CROST: a comprehensive repository of spatial transcriptomics.

The development of spatial transcriptome sequencing technology has revolutionized our comprehension of complex tissues and propelled life and health sciences into an era of spatial omics. However, the current availability of databases for accessing and analyzing spatial transcriptomic data is limited. In response, we have established CROST (https://ngdc.cncb.ac.cn/crost), a comprehensive repository of spatial transcriptomics. CROST encompasses high-quality samples and houses 182 spatial transcriptomic datasets from diverse species, organs, and diseases, comprising 1033 sub-datasets and 48 043 tumor-related spatially variable genes (SVGs). Additionally, it encompasses a standardized spatial transcriptome data processing pipeline, integrates single-cell RNA sequencing deconvolution spatial transcriptomics data, and evaluates correlation, colocalization, intercellular communication, and biological function annotation analyses. Moreover, CROST integrates the transcriptome, epigenome, and genome to explore tumor-associated SVGs and provides a comprehensive understanding of their roles in cancer progression and prognosis. Furthermore, CROST provides two online tools, single-sample gene set enrichment analysis and SpatialAP, for users to annotate and analyze the uploaded spatial transcriptomics data. The user-friendly interface of CROST facilitates browsing, searching, analyzing, visualizing, and downloading desired information. Collectively, CROST offers fresh and comprehensive insights into tissue structure and a foundation for understanding multiple biological mechanisms in diseases, particularly in tumor tissues.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

BACKGROUND & AIMS: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. METHODS: We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. RESULTS: We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. CONCLUSIONS: We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.

Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer.

BACKGROUND: Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients. RESULTS: To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome. CONCLUSIONS: The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

Annexin A1 may contribute to the morphological changes in podocytes by mediating endocytic vesicle fusion and transport via promotion of SNARE assembly in idiopathic membranous nephropathy.

BACKGROUND: Annexin A1 is a membrane-associated calcium-binding protein that participates in the progression of many diseases by facilitating vesicle aggregation. It has been documented that reducing vesicle formation alleviates podocyte injury and albuminuria in idiopathic membranous nephropathy (IMN). However, the role of Annexin A1 (ANXA1) in IMN is unknown. METHODS: Electron microscopy was used to observe the numbers of vesicles in podocytes. The expression of ANXA1 in IMN was investigated by bioinformatics analysis. We validated the hub genes with the Nephroseq V5 online tool and microarray data from the GEO. Immunohistochemical staining and qPCR were performed to measure gene and protein expression. RESULTS: The numbers of vesicles in IMN podocytes were significantly increased. Bioinformatics analysis showed that ANXA1, one of the differentially expressed genes, was upregulated in glomeruli from IMN patients. In the validation database and dataset, we confirmed that ANXA1 expression was upregulated in the glomeruli of IMN patients. We revealed that the increased expression of ANXA1 was negatively correlated with the glomerular filtration rate (GFR) and proteinuria. Moreover, ANXA1 was enriched in the biological process of vesicle fusion, in which the expression of SNAREs and the SNARE complex was increased. Finally, the expression of ANXA1 and genes related to SNAREs and the SNARE complex was upregulated in glomeruli from IMN patients according to immunohistochemical staining and qPCR. CONCLUSION: We conclude that ANXA1 may mediate endocytic vesicle fusion and transport by promoting SNARE assembly, contributing to the morphological changes in podocytes and massive proteinuria in IMN.

Wnt/ß-catenin Pathway Aggravates Renal Fibrosis by Activating PUM2 Transcription to Repress YME1L-mediated Mitochondrial Homeostasis.

