Development of an SI-traceable N-terminal pro-B-type natriuretic peptide certified reference material using structure-based impurity-corrected isotope dilution mass spectrometry approaches.

N-Terminal pro-B-type natriuretic peptide (NT-proBNP) is a pivotal biomarker for the diagnosis and prognosis of heart failure (HF). However, no SI-traceable certified reference material (CRM) or reference measurement procedure (RMP) is available for this biomarker, and so clinical testing results obtained in different laboratories cannot be traced to a higher-order standard, leading to incomparable measurements. Protein hydrolysis and protein cleavage isotope dilution mass spectrometry (AAA-IDMS and PepA-IDMS) were used to develop a CRM. Structurally related impurities were identified by high-resolution mass spectrometry. The quantitative AAA-IDMS results were corrected according to the amino acid compositions of the impurities. Using PepA-IDMS, two peptides from the proteolyzed product were confirmed as signature peptides. To obtain traceable and accurate results, the signature peptides were quantified using impurity-corrected AAA-IDMS. The candidate NT-proBNP solution was denatured and enzymatically digested using the Glu-C endoproteinase. The released signature peptides were measured using an isotopic dilution approach. The homogeneity and stability of the candidate CRM were characterized, and their uncertainties were combined with the value assignment process. The developed CRM can be considered a unique SI-traceable NT-proBNP reference material and is expected to be used as a primary calibrator for matrix NT-proBNP CRM development.

[22]Pentaphyrins(2.0.1.1.0) Displaying N-Fusion, Pyrrole-Rearrangement, and Dimerization Reactions Upon Oxidation and Metalation.

Exploration of expanded porphyrins with unprecedented reactivities has remained important. Here [22]pentaphyrins(2.0.1.1.0) were synthesized as a constitutional isomer of sapphyrin by acid-catalyzed cyclization of 1,14-dibromo-5,10-diaryltripyrrin with 1,2-di(pyrro-2-ly)ethenes. These pentaphyrins display roughly planar structures and varying aromaticities depending upon the vinylene structures. The 19,20-ditolyl pentaphyrin gave an N-fused product and an unprecedented pyrrole-rearranged product, depending upon the oxidation conditions. Remarkably, upon the metalation with CuCl, the N-fused product and the pyrrole-rearranged product afforded an inner ß-ß coupled face-to-face CuII complex dimer and an outer ß-ß coupled lateral CuII complex dimer, respectively, in fairly good yields. Further, [22]pentaphyrin(2.0.1.1.0) fused with a NiII porphyrin was effectively dimerized upon oxidation with MnO2 to give a 16-16' directly linked dl-dimer.

Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.

Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

A comprehensive analysis of renal cell carcinoma as first and second primary cancers.

OBJECTIVE: Second primary renal cell carcinoma (2nd RCC) refers to renal cell carcinoma (RCC) diagnosed after another unrelated malignancy. This study aims to compare the clinical manifestation, pathology, treatment, and prognostic features of patients with 2nd RCC and first primary renal cell carcinoma (1st RCC). MATERIALS AND METHODS: Data of the patients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. RESULTS: The most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than in those of 1st RCC patients. For 2nd RCC patients, fewer had clinical symptoms and renal masses tend to be smaller. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent a partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs were commonly identified in the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. CONCLUSIONS: Second RCC is not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately.

Development of hydrophilic PES membranes using F127 and HKUST-1 based on the RTIPS method: Mitigate the permeability-selectivity trade-off.

In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m2 h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.

Natural history of renal tumours in von Hippel-Lindau disease: a large retrospective study of Chinese patients.

BACKGROUND: Historically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease. METHODS: In this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease. RESULTS: The mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC. CONCLUSION: This large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.

A novel human lncRNA SANT1 cis-regulates the expression of SLC47A2 by altering SFPQ/E2F1/HDAC1 binding to the promoter region in renal cell carcinoma.

