Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Changes of paradigms about dental implant surfaces are highlighted.•Industrial and chair-side treatments enable surface decontamination and hydrophilization.•Implant’s surface characteristics at the ...time of surgical insertion are of clinical relevance.•Micro- and nanotopography as well as wettability modulate the early bioresponse.•Advanced tailored implant surfaces will further optimize future hard and soft tissue interfaces.
During the last decades, several changes of paradigm have modified our view on how biomaterials’ surface characteristics influence the bioresponse. After becoming aware of the role of a certain microroughness for improved cellular contact and osseointegration of dental titanium implants, the likewise important role of surface energy and wettability was increasingly strengthened. Very recently, synergistic effects of nanoscaled topographical features and hydrophilicity at the implant/bone interface have been reported.
Questions arise about which surface roughness and wetting data are capable to predict the bioresponse and, ultimately, the clinical performance. Current methods and approaches applied for topographical, wetting and surface energetic analyses are highlighted. Current knowledge of possible mechanisms explaining the influence of roughness and hydrophilicity at the biological interface is presented.
Most marketed and experimental surfaces are based on commonly available additive or subtractive surface modifying methods such as blasting, etching or anodizing. Different height, spatial, hybrid and functional roughness parameters have been identified as possible candidates able to predict the outcome at hard and soft tissue interfaces. Likewise, hydrophilic implants have been proven to improve the initial blood contact, to support the wound healing and thereby accelerating the osseointegration.
There is clear relevance for the influence of topographical and wetting characteristics on a macromolecular and cellular level at endosseous implant/biosystem interfaces. However, we are still far away from designing sophisticated implant surfaces with the best possible, selective functionality for each specific tissue or cavity interface. Firstly, because our knowledge of the respective surface related reactions is at best fragmentary. Secondly, because manufacturing of multi-scaled complex surfaces including distinct nanotopographies, wetting properties, and stable cleanliness is still a technical challenge and far away from being reproducibly transferred to implant surfaces.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this paper, we first study the Gorenstein projective/flat dimension of complexes of modules. The relation between the Gorenstein projective/flat dimension for complexes and that for modules are ...investigated. Then we study Tate, stable and unbounded homology for complexes of modules. In the case of module arguments, we get some results that improve the known results.
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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
Background
Liver resection is effective for hepatocellular carcinoma (HCC) exceeding the Milan criteria in selected patients. However, the benefit of anatomical resection (AR) versus non‐anatomical ...resection (NAR) has not been clarified in this patient subgroup. This study aimed to compare outcomes between AR and NAR for HCC exceeding the Milan criteria.
Methods
Data on consecutive patients with HCC exceeding the Milan criteria who underwent liver resection with curative intent over a recent 6‐year interval were extracted from a prospective single‐centre HCC database and examined retrospectively. The postoperative outcomes of patients were compared before and after propensity score matching.
Results
Some 546 patients were included: 264 in the AR and 282 in the NAR group. In the original cohort, the AR group contained more patients with larger tumours, multiple tumours, macroscopic portal vein tumour thrombi, incomplete tumour capsules and microscopic vascular invasion. After propensity score matching, 177 pairs of patients were selected. The baseline data, including liver function and tumour burden, were similar in the matched groups. The 3‐year recurrence‐free survival rate was comparable between the matched NAR and AR groups (36·5 versus 28·5 per cent; P = 0·448). Similar results were observed for 3‐year overall survival (57·5 versus 50·3 per cent; P = 0·385), recurrence patterns and early recurrence rates (57·6 per cent versus 59·9 per cent; P = 0·712).
Conclusion
AR and NAR achieved favourable and similar outcomes for HCC exceeding the Milan criteria in selected patients.
No difference
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Psoriasis is an immune‐mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, ...long‐term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti‐inflammatory, anti‐oxidant and anti‐cancerous properties. However, it is unknown whether kaempferol is also anti‐psoriatic. Here we established an imiquimod (IMQ)‐induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis‐like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3+ T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)‐6, IL‐17A and tumor necrosis factor (TNF)‐α, in the psoriatic skin lesion. It also down‐regulated proinflammatory nuclear factor kappa B (NF‐κB) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4+forkhead box protein 3 (FoxP3)+ regulatory T cell (Treg) frequency in the spleen and lymph nodes as well as FoxP3‐positive staining in the skin lesion. Conversely, depletion of CD4+CD25+ Tregs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL‐17A+CD4+ T cells in the spleen and lymph nodes of IMQ‐induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.