Chronic kidney disease (CKD) affects more than 10% of people worldwide and is a leading cause of death. However, the pathogenesis of CKD remains elusive. The oxidative stress and mitochondrial membrane potential were detected using Enzyme-linked immunosorbent assay and JC-1 assay. Co-immunoprecipitation, dual-luciferase assay, chromatin IP, RNA IP and RNA pull-down were used to validate the interactions among genes. Exploiting a H2O2-induced fibrosis model in vitro, PUM2 expression was upregulated in Human kidney 2 cell (HK-2) cells, along with reduced cell viability, enhanced oxidative stress, impaired mitochondrial potential, and upregulated expressions of fibrosis-associated proteins. While PUM2 knockdown reversed the H2O2-induced injury in HK-2 cells. Mechanically, Wnt/ß-catenin pathway activated PUM2 transcription via TCF4. It was further identified that Wnt/ß-catenin pathway inhibited YME1L expression through PUM2-mediated destabilizing of its mRNA. PUM2 aggravated H2O2-induced oxidative stress, mitochondrial dysfunction, and renal fibrosis in HK-2 cell via suppressing YME1L expression. Our study revealed that Wnt/ß-catenin aggravated renal fibrosis by activating PUM2 transcription to repress YME1L-mediated mitochondrial homeostasis, providing novel insights and potential therapeutic targets for the treatment of kidney fibrosis.

DKK3 promotes renal fibrosis by increasing MFF-mediated mitochondrial dysfunction in Wnt/ß-catenin pathway-dependent manner.

BACKGROUND: Chronic kidney disease (CKD) lacks effective treatments and renal fibrosis (RF) is one of CKD's outcomes. Dickkopf 3 (DKK3) has been identified as an agonist in CKD. However, the underlying mechanisms of DKK3 in CKD are not fully understood. METHODS: H2O2-treated HK-2 cells and ureteric obstruction (UUO) mice were used as RF models. Biomarkers, Masson staining, PAS staining, and TUNEL were used to assess kidney function and apoptosis. Oxidative stress and mitochondria function were also evaluated. CCK-8 and flow cytometry were utilized to assess cell viability and apoptosis. Western blotting, IHC, and qRT-PCR were performed to detect molecular expression levels. Immunofluorescence was applied to determine the subcellular localization. Dual luciferase assay, MeRIP, RIP, and ChIP were used to validate the m6A level and the molecule interaction. RESULTS: DKK3 was upregulated in UUO mouse kidney tissue and H2O2-treated HK-2 cells. Knockdown of DKK3 inhibited oxidative stress, maintained mitochondrial homeostasis, and alleviated kidney damage and RF in UUO mice. Furthermore, DKK3 silencing suppressed HK-2 cell apoptosis, oxidative stress, and mitochondria fission. Mechanistically, DKK3 upregulation was related to the high m6A level regulated by METTL3. DKK3 activated TCF4/ß-catenin and enhanced MFF transcriptional expression by binding to its promoter. Overexpression of MFF reversed in the inhibitory effect of DKK3 knockdown on cell damage. CONCLUSION: Upregulation of DKK3 caused by m6A modification activated the Wnt/ß-catenin pathway to increase MFF transcriptional expression, leading to mitochondrial dysfunction and oxidative stress, thereby promoting RF progression.

Three-Dimensional Hydrogen-Bonded Porous Metal-Organic Framework for Natural Gas Separation with High Selectivity.

A 3D hydrogen-bonded metal-organic framework, [Cu(apc)2]n (TJU-Dan-5, Hapc = 2-aminopyrimidine-5-carboxylic acid), was synthesized via a solvothermal reaction. The activated TJU-Dan-5 with permanent porosity exhibits a moderate uptake of 1.52 wt% of hydrogen gas at 77 K. The appropriate BET surface areas and decoration of the internal polar pore surfaces with groups that form extensive hydrogen bonds offer a more favorable environment for selective C2H6 adsorption, with a predicted selectivity for C2H6/CH4 of around 101 in C2H6/CH4 (5:95, v/v) mixtures at 273 K under 100 kPa. The molecular model calculation demonstrates a C-H···π interaction and a van der Waals host-guest interaction of C2H6 with the pore walls. This work provides a strategy for the construction of 3D hydrogen-bonded MOFs, which may have great potential in the purification of natural gas.

DNA methylation-based age prediction with bloodstains using pyrosequencing and random forest regression.

