys were immunized with the human immunodeficiency type 1 (HIV-1) strain R2 Env. Initially, the Env was expressed in vivo by an alphavirus replicon particle system, and then it was administered as soluble oligomeric gp140. Concurrently, groups of monkeys received expression vectors that encoded either simian immunodeficiency virus (SIV) gag/pol genes or no SIV genes in vivo to test the additional protective benefit of concurrent induction of virus-specific cell-mediated immune (CMI) responses. Groups of control monkeys received either the gag/pol regimen or sham immunizations. The antibodies induced by the Env immunization regimen neutralized diverse primary HIV-1 strains. Similarly, potent CMI responses were induced by the gag/pol regimen, as measured by gamma interferon enzyme-linked immunospot assays. Differences in the responses among groups of monkeys strongly suggested that there was interference between the Env and gag/pol immunization regimens. Complete protection of some of the monkeys against infection after intravenous challenge with the partially pathogenic SHIV(DH12R (Clone 7)) was associated independently with both neutralizing antibody and CMI responses. Protection was associated with SHIV(DH12 (Clone 7)) serum neutralizing antibody titers of > or =1:80 or with cellular immune responses corresponding to >2,000 spot forming cells per 10(6) peripheral blood mononuclear cells. Immunization was also associated with a reduction in the magnitude and duration of virus load. Induction of cross-reactive, primary HIV-1-neutralizing antibodies is feasible and, when potent, may result in complete protection against infection with a heterologous challenge virus strain.

AIDS Vaccines↗

[Animal immunocompetence and its effect on population regulation and life history trade-off].

Immunocompetence is a common conception in biomedical and animal sciences, and refers to the ability of organisms against diseases. In recent years, a new field, ecological immunology, has been received much attention, which deals with the variation of immunocompetence in wildlife by immune methods. This paper introduced the conception of immunocompetence, the factors affecting its performance, and its roles in regulating animal population dynamics. Some hypotheses on population regulation in small mammals, such as immunocompetence handicap hypothesis, immunocompetence selection hypothesis and winter immune enhancement hypothesis were summarized. The relationships among energy metabolism, endocrine controlling mechanism and immune system were introduced, and the recent progress on immunocompetence and life history trade-off was analyzed. The trade-off between survival and immunocompetence, as well as between reproduction and immunocompetence were discussed, and some developing perspectives and new problems in ecological immunology were proposed.

Animals↗

Analysis of polymerase II elongation complexes by native gel electrophoresis. Evidence for a novel carboxyl-terminal domain-mediated termination mechanism.

Genetic and proteomic approaches have identified numerous proteins that are potentially involved in regulating transcriptional elongation, but the mechanisms of action of these proteins remain largely unknown. We describe an experimental approach using native gel electrophoresis for studying interactions of elongation factors with isolated Pol II elongation complexes. The gel distinguishes Pol IIA and Pol IIB containing complexes. The interaction of DSIF (Spt4/Spt5) with the elongation complexes can be readily detected, and this association is not dependent on the carboxyl-terminal domain of the largest subunit of Pol II. We also report the surprising observation that a monoclonal antibody that binds the carboxyl-terminal domain of Pol II triggers the dissociation of the elongation complex. The action of the antibody could be mimicking the action of cellular factors involved in transcription termination.

Animals↗

[On the causes of mite pest outbreaks in mono- and poly-cultured moso bamboo forests].

In this paper, the damage of phytophagous mites Schizotetranychus nanjingensis Ma & Yuan, Aponychus corpuzae Rimando and Aculus bambusae Kuang to moso bamboo (Phyllostaychs pubescens) was examined for ten pairs of mono- and poly-cultured forests at six locations in Fujian, China. The results showed that the mite damage in mono-cultured forests (35%) was twice as high as that in poly-cultured forests (17.5% < the injury level of 20%), and the difference was significant by t-test. The total pest mites in the mono-cultured forests at six locations in Fujian were 289.29% as high as those in the poly-cultured stands. Typhlodromus bambusae, a nature enemy in the poly-cultured forests at five locations in Fujian, was 262.5% as high as that in the mono-cultured forests. The proportion of pest mite and nature enemy in the mono-cultured forests was 1:118, but was 1:13 in the poly-cultured forests. The change of bamboo cultivation (mono-culture, crowding of bamboo plants, and removal of underfloor plants) might be the major cause of mite pest outbreaks in moso bamboo forests.

