A novel cancer-associated fibroblasts risk score model predict survival and immunotherapy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs) are a special type of fibroblasts, which play an important role in the development and immune escape of tumors. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression module. In combination with univariate Cox regression and analysis of least absolute shrinkage operator (LASSO), characteristics associated with CAFs were developed for a prognostic model. The migration and proliferation of lung cancer cells were evaluated in vitro. Finally, the expression levels of proteins were analyzed by Western blot. LASSO Cox regression algorithm was then performed to select hub genes. Finally, a total of 2 Genes (COL5A2, COL6A2) were obtained. We then divided LUAD patients into high- and low-risk groups based on CAFs risk scores. Survival analysis, CAFs score correlation analysis and tumor mutation load analysis showed that COL5A2 and COL6A2 were high-risk genes for LUAD. Human Protein Atlas (HPA), western blot and PCR results showed that COL5A2 and COL6A2 were up-regulated in LUAD tissues. When COL5A2 and COL6A2 were knocked down, the proliferation, invasion and migration of lung cancer cells were significantly decreased. Finally, COL5A2 can affect LUAD progression through the Wnt/ß-Catenin and TGF-ß signaling pathways. Our CAFs risk score model offers a new approach for predicting the prognosis of LUAD patients. Furthermore, the identification of high-risk genes COL5A2 and COL6A2 and drug sensitivity analysis can provide valuable candidate clues for clinical treatment of LUAD.

Resveratrol augments paclitaxel sensitivity by modulating miR-671-5p/STOML2/PINK1/Parkin-mediated autophagy signaling in A549 cell.

BACKGROUND: Paclitaxel (PTX) resistance has become a notable clinical concern of Non-small cell lung cancer (NSCLC). Our study aim is to investigate the effects of Resveratrol (RES) on NSCLC cells that have developed resistance to PTX. The NSCLC cell line A549 was employed in this investigation to establish a PTX-resistant NSCLC cell line, denoted as A549/PTX, and established tumor transplantaton model. The presence of miR-671-5p, Stomatin-like protein 2 (STOML2), and mitophagy biomarkers was evaluated using quantitative teal-time PCR (qRT-PCR) and western blot, The assessment of cell proliferation and apoptosis was conducted through the utilisation of colony formation and flow cytometry assays. The investigation of mitochondrial autolysosomes was conducted using transmission electron microscopy (TEM). Our results showed that the application of RES therapy resulted in a substantial improvement in the sansitivity of A549/PTX cells. RES exhibited an augmentation of apoptosis and a suppression of mitophagy in A549/PTX cells. RES induced an upregulation in the expression of miR-671-5p. This, in turn, leaded to the inhibition of STOML2, a protein that directly interacts with PINK1. In summary, our research indicates that RES improved the susceptibility of A549/PTX cells to PTX through miR-671-5p-mediated STOML2 inhibition.

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer.

The immune checkpoint molecule CD70 and its receptor CD27 constitute the signal transduction axis, which is abnormally expressed in many solid tumors and is crucial for T cell co-stimulation and immune escape. Tumor cells regulate CD27 expression in the tumor microenvironment by expressing CD70, which promotes immune escape. Although current research evidence suggests a link between CD70 and tumors, no pan-cancer analysis is available. Using the Cancer Genome Atlas, Gene Expression Omnibus datasets, and online databases, we first explored the potential carcinogenic role of the CD70-CD27 signaling axis in human malignancies. Furthermore, qRT-PCR, Western blot, immunohistochemistry, and a T cell-mediated tumor cell killing assay were used to assess the biological function of the CD70-CD27 signaling axis. CD70 expression is upregulated in most cancers and has an obvious correlation with the prognosis of tumor patients. The expression of CD70 and CD27 is associated with the level of regulatory T cell (Treg) infiltration. In addition, T cell receptor signaling pathways, PI3K-AKT, NF-κB, and TNF signaling pathways are also involved in CD70-mediated immune escape. CD70 mainly regulates tumor immune escape by regulating T cell-mediated tumor killing, with Tregs possibly being its primary T cell subset. Our first pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of the CD70-CD27 signaling axis in different tumors.

