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Biomedical subjects

Peng Yang

Publications and source records attributed to Peng Yang.

At least 19 recordsLinked to original sources

A geroprotective probiotic and its functional metabolite counteract inflammaging to extend healthspan.

The gut microbiome profoundly influences host aging, yet the specific microbes and mechanisms governing divergent aging trajectories remain elusive. In this study, we delineated enterotype-specific gut microbial remodeling during aging and developed a microbiome-based aging clock (MicroAge) to track biological aging trajectories. We identified Bifidobacterium pseudocatenulatum (B. pseudocatenulatum) as a candidate geroprotective species consistently depleted during aging across both sexes and multiple Chinese cohorts. In naturally aged mice, oral B. pseudocatenulatum monotherapy rescued intestinal homeostasis, mitigated multiorgan inflammaging, enhanced cognitive-motor performance and extended healthspan. Mechanistically, we characterized 5-aminovaleric acid betaine (5-AVAB) as a key B. pseudocatenulatum-derived metabolite whose levels decline physiologically in aging humans. 5-AVAB supplementation partially recapitulated a broad spectrum of the systemic benefits observed with B. pseudocatenulatum treatment, including improved cognitive and motor function and suppressed multiorgan inflammaging. Our findings identify the B. pseudocatenulatum-5-AVAB axis as a promising target for microbiome-based interventions to promote healthy aging.

Animals↗

Landscape Genomics Reveals Divergent Adaptation Modes and Predicts Climate Vulnerability in Xinjiang Indigenous Sheep.

Climate change increasingly endangers precious indigenous sheep germplasm resources distributed across diverse Chinese landscapes, and systematically decoding their polygenic climate-adaptive genetic mechanisms is essential for targeted breed conservation and long-term sustainable pastoral production. Whole-genome resequencing data from 93 individuals covering six representative local sheep breeds were analyzed in this work. After filtering highly collinear climate variables, three mature landscape genomic approaches were jointly applied to identify environment-linked gene variants, while two predictive metrics across ten CMIP6 future climate scenarios quantified each breed's long-term adaptive risks. Six temperature- and water-related environmental factors jointly drove sheep population genetic differentiation, with temperature fluctuation indices showing markedly stronger explanatory power. Detected adaptive genes were significantly enriched in ion transport, energy metabolism and cellular stress response pathways. Future projections indicated western breeds (Bayinbuluke, Cele Black, Xiahe) face severe maladaptation risks under high-emission SSP370 scenarios by 2100, whereas central and eastern breeds possess much broader climate tolerance. This study systematically reveals the core genomic basis of ovine climate adaptation and quantifies distinct breed-specific climate vulnerability, providing solid reliable theoretical support for precision germplasm conservation and selective breeding of climate-resilient sheep varieties.

adaptive loci↗

Learning directed acyclic graphs for ligands and receptors based on spatially resolved transcriptomic data of ovarian cancer.

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST data. LRnetST utilizes a directed acyclic graph model with a novel approach to handle the zero-inflated distributions of ST data. It also leverages existing ligand-receptor regulation databases as prior information, and employs a bootstrap aggregation strategy to achieve robust network estimation. Application of LRnetST to ST data of high-grade serous ovarian tumor samples revealed both common and distinct ligand-receptor regulations across different tumors. Some of these interactions were validated through both a MERFISH dataset and a CosMx SMI dataset of independent ovarian tumor samples. These results cast light on biological processes relating to the communication between tumor and immune/stromal cells in ovarian tumors. An open-source R package of LRnetST is available on GitHub at https://github.com/jie108/LRnetST.

Humans↗

The ADAMs family: coordinators of nervous system development, plasticity and repair.

