Biomedical subjects

Li Zeng

Publications and source records attributed to Li Zeng.

At least 19 recordsLinked to original sources

PubMed2026

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P < 0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P < 0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P = 0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans↗

PubMed2026

Associations of clinical and laboratory parameters with pediatric urolithiasis composition: A retrospective, single-center study.

OBJECTIVE: To investigate demographic, clinical, and laboratory factors associated with distinct stone compositions in children. METHODS: This retrospective study included 237 children aged <14 years who underwent stone composition analysis between July 2008 and November 2023. Demographic, clinical, and laboratory data were collected, and propensity score matching (PSM) was used to control for confounding factors. RESULTS: The urate component (uric acid anhydrous, ammonium acid urate, and sodium urate) was most prevalent in infants, males, and non-Han children, whereas the calcium oxalate component predominated in older children. Analysis of coexisting components revealed urate is the most common partner to calcium oxalate (67.6%), and vice versa (82.8%). Struvite most frequently coexisted with carbonate apatite (60%), while carbonate apatite most often coexisted with calcium oxalate (54%). After PSM, the urate component was independently associated with host metabolic dysregulation, including lower high-density lipoprotein (β = -0.175, 95% CI: -0.279 to -0.071, p = 0.001) and with coagulation dysfunction, as evidenced by a prolonged prothrombin time (β = 0.595, 95% CI: 0.125 to 1.064, p = 0.014). Additionally, preoperative urinary tract infection (UTI) and congenital urinary tract anomalies were independently associated with both carbonate apatite and struvite components, with directionally consistent but quantitatively unstable signals in the struvite cohort, whereas the calcium oxalate component exhibited an inverse association with UTI (OR = 0.156, 95% CI: 0.030 to 0.819, p = 0.028). Furthermore, the carbonate apatite component was also independently associated with an elevated systemic immune-inflammation index (β = 416.53, 95% CI: 60.05 to 773.01, p = 0.024) and systemic inflammation response index (β = 1.286, 95% CI: 0.086 to 2.487, p = 0.038). CONCLUSION: Urate component was prevalent in infants, males, and non-Han children, whereas calcium oxalate predominated in older children. After adjusting for confounders, urate composition was associated with metabolic abnormalities, the carbonate apatite component was linked to infection and anatomical malformations, and a similar directional pattern was observed in the struvite cohort.

Humans↗

PubMed2026

Unveiling the BMI Risk Threshold for Osteoarthritis: Multi-Database Causal and Nonlinear Evidence.

OBJECTIVE: To characterize the nonlinear relationship between BMI and osteoarthritis (OA), and to identify BMI thresholds that inform precise prevention strategies. METHODS: This multi-database study integrated Global burden of disease 2021, National Health and Nutrition Examination Survey 2007-2018, and Genome-Wide Association Studies. A generalized additive model was performed to visualize the BMI-OA relationship, adjusting for multiple confounders. We applied segmented logistic regression models to identify potential threshold effects and used Mendelian randomization to estimate the causal effects of BMI on OA subtypes. RESULTS: From 1990 to 2021, the age-standardized prevalence and years lived with disability rates for OA were highest in regions with high SDI. OA prevalence rose nonlinearly with BMI, with breakpoints at 24.00 and 41.58 kg/m2. Each unit increase in BMI was associated with higher odds of OA between 24.00 and 41.58 kg/m2 (OR = 1.022, 95% CI: 1.003-1.041) and above 41.58 kg/m2 (OR = 1.055, 95% CI: 1.022-1.090). Women and individuals aged ≥ 45 years exhibited a higher susceptibility to knee osteoarthritis. BMI was causally associated with knee osteoarthritis (OR = 1.63, 95% CI 1.50-1.77) and hip osteoarthritis (OR = 1.54, 95% CI 1.40-1.70). CONCLUSIONS: These findings suggest that OA risk awareness and weight-management strategies should begin before BMI reaches the high range, particularly among individuals with BMI exceeding 24.00 kg/m2.

Humans↗

PubMed2025

An image-based protein-ligand binding representation learning framework via multi-level flexible dynamics trajectory pre-training.