SLC47A2 encodes MATE 2-K in the kidney, which mediates the secretion of certain endogenous and exogenous compounds. SLC47A2 was dramatically repressed in patients with renal cell carcinoma (RCC), and a lower level of SLC47A2 might act as a negative prognostic marker, although the mechanism is not well understood. In this study, we aimed to investigate the mechanism via which SLC47A2 is downregulated in RCC. Based on the annotation information of the SLC47A2 locus available in the UCSC genome browser database, we identified a novel lncRNA, which is transcribed from the SLC47A2 locus and named it SANT1. Overexpression and knock-down assays were performed to investigate the effects of SANT1 on cis-regulation of SLC47A2. We verified the direct binding between SANT1 and SFPQ/E2F1/HDAC1 using the cross-linking and immunoprecipitation (CLIP) assay. Chromatin immunoprecipitation was performed to confirm the molecular mechanism via which SANT1 activates the transcription of the SLC47A2 coding region. We observed that SANT1 can cis-regulate its own genetic locus. In tumour-adjacent tissues, the SLC47A2 locus highly expresses SANT1, which can remove the regulatory SFPQ/E2F1/HDAC1 suppressor complex from the promoter region, thereby significantly increasing the levels of the H3K27ac modification and RNAPII binding. Owing to a low SANT1 level, the binding of this inhibitory complex in the promoter region is upregulated in RCC, which results in silencing of the SLC47A2 coding region. In conclusion, we identified a novel lncRNA and elucidated the mechanism via which it regulates SLC47A2 expression in RCC.

A Review of Hyperspectral Imaging for Chicken Meat Safety and Quality Evaluation: Application, Hardware, and Software.

Food quality and safety issues have received widespread attention around the world. Traditional analytical methods are cumbersome, time consuming, and disruptive. Consumers and businesses are in desperate need of a fast, nondestructive test to evaluate the safety and quality of food. Chicken is an important food source for the human diet and has a high consumption rate. Its quality and safety issues are especially important. The hyperspectral imaging (HSI) technique combines the main characteristics of the spectroscopy technique and the imaging technique to achieve fast, nondestructive testing and demonstrates great potential for evaluating the food safety and quality of chicken. For the past few years, there have been many studies on the HSI technique for the detection and evaluation of chicken meat safety and quality. Therefore, the purpose of this article is to provide a detailed overview of the HSI technique for microbiological safety detection and quality attribute assessments of chicken meat. In addition, the hardware and software used in the HSI systems are also summarized and compared. Finally, some opinions on the focus of future research and its applications in the modern poultry industry are presented.

Renal Arterial Pseudoaneurysm and Renal Arteriovenous Fistula Following Partial Nephrectomy.

INTRODUCTION: Renal arterial pseudoaneurysm (RAP) and renal arteriovenous fistula (RAVF) are rare but can cause fatal bleeding. MATERIALS AND METHODS: A retrospective review was conducted for patients undergoing partial nephrectomy (PN) in our department. The clinical features and treatment methods were analysed, and the relationships between RAP/RAVF and the surgical methods and R.E.N.A.L. score were investigated. RESULTS: Eleven patients were diagnosed with RAP/RAVF (9 with RAP and 2 with RAVF). The incidence of RAP/RAVF after laparoscopic PN showed no significant difference compared to that after open PN (p = 0.47). A low R.E.N.A.L. score was present in 6 patients, while an intermediate/high score was present in the other 5 patients. The major clinical manifestations included haematuria and haemorrhagic shock, and the median time of occurrence was 8 days after the operation. Six patients underwent an ultrasound examination. Of the 4 patients who underwent enhanced CT, 2 patients were diagnosed with RAP. All 11 patients were diagnosed by renal angiography and were cured after super-selective arterial embolization. The serum creatinine levels before and after embolization showed no significant differences (p = 0.14). CONCLUSIONS: RAP/RAVF may not have any relationship with the surgical procedure or R.E.N.A.L. score. Renal angiography and super-selective arterial embolization are the preferred methods for diagnosing and treating RAP/RAVF.

Cytoreductive nephrectomy with thrombectomy before targeted therapy improves survival for metastatic renal cell carcinoma with venous tumor thrombus: a single-center experience.