Prognostic and immune microenvironment analysis of cuproptosis-related LncRNAs in breast cancer.

Breast cancer is the most common tumor and the leading cause of cancer death in women. Cuproptosis is a new type of cell death, which can induce proteotoxic stress and eventually lead to cell death. Therefore, regulating copper metabolism in tumor cells is a new therapeutic approach. Long non-coding RNAs play an important regulatory role in immune response. At present, cuproptosis-related lncRNAs in breast cancer have not been reported. Breast cancer RNA sequencing, genomic mutations, and clinical data were downloaded from The Cancer Genome Atlas (TCGA). Patients with breast cancer were randomly assigned to the train group or the test group. Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-related lncRNAs and to construct a risk prognostic model. The prediction performance of the model is verified and recognized. In addition, the nomogram was used to predict the prognosis of breast cancer patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immunoassay were used to detect the differences in biological function. Tumor mutation burden (TMB) was used to measure immunotherapy response. A total of 19 cuproptosis genes were obtained and a prognostic model based on 10 cuproptosis-related lncRNAs was constructed. Kaplan-Meier survival curves showed statistically significant overall survival (OS) between the high-risk and low-risk groups. Receiver operating characteristic curve (ROC) and principal component analysis (PCA) show that the model has accurate prediction ability. Compared with other clinical features, cuproptosis-related lncRNAs model has higher diagnostic efficiency. Univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic factor for breast cancer patients. In addition, the nomogram model analysis showed that the tumor mutation burden was significantly different between the high-risk and low-risk groups. Of note, the additive effect of patients in the high-risk group and patients with high TMB resulted in reduced survival in breast cancer patients. Our study identified 10 cuproptosis-related lncRNAs, which may be promising biomarkers for predicting the survival prognosis of breast cancer.

miR-101-3p contributes to the progression of preeclampsia by suppressing WDR5-mediated proliferation and invasion of trophoblast.

BACKGROUND: Decreased proliferation and invasion of trophoblast were proven to be involved in the pathogenesis of preeclampsia (PE). However, the regulatory network has not been clarified yet. This study aimed to explore the role of miR-101-3p in the progression of PE. METHODS: miR-101-3p expression in placentas of pregnant women with or without PE was analyzed by real-time quantitative PCR (RT-qPCR). Trophoblastic HTR-8/SVneo and HPT-8 cell lines were cultured and underwent hypoxia/reoxygenation (H/R) treatment to mimic PE in vitro. Cell proliferation and invasion were analyzed in gain-of and loss-of-function assays. Finally, we undertook in vivo studies to explore effects of miR-101-3p in the PE model. RESULTS: Compared to placentas from patients without PE, miR-101-3p expressed significantly higher in placentas from PE patients, and its level was positively correlated with the severity of patients. In vitro studies found that overexpression of miR-101-3p significantly suppressed cell proliferation and invasion, while knockdown of miR-101-3p reversed the impacts of H/R treatment. Further research showed that the expression of WD repeat domain 5 (WDR5) was significantly lower in placentas from patients with PE, and its level was negatively associated with the severity of patients. In vitro and in vivo studies confirmed that miR-101-3p promoted PE progression through the regulation of WD WDR5 expression. CONCLUSION: Increased expression of miR-101-3p in placenta contributes to the development of PE by suppressing WDR5-mediated proliferation and invasion of trophoblast.

Coupling urban 3-D information and circuit theory to advance the development of urban ecological networks.

