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Theranostic agents with fluorescence in the second near-infrared (NIR-II) window, especially in its long-wavelength region, and NIR-II-excitable photothermal effect is promising but challenging in tumor diagnosis and therapy. Here, we report a simple but effective strategy to develop semiconducting polymer nanoparticles-based theranostic agents (PBQ

Imine covalent organic frameworks (I-COFs), including imine-linked COFs and hydrazone-linked COFs, are a new type of crystalline porous organic materials constructed by the condensation of organic monomers by the Schiff-base reaction. Because they are composed of lightweight elements linked by strong covalent bonds, I-COF materials possess the advantages of low skeleton density, large surface area, high porosity, abundant monomer species, controllable pore size, functionalized structure, diverse synthetic methods, excellent adsorption performance, outstanding physical and chemical stabilities, etc. In recent years, interest in the field of I-COFs has increased tremendously because of their exceptional performance and broad applications in gas storage, gas separation, catalysis, sensing, photoelectric materials, sample pretreatment, drug delivery, and other fields. To date, imine bonds are one of the most widely used covalent bonds in COFs, and represent one of the most important ways to obtain I-COFs with excellent chemical stabilities. The synthesis methods for I-COFs include solvothermal synthesis, microwave synthesis, mechanochemical grinding synthesis, and room-temperature synthesis methods. Solvothermal synthesis is the most extensively used method for the production of I-COFs with high specific surface areas and good thermal stabilities. The microwave synthesis method is conducive to the rapid synthesis of COFs in industry, providing a more time-saving, simpler, and safer route for large-scale preparation of I-COFs. The mechanochemical grinding synthesis of porous solids has gained importance as an alternative to conventional solvothermal synthesis, because the process is quick, environment-friendly, and potentially scalable. The room-temperature method is characterized by mild reaction conditions and rapid reactions. It is an energy-saving, economic, safe, and green synthesis method, which has emerged as a hot spot in the preparation of I-COFs in recent years. Research progress over the past years on the application of I-COFs in the field of materials science has undoubtedly established the basis of its application in analytical chemistry. Owing to the excellent physical and chemical properties of I-COF materials, they are suitable for use as separation and enrichment media for trace target compounds in complex samples. The high specific surface area and porosity, extended conjugate network skeleton, and

Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

Circular RNAs (circRNAs) have been reported to play a significant role in tumorigenesis. However, the detailed function of circRNA in prostate cancer (PCa) is still largely unknown.We quantified circTFDP2 expression in PCa tissues and adjacent normal tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, transwell, and in vivo progression and metastasis assays were applied to reveal the proliferation and metastatic abilities of circTFDP2 in PCa cells. Mass spectrometry, RNA pulldown, RNA-immunoprecipitation (RIP), western blotting and immunofluorescence were used for the mechanistic studies. qRT-PCR and RIP assays were used to explore the regulatory role of eIF4A3 in the biogenesis of circTFDP2. Finally, functional assays showed the effect of circTFDP2-containing exosomes on PCa cell progression.circTFDP2 was upregulated in PCa tissues compared with adjacent normal tissues. Furthermore, high circTFDP2 expression was positively correlated with the Gleason score. Functionally, circTFDP2 promoted PCa cell proliferation and metastasis both in vivo and in vitro. Mechanistically, circTFDP2 interacted with poly(ADP-ribose) polymerase 1 (PARP1) protein in its DNA-binding domain to prevent it from active caspase-3-dependent cleavage, and finally relieved PCa cells from DNA damage. In addition, RNA-binding protein eIF4A3 can interact with the flanking region of circTFDP2 and promote the biogenesis of circTFDP2. Moreover, exosome-derived circTFDP2 promoted PCa cell progression.In general, our study demonstrated that circTFDP2 promoted PCa cell progression through the PARP1/DNA damage axis, which may be a promising therapeutic target for PCa.

Thermally induced spin control is one of the main directions for future spin devices. In this study, we synthesized single-phase polycrystalline ErFe[Formula: see text]CrxO3 and combined the magnetization curves and Mössbauer spectra to determine the macroscopic magnetism at room temperature (RT). The magnetization of the system at various temperatures is well simulated by molecular field theory. And it is found that under the Dzyaloshinskii–Moriya (DM) interaction, not only the B-site ions undergo a reorientation process, but the spins of the A-site ions also change at the same time. The effective spin is defined as the projection of Er[Formula: see text] on the Fe[Formula: see text]/Cr[Formula: see text] spin plane, and the whole reorientation process is obtained by fitting. This study will complement the actual process of ErFe[Formula: see text]CrxO3 spin reorientation and will lay a theoretical foundation for the fabrication of future spin-controlled devices.

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.