A disintegrin and metalloprotease (ADAM) transmembrane proteins have metalloprotease, integrin-binding, intracellular signaling and cell adhesion activities. In contrast to other metalloproteases, ADAMs are particularly important for cleavage-dependent activation of proteins such as Notch, amyloid precursor protein (APP) and transforming growth factor alpha (TGFalpha), and can bind integrins. Not surprisingly, ADAMs have been shown or suggested to play important roles in the development of the nervous system, where they regulate proliferation, migration, differentiation and survival of various cells, as well as axonal growth and myelination. On the eleventh anniversary of the naming of this family of proteins, the relatively unknown ADAMs are emerging as potential therapeutic targets for neural repair. For example, over-expression of ADAM10, one of the alpha-secretases for APP, can prevent amyloid formation and hippocampal defects in an Alzheimer mouse model. Another example of this potential neural repair role is the finding that ADAM21 is uniquely associated with neurogenesis and growing axons of the adult brain. This comprehensive review will discuss the growing literature about the roles of ADAMs in the developing and adult nervous system, and their potential roles in neurological disorders. Most excitingly, the expanding understanding of their normal roles suggests that they can be manipulated to promote neural repair in the degenerating and injured adult nervous system.

ADAM Proteins↗

Isoquino[4,5-bc]acridines: design, synthesis and evaluation of DNA binding, anti-tumor and DNA photo-damaging ability.

Several novel isoquino[4,5-bc]acridine derivatives have been designed and synthesized. Their DNA-binding, anti-tumor and DNA-photo-damaging properties were investigated. A4 exhibited the highest anti-tumor activities against both A 549 (human lung cancer cell) and P388 (murine leukemia cells). All these compounds were found to be more cytotoxic against P388 than against A549. Under 365-nm light irradiation, A3 damaged plasmid DNA pBR322 at <2 microM and cleaved DNA from form I to 100% form II by 50 microM. The mechanism studies revealed that A3 damaged DNA by electron transfer mechanism and singlet oxygen species.

Acridines↗

Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation.

BACKGROUND: Activation of naïve B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only stimulation through the B cell antigen receptor (BCR) induces apoptosis in resting splenic B cells. In order to define the common and unique biological responses to ligand stimulation, we compared the gene expression changes induced in normal primary B cells by a panel of ligands using cDNA microarrays and a statistical approach, CLASSIFI (Cluster Assignment for Biological Inference), which identifies significant co-clustering of genes with similar Gene Ontology annotation. RESULTS: CLASSIFI analysis revealed an overrepresentation of genes involved in ion and vesicle transport, including multiple components of the proton pump, in the BCR-specific gene cluster, suggesting that activation of antigen processing and presentation pathways is a major biological response to antigen receptor stimulation. Proton pump components that were not included in the initial microarray data set were also upregulated in response to BCR stimulation in follow up experiments. MHC Class II expression was found to be maintained specifically in response to BCR stimulation. Furthermore, ligand-specific internalization of the BCR, a first step in B cell antigen processing and presentation, was demonstrated. CONCLUSION: These observations provide experimental validation of the computational approach implemented in CLASSIFI, demonstrating that CLASSIFI-based gene expression cluster analysis is an effective data mining tool to identify biological processes that correlate with the experimental conditional variables. Furthermore, this analysis has identified at least thirty-eight candidate components of the B cell antigen processing and presentation pathway and sets the stage for future studies focused on a better understanding of the components involved in and unique to B cell antigen processing and presentation.

Algorithms↗

[Clinical evaluation of laparoscopic radical resection of colon cancer].