Ongoing, rapid urban growth accompanied by habitat fragmentation and loss challenges biodiversity conservation and leads to decreases in ecosystem services. Application of the concept of ecological networks in the preservation and restoration of connections among isolated patches of natural areas is a powerful conservation strategy. However, previous approaches often failed to objectively consider the impacts of complex 3-D city environments on ecological niches. We used airborne lidar-derived information on the 3-D structure of the built environment and vegetation and detailed land use and cover data to characterize habitat quality, niche diversity, and human disturbance and to predict habitat connectivity among 38 identified habitat core areas (HCAs) in Nanjing, China. We used circuit theory and Linkage Mapper to create a landscape resistance layer, simulate habitat connectivity, and identify and prioritize important corridors. We mapped 64 links by using current flow centrality to evaluate each HCA's contribution and the links that facilitate intact connectivity. Values were highest for HCA links located in the west, south, and northeast of the study area, where natural forests with complex 3-D structures predominate. Two smaller HCA areas had high centrality scores relative to their extents, which means they could act as important stepping stones in connectivity planning. The mapped pinch-point regions had narrow and fragile links among the HCAs, suggesting they require special protection. The barriers with the highest impact scores were mainly located at the HCA connections to Purple Mountain and, based on these high scores, are more likely to indicate important locations that can be restored to improve potential connections. Our novel framework allowed us to sufficiently convey spatially explicit information to identify targets for habitat restoration and potential pathways for species movement and dispersal. Such information is critical for assessing existing or potential habitats and corridors and developing strategic plans to balance habitat conservation and other land uses based on scientifically informed connectivity planning and implementation.

Acoplamiento de la Información Urbana en 3-D y la Teoría de Circuitos para Avanzar el Desarrollo de las Redes Ecológicas Urbanas Resumen El rápido crecimiento urbano en curso acompañado por la fragmentación y pérdida de hábitats obstaculizan la conservación de la biodiversidad y llevan a una disminución de los servicios ambientales. La aplicación del concepto de redes ecológicas en la preservación y restauración de las conexiones entre los fragmentos aislados de áreas naturales es una estrategia poderosa para la conservación. Sin embargo, las estrategias previas con frecuencia han fallado al no considerar de manera objetiva los impactos del ambiente complejo y tridimensional que tienen las ciudades sobre los nichos ecológicos. Usamos información derivada de lidar aéreos sobre la estructura tridimensional del ambiente construido y de la vegetación y detallamos la información sobre el uso y la cobertura del suelo para caracterizar la calidad del hábitat, la diversidad de nichos y la perturbación humana y así predecir la conectividad de hábitat entre 38 áreas nucleares de hábitat (ANHs) en Nanjing, China. Usamos la teoría de circuitos y el programa Linkage Mapper para crear una capa de resistencia de paisaje, simular la conectividad de hábitat e identificar y priorizar los corredores importantes. Mapeamos 64 conexiones mediante la centralidad del flujo de corriente para evaluar la contribución de cada ANH y las conexiones que facilitan la conectividad intacta. Los valores más altos fueron para las conexiones de ANH ubicadas en el oeste, sur y norte del área de estudio, en donde predominan los bosques naturales con estructuras tridimensionales complejas. Dos áreas más pequeñas de ANH tuvieron puntajes altos de centralidad en relación con sus extensiones, lo que significa que podrían fungir como pasos intermedios importantes en la planeación de la conectividad. Las regiones mapeadas de los puntos de fijación tuvieron conexiones estrechas y frágiles entre las ANHs, lo que sugiere que requieren de protección especial. Las barreras con los puntajes más elevados de impacto estuvieron localizadas principalmente en las conexiones entre las ANH y la Tierra de las Montañas Púrpuras. Con base en estos puntajes elevados hay mayor probabilidad de que indiquen localidades importantes que pueden ser restauradas para mejorar el potencial de las conexiones. Nuestro novedoso marco de trabajo nos permitió transmitir adecuadamente la información espacialmente explícita para identificar los objetivos de la restauración de hábitat y los caminos potenciales para el movimiento y la dispersión de las especies. Tal información es crítica para el análisis de los hábitats y corredores existentes o potenciales y para el desarrollo de planes estratégicos para equilibrar la conservación del hábitat y otros usos de suelo con base en la planeación e implementación de la conectividad científicamente informada.

