Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our ...study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR‐129‐5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR‐129‐5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR‐129‐5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR‐129‐5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR‐129‐5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR‐129‐5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR‐129‐5p in colon cancer. Taken together, our results indicated that MALAT1/miR‐129‐5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development.
We found that MALAT1 can be identified as an oncogene in colon cancer development, and for the first time, we reported a novel mechanism for MALAT1 in colon cancer. Our results revealed that MALAT1/miR‐129‐5p/HMGB1 axis was involved in colon cancer and can act as a therapeutic indicator.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Groundwater provides critical freshwater supply, particularly in dry regions where surface water availability is limited. Climate change impacts on GWS (groundwater storage) could affect the ...sustainability of freshwater resources. Here, we used a fully-coupled climate model to investigate GWS changes over seven critical aquifers identified as significantly distressed by satellite observations. We assessed the potential climate-driven impacts on GWS changes throughout the 21
st
century under the business-as-usual scenario (RCP8.5). Results show that the climate-driven impacts on GWS changes do not necessarily reflect the long-term trend in precipitation; instead, the trend may result from enhancement of evapotranspiration, and reduction in snowmelt, which collectively lead to divergent responses of GWS changes across different aquifers. Finally, we compare the climate-driven and anthropogenic pumping impacts. The reduction in GWS is mainly due to the combined impacts of over-pumping and climate effects; however, the contribution of pumping could easily far exceed the natural replenishment.
At present, agricultural robots are produced in large quantities and used in agricultural planting, and the traditional agricultural model is gradually shifting to rely on the Internet of Things and ...sensors to accurately detect crop growth information. The scientific and rational design of agricultural robots plays a huge role in planting and production efficiency, however, the factors affecting their design are complex and ambiguous, so it is necessary to use a rational evaluation system to make a preferential decision among multiple design options.
In order to reduce the subjectivity and blindness of program selection in the process of agricultural robot design, make the decision more objective and reasonable, and thus enhance the practicality and scientificity of the program, a new comprehensive evaluation method based on user requirements is proposed.
First, after researching and interviewing users and farming operations, obtaining raw information on requirements, using the Kano model to classify the requirements and establishing an evaluation index system. Secondly, the combination of hierarchical analysis(AHP) and entropy weighting method is used to assign weights to the evaluation index system, calculate the weight value and importance ranking of each index, and carry out various program designs based on the ranking. Finally, the VIKOR method was applied to evaluate and rank the design solutions.
The new evaluation method can better complete the preferential decision of the agricultural robot design scheme and get a more perfect design scheme, which reduces the influence of human subjective thinking in the decision-making process.
The method not only corrects the traditional evaluation method, but also effectively improves the accuracy and comprehensiveness of the design evaluation process. It also provides a reference for designers to preferably select design solutions and promotes the development of small mobile machines in the context of smart agriculture.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Land surface skin temperature, a critical indicator of climate change, connects the water and energy cycles between the land and the atmosphere. Here, we evaluate the simulations of land surface skin ...temperature from the Coupled Model Intercomparison Project Phase 5 (CMIP5) and CMIP6 models with satellite‐based datasets and reanalysis. We find systematic cold skin temperature biases over arid regions in CMIP5/CMIP6 simulations. Over arid and semi‐arid regions, latent heat biases drive skin temperature biases by evaporative cooling. Over humid regions, surface downward shortwave and albedo biases are relatively more critical. Spatial patterns of biases remain similar in the latest CMIP6 simulations, suggesting systematic biases in land‐atmosphere interactions. These biases need to be corrected or considered while using models for future projections.
Plain Language Summary
Earth system models are used for future climate assessment. This study diagnoses the model performance of variables in representing the land surface energy budgets. Results show systematic and persistent cold biases over arid regions in the latest Coupled Model Intercomparison Project Phase 6 simulations, associated with overestimated evapotranspiration cooling. The aridity‐dependent biases in skin temperatures show modeled deficiencies in land‐atmosphere interactions. Results suggest a higher priority to develop and improve related processes to eliminate temperature biases in state‐of‐art climate models in dry conditions.
Key Points
Systematic wide‐ranging cold biases are found in the modeled land surface skin temperature over arid regions
Spatial patterns of biases remain similar in Coupled Model Intercomparison Project Phase 5 (CMIP5) and CMIP6 simulations
These temperature biases must be corrected before the models are used for future projections
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
G protein‐coupled estrogen receptor‐1 (GPER), a member of the G protein‐coupled receptor (GPCR) superfamily, mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. ...However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non‐BCSCs of three patient‐derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER‐mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD‐Ser118 to sustain BCSC characteristics. Transfection with a dominant‐negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.
What's new?
G protein‐coupled estrogen receptor‐1 (GPER) mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, the role of GPER in breast cancer stem cells (BCSC) biology remains unclear. Here, using patient‐derived xenografts of ER–/PR+ breast cancer, the authors found higher expression of GPER in BCSCs than non‐BCSCs. Moreover, the results indicated that stemness features were sustained via GPER‐mediated PKA/BAD phosphorylation. Stimulation by the GPER ligand tamoxifen enhanced BCSC cell viability and population and BAD phosphorylation. The findings revealed a vital role of GPER‐mediated signaling pathways in BCSC survival, suggesting GPER as a potential therapeutic target for eradicating BCSCs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The precipitation partitioning between evapotranspiration (ET) and runoff (R) at the land surface is controlled by atmospheric boundary layer and terrestrial hydrological processes. These processes ...in land surface models are manifested primarily as stomatal conductance, soil moisture limitation factor to transpiration (β‐factor), turbulence, and runoff generation. What are the sensitivities of precipitation partitioning to the parameterizations of these processes? To address this overarching question, the annual and seasonal means of ET and R over the conterminous United States were simulated using 48 configurations of the Noah land surface model with multiparameterization options (Noah‐MP). The Sobol' total sensitive index was used to quantify the sensitivity of ET and R to the parameterizations of the four processes mentioned above. Results show that the sensitivities of the annual means depend on climatic conditions and the interplay between ET and R plays an important role. In humid regions, precipitation is mostly partitioned into R, whereas the simulations can be more sensitive to ET's parameterizations. In arid regions, ET accounts for the major partition, whereas the simulations can be more sensitive to the runoff parameterization. Seasonal means exhibit different sensitivities from the annual means. The seasonal mean ET is more sensitive to ET's parameterizations, and R is more sensitive to the runoff parameterization. The β‐factor, which is neglectable for the annual means, is important for summer‐time ET. Mediated by the terrestrial water storage memories, ET interplays R across seasons. The winter‐time R is still sensitive to the stomatal conductance that only modulates growing‐season ET.
