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1.
Nat Commun ; 15(1): 3369, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643171

ABSTRACT

One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( Δ 1 ~15 meV vs. Δ 2 ~10 meV) and pairing temperatures (Tp1~52.0 K vs. Tp2~37.3 K), and correspondingly two-step nonlinear V ~ I α behavior but a concurrent Berezinskii-Kosterlitz-Thouless (BKT)-like transition occurring at T BKT ~28.7 K. Moreover, the onset transition temperature T c onset ~54 K and zero-resistivity temperature T c zero ~31 K are consistent with Tp1 and T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.

3.
Transpl Immunol ; 84: 102021, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38452984

ABSTRACT

BACKGROUND: Antibody-mediated rejection (ABMR) emerged as a major cause of graft loss in renal transplantation. Needle biopsy is the gold standard for diagnosis of ABMR in renal allografts. Thus, noninvasive diagnosis methods of ABMR with high accuracy are urgently needed to prevent unnecessary biopsies. METHODS: We collected peripheral blood transcriptome data from two independent renal transplantation cohorts with patients with ABMR, stable well-functioning transplants (STA), and T-cell mediated rejection (TCMR). Differentially expressed genes (DEGs) were identified by comparing the ABMR group with the STA group. In addition, functional enrichment analysis and gene set enrichment analysis were performed to seek new key underlying mechanisms in ABMR. Subsequently, we utilized a Boruta algorithm and least absolute shrinkage and selection operator logistic algorithm to establish a diagnostic model which was then evaluated and validated in an independent cohort. RESULTS: According to functional enrichment analysis, autophagy was found to be the primary upregulated biological process in ABMR. Based on algorithms, three autophagy-associated genes, ubiquitin specific peptidase 33 (USP33), Ras homolog mTORC1 binding (RHEB), and ABL proto-oncogene 2 (ABL2), were selected to establish the diagnostic model in the training cohort. This autophagy-related gene model possessed good diagnostic value in distinguishing ABMR from STA blood samples in the training cohort (AUC = 0.907) and in the validation cohort (AUC = 0.972). In addition, this model also showed good discernibility in distinguishing ABMR from TCMR in the training and validation cohorts (AUCs = 0.908 and 0.833). CONCLUSION: We identified and validated an autophagy-associated diagnostic model with high accuracy for renal transplant patients with ABMR. Our study provided a new potential test for the non-invasive diagnosis of ABMR in clinical practice and highlighted the importance of autophagy in ABMR.

4.
Am J Transplant ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38452932

ABSTRACT

Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDRΔIEC) abolished the therapeutic effect of lithocholic acid on MMF-induced GI toxicity. Impressively, we discovered that paricalcitol, a Food and Drug Administration-approved VDR agonist that has been used in clinics for years, could effectively alleviate MMF-induced GI toxicity. Our study reveals a previously unrecognized mechanism of gut microbiota, BAs, and VDR signaling in MMF-induced GI side effects, offering potential therapeutic strategies for clinics.

5.
BMC Urol ; 24(1): 56, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468247

ABSTRACT

BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.


Subject(s)
Glomerulonephritis, IGA , Humans , Leflunomide/adverse effects , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/chemically induced , Immunosuppressive Agents/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/pharmacology , Glomerular Filtration Rate
6.
Front Immunol ; 15: 1340997, 2024.
Article in English | MEDLINE | ID: mdl-38495888