The use of DNA methylation to predict chronological age has shown promising potential for obtaining additional information in forensic investigations. To date, several studies have reported age prediction models based on DNA methylation in body fluids with high DNA content. However, it is often difficult to apply these existing methods in practice due to the low amount of DNA present in stains of body fluids that are part of a trace material. In this study, we present a sensitive and rapid test for age prediction with bloodstains based on pyrosequencing and random forest regression. This assay requires only 0.1 ng of genomic DNA and the entire procedure can be completed within 10 h, making it practical for forensic investigations that require a short turnaround time. We examined the methylation levels of 46 CpG sites from six genes using bloodstain samples from 128 males and 113 females aged 10-79 years. A random forest regression model was then used to construct an age prediction model for males and females separately. The final age prediction models were developed with seven CpG sites (three for males and four for females) based on the performance of the random forest regression. The mean absolute deviation was less than 3 years for each model. Our results demonstrate that DNA methylation-based age prediction using pyrosequencing and random forest regression has potential applications in forensics to accurately predict the biological age of a bloodstain donor.

APC ameliorates idiopathic membranous nephropathy by affecting podocyte apoptosis through the ERK1/2/YB-1/PLA2R1 axis.

Idiopathic membranous nephropathy (IMN) belongs to an important pathogenic category of adult nephrotic syndrome. PLA2R1 exposure is critical for triggering the pathogenesis of PLA2R1-related IMN. However, the pathogenesis of IMN and the molecular mechanism of treatment remain to be further clarified. The expression changes of activated protein C (APC) and PLA2R1 in IMN patients were quantified by qPCR. A zymosan activated serum (ZAS)-induced IMN podocyte model was established in vitro. Podocyte apoptosis was detected via flow cytometry and caspase­3 assay. The expression levels of APC, p-ERK1/2, ERK1/2, YB-1 and PLA2R1 were detected by western blotting. The regulation relationship between YB-1 and PLA2R1 was detected by dual fluorescent reporter system. In IMN patients, the expression level of PLA2R1 was increased, whereas the expression level of APC was decreased. When APC was added to podocytes in vitro, the phosphorylation of ERK1/2 was increased, which could promote the translocation of YB-1 to the nucleus that reduces the expression of PLA2R1 at the cellular transcriptional level, thereby inhibiting podocyte apoptosis. Our study is the first to report that APC can improve membranous nephropathy by affecting podocyte apoptosis through the ERK1/2/YB-1/PLA2R1 axis. This study will provide a new targeted therapy for IMN patients with high PLA2R1 expression.

DKK3 promotes oxidative stress injury and fibrosis in HK-2 cells by activating NOX4 via ß-catenin/TCF4 signaling.

Oxidative stress and fibrosis may accelerate the progression of chronic kidney disease (CKD). DKK3 is related to regulating renal fibrosis and CKD. However, the molecular mechanism of DKK3 in regulating oxidative stress and fibrosis during CKD development has not been clarified, which deserves to be investigated. Human proximal tubule epithelial cells (HK-2 cells) were treated with H2O2 to establish a cell model of renal fibrosis. The mRNA and protein expressions were analyzed using qRT-PCR and western blot, respectively. Cell viability and apoptosis were evaluated using MTT assay and flow cytometry, respectively. ROS production was estimated using DCFH-DA. The interactions among TCF4, ß-catenin and NOX4 were validated using luciferase activity assay, ChIP and Co-IP. Herein, our results revealed that DKK3 was highly expressed in HK-2 cells treated with H2O2. DKK3 depletion increased H2O2-treated HK-2 cell viability and reduced cell apoptosis, oxidative stress, and fibrosis. Mechanically, DKK3 promoted formation of the ß-catenin/TCF4 complex, and activated NOX4 transcription. Upregulation of NOX4 or TCF4 weakened the inhibitory effect of DKK3 knockdown on oxidative stress and fibrosis in H2O2-stimulated HK-2 cells. All our results suggested that DKK3 accelerated oxidative stress and fibrosis through promoting ß-catenin/TCF4 complex-mediated activation of NOX4 transcription, which could lead to novel molecules and therapeutic targets for CKD.

Roles of interferon regulatory factor 4 in the AKI-CKD transition, glomerular diseases and kidney allograft rejection.