MOTIVATION: Accurate prediction of protein-ligand binding (PLB) relationships plays a crucial role in drug discovery, which helps identify drugs that modulate the activity of specific targets. Traditional biological assays for measuring PLB relationships are time consuming and costly. In addition, models for predicting PLB relationships have been developed and widely used in drug discovery tasks. However, learning more accurate PLB representations is essential to meet the stringent standards required for drug discovery. RESULTS: We propose an image-based PLB representation learning framework, called ImagePLB, which equips ligand representation learner (LRL) and protein representation learner (PRL) to accept 3D multi-view ligand images and protein graphs as input, respectively, and learns rich interaction information between ligand and protein through a binding representation learner (BRL). Considering the scarcity of protein-ligand pairs, we further propose a multi-level next trajectory prediction (MLNTP) task to pre-train ImagePLB on the 4D flexible dynamics trajectory of 16 972 complexes, including ligand level, protein level, and complex level, to learn information related to trajectories. Besides, by introducing trajectory regularization (TR), we effectively alleviate the problem of high (even almost identical) feature similarity caused by adjacent trajectories. Compared with the current state-of-the-art methods, ImagePLB has achieved competitive improvements on PLB-related prediction tasks, including protein-ligand affinity and efficacy prediction tasks. This study opens the door to the image-based PLB learning paradigm. AVAILABILITY AND IMPLEMENTATION: All data and implementation details of code can be obtained from https://github.com/HongxinXiang/ImagePLB.

Ligands↗

PubMed2025

The proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health.

Nearly one-third of the global population is affected by cardio-kidney-metabolic (CKM) diseases; however, the molecular mechanisms underlying CKM diseases are poorly understood. Here we show that tissue proteomics provide critical insights not captured by tissue gene expression or blood proteomics information by performing whole-genome and RNA sequencing and proteomics analysis of human kidney samples (n = 337), and we generated a publicly available database. Via Bayesian co-localization and Mendelian randomization analyses of kidney protein quantitative trait loci and 36 CKM genome-wide association studies, we prioritized 89 proteins for CKM traits. We prioritized relationships that could underlie the interconnectedness of CKM traits and discovered multiple and targetable mechanisms for CKM diseases, including the potential role of kidney angiopoietin-like protein 3 (ANGPTL3) in serum lipid levels and kidney function as well as the role of charged multivesicular body protein 1A in kidney function and hypertension. Notably, we identify pathways with confluence of evidence from genetic loci, tissue gene expression and protein levels for CKM traits. In summary, our large-scale kidney proteomics study uncovers proteins and targetable mechanisms prioritized for CKM diseases.

Humans↗

PubMed2006

A selective turn-on fluorescent sensor for imaging copper in living cells.

We present the synthesis, properties, and biological applications of Coppersensor-1 (CS1), a new water-soluble, turn-on fluorescent sensor for intracellular imaging of copper in living biological samples. CS1 utilizes a BODIPY reporter and thioether-rich receptor to provide high selectivity and sensitivity for Cu+ over other biologically relevant metal ions, including Cu2+, in aqueous solution. This BODIPY-based probe is the first Cu+-responsive sensor with visible excitation and emission profiles and gives a 10-fold turn-on response for detecting this ion. Confocal microscopy experiments further establish that CS1 is membrane-permeable and can successfully monitor intracellular Cu+ levels within living cells.

Biosensing Techniques↗

PubMed2006

Asymmetric localization of numb in the chick somite and the influence of myogenic signals.

Whereas Notch signaling is known to play an essential role in the formation of somites, its role during later stages of somite maturation is less well understood. Here, we examine the signals and transcription factors that control the expression of the Notch antagonist, Numb, during somite maturation in the chick embryo. Numb mRNA is present in the epithelial somite and is increased in expression in the forming myotome. Numb protein displays a very specific subcellular localization and dynamic expression during somite maturation. Numb protein is asymmetrically localized in a cortical crescent on the basal side of dividing cells in the dorsomedial lip of the dermomyotome and is subsequently uniformly distributed throughout differentiated myotomal cells. Treatment of somites with either the combination of Wnt-3a and Shh, or ectodermal signals plus noggin, both of which induce somitic myogenesis, did not significantly affect Numb transcript levels but did lead to a dramatic increase in the levels of Numb protein, which was uniformly distributed throughout the cytoplasm of the resultant myotubes. Forced expression of MyoD in somites similarly induced high levels of Numb protein throughout the cytoplasm, without affecting Numb mRNA levels. We also found that signals that promote somitic myogenesis or forced MyoD expression induced expression of the Notch ligand, Serrate-2. Our findings suggest that Notch signals are specifically repressed in the myotome and that asymmetric expression of Numb in dividing cells of the dorsomedial lip of the dermomyotome may modulate whether these cells continue to divide or differentiate into myotomal cells.