ABSTRACT

Background: Renal ischemia-reperfusion injury (RIRI) is an inevitable complication in the process of kidney transplantation and lacks specific therapy. The study aims to determine the underlying mechanisms of RIRI to uncover a promising target for efficient renoprotection. Method: Four bulk RNA-seq datasets including 495 renal samples of pre- and post-reperfusion were collected from the GEO database. The machine learning algorithms were utilized to ascertain pivotal endoplasmic reticulum stress genes. Then, we incorporated correlation analysis and determined the interaction pathways of these key genes. Considering the heterogeneous nature of bulk-RNA analysis, the single-cell RNA-seq analysis was performed to investigate the mechanisms of key genes at the single-cell level. Besides, 4-PBA was applied to inhibit endoplasmic reticulum stress and hence validate the pathological role of these key genes in RIRI. Finally, three clinical datasets with transcriptomic profiles were used to assess the prognostic role of these key genes in renal allograft outcomes after RIRI. Results: In the bulk-RNA analysis, endoplasmic reticulum stress was identified as the top enriched pathway and three endoplasmic reticulum stress-related genes (PPP1R15A, JUN, and ATF3) were ranked as top performers in both LASSO and Boruta analyses. The three genes were found to significantly interact with kidney injury-related pathways, including apoptosis, inflammatory response, oxidative stress, and pyroptosis. For oxidative stress, these genes were more strongly related to oxidative markers compared with antioxidant markers. In single-cell transcriptome, the three genes were primarily upregulated in endothelium, distal convoluted tubule cells, and collecting duct principal cells among 12 cell types of renal tissues in RIRI. Furthermore, distal convoluted tubule cells and collecting duct principal cells exhibited pro-inflammatory status and the highest pyroptosis levels, suggesting their potential as main effectors of three key genes for mediating RIRI-associated injuries. Importantly, inhibition of these key genes using 4-phenyl butyric acid alleviated functional and histological damage in a mouse RIRI model. Finally, the three genes demonstrated highly prognostic value in predicting graft survival outcomes. Conclusion: The study identified three key endoplasmic reticulum stress-related genes and demonstrated their prognostic value for graft survival, providing references for individualized clinical prevention and treatment of postoperative complications after renal transplantation.


Subject(s)
Kidney Transplantation , Reperfusion Injury , Animals , Mice , Kidney Transplantation/adverse effects , Kidney , Reperfusion Injury/genetics , Disease Models, Animal , Endoplasmic Reticulum Stress/genetics , Ischemia , RNA
7.
Meat Sci ; 212: 109453, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38412752

ABSTRACT

Magnetic field combined with calcium chloride (CaCl2,) treatment is a highly promising technique for reducing sodium chloride (NaCl) in meat. Therefore, this paper investigated the effect of reducing NaCl addition (0-10%) by CaCl2 in combination with a magnetic field (3.8 mT) on the edible quality of low-salt pork mince. It is desired to drive the application of magnetic field and CaCl2 in low-sodium meat processing in this way. Results showed that the cooking yield, color, hardness, elasticity, mouthfeel, apparent texture, and orderliness of protein conformation of all minced pork were improved as compared to the control group, while the electron nose response values of their volatile sulfides and nitrogen oxides were decreased. In particular, the best edible quality and perceived salty intensity of minced pork gel was obtained by using CaCl2 in place of 5% NaCl under magnetic field mediation. In addition, energy dispersive X-ray spectroscopy scans showed that the reduced NaCl treatment by magnetic field combined with CaCl2 could increase the signal intensity of sodium in minced pork matrices to some extent. Magnetic field-mediated substitution of NaCl for CaCl2 treatment was also found to be favorable for inducing the transition of the protein secondary structure from an irregularly coiled to a ß-folded structure (demonstrated by infrared spectroscopy). In short, magnetic fields combined with CaCl2 instead of NaCl was a highly promising method of producing low-NaCl meats.


Subject(s)
Meat Products , Pork Meat , Red Meat , Animals , Swine , Sodium Chloride/chemistry , Calcium Chloride/chemistry , Meat Products/analysis , Proteins , Sodium , Gels/chemistry
8.
Nat Commun ; 15(1): 1726, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38409174

ABSTRACT

Electronic processors are reaching the physical speed ceiling that heralds the era of optical processors. Multifunctional all-optical logic gates (AOLGs) of massively parallel processing are of great importance for large-scale integrated optical processors with speed far in excess of electronics, while are rather challenging due to limited operation bandwidth and multifunctional integration complexity. Here we for the first time experimentally demonstrate a reconfigurable all-in-one broadband AOLG that achieves nine fundamental Boolean logics in a single configuration, enabled by ultrabroadband (400-4000 nm) plasmon-enhanced thermo-optical nonlinearity (TONL) of liquid-metal Galinstan nanodroplet assemblies (GNAs). Due to the unique heterogeneity (broad-range geometry sizes, morphology, assembly profiles), the prepared GNAs exhibit broadband plasmonic opto-thermal effects (hybridization, local heating, energy transfer, etc.), resulting in a huge nonlinear refractive index under the order of 10-4-10-5 within visual-infrared range. Furthermore, a generalized control-signal light route is proposed for the dynamic TONL modulation of reversible spatial-phase shift, based on which nine logic functions are reconfigurable in one single AOLG configuration. Our work will provide a powerful strategy on large-bandwidth all-optical circuits for high-density data processing in the future.