Kaempferol, a natural flavonol, is known to possess potent anti‐inflammatory and anti‐oxidant properties. Here, we found that kaempferol protected mice from developing psoriasis‐like skin inflammation and lesion induced by imiquimod. It also induced CD4+FoxP3+ regulatory T cells while inhibiting Th17 cell development in the psoriatic mice.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Fertilized soils have large potential for production of soil nitrogen oxide (NOx=NO+NO2), however these emissions are difficult to predict in high-temperature environments. Understanding these ...emissions may improve air quality modelling as NOx contributes to formation of tropospheric ozone (O3), a powerful air pollutant. Here we identify the environmental and management factors that regulate soil NOx emissions in a high-temperature agricultural region of California. We also investigate whether soil NOx emissions are capable of influencing regional air quality. We report some of the highest soil NOx emissions ever observed. Emissions vary nonlinearly with fertilization, temperature and soil moisture. We find that a regional air chemistry model often underestimates soil NOx emissions and NOx at the surface and in the troposphere. Adjusting the model to match NOx observations leads to elevated tropospheric O3. Our results suggest management can greatly reduce soil NOx emissions, thereby improving air quality.
Gastric cancer (GC) is among the most common malignancy in the world with poor prognosis and limited treatment options. It has been established that gastric carcinogenesis is caused by a complex ...interaction between host and environmental factors. Copy number variation (CNV) refers to a form of genomic structural variation that results in abnormal gene copy numbers, including gene amplification, gain, loss and deletion. DNA CNV is an important influential factor for the expression of both protein-coding and non-coding genes, affecting the activity of various signaling pathways. CNV arises as a result of preferential selection that favors cancer development, and thus, targeting the amplified 'driver genes' in GC may provide novel opportunities for personalized therapy. The detection of CNVs in chromosomal or mitochondrial DNA from tissue or blood samples may assist the diagnosis, prognosis and targeted therapy of GC. In this review, we discuss the recent CNV discoveries that shed light on the molecular pathogenesis of GC, with a specific emphasis on CNVs that display diagnostic, prognostic or therapeutic significances in GC.
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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
Our study examines the urban vegetation – air temperature (Ta) – land surface temperature (LST) nexus at micro- and regional-scales to better understand urban climate dynamics and the uncertainty in ...using satellite-based LST for characterizing Ta. While vegetated cooling has been repeatedly linked to reductions in urban LST, the effects of vegetation on Ta, the quantity often used to characterize urban heat islands and global warming, and on the interactions between LST and Ta are less well characterized. To address this need we quantified summer temporal and spatial variation in Ta through a network of 300 air temperature sensors in three sub-regions of greater Los Angeles, CA, which spans a coastal to desert climate gradient. Additional sensors were placed within the inland sub-region at two heights (0.1m and 2m) within three groundcover types: bare soil, irrigated grass, and underneath citrus canopy. For the entire study region, we acquired new imagery data, which allowed calculation of the normalized difference vegetation index (NDVI) and LST. At the microscale, daytime Ta measured along a vertical gradient, ranged from 6 to 3°C cooler at 0.1 and 2m, underneath tall canopy compared to bare ground respectively. At the regional scale NDVI and LST were negatively correlated (p<0.001). Relationships between diel variation in Ta and daytime LST at the regional scale were progressively weaker moving away from the coast and were generally limited to evening and nighttime hours. Relationships between NDVI and Ta were stronger during nighttime hours, yet effectiveness of mid-day vegetated cooling increased substantially at the most arid region. The effectiveness of vegetated Ta cooling increased during heat waves throughout the region. Our findings suggest an important but complex role of vegetation on LST and Ta and that vegetation may provide a negative feedback to urban climate warming.
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•We investigated the vegetation – air temperature – land surface temperature nexus in southern California.•We coupled 300 in-situ air temperature sensors with airborne measurements of a vegetation index and surface temperature.•Vegetation was associated with cooler land surface temperature during the day and air temperature at night.•Vegetation provides cooling benefits although the effects on microclimate vary by temperature, vegetation, and time of day.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We consider two-body bound states in a flat band of a multiband system. The existence of pair dispersion predicts the possibility of breaking the degeneracy of the band and creating order, such as ...superconductivity. Within a separable interaction potential approximation, we find that the finiteness of the effective mass of a bound pair is determined by a band-structure invariant, which in the uniform case becomes the quantum metric. The results offer a simple foundation to understand and predict flat-band superconductivity. We propose an experiment to test the interaction-induced pair motion.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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