Animals↗

PubMed2006

Cloning and characterization of a novel KRAB-domain-containing zinc finger gene (ZNF284L).

The zinc finger gene (ZNF) family plays an important role in the regulation of transcription. This study reports the cloning and characterization of a novel human zinc finger protein cDNA (ZNF284L) from fetal brain cDNA library. The ZNF284L cDNA is 2223 bp in length encoding a 593-aa polypeptide. The protein contains a KRAB A+b box and eleven C2H2 type zinc finger motifs. ZNF284L gene is mapped to 19q13.2-19q13.3 with 5 exons, and the expression pattern of ZNF284L gene was also examined by reverse transcription polymerase chain reaction (RT-PCR). The transcripts were detected in the human lung, liver, pancreas, thymus, heart, placenta, spleen, prostate, ovary, small intestine and colon, but in human brain, skeletal muscle, kidney, testis and peripheral blood leukocyte, no expression was detected.

Amino Acid Sequence↗

PubMed2006

[Effects of N-linked oligosaccharide chains on expression of integrin beta1 and apoptosis in glomerular mesangial cells].

OBJECTIVE: The effects of N-linked oligosaccharide chains (TM), an inhibitor of N-glycosylation of proteins, on the expression of beta1 integrin and the apoptosis of glomerular mesangial cells (GMC) were observed for exploring the role of inhibitors of N-linked oligosaccharide chains in cell apoptosis, proliferation, and expression of beta1 integrin and cyclin D1, and hence finding a new approach to the synteresis of proliferative nephropathy. METHODS: Cultured rat mesangial cells were divided into 4 groups: control group, and 0.5, 1.0 and 2.0 microg/mL TM-treatment groups. The expression of beta1 integrin and apoptosis rate were measured by flow cytometry; the expression of cyclin D, was measured by immunohistochemistry, and proliferation of GMCs was measured by MTT. RESULTS: The expression of beta1 integrin and cyclin D1 were decreased notably by inhibitors of N-linked oligosaccharide chains-TM. TM increased apoptosis and decreased the proliferative abilitiy of cells, and all the effects of TM were dose-dependent. CONCLUSION: Through repressed glycosylation of glycoprotein, TM can suppress the expression of beta1, integrin, affect the adhesion of cells, and increase the apoptosis rate; at the same time, the expression of cyclin D1 and the proliferative ability of cells were decreased, and all these were dose-dependent.

Animals↗

PubMed2006

[Effects of rosiglitazone on the expression of beta1, integrin and ICAM-1 in high glucose-induced rat glomerular mesangial cells].

OBJECTIVE: To observe the effects of PPARgamma activators thiazolidinediones (Rosiglitazone) on the expression of intercellular adhesion molecule-1 (ICAM-1) and beta1 integrin in high glucose-induced rat glomerular mesangial cells (GMC) in order to elucidate the relationship between PPARgamma and adhesion molecules. METHODS: Rat HBZY-1 GMCs were cultured in vitro and divided into 9 groups: Normal Glucose group (N), High Glucose group (H), Mannitiol group (M), Normal and High Glucose plus 1, 5, 10 micromol/L Rosiglitazone. Every group was treated for 24 hours. The expression of ICAM-1 was measured by immunohistochemistry, the expression of beta1 integrin by indirect immunofluorescence staining and flow cytometry. RESULTS: It was found that high glucose can significantly increase the expression of ICAM-1 and beta1 integrin in GMCs, which is independent of the osmotic pressure. Rosiglitazone can inhibit the expression of ICAM-1 and beta1 integrin in normal and high glucose treated GMCs, and the inhibition is stronger in high glucose treated-group, which is in a dose-dependent manner. The expression of beta1 integrin is positively correlated with ICAM-1. CONCLUSION: Adhesion molecules involves in the pathogenesis of diabetic nephropathy (DN). PPARgamma activators-Rosiglitazone may exert effect on mesangial expansion and glomerulosclerosis in DN through the inhibition of expressions of adhesion molecules induced by high glucose.

Animals↗

PubMed2006

[Pathological changes in the testes of the rats with hypospadia induced by dichlorvos].