Interferon regulatory factor 4 (IRF4) is expressed in immune cells and is a member of the interferon regulatory factor family. Recently, it has been found that IRF4 plays important roles in the acute kidney injury (AKI)-chronic kidney disease (CKD) transition, glomerular diseases and kidney allograft rejection. In particular, the relationship between IRF4 and the AKI-CKD transition has attracted widespread attention. Furthermore, it was also found that the deficiency of IRF4 hindered the transition from AKI to CKD through the suppression of macrophage-to-fibroblast conversion, inhibition of M1-M2 macrophage polarization, and reduction in neutrophil inward flow. Additionally, an examination of the crucial role of IRF4 in glomerular disease was conducted. It was reported that inhibiting IRF4 could alleviate the progression of glomerular disease, and potential physiopathology mechanisms associated with IRF4 were postulated. Lastly, IRF4 was found to have detrimental effects on the development of antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR).

Overview of multi-omics research in gout.

Gout is a self-limiting inflammation disease triggered by deposition of monosodium urate with a variety of comorbidities. With the improvement of living standards, the global incidence of gout is increasing year by year, which seriously affects people's health. As an effective tool to study diseases, omics technology has been widely used to discover potential biomarkers and risk factors of gout. The identified variation sites or different-expressed products provide different dimensions of insights for the study of the pathogenesis and disease progression of gout. In this review, the application and research results of multi-omics technology in gout were analyzed and summarized through PubMed literature retrieval. Meanwhile, the recent research progress of multi-omics technology in the field of gout was reviewed to understand the specific changes of gout patients at different molecular levels, and to provide ideas and directions for further research on gout in the future.

Global Quantification of Glutathione S-Transferases in Human Serum Using LC-MS/MS Coupled with Affinity Enrichment.

The members of the glutathione S-transferase (GST) superfamily often exhibit functional overlap and can compensate for each other. Their concentrations in serum are considered as disease biomarkers. A global and quantitative evaluation of serum GSTs is therefore urgent, but there is a lack of efficient approaches due to technological limitations. GSH magnetic beads were examined for their affinity to enrich GSTs in serum, and the enriched GSTs were quantitatively targeted using a Q Exactive HF-X mass spectrometer in parallel reaction monitoring (PRM) mode. To optimize the quantification of GST peptides, sample types, trypsin digestion, and serum loading were carefully assessed; a biosynthetic method was employed to generate isotope-labeled GST peptides, and instrumental parameters were systematically optimized. A total of 134 clinical sera were collected for GST quantification from healthy donors and patients with four liver diseases. Using the new approach, GSTs in healthy sera were profiled: 14 GST peptides were quantified, and the abundance of five GST families was ranked GSTM > GSTP > GSTA > MGST1 > GSTT1, ranging from 0.1 to 4 pmol/L. Furthermore, combining the abundance of multiple GST peptides could effectively distinguish different types of liver diseases. Quantification of serum GSTs through targeted proteomics, therefore, has apparent clinical potential for disease diagnosis.

Platform-independent approach for cancer detection from gene expression profiles of peripheral blood cells.

Peripheral blood gene expression intensity-based methods for distinguishing healthy individuals from cancer patients are limited by sensitivity to batch effects and data normalization and variability between expression profiling assays. To improve the robustness and precision of blood gene expression-based tumour detection, it is necessary to perform molecular diagnostic tests using a more stable approach. Taking breast cancer as an example, we propose a machine learning-based framework that distinguishes breast cancer patients from healthy subjects by pairwise rank transformation of gene expression intensity in each sample. We showed the diagnostic potential of the method by performing RNA-seq for 37 peripheral blood samples from breast cancer patients and by collecting RNA-seq data from healthy donors in Genotype-Tissue Expression project and microarray mRNA expression datasets in Gene Expression Omnibus. The framework was insensitive to experimental batch effects and data normalization, and it can be simultaneously applied to new sample prediction.

Terahertz spin-selective perfect absorption enabled by quasi-bound states in the continuum.