BACKGROUND: The aim of the study is to evaluate the role of cytoreductive nephrectomy (CN) with thrombectomy before targeted molecular therapy (TMT) on survival in metastatic renal cell carcinoma (mRCC) with venous tumor thrombus. METHODS: We performed a retrospective analysis of 47 patients treated in our center from April 2008 to October 2014. In the study, 20 patients underwent CN with thrombectomy followed by targeted therapy (group 1); 15 patients received targeted therapy alone (group 2); and 12 patients underwent CN with thrombectomy alone (group 3). The overall survival (OS) and cancer-specific survival (CSS) were calculated according to the Kaplan-Meier survival curve method, and prognostic variables were assessed by Cox regression analyses. RESULTS: The median follow-up times of group 1, group 2, and group 3 were 24.5, 12, and 6.5 months, respectively. During follow-up, in both group 1 and group 3, 12 patients died. In group 2, 14 patients died. The median OS of group 1, group 2, and group 3 was 22, 12, and 6 months, respectively (P < 0.001). Compared with surgery alone and targeted therapy alone, patients with cytoreductive surgery before targeted therapy had statistically better survival benefits (P < 0.001, P = 0.009, respectively). On univariate analysis, the number of metastatic sites (P = 0.004) was a statistically significant prognostic factor influencing OS. CONCLUSIONS: Our single-center experience showed that CN with thrombectomy before targeted therapy improved the survival of patients with mRCC with venous tumor thrombus. The number of metastatic sites was an independent prognostic factor influencing OS.

Validation and identification of anoikis-related lncRNA signatures for improving prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell carcinoma (ccRCC) usually has a high metastasis rate and high mortality rate. To enable precise risk stratification, there is a need for novel biomarkers. As one form of apoptosis, anoikis results from the disruption of cell-cell connection or cell-ECM attachment. However, the impact of anoikis-related lncRNAs on ccRCC has not yet received adequate attention. METHODS: The study utilized univariate Cox regression analysis in order to identify the overall survival (OS) associated anoikis-related lncRNAs (ARLs), followed by the LASSO algorithm for selection. On this basis, a risk model was subsequently established using five anoikis-related lncRNAs. To dig the inner molecular mechanism, KEGG, GO, and GSVA analyses were conducted. Additionally, the immune infiltration landscape was estimated using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. RESULTS: The study constructed a novel risk model based on five ARLs (AC092611.2, AC027601.2, AC103809.1, AL133215.2, and AL162586.1). Patients categorized as low-risk exhibited significantly better OS. Notably, the study observed marked different immune infiltration landscapes and drug sensitivity by risk stratification. Additionally, the study preliminarily explored potential signal pathways associated with risk stratification. CONCLUSION: The study exhibited the crucial role of ARLs in the carcinogenesis of ccRCC, potentially through differential immune infiltration. Furthermore, the established risk model could serve as a valuable stratification factor for predicting OS prognosis.

Carbazole Based Smaragdyrins: Synthesis, Aromaticity Switching, and Formation of a Spiro-Dimer.

Carbazole-incorporated smaragdyrin BF2-complex 3 was synthesized by SNAr reaction of 3,5-dibromo-8-mesityl-BODIPY 1 with 3,6-di(tert-butyl)-1,8-di(pyrrol-2-yl)carbazole 2 as a nucleophile. Demetalation of 3 with ZrCl4 gave the corresponding smaragdyrin free base 4 in a good yield. Oxidations of 3 and 4 with MnO2 gave smaragdyrins 5 and 6, respectively, both followed by aromaticity switching, since the oxidized products showed a moderate paratropic ring current owing to their 20π-electronic circuits. Further, treatment of 4 with [RhCl(CO)2]2 in the presence of NaOAc gave RhI complex 7, and oxidation of 3 with RuCl3 in the presence of triethylamine led to the formation of a spiro dimer product, 8.

RC48-Antibody-Drug Conjugate in Metastatic Urothelial Carcinoma: A Multicenter Real-World Study in China.

