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Pengfei Wu

Publications and source records attributed to Pengfei Wu.

13 recordsLinked to original sources

Unveiling m7G modification patterns and causal drivers governing intracranial aneurysm rupture risk through multi-omics validation and m7G-MeRIP-seq profiling.

Intracranial aneurysm (IA) rupture causes severe brain hemorrhage with high mortality, yet its molecular drivers remain unclear and better risk prediction is urgently needed. Using transcriptomics, single-cell analysis, and genetic data, we investigated the role of N7-methylguanosine (m7G) RNA modification in IA. We identified distinct m7G modification patterns, validated their methylation features in patient samples, and incorporated these patterns into a machine learning-based rupture prediction model. The presence and characteristics of m7G patterns significantly improved model performance, achieving high predictive accuracy across three independent cohorts (AUC 0.91-0.95). Genetic analyses further identified three causal m7G-related genes (NSUN2, IFIT5, SNUPN), and laboratory experiments confirmed their altered expression and methylation in ruptured aneurysms. Overall, our findings demonstrate that m7G modifications play a key role in IA rupture. The validated prediction model offers strong clinical potential for rupture risk assessment, and the identified genes represent promising therapeutic targets.

Humans↗

Chemoselective Tagging of Protein Methacrylation.

Protein lysine methacrylation (Kmea) is a recently identified post-translational modification whose biofunction remains poorly understood. Until now, there has been no chemical labeling method for Kmea modification, which has severely hindered the discovery and functional studies of methacrylated proteins. Here, we developed a photocatalytic thia-Michael reaction system for the chemoselective labeling of protein methacrylation. By exploiting the dual effect of steric hindrance and the stability of the generated C-center radical, the reaction interference of the structural isomer crotonylation can be efficiently avoided. Based on this reaction, a multifunctional water-soluble benzenethiol-azide probe azDSH was designed and synthesized, and a workflow for the specific labeling, enrichment, and identification of Kmea proteins was developed. Proteomic identification of histone and nuclear protein extracts and whole-cell lysate revealed a number of novel Kmea proteins and modification sites besides histones, such as HMGB1, TdIF2, UHRF1, HNRPD, BRWD1, TAF1, TACC1, and SETD3, providing new targets for the study of epigenetic regulation. This study provides an effective method for the analysis of protein methacrylation modifications in biological systems.

Humans↗

Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation.

The PDC (pyruvate dehydrogenase complex) is strongly inhibited by phosphorylation during starvation to conserve substrates for gluconeogenesis. The role of PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) in regulation of PDC by this mechanism was investigated with PDHK4-/- mice (homozygous PDHK4 knockout mice). Starvation lowers blood glucose more in mice lacking PDHK4 than in wild-type mice. The activity state of PDC (percentage dephosphorylated and active) is greater in kidney, gastrocnemius muscle, diaphragm and heart but not in the liver of starved PDHK4-/- mice. Intermediates of the gluconeogenic pathway are lower in concentration in the liver of starved PDHK4-/- mice, consistent with a lower rate of gluconeogenesis due to a substrate supply limitation. The concentration of gluconeogenic substrates is lower in the blood of starved PDHK4-/- mice, consistent with reduced formation in peripheral tissues. Isolated diaphragms from starved PDHK4-/- mice accumulate less lactate and pyruvate because of a faster rate of pyruvate oxidation and a reduced rate of glycolysis. BCAAs (branched chain amino acids) are higher in the blood in starved PDHK4-/- mice, consistent with lower blood alanine levels and the importance of BCAAs as a source of amino groups for alanine formation. Non-esterified fatty acids are also elevated more in the blood of starved PDHK4-/- mice, consistent with lower rates of fatty acid oxidation due to increased rates of glucose and pyruvate oxidation due to greater PDC activity. Up-regulation of PDHK4 in tissues other than the liver is clearly important during starvation for regulation of PDC activity and glucose homoeostasis.

Animals↗

Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.

Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRalpha/RARalpha/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRalpha/RARalpha/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

Acetylation↗

Controllable snail-paced light in biological bacteriorhodopsin thin film.

We observe that the group velocity of light is reduced to an extremely low value of 0.091 mm/s in a biological thin film of bacteriorhodopsin at room temperature. By exploiting unique features of a flexible photoisomerization process for coherent population oscillation, the velocity is all-optically controlled over an enormous span, from snail-paced to normal light speed, with no need of modifying the characteristics of the incident pulse. Because of the large quantum yield for the photoreaction in this biochemical system, the ultraslow light is observed even at low light levels of microwatts, indicating high energy efficiency.

Bacteriorhodopsins↗

Spectral phase based medical image processing.