Spin-selective absorption is broadly applicable to numerous photonic devices. Here, based on a stereoscopic full metallic resonator array, a terahertz chiral metasurface with a single-layer structure is proposed and numerically demonstrated. By employing the coupled-mode theory, we demonstrate that the chiral metasurface can near-perfectly absorb one circularly polarized wave in the quasi-bound states in the continuum-induced critical coupling region but non-resonantly reflect its counterparts. Interestingly, the linewidths and handedness of the proposed chiral metasurface can be flexibly controlled by an in-plane symmetry perturbation. Our designs might offer an alternative strategy to develop chiral metasurfaces apart from conventional methods and might stimulate many potential applications for emerging terahertz technologies.

Significance of tumor deposits combined with lymph node metastasis in stage III colorectal cancer patients: a retrospective multi-center cohort study from China.

PURPOSE: The study aimed to explore the value of tumor deposits in stage III colorectal cancer (CRC) and verify whether patients with more tumor deposit numbers have higher risk of recurrence. METHODS: The retrospective cohort analysis was performed at two cancer centers of China. Stage III CRC patients who underwent radical resection at the center between April 2008 and February 2019 were identified. The Univariate/Multivariate Cox regression, Kaplan-Meier analysis, and PSM were recurrence-free survival (RFS) used. RESULTS: Total 1080 stage III CRC patients (634 [58.7%] men; median [IQR] age, 60 [50-68] years) who underwent radical surgical resection were identified for inclusion in this study. Patients with tumor deposits had a 12.8% lower 3-year RFS (n = 236 [69.9%]) than the patients without tumor deposits (n = 844 [82.7%]) (P ≤ 0.0001). The 3-year RFS of patients with stage N2 (n = 335 [61.2%]) was 18.6% lower (P ≤ 0.0001) than the original cohort of patients with stage N1 (n = 745 [79.8%]), but it was similar to the RFS of patients with 4 or more tumor deposits plus lymph node metastases (n = 58 [61.4%]) (P = 0.91). The RFS for patients with 4 or more tumor deposits plus number of lymph node metastases (n = 58 [61.4%]) was 15.8% lower than the cohort of patients with 1-3 tumor deposits + number of lymph node metastases (n = 687 [77.2%]) (P = 0.001). Multivariate analysis confirmed that patients with 4 or more tumor deposits + the number of lymph node metastases (hazard ratio [HR], 1.88; 95% CI, 1.24-2.87) were independently associated with a shorter RFS. CONCLUSION: The number of tumor deposits is an indicator of poor postoperative prognosis. It is necessary to incorporate the number of tumor deposits combined with the number of lymph node metastases to stratify postoperative stratification of stage III CRC, which may provide a new theoretical basis for adjuvant therapy for patients with N1 stage CRC after surgery.

LncRNA Dlx6os1 Accelerates Diabetic Nephropathy Progression by Epigenetically Repressing SOX6 via Recruiting EZH2.

INTRODUCTION: Diabetic nephropathy (DN) is the leading cause of kidney failure worldwide. To explore the pathogenesis and effective biological target of DN is beneficial to seeking novel treatment strategies. OBJECTIVE: This study aimed to investigate the role of the lncRNA Dlx6os1/SOX6/EZH2 axis in DN progression. METHODS: PAS staining was performed to evaluate extracellular matrix accumulation; ELISA was carried out to assess the levels of urine microalbumin and blood glucose concentration; RT-qPCR was carried out to detect the levels of lncRNA Dlx6os1, TNF-α, IL-1ß, IL-6, SOX6, and EZH2. Western blot was performed to assess the levels of Col-IV, FN, TGF-ß1, and SOX6 proteins. RIP assay was carried out to verify the interaction between lncRNA Dlx6os1 and EZH2. ChIP-qPCR was conducted to verify the interaction between EZH2 and SOX6 promoter. RESULTS: Our results illustrated that lncRNA Dlx6os1 was highly expressed in DN mice and HG-induced SV40 MES13 cells. LncRNA Dlx6os1 knockdown inhibited HG-induced SV40 MES13 cell proliferation, fibrosis, and inflammatory cytokine release. LncRNA Dlx6os1 inhibited SOX6 expression by recruiting EZH2 in HG-SV40 MES13 cells, and SOX6 mediated the effects of lncRNA Dlx6os1 on proliferation, fibrosis, and inflammatory factor release of HG-induced SV40 MES13 cells. CONCLUSION: LncRNA Dlx6os1 accelerates the progression of DN by epigenetically repressing SOX6 via recruiting EZH2.