9.
Sci Rep ; 14(1): 3893, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38365923

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is characterized by high heterogeneity and recurrence rates, posing significant challenges for stratification and treatment. Basement membrane-related genes (BMGs) play a crucial role in tumor initiation and progression. Clinical and transcriptomic data of ccRCC patients were extracted from TCGA and GEO databases. We employed univariate regression and LASSO-Cox stepwise regression analysis to construct a BMscore model based on BMGs expression level. A nomogram combining clinical features and BMscore was constructed to predict individual survival probabilities. Further enrichment analysis and immune-related analysis were conducted to explore the enriched pathways and immune features associated with BMGs. High-risk individuals predicted by BMscore exhibited poorer overall survival, which was consistent with the validation dataset. BMscore was identified as an independent risk factor for ccRCC. Functional analysis revealed that BMGs were related to cell-matrix and tumor-associated signaling pathways. Immune profiling suggests that BMGs play a key role in immune interactions and the tumor microenvironment. BMGs serve as a novel prognostic predictor for ccRCC and play a role in the immune microenvironment and treatment response. Targeting the BM may represent an alternative therapeutic approach for ccRCC.


Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Basement Membrane , Prognosis , Risk Factors , Tumor Microenvironment/genetics , Kidney Neoplasms/genetics
10.
Apoptosis ; 29(5-6): 693-708, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38296888

ABSTRACT

The role of disulfidptosis in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated disulfidptosis-related biomarkers for KIRC prognosis prediction and individualized treatment. KIRC patients were clustered by disulfidptosis profiles. Differential expression analysis, survival models, and machine learning were used to construct the disulfidptosis-related prognostic signature (DRPS). Characterizations of the tumor immune microenvironment, genetic drivers, drug sensitivity, and immunotherapy response were explored according to the DRPS risk stratification. Markers included in the signature were validated using single-cell, spatial transcriptomics, quantitative RT-qPCR, and immunohistochemistry. In the discovery cohort, we unveiled two clusters of KIRC patients that differed significantly in disulfidptosis regulator expressions and overall survival (OS). After multiple feature selection steps, a DRPS prognostic model with four features (CHAC1, COL7A1, FOXM1, SHOX2) was constructed and validated. Combined with clinical factors, the model demonstrated robust performance in the discovery and external validation cohorts (5-year AUC = 0.793 and 0.846, respectively). KIRC patients with high-risk scores are characterized by inferior OS, less tumor purity, and increased infiltrations of fibroblasts, M1 macrophages, and B cells. High-risk patients also have higher frequencies of BAP1 and AHNAK2 mutation. Besides, the correlation between the DRPS score and the chemotherapy-response signature indicated the potential effect of Gefitinib for high-risk patients. Among the signature genes, FOXM1 is highly expressed in cycling tumor cells and exhibits spatial aggregation, while others are expressed sparsely within tumor samples. The DRPS model enables improved clinical management and personalized KIRC therapy. The identified biomarkers and immune characteristics offer new mechanistic insight into disulfidptosis in KIRC.


