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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The accurate prediction of soybean yield is of great significance for agricultural production, monitoring and early warning. Although previous studies have used machine learning algorithms to predict ...soybean yield based on meteorological data, it is not clear how different models can be used to effectively separate soybean meteorological yield from soybean yield in various regions. In addition, comprehensively integrating the advantages of various machine learning algorithms to improve the prediction accuracy through ensemble learning algorithms has not been studied in depth. This study used and analyzed various daily meteorological data and soybean yield data from 173 county-level administrative regions and meteorological stations in two principal soybean planting areas in China (Northeast China and the Huang–Huai region), covering 34 years. Three effective machine learning algorithms (K-nearest neighbor, random forest, and support vector regression) were adopted as the base-models to establish a high-precision and highly-reliable soybean meteorological yield prediction model based on the stacking ensemble learning framework. The model’s generalizability was further improved through 5-fold cross-validation, and the model was optimized by principal component analysis and hyperparametric optimization. The accuracy of the model was evaluated by using the five-year sliding prediction and four regression indicators of the 173 counties, which showed that the stacking model has higher accuracy and stronger robustness. The 5-year sliding estimations of soybean yield based on the stacking model in 173 counties showed that the prediction effect can reflect the spatiotemporal distribution of soybean yield in detail, and the mean absolute percentage error (MAPE) was less than 5%. The stacking prediction model of soybean meteorological yield provides a new approach for accurately predicting soybean yield.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Since its emergence in December 2019, corona virus disease 2019 (COVID-19) has impacted several countries, affecting more than 90 thousand patients and making it a global public threat. The routes of ...transmission are direct contact, and droplet and possible aerosol transmissions. Due to the unique nature of dentistry, most dental procedures generate significant amounts of droplets and aerosols, posing potential risks of infection transmission. Understanding the significance of aerosol transmission and its implications in dentistry can facilitate the identification and correction of negligence in daily dental practice. In addition to the standard precautions, some special precautions that should be implemented during an outbreak have been raised in this review.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating ...evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL-1β)-treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model. Knockdown of circRNA.33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP-13) expression. Knockdown of circRNA.33186 also promoted proliferation and inhibited apoptosis in IL-1β-treated chondrocytes. Silencing of circRNA.33186 in vivo markedly alleviated DMM-induced OA. Mechanistic study showed that circRNA.33186 directly binds to and inhibits miR-127-5p, thereby increasing MMP-13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.
Zhu and colleagues demonstrate that circRNA.33186 regulates chondrocyte functions, including ECM catabolism, proliferation, and apoptosis. Silencing of circRNA.33186 alleviated OA by acting as a sponge of miR-127-5p. These findings reveal a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell ...therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved.
To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization.
DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo.
Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in ...intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients.
Materials and Methods
The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor‐stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin‐stained tumor sections. CD3, CD8, and α‐smooth muscle actin (α‐SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10‐fold cross‐validation.
Results
Rich tumor stroma and strong α‐SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence‐free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor‐infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems.
Conclusion
Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients.
Implications for Practice
Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor‐node‐metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.
摘要
背景。纤维化肿瘤间质 (FTS) 被认为与促进某些肿瘤发展密切相关。在肝内胆管癌 (ICC) 样本的临床常规方面,FTS的组织学特征方便易取。本研究的目标是探求 FTS 的数量及成熟度对外科手术 ICC 患者的预后影响。此外,我们计划为术后 ICC 患者提供一份有效的预后列线图。
材料和方法。回顾性分析连续154位术后 ICC 患者的临床特征。在苏木精和伊红染色的肿瘤切片上对肿瘤间质比率和 FTS 的形态学成熟度进行了评估。在相应的组织微阵列上进行了 CD3、CD8 和 α 平滑肌肌动蛋白 (α‐SMA) 染色。列线图通过多元分析选定的变量制定而成,并经过十倍交叉验证。
结果。丰富的肿瘤基质和较强的 α‐SMA 表达与较差的总生存 (OS) 相关。但是,在多元分析中,这两种生物指标未能将 OS 和无复发生存 (RFS) 分层。未成熟的 FTS 与肿瘤多发率、临床晚期及稀少的 CD3 和 CD8 阳性肿瘤浸润性淋巴细胞 (TIL) 相关,并被认定为 OS 和 RFS 的独立预后指标。与传统的分期系统相比,由 FTS 成熟度、肿瘤数量、微血管侵犯和淋巴结转移组成的列线图具有更高的预测能力。
结论。未成熟的 FTS 是影响生存率的独立危险因素,且与 ICC 中稀少的 CD3 和 CD8 阳性 TIL 相关。整合 FTS 成熟度的预后列线图会为术后 ICC 患者提供更为准确的危险分层
This article evaluates the prognostic significance of tumor‐stroma and the maturity of fibrotic tumor stroma and α‐smooth muscle actin expression in a larger cohort of intrahepatic cholangiocarcinoma. A prognostic nomogram was established based on the findings, and it offers a simple way to predict survival with reference to the histological features of FTS in ICC.
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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Single‐ligand‐based electronically conductive porous coordination polymers/metal–organic frameworks (EC‐PCPs/MOFs) fail to meet the requirements of numerous electronic applications owing to their ...limited tunability in terms of both conductivity and topology. In this study, a new 2D π‐conjugated EC‐MOF containing copper units with mixed trigonal ligands was developed: Cu3(HHTP)(THQ) (HHTP=2,3,6,7,10,11‐hexahydrotriphenylene, THQ=tetrahydroxy‐1,4‐quinone). The modulated conductivity (σ≈2.53×10−5 S cm−1 with an activation energy of 0.30 eV) and high porosity (ca. 441.2 m2 g−1) of the Cu3(HHTP)(THQ) semiconductive nanowires provided an appropriate resistance baseline and highly accessible areas for the development of an excellent chemiresistive gas sensor.
Makes sense: As two ligands offer more opportunity than one to tune MOF conductivity and topology, a 2D π‐conjugated copper‐based electronically conductive MOF with two different trigonal organic ligands was developed (see structure). The semiconductivity and high porosity of the resulting nanowires provided a low conductivity baseline and highly accessible surface areas, thus resulting in excellent room‐temperature chemiresistive sensing properties.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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