OBJECTIVES: RC48 is an antibody-drug conjugate (ADC) that targets HER2. In China, RC48 is approved for patients with HER-2-positive metastatic urothelial carcinoma (mUC) who have failed at least platinum-based chemotherapy. This study aimed to evaluate RC48 for mUC in a cohort of real-world patients. MATERIALS AND METHODS: We retrospectively collected data from 103 mUC patients from 12 centers between July 2021 and August 2023 in China. RC48 alone or with immunotherapy was administered until disease progression, intolerable toxicity, death, or other reasons. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of treatment-related adverse events (TRAEs) were evaluated. RESULTS: The median age of the patients was 68 years, and 68.0% were men. Twenty-nine (28.2%) patients received RC48 alone; 73 (70.9%) received RC48 combination therapy. The response rates were as follows: complete response in 2 (1.9%) patients, partial response in 50 (48.5%) patients, stable disease in 30 (29.1%) patients. The ORR was 50.5%. In patients with ≥80 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 and creatinine clearance rate (CCr) <30 mL/min, the ORR was 75%, 48.6%, and 40.0%, respectively. The median PFS was 6 (3.9-8.1) months, and the median OS was not reached. The most reported TRAEs were peripheral sensory neuropathy (53.4%), alopecia (42.7%), asthenia (38.8%), decreased appetite (35.9%) and weight loss (35.9%) and TRAE did not increase in patients with poor condition or impaired renal function. CONCLUSION: Administration of RC48 for real-world patients is both effective and safe. mUC patients can benefit from RC48-based therapy, regardless of their poor condition or impaired renal function.

Deciphering the Transcriptional Regulatory Network Governing Starch and Storage Protein Biosynthesis in Wheat for Breeding Improvement.

Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis, transcriptome, and epigenome profiling is conducted across key endosperm developmental stages, revealing that chromatin accessibility, H3K27ac, and H3K27me3 collectively regulate SSP and starch genes with varying impact. Population transcriptome and phenotype analyses highlight accessible promoter regions' crucial role as a genetic variation resource, influencing grain yield and quality in a core collection of wheat accessions. Integration of time-serial RNA-seq and ATAC-seq enables the construction of a hierarchical transcriptional regulatory network governing starch and SSP biosynthesis, identifying 42 high-confidence novel candidates. These candidates exhibit overlap with genetic regions associated with grain size and quality traits, and their functional significance is validated through expression-phenotype association analysis among wheat accessions and loss-of-function mutants. Functional analysis of wheat abscisic acid insensitive 3-A1 (TaABI3-A1) with genome editing knock-out lines demonstrates its role in promoting SSP accumulation while repressing starch biosynthesis through transcriptional regulation. Excellent TaABI3-A1Hap1 with enhanced grain weight is selected during the breeding process in China, linked to altered expression levels. This study unveils key regulators, advancing understanding of SSP and starch biosynthesis regulation and contributing to breeding enhancement.

Treatment options and prognostic risk factors for urachal carcinoma: A multicetnter retrospective study.

PURPOSE: Urachal carcinoma (UC) is a rare genitourinary cancer with an insidious onset, high risk of recurrence, and a poor prognosis. Surgical resection alone has difficulty in controlling the tumor. We aim to explore treatment options and prognostic risk factors for UC based on a multicenter cohort and long-term follow-up database. MATERIALS AND METHODS: The clinical data, treatment and follow-up results of 163 patients with UC in 6 medical centers were analyzed retrospectively. Kaplan-Meier analysis and a Cox proportional hazards model were used to assess the treatment options and prognostic risk factors for UC. RESULTS: Kaplan-Meier analysis showed no difference in the 5-year recurrence-free survival rate (P =0.282) or overall survival rate (P =0.673) between extended partial cystectomy (EPC) and radical cystectomy (RC) for patients at stage III and below. Whether bilateral pelvic lymph nodes were dissected was also not significantly correlated with the patient's recurrence (P =0.921) or prognosis (P =0.741). Postoperative adjuvant chemotherapy significantly reduced the recurrence rate of patients with stage Ⅲb or below (P =0.005). Combined treatment of postoperative recurrence patients prolonged the survival time of patients compared with single chemotherapy or conservative treatment (34.022±5.031 vs. 12.837±2.349 or 6.192±0.875 months, P <0.001). Kaplan-Meier and univariate Cox regression analyses showed that age >55 years, Sheldon stage, carbohydrate antigen 19-9 (CA19-9) >9.935 U/mL, carbohydrate antigen 72-4 (CA724) >6.02 U/mL, and postoperative adjuvant chemotherapy were closely related to the overall survival and recurrence-free survival of patients (P <0.05). Multivariate Cox proportional hazard regression confirmed that the Sheldon stage and CA724 >6.02 U/mL were independent recurrence risk factors. CONCLUSIONS: EPC or RC provides similar oncologic results for UC, but bilateral pelvic lymph node dissection is not necessary in early-stage patients. Postoperative adjuvant chemotherapy can significantly reduce the recurrence rate, and combination therapy may provide better survival outcomes. CA724 can predict tumor recurrence or metastasis at an early stage.

