Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause ...of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.
lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.
The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.
MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.
Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate‐induced ...colitis in mice. Based on flow cytometry, colitis‐associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell‐null Rag1−/− mice or upon anti‐IL‐17‐A antibody‐treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA‐driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti‐colitis effect in RAR‐α ‐mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA‐SAA1/2‐Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.
By improving retinoic acid synthesis, a novel probiotic L. intestinalis exerts a protective effect against colitis. Retinoic acid triggers epithelial gene alteration, including SAA1, SAA2, and C/EBPA, to downregulate RORγt+ Th17 cells. L. intestinalis and its associated metabolite, retinoic acid, have potential therapeutic effects for suppressing colonic inflammation.
Non‐aqueous solvents, in particular N,N‐dimethylaniline (NMP), are widely applied for electrode fabrication since most sodium layered oxide cathode materials are readily damaged by water molecules. ...However, the expensive price and poisonousness of NMP unquestionably increase the cost of preparation and post‐processing. Therefore, developing an intrinsically stable cathode material that can implement the water‐soluble binder to fabricate an electrode is urgent. Herein, a stable nanosheet‐like Mn‐based cathode material is synthesized as a prototype to verify its practical applicability in sodium‐ion batteries (SIBs). The as‐prepared material displays excellent electrochemical performance and remarkable water stability, and it still maintains a satisfactory performance of 79.6% capacity retention after 500 cycles even after water treatment. The in situ X‐ray diffraction (XRD) demonstrates that the synthesized material shows an absolute solid‐solution reaction mechanism and near‐zero‐strain. Moreover, the electrochemical performance of the electrode fabricated with a water‐soluble binder shows excellent long‐cycling stability (67.9% capacity retention after 500 cycles). This work may offer new insights into the rational design of marvelous water stability cathode materials for practical SIBs.
An intrinsic stable layered oxide cathode material with absolute solid‐solution reaction, near‐zero‐strain, and marvelous water stability is designed for demonstrating the feasibility of fabricating an electrode with a water‐soluble binder. The electrode using a water‐soluble binder exhibits comparable electrochemical performance to that fabricated with an organic‐solution binder. This work will inspire the exploration of highly water‐stable sodium layered oxide cathode materials.
We present a facile route towards a dual single‐atom nanozyme composed of Zn and Mo, which utilizes the non‐covalent nano‐assembly of polyoxometalates, supramolecular coordination complexes as the ...metal‐atom precursor, and a macroscopic amphiphilic aerogel as the supporting substrate. The dual single‐atoms of Zn and Mo have a high content (1.5 and 7.3 wt%, respectively) and exhibit a synergistic effect and a peroxidase‐like activity. The Zn/Mo site was identified as the main active center by X‐ray absorption fine structure spectroscopy and density functional theory calculation. The detection of versatile analytes, including intracellular H2O2, glucose in serum, cholesterol, and ascorbic acid in commercial beverages was achieved. The nanozyme has an outstanding stability and maintained its performance after one year's storage. This study develops a new peroxidase‐like nanozyme and provides a robust synthetic strategy for single‐atom catalysts by utilizing an aerogel as a facile substrate that is capable of stabilizing various metal atoms.
A new synthesis strategy for a dual single‐atom nanozyme has been developed by using a macroscopic polymer aerogel as the supporting substrate and supramolecular coordination complexes/polyoxometalates as the metal precursor. The nanozyme with high catalytic activity and super‐long stability has been applied in the detection of various analytes including intracellular H2O2, glucose in serum, cholesterol, and ascorbic acid in commercial beverages.
The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined ...by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06-1.19), cancer-specific mortality (1.21, 1.16-1.26), and all-cause mortality in cancer patients (1.24, 1.13-1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8-50.2) for cancer incidence and 28.2 events/100,000 person years (21.5-34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.