RATIONALE AND OBJECTIVES: To exploit the spectral phase characteristics of digital or digitized mammograms for early detection of microcalcifications, shape, and sizes of suspected lesions and to demonstrate its use for training radiologists to discriminate signal features in different spatially varying backgrounds. MATERIALS AND METHODS: We propose two algorithms: in the phase-only image (POI) reconstruction algorithm the spectral phase of the digital mammogram is extracted from its Fourier spectrum. This is coupled with unit magnitude and inverse Fourier transformed to reconstruct the POI thus enhancing the features of interest such as microcalcifications, shape, and sizes of suspected lesions. In the algorithm for image reconstruction from a priori phase-only information, spectral phase is used to extract signal features of the digital mammogram and then this is combined with spectral magnitude that is extracted and averaged over an ensemble of unrelated digital mammograms. RESULTS: The results for several digital phantoms and mammograms show that POI reconstructs only high spatial frequencies related to the features such as microcalcifications, shape, and size of masses like cysts and tumors. The results on image reconstruction from a priori phase-only information demonstrate the changes in the visibility of signal features when buried in a wide variety of real world mammogram backgrounds with different densities. CONCLUSION: The POI can aid radiologists in early detection of microcalcifications, lesions, and other masses of interest in digital mammograms. This reconstruction method is self-adaptive to changes in the background. The image reconstruction from a priori phase-only information can help the radiologist as a training tool in his decision-making process. Preliminary experiments indicate the potential of the techniques for early diagnosis of breast cancer. Clinical studies on these algorithm procedures are in progress for application as a diagnostic CAD tool in digital mammography. These methods can in general be applied to other medical images such as CT and MRI images.

Algorithms↗

[Net primary productivity of several mangrove species under controlled habitats].

Three mangrove species Sonneratia caseolaris, Kandelia candel and Aegiceras corniculatum were planted in different fishponds in April 2002 with three planting--breeding area proportions of 45 : 55, 30 : 70 and 15 : 85, respectively, and the growth of test mangrove plants were surveyed during 2 years after planting. The results showed that S. caseolaris and A. comiculatum could grow well in the coupling system, while K. candel could not. The survival percentage of S. caseolaris, K. candel and A. corniculatum was 92.9%, 93.9% and 44.7%, respectively. During the 2 years, the height of S. caseolaris increased 457.0 cm, and its basal diameter increased from 12.6 mm to 98.7 mm. A. corniculatum had an increment of 26.1 cm in height and 36.5 mm in basal diameter, while K. candel only had an increment of 20.4 cm in height and 26.4 mm in basal diameter. Based on the height, basal diameter, and biomass of trunk, branch, leaf and root, regressive equations of the four organs' biomass were obtained, and the whole biomass of standing trees in the coupling system was calculated. The average biomass of S. caseolaris was 5 597.8 g x m(-2) in April 2004, being increased 5 559.5 g x m(-2) in 2 years. At the same period, the standing biomass of A. corniculatum and K. candel was 962.5 g x m(-2) and 66.0 g x m(-2), with an increase of 932.7 g x m(-2) and 57.0 g x m(-2), respectively. The biomass of plant organs was in the order of stem > branch > root > leaf for S. caseolaris, leaf > branch > stem > root for A. corniculatum, and stem > root > leaf > branch for K. candel. The litter fall production of mangrove plants in 2 years was 1 149.2 g x m(-2), 170.8 g x m(-2) and 7.1 g x m(-2) for S. caseolaris, A. corniculatum and K. candel, respectively. Leaf litter took up more than half of the whole litter fall. From April 2002 to April 2004, the net primary production of S. caseolaris, A. corniculatum and K. candel was 7 048.9 g x m(-2), 1 105.9 g x m(-2) and 93.0 g x m(-2), respectively. The litter fall production occupied 20.5% of the net primary production for S. caseolaris, 15.4% for A. corniculatum, and 7.6% for K. candel, which meant that high productivity was accompanied by high return rate.

Biodegradation, Environmental↗

PPAR alpha ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity.

Previous studies demonstrated that during cisplatin-induced acute renal failure, there is a significant reduction in proximal tubule fatty acid oxidation. We now report on the effects of peroxisome proliferator-activated receptor-alpha (PPAR alpha) ligand Wy-14643 (WY) on the abnormalities of medium chain fatty acid oxidation and pyruvate dehydrogenase complex (PDC) activity in kidney tissue of cisplatin-treated mice. Cisplatin causes a significant reduction in mRNA levels and enzyme activity of mitochondrial medium chain acyl-CoA dehydrogenase (MCAD). PPAR alpha ligand WY ameliorated cisplatin-induced acute renal failure and prevented cisplatin-induced reduction of mRNA levels and enzyme activity of MCAD. In contrast, in cisplatin-treated PPAR alpha null mice, WY did not protect kidney function and did not reverse cisplatin-induced decreased expression of MCAD. Cisplatin inhibited renal PDC activity before the development of acute tubular necrosis, and PDC inhibition was reversed by pretreatment with PPAR alpha agonist WY. Cisplatin also induced increased mRNA and protein levels of pyruvate dehydrogenase kinase-4 (PDK4), and PPAR alpha ligand WY prevented cisplatin-induced increased expression of PDK4 protein levels in wild-type mice. We conclude that PPAR alpha agonists have therapeutic potential for cisplatin-induced acute renal failure. Use of PPAR alpha ligands prevents acute tubular necrosis by ameliorating cisplatin-induced inhibition of two distinct metabolic processes, MCAD-mediated fatty acid oxidation and PDC activity.