Effects of Different Combinations of Sodium Butyrate, Medium-Chain Fatty Acids and Omega-3 Polyunsaturated Fatty Acids on the Reproductive Performance of Sows and Biochemical Parameters, Oxidative Status and Intestinal Health of Their Offspring.

The aim of the study was to investigate the comparative effects of different combinations of sodium butyrate (SB), medium-chain fatty acids (MCFAs), and omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the reproductive performances of sows, as well as on the biochemical parameters, oxidative statuses, and intestinal health of the sucking piglets. A total of 30 sows were randomly allocated to five treatments: (1) control diet (CON); (2) CON with 1 g/kg of coated SB and 7.75 g/kg of coated MCFAs (SM); (3) CON with 1 g/kg of coated SB and 68.2 g/kg of coated n-3 PUFAs (SP); (4) CON with 7.75 g/kg of coated MCFAs and 68.2 g/kg of coated n-3 PUFAs (MP); (5) CON with 1 g/kg of coated SB, 7.75 g/kg of coated MCFAs and 68.2 g/kg of coated n-3 PUFA (SMP). The results showed that sows fed the SP, MP, and SMP diets had shorter weaning-to-estrus intervals than those fed the CON diet (p < 0.01). The piglets in the SM, SP, and MP groups showed higher increases in the plasma catalase and glutathione peroxidase activities than those of the CON group (p < 0.01). The diarrhea incidence of piglets in the SM, SP and SMP groups was lower than that of piglets in the CON group (p < 0.01). Additionally, the addition of SM, SP, MP, and SMP to the sow diets increased the contents of immunoglobulin A, immunoglobulin G, fat, and proteins in the colostrum (p < 0.01), as well as the plasma total superoxide dismutase activities (p < 0.01) in the suckling piglets, whereas it decreased the mRNA expressions of tumor necrosis factor-α, interleukin-1ß, and toll-like receptor 4 in the jejunum mucosa of the piglets. The relative abundances of Prevotella, Coprococcus, and Blautia in the colonic digesta of the piglets were increased in the SM group (p < 0.05), and the relative abundances of Faecalibacterium increased in the SMP group (p < 0.05), compared with the CON group. The relative abundances of Collinsella, Blautia, and Bulleidia in the MP group were higher than those in the CON group (p < 0.05). Collectively, dietary combinations of fatty acids with different chain lengths have positive effects on the growth performances and intestinal health of suckling piglets.

ZNF582 overexpression restrains the progression of clear cell renal cell carcinoma by enhancing the binding of TJP2 and ERK2 and inhibiting ERK2 phosphorylation.

Recent evidences have suggested that Zinc finger protein 582 (ZNF582) plays different important roles in various tumors, but its clinical role, biological function and regulatory mechanism in clear cell renal cell carcinoma (ccRCC) are still vague. Through analyzing GEO and TCGA-KIRC data and validation with local samples, we identified the low expression pattern of ZNF582 in ccRCC. Decreased ZNF582 expression is correlated with higher tumor stage and grade, distant metastasis and poor prognosis. By analyzing the DNA methylation data of ccRCC in TCGA-KIRC and using Massarray DNA methylation and demethylation analysis, we confirmed the hypermethylation status of ZNF582 in ccRCC and its negative regulation on ZNF582 expression. Using cell phenotype experiments and orthotopic kidney tumor growth models, we determined the inhibitory effect of ZNF582 overexpression on ccRCC growth and metastasis in vivo and in vitro. Mechanistically, using TMT (Tandem mass tags) quantitative proteomics test, Co-IP (Co-immunoprecipitation) and Western Blot experiments, we clarified that ZNF582 binds to TJP2 and up-regulates TJP2 protein expression. Increased TJP2 protein combines with ERK2 to promote ERK2 protein expression and suppresses the phosphorylation of ERK2, thereby inhibiting the growth and metastasis of ccRCC. In general, our findings provide the first solid theoretical rationale for targeting ZNF582/TJP2/ERK2 axis to improve ccRCC treatment.