OBJECTIVE: To investigate the clinical effect of laparoscopic radical resection of colon cancer. METHODS: Patients with colon cancer who underwent radical resection during January 2000 to January 2004 in Sir Run Run Shaw Hospital (Medical College of Zhejiang University) were divided into open and laparoscopic groups for a non-randomized case-control study. All the patients were followed up and their clinical and pathological results were compared. RESULTS: No difference was seen between the two groups on the patients' age, gender, lymph node numbers and Dukes staging. The laparoscopic group had a longer mean operation time [(182 +/- 62) min vs (141 +/- 37) min] and shorter hospital stay [(5.3 +/- 1.9) d vs (8.2 +/- 1.2) d] than the open group. All surgical margins were pathological negative. Post-operation follow up was 12-18 months (mean 21 months). No incision recurrence was found in neither group. As far the local recurrence and distal metastasis rate were similar in both groups. CONCLUSIONS: Laparoscopic radical resection of colon cancer has minimal invasion and shorter recuperation than open procedure, the radicalness and either local recurrence or distal metastasis rate after surgery are similar when compared with open group.

Adult↗

A comprehensive survey of DNA-binding transcription factor gene expression in human fetal and adult organs.

A global survey of RNA from 14 fetal and 12 adult human organs by RT-PCR determined the expression patterns of 790 genes encoding DNA-binding transcription factors. The data can be sorted to identify sets of transcription factors with expression relatively restricted to a given organ or to particular organ groups. These data are a resource to help define the spectrum of transcription factor control, contribute to the elucidation of transcription factor cascades responsible for the development and maintenance of each organ, and provide a baseline to study the effects of disease or developmental defects.

Cluster Analysis↗

[Laparoscopic distal pancreatectomy with preservation of the spleen].

OBJECTIVE: To summarize the experience of laparoscopic distal pancreatectomy with preservation of the spleen. METHODS: From Nov 2003 to Dec 2004, 2 patients with cystic lesions in the body and tail of the pancreas underwent laparoscopic distal pancreatectomy with preservation of the spleen. RESULTS: Both of the operations were successful with the operative time of 220 min and 190 min respectively, and the blood loss were 450 ml and 350 ml. There was no postoperative complication and the pathological diagnosis was pancreatic serous cystadenoma. Both patients' symptom disappeared after operation without recurrence during the follow-up of 18 and 5 months. CONCLUSION: Laparoscopic distal pancreatectomy with preservation of the spleen is safe and feasible for the management of benign tumor in the body and tail of pancreas with the advantages of reduced injury, earlier recovery and less complication.

Adult↗

Micro/nanoscale well and channel fabrication on organic polymer substrates via a combination of photochemical and alkaline hydrolysis etchings.

With the utilization of photomasks, micro/nanoscale wells and channels with depths ranging from nanometers to several micrometers were fabricated on a poly(ethylene terephthalate) (PET) surface by a simple combination of photochemical and alkaline hydrolysis etching. The PET surface region could be directly and photochemically etched by UV light and N,N-dimethylformamide (DMF) to create 125-350 nm etching depths (step 1). In step 2, the depth could be further enlarged to 250-1400 nm by potassium hydroxide (KOH) developing. More importantly, when this combination etching was repeated with the same photomask, the depth increased with increasing etching times. For instance, the depth reached approximately 6 microm after a series of three combination etchings. The cross-sectional shape of the final structure was trapezoidal with smooth corners. No obvious widening effect in lateral size was observed after one combination etching, whereas the top width of the microfabricated channels was enlarged from 50 microm (the designed feature of the photomask used) to 100 microm after two or three combination etchings. Even more interesting was that step 1 resulted in the formation of a kind of aminated surface in the channel (6.5% amine content), but when step 2 was conducted, the aminated surface was erased. This process could be reversibly carried out by repeating step 1 (amination) and step 2 (erasing). Electrostatical self-assembly of an antibody, fluorescein isothiocyanate-labeled immunoglobulin G (FITC-IgG, goat anti-rabbit), was achieved on the aminated surface of the etched channels, which demonstrated that by this combination strategy, micro/nanoscale channels or wells featuring tunable depths and functional channel surfaces could be readily fabricated. Undoubtedly, these functionalized channels or wells onto organic substrates could provide a potential platform for microchips toward various functions such as microarrays, heterogeneous immunoassays, biosensors, concentrations, filtrations, and microanalysis.