Clinical study on the use of advanced magnetic resonance imaging in lupus nephritis.

OBJECTIVES: To investigate the correlation between the histopathology of the kidney and clinical indicators in patients with lupus nephritis (LN) using magnetic resonance imaging (MRI). METHODS: A total 50 female participants were enrolled in the study. Thirty patients with LN were divided into types 2, 3, 4, and 5, according to their pathological features. The control group consisted of 20 healthy female volunteers. Serum creatinine, C3, C1q, and anti-ds-DNA were measured. Conventional MRI, DTI, DWI, and BOLD scanning was performed to obtain the FA, ADC, and R2* values for the kidney. RESULTS: Compared with the control group, FA and the ADC were decreased in patients with LN, while the R2* value was increased (P < 0.05). The overall comparison of the SLEDAI (Activity index of systemic lupus erythematosus) score, total pathological score, AI, and serum creatinine C3 showed that these were significantly different between the two groups (P < 0.05). FA and the ADC were negatively correlated with urinary, blood ds-DNA, and serum creatinine and positively correlated with C1q (P < 0.05). The R2* value was positively correlated with urinary NGAL, blood ds-DNA, and serum creatinine (P < 0.05). FA and the ADC were negatively correlated with the SLEDAI score, total pathological score, AI, CI, nephridial tissue C3, and C1q. The R2* value was positively correlated with the SLEDAI score, total pathological score, AI, CI, nephridial tissue C3, and C1q (P < 0.05). CONCLUSIONS: MRI examination in female patients with LN was correlated with pathologic test results, which may have clinical significance in determining the disease's severity, treatment, and outcome.

VEGFA promotes the occurrence of PLA2R-associated idiopathic membranous nephropathy by angiogenesis via the PI3K/AKT signalling pathway.

BACKGROUND: The M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) is a common immune-related disease in adults. Vascular endothelial growth factor A (VEGFA) is the key mediator of angiogenesis, which leads to numerous kidney diseases. However, the role of VEGFA in IMN is poorly understood. METHODS: In the present study, we downloaded the microarray data GSE115857 from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified with R software. The cytoHubba plug-in were used to identify hub genes from the protein-protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signalling pathway in IMN. CCK8 was performed to assess the cell viability in human vascular endothelial cells (HVECs). Then, passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Animals treated with VEGFA inhibitor bevacizumab (BV), with saline as a positive control. Proteinuria was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expression. Electron microscopy was performed to observe the thickness of the glomerular basement membrane (GBM). RESULTS: We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. Pathway enrichment analysis found that the biological process induced by VEGFA is associated with PI3K/Akt signalling. GSEA showed that the signalling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. We confirmed the high expression of VEGFA, PI3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell viability in a time and dose dependent manner. In vivo, we found low dose of BV attenuates proteinuria via inhibiting VEGFA/PI3K/AKT signalling. Meanwhile, low dose of BV alleviates the thickening of the GBM. CONCLUSION: VEGFA/PI3K/AKT signalling may play significant roles in the pathogenesis of IMN, which may provide new targets for the treatment of IMN.

BN-Embedded Perylenes.

Transition metal catalyzed coupling reaction strategy has been utilized in the synthesis of two novel BN-perylenes starting from halogenated BN-naphthalene derivatives. The molecular structures and packing modes of BN-perylenes were confirmed by NMR spectroscopy and X-ray single-crystal diffraction experiments. Their photophysical properties were further investigated using UV-vis and fluorescence spectroscopy and DFT calculations. Interestingly, the isosteric BN-insertion in perylene system resulted in stronger π-π stacking interaction both in solid and solution phases. The synthesized BN-perylenes are proved to be highly stable and thus provide a new valuable platform for novel organic materials applications which is otherwise inaccessible to date.