OBJECTIVE: To study the mechanism of dichlorvos leading to hypospadia of rats. METHODS: From the 12th to the 17th day of conception, 20 pregnant female rats (the experiment group) were given 10 mg/(kg x d) dichlorvos, while another 10 (the control group) administered 1.5 ml 0.9% NaCl/day. Out of 88 male newborns of the 20 experimental mother rats, 22 had hypospadia, while out of the 33 male newborns of the 10 controls, none had the problem. Five hypospadia newborns from the experiment group and another 5 normal ones from the control group were raised to sexual maturity, and then their testes were excised and embedded in paraffin, and the tissue sections were analyzed by regular HE staining and SP immunohistochemical staining with Calretinin. RESULTS: HE staining showed that the number of Leydig cells in the testis tissues of the hypospadia rats decreased significantly compared with the normal ones, but no change was observed either in the number or in the morphology of the seminiferous tubules. Moreover, the Calretinin positive Leydig cells were reduced dramatically in the testes of the hypospadia rats. CONCLUSION: Pregnant female rats, when exposed to dichlorvos, may cause reduction of testis Leydig cells in their male offsprings. Thus the probable mechanism of rat hypospadia induced by dichlorvos may lie in the decrease of the testosterone level caused by damage to Leydig cells from dichlorvos toxicity.

Animals↗

PubMed2005

Saccharomyces cerevisiae RAD53 (CHK2) but not CHK1 is required for double-strand break-initiated SCE and DNA damage-associated SCE after exposure to X rays and chemical agents.

Saccharomyces cerevisiae RAD53 (CHK2) and CHK1 control two parallel branches of the RAD9-mediated pathway for DNA damage-induced G(2) arrest. Previous studies indicate that RAD9 is required for X-ray-associated sister chromatid exchange (SCE), suppresses homology-directed translocations, and is involved in pathways for double-strand break repair (DSB) repair that are different than those controlled by PDS1. We measured DNA damage-associated SCE in strains containing two tandem fragments of his3, his3-Delta5' and his3-Delta3'::HOcs, and rates of spontaneous translocations in diploids containing GAL1::his3-Delta5' and trp1::his3-Delta3'::HOcs. DNA damage-associated SCE was measured after log phase cells were exposed to methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4-NQO), UV, X rays and HO-induced DSBs. We observed that rad53 mutants were defective in MMS-, 4-NQO, X-ray-associated and HO-induced SCE but not in UV-associated SCE. Similar to rad9 pds1 double mutants, rad53 pds1 double mutants exhibited more X-ray sensitivity than the single mutants. rad53 sml1 diploid mutants exhibited a 10-fold higher rate of spontaneous translocations compared to the sml1 diploid mutants. chk1 mutants were not deficient in DNA damage-associated SCE after exposure to DNA damaging agents or after DSBs were generated at trp1::his3-Delta5'his3-Delta3'::HOcs. These data indicate that RAD53, not CHK1, is required for DSB-initiated SCE, and DNA damage-associated SCE after exposure to X-ray-mimetic and UV-mimetic chemicals.

4-Nitroquinoline-1-oxide↗

PubMed2005

Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants.

DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MATa and MATalpha inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-Delta5' and his3-Delta3'::HOcs is enhanced in haploids and diploids expressing both MATa and MATalpha genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-Delta3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent.

DNA Damage↗

PubMed2005

Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression.

Expression of BCR-ABL is the leading cause of chronic myelogenous leukemia. In chronic myelogenous leukemia cells, c-Abl expression is silenced by promoter methylation. In addition, the level of c-Abl needs to be tightly and constantly regulated due to its cytotoxicity and its rapid degradation after activation. Yet the regulation of c-Abl expression remains unclear. In an effort to gain better understanding of c-Abl function, we performed a glutathione S-transferase-Abl pull-down screen and identified TopBP1, a topoisomerase IIbeta-binding protein that contains Brca1 C-terminal motifs and has been implicated in DNA damage response. Their physical interaction was verified by in vitro and in vivo assays with TopBP1 found as a substrate of Abl proteins. TopBP1 could repress the expression of c-Abl at both mRNA and protein levels. Reporter assays indicate that TopBP1 directly repressed the promoter activity of c-Abl. Furthermore, TopBP1 repressed expression of c-Abl through a novel mechanism that involved histone deacetylation and DNA methylation. This transcriptional repression was inhibited by c-Abl in a kinase-dependent manner. The dual antagonistic interplay between c-Abl and TopBP1 may also provide a mechanism for fine-tuning of c-Abl levels.