Biosensing Techniques↗

Novel synthetic isoquinolino[5,4-ab]phenazines: inhibition toward topoisomerase I, antitumor and DNA photo-cleaving activities.

The novel DNA interactive isoquinolino[5,4-ab]phenazine derivatives were designed and synthesized. Their inhibitory abilities toward topoisomerase I, antitumor activities and DNA photo-cleaving abilities were examined. The substituents at peri sites of two phenazine N atoms played very important roles for all these biological activities. At a concentration of 100 microM, all these phenazine derivatives (but A2 and A6) exhibited an inhibitory activity toward topoisomerase I. A6 had efficient antitumor activities against both human lung cancer cell (A549) and murine leukemia cell (P388). A1, A5, and A6 exhibited antitumor activities selectively against P388. A2 was the most efficient DNA photocleaver, which had converted supercoiled DNA from form I to form II at <1 microM. Under anaerobic conditions, the electron transfer mechanism mainly contributed to DNA photo-induced cleavage, while under aerobic conditions, superoxide anion was also involved in this process.

Antineoplastic Agents↗

Degradation of 4-chlorophenol by a microwave assisted photocatalysis method.

In this work, the degradation of 4-chlorophenol (4CP) under simultaneous microwave assisted UV (electrodeless discharge lamp) photocatalysis technique (MW/UV/TiO2) was investigated. Several factors affecting the degradation of 4CP by MW/UV/TiO2 method, such as the dosage of photocatalysts, the initial pH value of the solutions, gas bubbling, light intensity and addition of H2O2 oxidant, were studied in detail. The synergistic effects between microwave irradiation and TiO2 photocatalysis were also studied. The major intermediates were found to be chlorobenzene, phenol, hydroquinone, benzoquinone and 4-chlorocatechol. Based on the results, a general reaction pathway for the degradation of 4CP was proposed.

Catalysis↗

A disintegrin and metalloprotease 21 (ADAM21) is associated with neurogenesis and axonal growth in developing and adult rodent CNS.

We have reported that alpha6beta1 integrin regulates the directed migration of neuroblasts from the adult rodent subventricular zone (SVZ) through the rostral migratory stream (RMS). ADAM (a disintegrin and metalloprotease) proteins bind integrins. Here, we show that ADAM21, but not ADAM2, -3, -9, -10, -12, -15, or -17, is expressed in adult rats and mice by ependyma and SVZ cells with long basal processes, and in radial glia at early postnatal times. ADAM21-positive processes projected into the RMS, contacted blood vessels, and were present within the RMS intermingled with neuroblasts up to where neuroblasts start their radial migration and differentiation in the olfactory bulb. Tissue inhibitors of metalloproteases (TIMPs) 1, 2, and 3 are present in the ependymal layer but not in the SVZ and RMS. Thus, ADAM21 could regulate neurogenesis and guide neuroblast migration through cleavage-dependent activation of proteins and integrin binding. ADAM21 is also present in growing axonal tracts during postnatal development and in growing primary olfactory axons in adults. In the olfactory nerve layer, ADAM21 often, but not always, colocalizes with OMP, a marker of mature olfactory neurons, but is not colocalized with the immature marker betaIII-tubulin. This suggests that ADAM21 is involved in the final axonal outgrowth phase and/or synapse formation. TIMP3 is present in periglomerular neurons, where it could restrict ADAM21-mediated axonal growth to the glomeruli. ADAM21's unique disintegrin and metalloprotease sequences and its restricted expression suggest that it might be a good target for influencing neurogenesis and neuronal plasticity.

ADAM Proteins↗

A positive feedback loop between glycogen synthase kinase 3beta and protein phosphatase 1 after stimulation of NR2B NMDA receptors in forebrain neurons.