Osteoarthritis (OA) is a chronic disease pathologically characterized by articular cartilage degeneration and damage. Currently, studies have found that circular RNA (circRNA) is involved in ...intracellular RNA regulating network and is closely related to the occurrence and development of diseases, therefore it may become a new biological marker and therapeutic target. After stimulating chondrocytes with interleukin-1 beta (IL-1β), hsa_circ_0005105 expression was significantly upregulated, while miR-26a expression was significantly inhibited. Hsa_circ_0005105 did not influence miR-26a expression but inhibited its transcriptional activity so as to upregulate the expression of its target NAMPT. Studies further indicated that hsa_circ_0005105 can inhibit the expression of type II collagen and aggrecan, promote the expression of MMP-13 and ADAMTS-4, and the generation of PGE2, IL-6, and IL-8, but the linear sequence of hsa_circ_0005105 cannot. MiR-26a has the opposite effect, and hsa_circ_0005105 can antagonize the function of miR-26a. When NAMPT expression was downregulated, the above function of hsa_circ_0005105 was significantly weakened. Therefore, hsa_circ_0005105 can promote extracellular matrix (ECM) degradation by regulating the expression of miR-26a target NAMPT. These findings will provide new targets for treatment and prevention of OA and other orthopedic diseases.
ObjectiveTo monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer ...(mGC).DesignTargeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+ to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.ResultsThe results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.ConclusionLongitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.
Background
Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR‐125b‐2‐3p, has been identified for predicting ...chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR‐125b‐2‐3p in advanced CRC under chemotherapy have yet to be elucidated.
Methods
MiR‐125b‐2‐3p expression was detected by real‐time PCR (RT‐PCR) in CRC tissues. The effects of miR‐125b‐2‐3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR‐125b‐2‐3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on.
Results
MiR‐125b‐2‐3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR‐125b‐2‐3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR‐125b‐2‐3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR‐125b‐2‐3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR‐125b‐2‐3p inhibited the proliferation and epithelial‐mesenchymal transition (EMT) of CRC induced by lncRNA XIST.
Conclusions
Lower miR‐125b‐2‐3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. LncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC.
Low expression of miR‐125b‐2‐3p in CRC was linked to lower chemotherapeutic sensitivity and poor survival. The lncRNA XIST promoted CRC invasion and migration by functioning as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. Our findings suggest that the lncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC, which may shed light on their targeted applications.
Controlling gas sorption by simple pore modification is important in molecular recognition and industrial separation processes. In particular, it is challenging to realize the inverse selectivity, ...which reduces the adsorption of a high‐affinity gas and increases the adsorption of a low‐affinity gas. Herein, an “opposite action” strategy is demonstrated for boosting CO2/C2H2 selectivity in porous coordination polymers (PCPs). A precise steric design of channel pores using an amino group as an additional interacting site enabled the synergetic increase in CO2 adsorption while suppressing the C2H2 adsorption. Based on this strategy, two new ultramicroporous PCP physisorbents that are isostructural were synthesised. They exhibited the highest CO2 uptake and CO2/C2H2 volume uptake ratio at 298 K. Origin of this specific selectivity was verified by detailed density functional theory calculations. The breakthrough separation performances with remarkable stability and recyclability of both the PCPs render them relevant materials for C2H2 purification from CO2/C2H2 mixtures.
Boosting inverse CO2/C2H2 selectivity is achieved through precise steric design of amino groups in the pore surface to provide enhanced CO2–framework interactions and suppressed C2H2 adsorption. The obtained two new porous coordination polymers (PCPs) exhibit high CO2 uptake and strong separation performance for one‐step C2H2 purification at room temperature, which can be considered as new physisorbents with this specific inverse selectivity.
Despite wide applications of bimetallic electrocatalysis in oxygen evolution reaction (OER) owing to their superior performance, the origin of the improved performance remains elusive. The underlying ...mechanism was explored by designing and synthesizing a series of stable metal–organic frameworks (MOFs: NNU‐21–24) based on trinuclear metal carboxylate clusters and tridentate carboxylate ligands. Among the examined stable MOFs, NNU‐23 exhibits the best OER performance; particularly, compared with monometallic MOFs, all the bimetallic MOFs display improved OER activity. DFT calculations and experimental results demonstrate that introduction of the second metal atom can improve the activity of the original atom. The proposed model of bimetallic electrocatalysts affecting their OER performance can facilitate design of efficient bimetallic catalysts for energy storage and conversion, and investigation of the related catalytic mechanisms.
An iron atom in an Fe3 cluster is replaced by a second metal to form Fe2M clusters, which can serve as nodes to bridge with organic ligands and construct stable bimetallic MOFs. The introduction of the second metal atom can improve the activity of the original atom and thus improve the oxygen evolution reaction performance of electrocatalysts.
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