Subject(s)
Biomarkers, Tumor , Carcinoma, Renal Cell , Kidney Neoplasms , Precision Medicine , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic , Male , Female , Transcriptome
11.
Nano Lett ; 24(4): 1303-1308, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38232135

ABSTRACT

A nonlinear holographic technique is capable of processing optical information in the newly generated optical frequencies, enabling fascinating functions in laser display, security storage, and image recognition. One popular nonlinear hologram is based on a periodically poled lithium niobate (LN) crystal. However, due to the limitations of traditional fabrication techniques, the pixel size of the LN hologram is typically several micrometers, resulting in a limited field-of-voew (FOV) of several degrees. Here, we experimentally demonstrate an ultra-high-resolution LN hologram by using the laser poling technique. The minimal pixel size reaches 200 nm, and the FOV is extended above 120° in our experiments. The image distortions at large view angles are effectively suppressed through the Fourier transform. The FOV is further improved by combining multiple diffraction orders of SH fields. The ultimate FOV under our configuration is decided by a Fresnel transmission. Our results pave the way for expanding the applications of nonlinear holography to wide-view imaging and display.

12.
Genes Immun ; 25(1): 66-81, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38246974

ABSTRACT

Interferon-γ (IFN-γ) is an important cytokine in tissue homeostasis and immune response, while studies about it in antibody-mediated rejection (ABMR) are very limited. This study aims to comprehensively elucidate the role of IFN-γ in ABMR after renal transplantation. In six renal transplantation cohorts, the IFN-γ responses (IFNGR) biological process was consistently top up-regulated in ABMR compared to stable renal function or even T cell-mediated rejection in both allografts and peripheral blood. According to single-cell analysis, IFNGR levels were found to be broadly elevated in most cell types in allografts and peripheral blood with ABMR. In allografts with ABMR, M1 macrophages had the highest IFNGR levels and were heavily infiltrated, while kidney resident M2 macrophages were nearly absent. In peripheral blood, CD14+ monocytes had the top IFNGR level and were significantly increased in ABMR. Immunofluorescence assay showed that levels of IFN-γ and M1 macrophages were sharply elevated in allografts with ABMR than non-rejection. Importantly, the IFNGR level in allografts was identified as a strong risk factor for long-term renal graft survival. Together, this study systematically analyzed multi-omics from thirteen independent cohorts and identified IFN-γ and IFNGR as determinants of ABMR and clinical outcomes in patients after renal transplantation.


Subject(s)
Kidney Transplantation , Humans , Antibodies , Graft Rejection/etiology , Interferon-gamma , Risk Factors
13.
Appl Biochem Biotechnol ; 196(2): 1142-1153, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37351778

ABSTRACT

Breast cancer is the most malignant subtype of gynecological tumors and with aggressive biological behavior and poor outcome. Ultra-conserved non-coding RNA (ucRNA) is a newly discovered class of long non-coding RNAs (lncRNAs) which involved in the regulation of interaction network of genes. However, the exact function and mechanism by which ucRNA modulates breast cancer aggressive has not yet to be completely elucidated. In the present study, we demonstrated that the expression of uc.246 was significantly upregulated in metastatic breast cancer patients and TNBC cell lines, compared with those in controls. Furthermore, overexpression of uc.246 in MCF-7 cell lines enhanced the capacity of breast cancer cells to induce tube formation and migration of HUVECs, and, finally, enhanced breast cancer cells metastasis. Meanwhile, uc.246 overexpressing enhances the EMT phenotype of TNBC cells. Mechanistically, we found that uc.246 promoted malignant progression of breast cancer via upregulating the levels of VEGF-C and increased the levels of mesenchymal marker protein. Our results demonstrated that uc.246 induced angiogenesis, migration, and EMT phenotype and may represent a novel prognostic biomarker and therapeutic target for patients with breast cancer.


Subject(s)
Breast Neoplasms , RNA, Long Noncoding , Triple Negative Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Triple Negative Breast Neoplasms/drug therapy , Angiogenesis , MCF-7 Cells , Phenotype , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Cell Movement/genetics , Cell Proliferation
14.
Transplantation ; 108(2): 430-444, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37677931