N-methyl-D-aspartate receptors (NMDARs) are critical for neuronal plasticity and survival, whereas their excessive activation produces excitotoxicity and may accelerate neurodegeneration. Here, we report that stimulation of NMDARs in cultured rat hippocampal or cortical neurons and in the adult mouse brain in vivo disinhibited glycogen synthase kinase 3beta (GSK3beta) by protein phosphatase 1(PP1)-mediated dephosphorylation of GSK3beta at the serine 9 residue. NMDA-triggered GSK3beta activation was mediated by NMDAR that contained the NR2B subunit. Interestingly, GSK3beta inhibition reduced inhibitory phosphorylation of the PP1 inhibitor 2 (I2) and attenuated serine 9 dephosphorylation by PP1. These data suggest existence of a feedback loop between GSK3beta and PP1 that results in amplification of PP1 activation by GSK3beta. In addition, GSK3beta inhibition decreased PP1-mediated dephosphorylation of the cAMP-response element-binding protein (CREB) at the serine 133 residue in NMDA-stimulated neurons. Conversely, overexpression of GSK3beta abolished non-NR2B-mediated activation of CRE-driven transcription. These data suggest that cross-talk between GSK3beta and PP1 contributes to NR2B NMDAR-induced inhibition of CREB signaling by non-NR2B NMDAR. The excessive activation of NR2B-PP1-GSK3beta-PP1 circuitry may contribute to the deficits of CREB-dependent neuronal plasticity in neurodegenerative diseases.

Animals↗

Involvement of midgastric transverse band in gastric emptying delay of functional dyspepsia.

BACKGROUND: Midgastric transverse band (MTB) was first observed over 100 years ago, after that many researchers worked on the subject postulated its physiologic role and the role in gastrointestinal diseases, but its function remains unclear. With progress of imaging methods, the nature of MTB is unveiling. In this study we investigated the effect of MTB on the gastric emptying delay in functional dyspepsia (FD) and explored the mechanism. METHODS: A total of 60 patients with FD and 65 age- and sex-matched healthy people who served as controls were studied. With (99m)Tc-DTPA labeled semi-solid fat-parched flour served as test meal, gastric emptying was examined in all subjects by using single photon emission computed tomography. Test meal was designated as general (60 g fat-parched flour) or large (80 g fat-parched flour) meal. Stomach was divided into proximal and distal parts by MTB. Half gastric emptying time, areas of different gastric parts, intragastric food distribution and MTB width were tested with in given times. RESULTS: Patients with FD showed a delayed gastric emptying and increased intragastric residue. Global and regional gastric emptying velocity was decreased. The areas of distal stomach and MTB were significantly greater in the FD patients than in the controls. Throughout the whole test period a distal stomach-dominated food distribution was shown. Those who took a large meal had longer half gastric emptying time and greater MTB area than those who took a general meal. CONCLUSIONS: Gastric emptying delay is related to enlarged MTB area. Some dyspeptic symptoms may be induced by abnormal distribution and increased retention of food in distal stomach. MTB, being like atria-ventricular valve that controls blood flow in heart, regulates transport, distribution, and emptying of food in the stomach.

Adult↗

A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.

During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.

Analysis of Variance↗

Angiotensin-converting enzyme 2 protects from severe acute lung failure.

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus. At present, there are no effective drugs for improving the clinical outcome of ARDS. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs. Here we report that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type 1a receptor (AT1a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.

Acids↗

Characteristics of three-phase internal loop airlift bioreactors with complete gas recirculation for non-Newtonian fluids.

Hydrodynamic and gas-liquid mass transfer characteristics, such as liquid velocity, gas holdup, solid holdup and gas-liquid volumetric mass transfer coefficient, in the riser and downcomer of the gas-liquid-solid three-phase internal loop airlift bioreactors with complete gas recirculation for non-Newtonian fluids, were investigated. A mathematical model for the description of flow behavior and gas-liquid mass transfer of these bioreactors was developed. The predicted results of this model agreed well with the experimental data.

Bioreactors↗