Determination of runoff response to variation in overland flow area by flow routes using UAV imagery.

Surface runoff can be routed to both pervious areas (PAs) and drainage systems during an overland flow. Excessive runoff from an impervious area (IA) flowing into a drainage system causes an overload, which can be relieved by diverting runoff to PAs. However, the hydrological link between IAs and PAs, especially the runoff response to variation in overland flow areas (OFAs), has not well been considered in runoff simulations due to the complexity of routing. To understand how the OFA within an IA contributes to runoff generation, a novel classification approach was applied to categorize the IA in a study area in Nanjing University, Xianlin campus, China into directly connected impervious area (DCIA) and indirectly connected impervious area (ICIA) by flow routes using high-resolution ground-based images (0.5 m) from an unmanned aerial vehicle. The OFAs then include DCIA and the total impervious area (TIA), which is the sum of DCIA and ICIA. The runoff simulations were supported by Storm Water Management Model (SWMM) calibrated with observed rainfall and runoff data. The resulting proportions of DCIA and ICIA of the study area were 34.13% and 10.99%, respectively. The spatial distributions of DCIA and ICIA are characterized by the subcatchment landscape heterogeneity resulting from vegetation, imperviousness, and slope. The observed runoff coefficients and peak flows were positively correlated with the percentages of DCIA and TIA. The runoff coefficient was significantly correlated with the DCIA in a light rainfall event of 18.4 mm (R2 =0.82) and with the TIA in a heavy rainfall event of 119 mm (R2 =0.92). Runoff generation is affected by both the characteristics of the rainfall event and the accompaning variations in OFAs. Results indicate that increasing of the flow connectivity from IAs to PAs and increasing the water retention capacity of PAs may be effective strategies for optimizing landscape patterns for stormwater management.

Resveratrol raises in vitro anticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression.

The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The 10 µg/ml of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or 10 µg/ml of PA also had no effect on MRC-5 normal cells. PA-L (5 µg/ml) and PA-H (10 µg/ml) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res (5 µg/ml)+PA-H (10 µg/ml) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, NF-κB, Bcl-2, Bcl-xL, procollagen I, collagen I, collagen III and CTGF, TNF-α, IL-1ß, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, IκB-α, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

Satellite-derived subsurface urban heat island.

The subsurface urban heat island (SubUHI) is one part of the overall UHI specifying the relative warmth of urban ground temperatures against the rural background. To combat the challenge on measuring extensive underground temperatures with in situ instruments, we utilized satellite-based moderate-resolution imaging spectroradiometer data to reconstruct the subsurface thermal field over the Beijing metropolis through a three-time-scale model. The results show the SubUHI's high spatial heterogeneity. Within the depths shallower than 0.5 m, the SubUHI dominates along the depth profiles and analyses imply the moments for the SubUHI intensity reaching first and second extremes during a diurnal temperature cycle are delayed about 3.25 and 1.97 h per 0.1 m, respectively. At depths shallower than 0.05 m in particular, there is a subsurface urban cool island (UCI) in spring daytime, mainly owing to the surface UCI that occurs in this period. At depths between 0.5 and 10 m, the time for the SubUHI intensity getting to its extremes during an annual temperature cycle is lagged 26.2 days per meter. Within these depths, the SubUHI prevails without exception, with an average intensity of 4.3 K, varying from 3.2 to 5.3 K.

The role of inflammation in central serous chorioretinopathy: From mechanisms to therapeutic prospects.

Central serous chorioretinopathy (CSC) is a leading cause of permanent vision loss, ranking fourth among macular diseases, trailing only age-related macular degeneration, diabetic retinopathy, and retinal vein obstruction. While mounting evidence implicates inflammation as a pivotal factor in the onset and advancement of CSC, the specific pathophysiological process and molecular mechanisms underlying inflammation remain incompletely understood. A complex network of cytokines, chemokines, and adhesion molecules interplay to trigger inflammatory and pathological cascades, highlighting the need for a comprehensive comprehension of the inflammation-related mechanisms behind CSC progression. In this piece, we examine the existing comprehension of CSC's pathology and pathogenesis. Additionally, we present an overview of the mechanisms underlying the onset and progression of CSC inflammation, followed by a thorough analysis and discussion of the potential of targeted inflammatory intervention for both preventing and treating CSC.