ABSTRACT

BACKGROUND: T cell-mediated rejection (TCMR) is a severe issue after renal transplantation, but research on its T cell-receptor (TCR) repertoire is lacking. This study intended to elucidate the TCR repertoire landscape in TCMR and hence identify novel potential targets. METHODS: A total of 12 multiomics data sets were collected. The TRUST4 algorithm was used to construct and analyze the TCR repertoire in renal allografts with TCMR and stable renal function. Then, novel TCR-related key genes were identified through various criteria and literature research. In bulk transcriptome, cell line, single-cell transcriptome data sets, multiple immune cell infiltration algorithms, and gene set enrichment analysis were used to analyze potential mechanisms of the identified key gene. Twenty-three pathological sections were collected for immunofluorescence staining in the clinical cohort. Finally, the diagnostic and prognostic values of ANXA2R were evaluated in multiple renal transplant data sets. RESULTS: Allografts with TCMR showed significantly increased clonotype and specific clonal expansion. ANXA2R was found to be a novel key gene for TCMR and showed strong positive connections with the TCR complex and lymphocyte cells, especially CD8 + T cells. Immunofluorescence staining confirmed the existence of ANXA2R + CD8 + T cells, with their percentage significantly elevated in TCMR compared with stable renal function. Finally, both mRNA and protein levels of ANXA2R showed promising diagnostic and prognostic value for renal transplant recipients. CONCLUSIONS: ANXA2R , identified as a novel TCR-related gene, had critical roles in clinicopathology, diagnosis, and prognosis in renal transplantation, which offered promising potential therapeutic targets.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Multiomics , Kidney/pathology , CD8-Positive T-Lymphocytes , Receptors, Antigen, T-Cell/genetics , Graft Rejection
17.
Opt Lett ; 48(22): 5951-5954, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37966760

ABSTRACT

Spatiotemporal vortices (STOVs) are a new, to the best of our knowledge, type of structured light in which the optical phase circulates in space-time. In this work, we propose to generate STOVs via second harmonic generation in lithium niobate nonlinear photonic crystals (NPCs) with a linearly chirped Gaussian pulse as the fundamental wave. The structural function of the NPC is derived by the inverse design method. Numerical simulations of the intensity and phase profiles of the generated second harmonic waves are performed with both the amplitude-phase-modulated and the simplified binary-phase-modulated NPCs. We anticipate our study will be valuable for the experimental generation and manipulation of STOVs in NPCs.

18.
Math Biosci Eng ; 20(9): 17384-17406, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37920059

ABSTRACT

The accurate and fast segmentation method of tumor regions in brain Magnetic Resonance Imaging (MRI) is significant for clinical diagnosis, treatment and monitoring, given the aggressive and high mortality rate of brain tumors. However, due to the limitation of computational complexity, convolutional neural networks (CNNs) face challenges in being efficiently deployed on resource-limited devices, which restricts their popularity in practical medical applications. To address this issue, we propose a lightweight and efficient 3D convolutional neural network SDS-Net for multimodal brain tumor MRI image segmentation. SDS-Net combines depthwise separable convolution and traditional convolution to construct the 3D lightweight backbone blocks, lightweight feature extraction (LFE) and lightweight feature fusion (LFF) modules, which effectively utilizes the rich local features in multimodal images and enhances the segmentation performance of sub-tumor regions. In addition, 3D shuffle attention (SA) and 3D self-ensemble (SE) modules are incorporated into the encoder and decoder of the network. The SA helps to capture high-quality spatial and channel features from the modalities, and the SE acquires more refined edge features by gathering information from each layer. The proposed SDS-Net was validated on the BRATS datasets. The Dice coefficients were achieved 92.7, 80.0 and 88.9% for whole tumor (WT), enhancing tumor (ET) and tumor core (TC), respectively, on the BRTAS 2020 dataset. On the BRTAS 2021 dataset, the Dice coefficients were 91.8, 82.5 and 86.8% for WT, ET and TC, respectively. Compared with other state-of-the-art methods, SDS-Net achieved superior segmentation performance with fewer parameters and less computational cost, under the condition of 2.52 M counts and 68.18 G FLOPs.