Acute Kidney Injury↗

Optical power limiting with photoinduced anisotropy of azobenzene films.

We study the power-limiting properties of photoanisotropic azobenzene films with low-power laser. The trans-cis photoisomerization and molecular reorientation of azobenzene molecules induced by polarized laser beams result in intensity-dependent anisotropic effects. Consequently, the transmittance of the input beam that passes through the film between two crossed polarizers becomes enhanced at low intensities and clamped at high intensities. The limiting threshold is adjustable by changing the intensity of excitation beam.

Journal Article↗

Starvation and diabetes reduce the amount of pyruvate dehydrogenase phosphatase in rat heart and kidney.

The pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during starvation and diabetes to conserve three-carbon compounds for gluconeogenesis. This is achieved by an increase in the extent of PDC phosphorylation caused in part by increased pyruvate dehydrogenase kinase (PDK) activity due to increased PDK expression. This study examined whether altered pyruvate dehydrogenase phosphatase (PDP) expression also contributes to changes in the phosphorylation state of PDC during starvation and diabetes. Of the two PDP isoforms expressed in mammalian tissues, the Ca(2+)-sensitive isoform (PDP1) is highly expressed in rat heart, brain, and testis and is detectable but less abundant in rat muscle, lung, kidney, liver, and spleen. The Ca(2+)-insensitive isoform (PDP2) is abundant in rat kidney, liver, heart, and brain and is detectable in spleen and lung. Starvation and streptozotocin-induced diabetes cause decreases in PDP2 mRNA abundance, PDP2 protein amount, and PDP activity in rat heart and kidney. Refeeding and insulin treatment effectively reversed these effects of starvation and diabetes, respectively. These findings indicate that opposite changes in expression of specific PDK and PDP isoenzymes contribute to hyperphosphorylation and therefore inactivation of the PDC in heart and kidney during starvation and diabetes.

Animals↗

Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin.

Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC). Two isoforms of this mitochondrial kinase (PDK2 and PDK4) are induced in a tissue-specific manner in response to starvation and diabetes. Inactivation of PDC by increased PDK activity promotes gluconeogenesis by conserving three-carbon substrates. This helps maintain glucose levels during starvation, but is detrimental in diabetes. Factors that regulate PDK2 and PDK4 expression were examined in Morris hepatoma 7800 C1 cells. The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY-14,643 and the glucocorticoid dexamethasone increased PDK4 mRNA levels. Neither compound affected the half-life of the PDK4 message, suggesting that both increase gene transcription. Fatty acids caused an increase in the PDK4 message comparable to that induced by WY-14,643. Insulin prevented and reversed the stimulatory effects of dexamethasone on PDK4 gene expression, but was less effective against the stimulatory effects of WY-14,643 and fatty acids. Insulin also decreased the abundance of the PDK2 message. The findings suggest that decreased levels of insulin and increased levels of fatty acids and glucocorticoids promote PDK4 gene expression in starvation and diabetes. The decreased level of insulin is likely responsible for the increase in PDK2 mRNA level in starvation and diabetes.

Animals↗

Nonlinear optical Fourier filtering technique for medical image processing.

Real-time nonlinear optical Fourier filtering for medical image processing is demonstrated, exploiting light modulating characteristics of thin films of the biophotonic material bacteriorhodopsin (bR). The nonlinear transmission of bR films for a 442 nm probe beam with a 568 nm control beam and vice versa is experimentally studied in detail. The spatial frequency information carried by the blue probe beam is selectively manipulated in the bR film by changing the position and intensity of the yellow control beam. The feasibility of the technique is first established with different shapes and sizes of phantom objects. The technique is applied to filter out low spatial frequencies corresponding to soft dense breast tissue and displaying only high spatial frequencies corresponding to microcalcifications in clinical screen film mammograms. With the aid of an electrically addressed spatial light modulator (SLM), we successfully adapt the technique for processing digital phantoms and digital mammograms. Unlike conventional optical spatial filtering techniques that use masks, the technique proposed can easily accommodate the changes in size and shape of details in a mammogram.

Algorithms↗