Mechanism Explanation on Improved Cognitive Ability of D-Gal Inducing Aged Mice Model by Lactiplantibacillus plantarum MWFLp-182 via the Microbiota-Gut-Brain Axis.

Gut microbiota can influence cognitive ability via the gut-brain axis. Lactiplantibacillus plantarum MWFLp-182 (L. plantarum MWFLp-182) was obtained from feces of long-living individuals and could exert marked antioxidant ability. Interestingly, this strain reduced the D-galactose-induced impaired cognitive ability in BALB/c mice. To comprehensively elucidate the underlying mechanism, we evaluated the colonization, antioxidant, and anti-inflammatory activities of L. plantarum MWFLp-182, along with the expression of potential genes associated with cognitive ability influenced and gut microbiota. L. plantarum MWFLp-182 enhanced the expression of anti-inflammatory cytokines, reduced the expression of proinflammatory cytokines, and increased tight junction protein expression in the colon. Moreover, L. plantarum MWFLp-182 could modify the gut microbiota. Notably, treatment with L. plantarum MWFLp-182 upregulated the expression of postsynaptic density protein-95, nuclear factor erythroid 2-related factor, nerve growth factor, superoxide dismutase, and brain-derived neurotrophic factor/neuronal nuclei, while downregulating the expression of bcl-2-associated X and malondialdehyde in the hippocampus and upregulating short-chain fatty acids against D-galactose-induced mouse brain deficits. Accordingly, L. plantarum MWFLp-182 could improve cognitive ability in a D-galactose-inducing mouse model.

Effect of salt concentration on the quality and microbial community during pickled peppers fermentation.

This work aimed to investigate the effect of salt concentration on the quality and microbial community of pickled peppers during fermentation, and the cross-correlation between microorganisms and quality was also revealed. The results showed that 9 volatile flavor compounds were unique to the low salt concentration group (D group), which also contained higher content of FAA, lactic acid and acetic acid than high salt concentration group (G group). Meanwhile, the samples of D2 group have a better texture properties. Firmicutes, Proteobacteria, Ascomycota, Lactobacillus, Pectobacterium, and Pseudomonas were detected as the main microbial community during the fermentation with different salt concentrations. Furthermore, the correlations analysis results indicated that the salt concentration has a significant effect on the microbial community of pickled peppers (p < 0.001), and Pediococcus, Lactobacillus, Cedecca, Issatchenkia, Pichia, Kazachstania, and Hanseniaspora were significantly correlated with flavors, which played crucial roles in the unique flavor formation of pickled peppers.

Mechanism underlying the effect of Pulsatilla decoction in hepatocellular carcinoma treatment: a network pharmacology and in vitro analysis.

BACKGROUND: Currently, hepatocellular carcinoma (HCC) is associated with a poor prognosis. Moreover, there exist limited strategies for treating HCC. Pulsatilla decoction (PD), a traditional Chinese medicine formula, has been used to treat inflammatory bowel disease and several cancer types. Accordingly, we explored the mechanism of PD in HCC treatment via network pharmacology and in vitro experiments. METHODS: Online databases were searched for gene data, active components, and potential target genes associated with HCC development. Subsequently, bioinformatics analysis was performed using protein-protein interaction and Network Construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) to screen for potential anticancer components and therapeutic targets of PD. Finally, the effect of PD on HCC was further verified by in vitro experiments. RESULTS: Network pharmacological analysis revealed that 65 compounds and 180 possible target genes were associated with the effect of PD on HCC. These included PI3K, AKT, NF-κB, FOS, and NFKBIA. KEGG analysis demonstrated that PD exerted its effect on HCC mainly via the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments revealed that PD could significantly inhibit cancer cell proliferation and kill HCC cells by inducing apoptosis. Furthermore, western blotting confirmed that apoptosis was mediated primarily via the PI3K-AKT, IL-17, and TNF signaling pathways. CONCLUSION: To the best of our knowledge, this is the first study to elucidate the molecular mechanism and potential targets of PD in the treatment of HCC using network pharmacology.