Subject(s)
Brain Neoplasms , Humans , Brain Neoplasms/diagnostic imaging , Brain , Neural Networks, Computer , Image Processing, Computer-Assisted
19.
Front Immunol ; 14: 1279603, 2023.
Article in English | MEDLINE | ID: mdl-37965311

ABSTRACT

Background: Oxidative stress is the primary cause of ischemia-reperfusion injury (IRI) in kidney transplantation, leading to delayed graft function (DGF) and implications on patient health. Necroptosis is believed to play a role in renal IRI. This research presents a comprehensive analysis of necroptosis-related genes and their functional implications in the context of IRI in renal transplantation. Methods: The necroptosis-related differentially expressed genes (NR-DEGs) were identified using gene expression data from pre- and post-reperfusion renal biopsies, and consensus clustering analysis was performed to distinguish necroptosis-related clusters. A predictive model for DGF was developed based on the NR-DEGs and patients were divided into high- and low-risk groups. We investigated the differences in functional enrichment and immune infiltration between different clusters and risk groups and further validated them in single-cell RNA-sequencing (scRNA-seq) data. Finally, we verified the expression changes of NR-DEGs in an IRI mouse model. Results: Five NR-DEGs were identified and were involved in various biological processes. The renal samples were further stratified into two necroptosis-related clusters (C1 and C2) showing different occurrences of DGF. The predictive model had a reliable performance in identifying patients at higher risk of DGF with the area under the curve as 0.798. Additionally, immune infiltration analysis indicated more abundant proinflammatory cells in the high-risk group, which was also found in C2 cluster with more DGF patients. Validation of NR-DEG in scRNA-seq data further supported their involvement in immune cells. Lastly, the mouse model validated the up-regulation of NR-DEGs after IR and indicated the correlations with kidney function markers. Conclusions: Our research provides valuable insights into the identification and functional characterization of NR-DEGs in the context of renal transplantation and sheds light on their involvement in immune responses and the progression of IRI and DGF.


Subject(s)
Kidney Transplantation , Reperfusion Injury , Animals , Mice , Humans , Necroptosis/genetics , Kidney , Kidney Transplantation/adverse effects , Risk Factors
20.
Obes Surg ; 33(11): 3402-3410, 2023 11.
Article in English | MEDLINE | ID: mdl-37804469

ABSTRACT

INTRODUCTION: Bariatric surgery alleviates certain aspects of pelvic floor disorder, but the effect on pelvic organ prolapse (POP) is unclear. To assess the effect of bariatric surgery on POP we conducted the present meta-analysis and firstly performed a subgroup analysis based on the duration of follow-up. METHODS: Four databases including PubMed, The Cochrane Library, Web of Science, and Embase were searched to identify relevant studies published before February 24, 2023. The main outcome was the prevalence and severity of POP symptoms before and after bariatric surgery. Then we assessed the heterogeneity, publication bias and performed subgroup analyses based on follow-up time, study quality and region. RESULTS: Eleven studies with a total of 696 participants met the inclusion criteria. The results showed that the prevalence of POP decreased after bariatric surgery (odds ratio[OR] = 2.29, 95% confidence interval[CI]: 1.05, 5.01; P = 0.04, I2 = 78%), with significant differences observed both at 3-6 months (OR = 2.24, 95% CI: 1.25, 4.01; P = 0.007, I2 = 59%) and 12 months (OR = 4.64, 95% CI: 2.83, 7.58; P < 0.0001, I2 = 0%) of follow-up compared with pre-surgery. Pelvic Organ Prolapse Distress Inventory scores 6-item also decreased after bariatric surgery (mean difference [MD] = 2.11, 95% CI: 0.32, 3.89; P = 0.02, I2 = 55%) with significant differences observed both at 3-6 months (MD = 3.72; 95% CI: [0.10, 7.34], P = 0.04, I2 = 70%) and ≥ 12 months (MD = 3.24; 95% CI: [0.56, 5.91], P = 0.02, I2 = 56%) of follow-up. CONCLUSION: Bariatric surgery alleviated POP symptoms in women with obesity both during short-term (3-6 months) and long-term (≥ 12 months) follow-up.


Subject(s)
Obesity, Morbid , Pelvic Floor Disorders , Pelvic Organ Prolapse , Female , Humans , Obesity, Morbid/surgery , Pelvic Organ Prolapse/surgery , Obesity/surgery , Pelvic Floor Disorders/epidemiology , Weight Loss
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