Key Points
The sensitivity of precipitation partitioning to land surface parameterizations is quantified using the Sobol' sensitivity index
The parameterization sensitivity depends on climatic conditions and seasons and varies with the time scale
The influence of stomatal conductance can extend beyond growing seasons due to the terrestrial water storage memories
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Pathological cardiac fibrosis is a common feature in multiple cardiovascular diseases that contributes to the occurrence of heart failure and life-threatening arrhythmias. Our previous study ...demonstrated that matrine could attenuate doxorubicin-induced oxidative stress and cardiomyocyte apoptosis. In this study, we investigated the effect of matrine on cardiac fibrosis. Mice received aortic banding (AB) operation or continuous injection of isoprenaline (ISO) to generate pathological cardiac fibrosis and then were exposed to matrine lavage (200 mg·kg
·d
) or an equal volume of vehicle as the control. We found that matrine lavage significantly attenuated AB or ISO-induced fibrotic remodeling and cardiac dysfunction. We also showed that matrine (200 μmol/L) significantly inhibited the proliferation, migration, collagen production, and phenotypic transdifferentiation of cardiac fibroblasts. Mechanistically, matrine suppressed p38 activation in vivo and in vitro, and overexpression of constitutively active p38 completely abolished the protective effects of matrine. We also demonstrated that ribosomal protein S5 (RPS5) upregulation was responsible for matrine-mediated inhibition on p38 and fibrogenesis. More importantly, matrine was capable of ameliorating preexisting cardiac fibrosis in mice. In conclusion, matrine treatment attenuates cardiac fibrosis by regulating RPS5/p38 signaling in mice, and it might be a promising therapeutic agent for treating pathological cardiac fibrosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells ...in patients with progressive relapsed or refractory Hodgkin lymphoma.
Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).
Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 10
CAR-positive T cell per kg (SD, 0.25; range, 1.1-2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.
CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment.
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This study investigated the polyphenol content, antioxidant activity, and inhibition ability of mushroom tyrosinase and melanogenesis of
(DT) extract. Ground DT was extracted using deionized water ...(W) or 50% ethanol (50E) at room temperature (RT) or 50 °C (50T) for 20 min. The 50T + 50E extract exhibited the highest total phenol content 47.0 ± 4.0 mg gallic acid equivalent/g DT extract, the highest level of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) free-radical scavenging 66.0 ± 3.0 mg Trolox equivalent/g DT extract, and the highest reducing power 12.00 ± 0.50 mg vitamin C equivalent/g DT extract. The RT + W extract had the highest total flavonoid content 110.0 ± 3.0 mg quercetin equivalent/g DT extract. The RT + 50E extract had the lowest half maximal inhibitory concentration 1.30 ± 0.00 mg/mL for 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging, and the lowest half maximal inhibitory concentration 6.40 ± 0.30 mg/mL for mushroom tyrosinase inhibition activity. DT extracts, especially RT + W and 50T + W, exhibited potent inhibitory effects on melanogenesis of B16/F10 cells. These results demonstrated the application potential of DT extract for skincare.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chimeric antigen receptor (CAR) T cells targeting CD19 have achieved breakthroughs in the treatment of hematological malignancies, such as relapsed/refractory non-Hodgkin lymphoma (r/rNHL); however, ...high rates of treatment failure and recurrence after CAR T-cell therapy are considerable obstacles to overcome. In this study, we designed a series of tandem CARs (TanCARs) and found that TanCAR7 T cells showed dual antigen targeting of CD19 and CD20, as well as formed superior and stable immunological synapse (IS) structures, which may be related to their robust antitumor activity. In an open-label single-arm phase 1/2a trial (NCT03097770), we enrolled 33 patients with r/rNHL; 28 patients received an infusion after conditioning chemotherapy. The primary objective was to evaluate the safety and tolerability of TanCAR7 T cells. Efficacy, progression-free survival, and overall survival were evaluated as secondary objectives. Cytokine release syndrome occurred in 14 patients (50%): 36% had grade 1 or 2 and 14% had grade 3. No cases of CAR T-cell–related encephalopathy syndrome (CRES) of grade 3 or higher were confirmed in any patient. One patient died from a treatment-associated severe pulmonary infection. The overall response rate was 79% (95% confidence interval CI, 60-92%), and the complete response rate was 71%. The progression-free survival rate at 12 months was 64% (95% CI, 43-79%). In this study, TanCAR7 T cells elicited a potent and durable antitumor response, but not grade 3 or higher CRES, in patients with r/rNHL.
•TanCAR7 T cells showed dual antigen targeting and formed superior IS structures, which may be related to their robust antitumor activity.•TanCAR7 T cells elicited a potent and durable antitumor response but not grade 3 or higher CRES in patients with r/rNHL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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