Animals↗

A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth.

The goal of our study was to raise monoclonal antibodies (mAbs) against endothelial cell-surface proteins specific for tumor vasculature. Here, we describe the generation and intensive characterization of mAb AA98, including its functional properties and its antigen identification. In our study, an enhanced mAb AA98 immunoreactivity was observed on stimulated human umbilical vein endothelial cells (HUVECs). In addition, mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared with blood vessels of normal tissues. We identified the AA98 antigen as human CD146, an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146; however, the role of CD146 in vivo is largely unknown. Here, we show that mAb AA98 displays antiangiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane (CAM) assays and tumor growth in 3 xenografted human tumor models in mice. Our data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology.

Animals↗

[Characteristics of soil water infiltration in sub-alpine dark coniferous ecosystem of upper reaches of Yangtze River].

Dark coniferous forest is the predominant type of vegetation in the upper reaches of Yangtze River. Difference among different types of soil exists. The sand content of soil is higher and the soil texture is coarser in the early stage of forest succession. The sand content of soil decreases with the advancement of the forest succession while that of soil in Abies fabri over-mature forest is the lowest. In slope wash soil, the sand content of soil decreases with the increasing soil depth. The soil porosity and soil water-holding capacity increases and soil bulk density decreases with the advancement of forest succession and decrease of soil depth. The deeper soil depth or the smaller soil water content are, the smaller the unsaturated hydraulic conductivity of soil measured by CGA method. Moreover, the correlation of soil water content with unsaturated hydraulic conductivity of soil can be simulated by an exponential function. The saturated hydraulic conductivity of soil decreases exponentially with the increasing soil depth. The time to attain the stable infiltration rate is different among different soil depth, while the deeper the soil depth is, the longer the time needs. The variation in soil texture, soil physical properties and the high infiltration rate of soil there implicated that there are scarce surface runoff, but abundant in subsurface flow, return flow and seepage, which is the result of regulation by dark coniferous forest on hydrological processes.

China↗

[Advance in researches on the effect of forest on hydrological process].

According to the effects of forest on hydrological process, forest hydrology can be divided into three related aspects: experimental research on the effects of forest changing on hydrological process quantity and water quality; mechanism study on the effects of forest changing on hydrological cycle, and establishing and exploitating physical-based distributed forest hydrological model for resource management and engineering construction. Orientation experiment research can not only support the first-hand data for forest hydrological model, but also make clear the precipitation-runoff mechanisms. Research on runoff mechanisms can be valuable for the exploitation and improvement of physical based hydrological models. Moreover, the model can also improve the experimental and runoff mechanism researches. A review of above three aspects are summarized in this paper.

Conservation of Natural Resources↗

[Ecological footprint calculation and development capacity analysis of China in 1999].

The ecological footprint method put forward and improved by William Rees and Mathis Wackernagel presents a methodologically simple but integrated framework for national natural capital accounting, which is capable of measuring the impact of Human's consumption on ecosystem. Based on the ecological footprint theory and calculation method, a flow network analysis method was introduced to illuminate the structure of complex ecological economic system, and the relationship among ecological footprint, diversity and development capacity was analyzed. In this paper, the ecological footprints of China and its provinces was calculated and compared with the national and local ecological carrying capacity. The results showed that the ecological footprints of China and most of its provinces were beyond the available ecological capacity, and China and its most provinces run 'national or regional ecological deficit'. In case of China, the national ecological deficit was 0.645 hm2 per cap in 1999. Secondly, we introduced a flow network analysis method, taking various ecological productive area as note, and adopted Ulanowicz's development capacity formula to analyze the relationship among ecological footprint diversity, development capacity and output. The results demonstrated that Ulanowicz's development capacity was a good predictor of economic system output. At the same time, two distinct ways to change development capacity were produced. Increasing ecological footprint or increasing ecological footprint's diversity would both increase development capacity. Due to the fact that the ecological footprints had already been beyond bio-capacities, the only way to increase development capacity was to increase ecological footprint's diversity. The positive relationship between ecological footprint diversity and resources utilization efficiency demonstrated that there was no conflict between increasing ecological footprint's diversity and reducing footprints while not comprising our quality of life.