Determining the mechanism of pulsatilla decoction for treating gastric cancer: a network pharmacology-based study.

Background and aim: Gastric cancer (GC) is a prevalent malignancy worldwide. Pulsatilla decoction (PD), a traditional Chinese medicine formula, can treat inflammatory bowel disease and cancers. In this study, we explored the bioactive components, potential targets, and molecular mechanisms of PD in the treatment of GC. Methods: We conducted a thorough search of online databases to gather gene data, active components, and potential target genes associated with the development of GC. Subsequently, we conducted bioinformatics analysis utilizing protein-protein interaction (PPI), network construction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify potential anticancer components and therapeutic targets of PD. Finally, the efficacy of PD in treating GC was further validated through in vitro experiments. Results: Network pharmacological analysis identified 346 compounds and 180 potential target genes associated with the impact of PD on GC. The inhibitory effect of PD on GC may be mediated through modulation of key targets such as PI3K, AKT, NF-κB, FOS, NFKBIA, and others. KEGG analysis showed that PD mainly exerted its effect on GC through the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments showed that PD could significantly inhibit proliferation and kill GC cells. Moreover, PD primarily induces apoptosis in GC cells. Western blotting analysis confirmed that the PI3K-AKT, IL-17, and TNF signaling pathways are the main mechanisms by which PD exerts its cytotoxic effects on GC cells. Conclusion: We have validated the molecular mechanism and potential therapeutic targets of PD in treating GC through network pharmacological analysis, thereby demonstrating its anticancer efficacy against GC.

Temporal and spatial patterns of habitat of Nipponia nippon in China under the background of climate change.

Crested ibis (Nipponia nippon) is one of the endangered species in the International Union for Conservation of Nature. It is of great significance to pay attention to the changes of its suitable habitat in the context of climate change. Based on the geographical distribution data of crested ibis, the MaxEnt model was used to predict the suitable habitat of crested ibis under current scenario and future climate change. The results showed that the prediction accuracy of MaxEnt model was high, with an AUC value of 0.989. The minimum temperature of the coldest month, the mean temperature of the coldest quarter, and the mean annual rainfall were the dominant environmental factors affecting the habitat of crested ibis. Under current climate scenario, the area of moderately and highly suitable area of Chinese crested ibis was 10.65×104 km2, mainly distributed in Shaanxi, Sichuan, Hubei, Henan, and Gansu. In the future, the suitable habitat area of crested ibis would increase significantly under climate change, mainly distributed in Anhui, Chongqing, Guizhou, Jiangsu, Hunan, Shandong, Shaanxi, Jiangxi, Taiwan, Yunnan, Liaoning, and Fujian. In the SSP126 scenario from 2041 to 2060, the suitable habitat area of crested ibis would reach the maximum, being 139.53×104 km2 higher than that of the current climate scenario, accounting for 19.6% of the land area. This study could provide a basis for policy making on the conservation of crested ibis under global climate change.

Mixed medullary­follicular thyroid carcinoma: A case report and literature review.

Papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC) originate from follicular and neuroendocrine parafollicular C cells, respectively. PTC and MTC simultaneously exist in tumors containing both MTC and PTC features in a rare condition known as mixed medullary-follicular thyroid carcinoma (MMFTC). In the present study, a 60-year-old female presented with a small mass on the left side of the neck. Ultrasonography indicated a hyperechoic nodule measuring ~11.9×9.7 mm2 in the left lobe of the thyroid gland. The preoperative calcitonin serum value was elevated and total thyroidectomy and bilateral central compartment lymph node dissection was performed. Histological and immunohistochemical analysis of the tumor demonstrated MMFTC. No metastasis was observed in lymph nodes isolated from the bilateral central compartment. Given the rarity of MMFTC, enhancing understanding and management of such tumors is crucial.