Amino Acid Motifs↗

PubMed2005

ERK phosphorylates p66shcA on Ser36 and subsequently regulates p27kip1 expression via the Akt-FOXO3a pathway: implication of p27kip1 in cell response to oxidative stress.

Mice deficient for p66shcA represent an animal model to link oxidative stress and aging. p66shcA is implicated in oxidative stress response and mitogenic signaling. Phosphorylation of p66shcA on Ser36 is critical for its function in oxidative stress response. Here we report the identification of ERK as the kinase phosphorylating p66shcA on Ser36. Activation of ERKs was necessary and sufficient for Ser36 phosphorylation. p66shcA interacted with ERK and was demonstrated to be a substrate for ERK, with Ser36 being the major phosphorylation site. Furthermore, in response to H2O2, inhibition of ERK activation repressed p66shcA-dependent phosphorylation of FOXO3a and the down-regulation of its target gene p27kip1. Down-regulation of p27 might promote cell survival, as p27 played a proapoptotic role in oxidative stress response. As a feedback regulation, Ser36 phosphorylated p66shcA attenuated H2O2-induced ERK activation, whereas p52/46shcA facilitated ERK activation, which required tyrosine phosphorylation of CH1 domain. p66shcA formed a complex with p52/46ShcA, which may provide a platform for efficient signal propagation. Taken together, the data suggest there exists an interplay between ERK and ShcA proteins, which modulates the expression of p27 and cell response to oxidative stress.

Adaptor Proteins, Signal Transducing↗

PubMed2005

[Methods of modern clinical research design].

Explore the source record for details and available documents.

Clinical Medicine↗

PubMed2005

The Saccharomyces cerevisiae PDS1 and RAD9 checkpoint genes control different DNA double-strand break repair pathways.

In response to DNA damage, the Saccharomyces cerevisiae securin Pds1 blocks anaphase promotion by inhibiting ESP1-dependent degradation of cohesins. PDS1 is positioned downstream of the MEC1- and RAD9-mediated DNA damage-induced signal transduction pathways. Because cohesins participate in postreplicative repair and the pds1 mutant is radiation sensitive, we identified DNA repair pathways that are PDS1-dependent. We compared the radiation sensitivities and recombination phenotypes of pds1, rad9, rad51 single and double mutants, and found that whereas pds1 rad9 double mutants were synergistically more radiation sensitive than single mutants, pds1 rad51 mutants were not. To determine the role of PDS1 in recombinational repair pathways, we measured spontaneous and DNA damage-associated sister chromatid exchanges (SCEs) after exposure to X rays, UV and methyl methanesulfonate (MMS) and after the initiation of an HO endonuclease-generated double-strand break (DSB). The rates of spontaneous SCE and frequencies of DNA damage-associated SCE were similar in wild type and pds1 strains, but the latter exhibited reduced viability after exposure to DNA damaging agents. To determine whether pds1 mutants were defective in other pathways for DSB repair, we measured both single-strand annealing (SSA) and non-homologous end joining (NHEJ) in pds1 mutants. We found that the pds1 mutant was defective in SSA but efficient at ligating cohesive ends present on a linear plasmid. We therefore suggest that checkpoint genes control different pathways for DSB repair, and PDS1 and RAD9 have different roles in recombinational repair.

Cell Cycle Proteins↗

PubMed2005

Isolation and characterization of ubiquitin-activating enzyme E1-domain containing 1, UBE1DC1.

Ubiquitin and other ubiquitin-like proteins play important roles in post-translational modification. They are phylogenetically well-conserved in eukaryotes. Activated by other proteins, ubiquitin and ubiquitin-like proteins can covalently modify target proteins. The enzymes responsible for the activation of this modification have been known to include UBA1, SAE2, UBA3, SAE1 and ULA1. Here we report a new ubiquitin activating enzyme like cDNA, named ubiquitin activating enzyme E1-domain containing 1 (UBE1DC1), whose cDNA is 2654 base pairs in length and contains an open reading frame encoding 404 amino acids. The UBE1DC1 gene consists of 12 exons and is located at human chromosome 3q22. The result of RT-PCR showed that UBE1DC1 is expressed in most of human tissues.

Amino Acid Sequence↗