China↗

[Basic study of biodegradable controlled release chemotherapy].

This study sought to assess the biocompatibility of P(DA-SA)-Adriamycin, a new controlled-release chemotherapy system, in rabbit brain, and to examine its controlled release effect both in vitro and in vivo and its curative effects in vitro. The reaction of animal brain to the implanted P(DA-SA) or P(DA-SA)-Adriamycin was observed. The controlled-release profiles in phosphate buffer solutions and in rabbit brain were measured by UV spectrometry. Then, through flow cytometer, the rate of apoptosis in cultured glioma cells was tested. The reaction of rabbit brain to P(DA-SA) polymer was moderate and not significantly different from that to Gelfoam. The controlled-release rate of P(DA-SA)-Adriamycin in vitro and in vivo was stable and the duration of controlled-release of P(DA-SA)-Adriamycin spanned three weeks. The rate for apoptosis of glioma cells of P(DA-SA)-Adriamycin group was 69.9%, which was significantly higher than that of the control group. In conclusion, P (DA-SA)-Adriamycin controlled release chemotherapy system that bears curative effect has favorable controlled-release effect and good biocompatibility in rabbit brain. This system has potential value in treatment of malignant brain tumor.

Animals↗

Extractable organic matter in PM10 from LiWan district of Guangzhou City, PR China.

PM10 (particulate matter with aerodynamic diameter <10 microm) samples were collected at LiWan District of Guangzhou, PR China during April and July 2001 using a high volume air sampler to determine the distributions of homologous compounds and biomarkers. Polycyclic aromatic hydrocarbons (PAHs) including non-alkylated PAHs, methyl-alkylated PAHs, and some PAHs containing S/O atoms and n-alkanes were measured using gas chromatography/mass spectrometry analysis. The sigma(n)-alkane and sigmaPAHs ranged from 26.4 to 719.2 ng/m3 and 7.4 to 159.4 ng/m3, respectively. A seasonal fluctuation was clearly evident with higher concentrations occurring during the colder months (April). In addition, some compositional differences are observed for the organic compounds in samples collected from different heights above ground level. Higher sites had a significant contribution from vascular plant wax. The presence of petroleum products with no carbon number preference, pristane, phytane and a significant unresolved complex mixture (UCM) with unresolved to resolved components ratio (U/R) of 6.2-13.2 confirm the petroleum component. The relative distribution of n-alkanes and the values of molecular diagnostic ratio, such as carbon preference index (CPI) values ranging from 1.0 to 1.4 (for the whole range of n-alkanes), indicated the importance of petroleum and diesel residues and gasoline emissions, as well as the minor contribution of n-alkanes emitted directly from epicuticular waxes. Indeed, the percent contribution of leaf 'wax' n-alkanes (5.2-19.4%) indicated a low contribution of biogenic sources. The fossil fuel biomarkers, hopanes and steranes were observed in the PM10 samples, which indicate a petroleum origin. The distribution pattern of PAHs was characteristic of anthropogenic emissions. Coupling carbon number maximum (Cmax), CPI, U/R values, molecular marker and molecular diagnostic ratios for alkanes and PAHs revealed a classification of natural biogenic and anthropogenic components of atmospheric aerosols. These analyses support the conclusion that vehicular emission was the major source of organic compounds during the study period, while the contribution of epicuticular waxes emitted by terrestrial plants was minor.

Air Pollutants↗