Nanobodies, also known as single domain or VHH antibodies, are the artificial recombinant variable domains of heavy-chain-only antibodies. Nanobodies have many unique properties, including small size, good solubility, superior stability, rapid clearance from blood, and deep tissue penetration. Therefore, nanobodies have emerged as promising tools for diagnosing and treating diseases. In recent years, many deep-learning-based protein structure prediction methods have emerged that require only protein sequences as input to obtain highly-credible 3D protein structures. Among them, AlphaFold2, RoseTTAFold, DeepAb, NanoNet, and tFold performed excellently in protein prediction or antibody/nanobody prediction. In this study, we selected 60 nanobody samples with known experimental 3D structures in the Protein Data Bank (PDB). Next, we predicted their 3D structures using these five prediction algorithms from only their 2D amino acid sequences. Then, we individually compared the predicted and experimental structures. Finally, the results are analyzed and discussed.

Ultrafast spin control plays a pivotal role in condensed matter physics. In this study, we analyzed the macroscopic magnetization of the PrFe0.1Cr0.9O3 system by molecular field model fitting. And the whole process of system spin reorientation is accurately calculated in the fitting process. It is found that, unlike the rare-earth perovskites we have previously studied, PrFe0.1Cr0.9O3 exhibits spin-reversion properties during the reorientation process. This research will lay a theoretical foundation for precise spin control in the future., arXiv admin note: text overlap with arXiv:2207.03220

Nerves are important pathological elements of the microenvironment of tumors, including those in pancreatic, colon and rectal, prostate, head and neck, and breast cancers. Recent studies have associated perineural invasion with tumor progression and poor outcomes. In turn, tumors drive the reprogramming of neurons to recruit new nerve fibers. Therefore, the crosstalk between nerves and tumors is the hot topic and trend in current cancer investigations. Herein, we reviewed recent studies presenting direct supporting evidences for a better understanding of nerve–tumor interactions.

Metabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite l‐2‐hydroxyglurate (L‐2HG). L‐2HG has been reported to inhibit the activity of some α‐ketoglutarate‐dependent dioxygenases such as TET enzymes, which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L‐2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L‐2HG was significantly elevated in tumor tissues compared to adjacent tissues. Furthermore, we demonstrated that L‐2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L‐2HG‐induced VM formation. In conclusion, these findings highlighted the pathogenic link between L‐2HG and VM and suggested a novel therapeutic target for RCC., What's new? Metabolic reprograming, a hallmark of cancer, influences tumor progression. In the case of renal cell carcinoma (RCC) specifically, progression appears to be facilitated by the oncometabolite L‐2‐hydroxyglurate (L‐2HG), though underlying mechanisms remain enigmatic. Here, the authors investigated the ability of L‐2HG in RCC to promote vasculogenic mimicry (VM), in which aggressive cancer cells form vessel‐like networks that support tumor growth. Analyses of RCC patient tissues revealed elevated L‐2HG levels, wherein tumor cells with greater L‐2HG levels exhibited more VM structures. TCGA data and high‐throughput sequencing analyses further show that L‐2HG contributes to VM formation via reduction of PHLDB2 levels.

A lipid droplet (LD) is an organelle that consists of a phospholipid monolayer and a neutral lipid core, with proteins embedded in or attached to its surface. Until recently, cancers had long been regarded as genetic disorders with the abnormal activation of oncogenes and inactivation of tumor suppressor genes before their quality of a metabolic disorder began to be recognized. The last decade has witnessed the recognition of several metabolic characteristics of cancer cells, among which one is the accumulation of lipid droplets; therefore, attention has been given to exploring the role of LDs in carcinomas. In addition, there has been a remarkable expansion in understanding the complexity of LD's function in cellular homeostasis, including but not limited to energy supply, endoplasmic reticulum (ER) stress and oxidative stress management, or lipotoxicity alleviation. Thus, lipid droplet-associated proteins, which to a great extent determine the dynamics of a lipid droplet, have attracted the interest of numerous cancer researchers and their potential as cancer diagnostic biomarkers and therapeutic targets has been affirmed by emerging evidence. In this review, we systematically summarize the critical role of LDs in cancer and then focus on four categories of lipid droplet-associated proteins having the most direct influence on LD biosynthesis (diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2)), degradation (adipose triglyceride lipase (ATGL)), and two renowned protein families on the LD surface (perilipins and cell death-inducing DNA fragmentation factor alpha-like effectors (CIDEs)). In this way, we aim to highlight their important role in tumor progression and their potential in clinical applications.

Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

Covalent organic frameworks with tunable porous crystallinity and outstanding stability have exhibited fascinating pretreatment performance as ideal extraction media. Herein, the β-ketoenamine-linked TpPa-1 synthesized by 1,3,5-triformylphloroglucinol and paraphenylenediamine was employed as the absorbent for online micro-solid phase extraction of trace bisphenols combined with high-performance liquid chromatography detection. A series of characterizations indicated that the TpPa-1 possessed large surface areas, high stability, and hydrophobicity. The main experimental parameters affecting the extraction efficiency were optimized in detail. Compared with four commercial sorbents, the TpPa-1 exhibited superior enrichment capacity for extracting bisphenols. Under the optimum conditions, the established method demonstrated a wide linear range and high sensitivity with the limit of detection ranging from 0.05-0.06 μg/L. Furthermore, the developed method was successfully applied to determine bisphenols in plastic samples. Bisphenol A was actually detected in a transparent box with a concentration of 0.31 μg/g, and the recoveries of the four bisphenols in the plastic samples were 80.5-116% with the relative standard deviation less than 9.2%. Such performance was attributed to recognition affinity, including the π-π affinity, hydrophobic effect, and hydrogen bond. These results demonstrated that TpPa-1 possessed great potential to be an excellent pretreatment medium for online separation and analysis of trace analytes in complex samples.

Circular RNAs (circRNAs) have been recognized as important regulators in tumorigenesis. However, the specific role of circRNAs in prostate cancer is still largely unknown. Here, we identified that circPHF16 was downregulated in prostate cancer (PCa) tissues compared with normal tissues. Functionally, circPHF16 restrained prostate cancer metastasis both in vivo and in vitro. Mechanistically, circPHF16 directly interacted with miR-581, leading to the downregulation of ring finger protein 128 (RNF128) and inhibiting the metastatic ability of PCa. Furthermore, circPHF16-dependent upregulation of RNF128 inactivated Wnt/β-catenin signaling. In total, our findings revealed that circPHF16 suppressed prostate cancer metastasis through the circPHF16/miR-581/Wnt/β-catenin pathways.

Optimized excitation wavelength and emission window are essential for fluorescence imaging with high quality. Semiconducting polymer nanoparticles (SPNs) as fluorescent contrast agents have been extensively studied, but their imaging abilities in the second near-infrared IIb window (NIR-IIb, 1500–1700 nm) with long excitation wavelength have not been reported yet. Herein, as a proof-of-concept, we demonstrate for the first time that an SPN named L1057 nanoparticles (NPs) exhibit intense NIR-IIb signal due to its ultra-high brightness and broad emission spectrum. After screening 915 nm as an optimal excitation wavelength, we applied L1057 NPs to visualize the whole-body vessels, cerebral vessels, gastrointestinal tract, and tumor progression in different stages, achieving superior spatial resolution and signal to background ratio in the NIR-IIb window with respect to NIR-II window (1000–1700 nm). This study reveals that simultaneous optimization of excitation wavelength and emission window is an efficient strategy to enhance imaging quality and that L1057 NPs can serve as a promising NIR-IIb contrast agent for high-resolution and deep-tissue imaging.

Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear.RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis.We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment.Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Prostate cancer is one of the most prevalent forms of cancer around the world. Androgen-deprivation treatment and chemotherapy are the curative approaches used to suppress prostate cancer progression. However, drug resistance is extensively and hard to overcome even though remarkable progress has been made in recent decades. Noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, are a group of cellular RNAs which participate in various cellular processes and diseases. Recently, accumulating evidence has highlighted the vital role of non-coding RNA in the development of drug resistance in prostate cancer. In this review, we summarize the important roles of these three classes of noncoding RNA in drug resistance and the potential therapeutic applications in this disease.

e15125 Background: Upper tract urothelial carcinoma (UTUC) is histologically similar to bladder urothelial carcinoma (BUC), yet several clinical, biological and molecular features are unique to UTUC. UTUC may have unique genomic factors compared to BUC, while major knowledge gaps remain in our understanding of the biology and genomic landscape of UTUC. Methods: We retrospectively sequenced tumor samples and matched germline DNA using targeted next-generation sequencing methods and analyzed at least 642 cancer-associated genes. The cohort included 35 UTUC patients and 36 BUC patients. Results: Among all cases, KMT2D and TP53 were the most common mutations (account for 66% and 75% in UTUC and BUC, respectively). The most frequently mutated genes in UTUC were KMT2D (37%), TP53 (29%), ELF3 (26%), FGFR3 (23%), ASXL1 (20%), DKN2A (20%), DKN2B (17%), REBBP (17%), MT3B (17%), GNAS (17%) and PIK3CA (17%). The most frequently mutated genes in BUC were KMT2D (36%), TP53 (39%), MUC17 (14%), ARID1A (22%), GNAS (19%), RB1 (19%), BCL6 (19%), E2F3 (19%), EIF4A2 (19%) and FGF3 (19%). However significant differences in the prevalence of mutations in individual genes were observed. FGFR3 (23% vs. 8%) and ELF3 (26% vs. 11%) were more frequently altered, whereas RB1 (6% vs. 19%), E2F3 (3% vs. 19%) and BCL6 (3% vs. 19%) were less frequently altered in UTUC (P < 0.05). FGFR3 mutations have been shown to be oncogenic and RB1 inactivation has been associated with genomic instability in urothelial cancer in previous researches, which represent potential therapeutic targets. Conclusions: Â UTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