Dynamic chromatin regulatory programs during embryogenesis of hexaploid wheat.

BACKGROUND: Plant and animal embryogenesis have conserved and distinct features. Cell fate transitions occur during embryogenesis in both plants and animals. The epigenomic processes regulating plant embryogenesis remain largely elusive. RESULTS: Here, we elucidate chromatin and transcriptomic dynamics during embryogenesis of the most cultivated crop, hexaploid wheat. Time-series analysis reveals stage-specific and proximal-distal distinct chromatin accessibility and dynamics concordant with transcriptome changes. Following fertilization, the remodeling kinetics of H3K4me3, H3K27ac, and H3K27me3 differ from that in mammals, highlighting considerable species-specific epigenomic dynamics during zygotic genome activation. Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition is important for embryo establishment. Later H3K27ac, H3K27me3, and chromatin accessibility undergo dramatic remodeling to establish a permissive chromatin environment facilitating the access of transcription factors to cis-elements for fate patterning. Embryonic maturation is characterized by increasing H3K27me3 and decreasing chromatin accessibility, which likely participates in restricting totipotency while preventing extensive organogenesis. Finally, epigenomic signatures are correlated with biased expression among homeolog triads and divergent expression after polyploidization, revealing an epigenomic contributor to subgenome diversification in an allohexaploid genome. CONCLUSIONS: Collectively, we present an invaluable resource for comparative and mechanistic analysis of the epigenomic regulation of crop embryogenesis.

Epigenetic modifications regulate cultivar-specific root development and metabolic adaptation to nitrogen availability in wheat.

The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture, but the involvement of epigenetic modifications remains unexplored. Here, we analyze the chromatin landscapes of two wheat cultivars (KN9204 and J411) that differ in NUE under varied nitrogen conditions. The expression of nitrogen metabolism genes is closely linked to variation in histone modification instead of differences in DNA sequence. Epigenetic modifications exhibit clear cultivar-specificity, which likely contributes to distinct agronomic traits. Additionally, low nitrogen (LN) induces H3K27ac and H3K27me3 to significantly enhance root growth in KN9204, while remarkably inducing NRT2 in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of H3K27me3 methyltransferase shows that changes in epigenetic modifications could alter the strategy preference for root development or nitrogen uptake in response to LN. Here, we show the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.

Collecting Duct Carcinoma of the Kidney: Analysis of 74 Cases From Multiple Centers.

OBJECTIVE: To comprehensively describe the manifestations, diagnosis, treatment and prognosis of the collecting duct carcinoma (CDC) of the kidney. MATERIALS AND METHODS: We retrospectively collected data from 74 patients with CDC from two centers between January 2001 and December 2020. The clinical characteristics, imaging and pathological features, and diagnostic and treatment methods were analyzed. RESULTS: The mean age of the patients was 61.5 years, and 54.1% were males. The most common symptoms were low back pain, hematuria, and fatigue. Computed tomography was not specific, with 10.8% of the patients diagnosed with urothelial carcinoma and 4.1% with infectious disease. Thirty-two patients had metastasis at presentation, while 17.6% had tumor thrombus in the venous system. Twenty-two patients underwent renal biopsy, and 50% of the patients were diagnosed with CDC. Sixty-one renal surgeries were performed, and the pathological median diameter was 6.5 cm. Eight patients received immune checkpoint inhibitors, and the objective remission rate was 50%. The median follow-up time was 16 months, while the median overall survival was 24.0 months. The univariate and multivariable analysis showed that sarcomatoid differentiation and absence of renal surgery were predictors of mortality. CONCLUSION: CDC is highly aggressive. Patients are commonly diagnosed at an advanced stage. Early surgical treatment can improve prognosis. Though there is still a lack of standard treatment, immune checkpoint inhibitors bring new hope for the treatment of CDC.