Carbon emission reduction potential assessment in food transportation by urban agriculture: A case study of main urban area of Nanjing, China.

As an emerging urban green infrastructure and continuous productive urban landscape, urban agriculture can increase the resilience of urban food systems and reduce carbon emission in food transportation. However, there are few studies in China on the potential of urban agriculture and its role in carbon emission reduction. With semantic segmentation and spatial analysis method to identify urban agricultural potential spaces on the ground and rooftops based on satellite images and Lidar point cloud data in the main urban area of Nanjing, we estimated their potential in vegetable production and the CO2 emission reduction effect in food transportation. The results showed that there were 2904.39 hm2 of ground and 2976.96 hm2 of rooftops in the study area with the potential to be used for urban agriculture. Under a scenario with 80% potential space utilization, it could produce approximately 225000 t of vegetables per year, which equated to 43.6% of annual vegetable consumption in the study area. Meanwhile, it would reduce CO2 emission in long distance food transportation by 63700 t per year.

WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B.

PURPOSE: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. METHODS: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. RESULTS: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. CONCLUSIONS: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.

Systematic analysis of the expression profile and prognostic significance of m6A regulators and PD-L1 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. N6-methyladenosine (m6A) modification has dual biological functions in RNA modification and plays an important role in HCC. METHODS: The GEO, TCGA, ONCOMINE, UALCAN, GEPIA, Kaplan-Meier plotter, cBioPortal for Cancer Genomics, STRING and TIMER2 databases were used for bioinformatic analyses. Quantitative polymerase chain reaction and western blotting were used to detect the expression of m6A regulators in HCC tissues. RESULTS: The transcription of m6A regulators was upregulated in patients with HCC, and overexpression of YTHDF1/2, YTHDC1, RBM15 and METTL3 was significantly correlated with clinical stages of HCC. In addition, downregulation of ZC3H13 and METTL14 and upregulation of other m6A regulators were associated with a poor prognosis. A high mutation rate (89%) of m6A regulators was also observed in patients with HCC, and mutations in methylation regulators were associated with poor overall survival and disease-free survival. Finally, the expression of the YTHDF family was significantly associated with immune infiltration in the HCC microenvironment. CONCLUSION: m6A regulators and programmed death-ligand 1 may play an important role in the tumorigenesis and immune invasion and escape of HCC and may be risk factors affecting the survival of patients with HCC.

Role of N6-Methyladenosine Methylation Regulators in the Drug Therapy of Digestive System Tumours.

Digestive system tumours, including stomach, colon, esophagus, liver and pancreatic tumours, are serious diseases affecting human health. Although surgical treatment and postoperative chemoradiotherapy effectively improve patient survival, current diagnostic and therapeutic strategies for digestive system tumours lack sensitivity and specificity. Moreover, the tumour's tolerance to drug therapy is enhanced owing to tumour cell heterogeneity. Thus, primary or acquired treatment resistance is currently the main hindrance to chemotherapy efficiency. N6-methyladenosine (m6A) has various biological functions in RNA modification. m6A modification, a key regulator of transcription expression, regulates RNA metabolism and biological processes through the interaction of m6A methyltransferase ("writers") and demethylase ("erasers") with the binding protein decoding m6A methylation ("readers"). Additionally, m6A modification regulates the occurrence and development of tumours and is a potential driving factor of tumour drug resistance. This review systematically summarises the regulatory mechanisms of m6A modification in the drug therapy of digestive system malignancies. Furthermore, it clarifies the related mechanisms and therapeutic prospects of m6A modification in the resistence of digestive system malignancies to drug therapy.