Highlights • SncRNAs contribute to the progress of renal cell carcinoma. • SncRNAs are promising biomarkers for diagnosis and prognosis of renal cell carcinoma. • Despite the potential of sncRNA-based cancer therapy, some obstacles remain, including several severe adverse effect., Noncoding RNAs are transcribed in the most regions of the human genome, divided into small noncoding RNAs (less than 200 nt) and long noncoding RNAs (more than 200 nt) according to their size. Compelling evidences suggest that small noncoding RNAs play critical roles in tumorigenesis and tumor progression, especially in renal cell carcinoma. MiRNA, the most famous small noncoding RNA, has been comprehensively explored for its fundamental role in cancer. And several miRNA-based therapeutic strategies have been applied to several ongoing clinical trials. However, piRNAs and tsRNAs, have not received as much research attention, because of several technological limitations. Nevertheless, some studies have revealed the presence of aberration of piRNAs and tsRNAs in renal cell carcinoma, highlighting a potentially novel mechanism for tumor onset and progression. In this review, we provide an overview of three classes of small noncoding RNA: miRNAs, piRNAs and tsRNAs, that have been reported dysregulation in renal cell carcinoma and have the potential for advancing diagnosis, prognosis and therapeutic applications of this disease., Graphical abstract Image, graphical abstract

The K0.4Co1.3[Fe(CN)6]•nH2O samples were prepared by co-precipitation method. Powder X-ray diffraction showed that only one HT phase existed in the sample prepared at room temperature ([KCoFe]RT). When the preparation temperature rises to 80℃([KCoFe]80℃), the diffraction peak intensity of primary HT phase weakened and another LT phase appeared. The HT and LT phase are both FCC crystal structure with structural parameters of 10.23 A and 9.93 A, respectively. Infrared and Mossbauer spectra indicated that part of Fe LS III –CN- Co HS II were transformed to Fe LS II –CN- Co LS III configuration when preparation temperature rises to 80℃. It indicated that preparation temperature induced charge transfer from Co II to Fe III ions occurred in present sample. Magnetic analysis showed that these cobalt iron cyanides are both ferrimagnetic. The difference of magnetic moments between the two compounds over the entire temperature range is ascribed to the fact that [KCoFe]RT has more paramagnetic central ions than [KCoFe]80℃. The difference between room temperature theoretical and experimental magnetic moments may be attributed to the weak spin–orbit coupling existing for both ions.

Nowadays, gene expression profiling has been widely used in screening out prognostic biomarkers in numerous kinds of carcinoma. Our studies attempt to construct a clinical nomogram which combines risk gene signature and clinical features for individual recurrent risk assessment and offer personalized managements for clear cell renal cell carcinoma. A total of 580 differentially expressed genes (DEGs) were identified via microarray. Functional analysis revealed that DEGs are of fundamental importance in ccRCC progression and metastasis. In our study, 338 ccRCC patients were retrospectively analysed and a risk gene signature which composed of 5 genes was obtained from a LASSO Cox regression model. Further analysis revealed that identified risk gene signature could usefully distinguish the patients with poor prognosis in training cohort (hazard ratio [HR] = 3.554, 95% confidence interval [CI] 2.261‐7.472, P

Currently, high‑throughput quantitative proteomic and transcriptomic approaches have been widely used for exploring the molecular mechanisms and acquiring biomarkers for cancers. Our study aimed to illuminate the multi-dimensional molecular mechanisms underlying renal cell carcinoma (RCC) via investigating the quantitative global proteome and the profile of phosphorylation. A total of 5,428 proteins and 8,632 phosphorylation sites were quantified in RCC tissues, with 709 proteins and 649 phosphorylation sites found to be altered in expression compared with the matched adjacent non‑tumor tissues. These differentially expressed proteins were mainly involved in metabolic process terms involving the glycolysis pathway, oxidative phosphorylation and fatty acid metabolism which have been considered to be a potential mechanism of RCC progression. Moreover, phosphorylation analysis indicated that these upregulated phosphorylated proteins are implicated in the glucagon signaling pathway and cholesterol metabolism, while the downregulated phosphorylated proteins were found to be predominantly involved in glycolysis, the pentose phosphate pathway, carbon metabolism and biosynthesis of amino acids. In addition, several new candidate proteins, CD14, MPO, NCF2, SOD2, PARP1, were found to be upregulated and MUT, ACADM, PCK1 were downregulated in RCC. These proteins may be recognized as new biomarkers for RCC. These findings could broaden our insight into the underlying molecular mechanisms of RCC and identify candidate biomarkers for the treatment of RCC.