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Aims The dysregulation of TGF‐β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF‐β signaling in glioma is currently unclear. Methods Data on glioma's RNA‐seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. “ELMER v.2” was used to reconstruct TF‐methylation‐gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. Results In glioma, a TGF‐β signaling‐related 15‐lncRNA signature was constructed, including AC010173.1, HOXA‐AS2, AC074286.1, AL592424.1, DRAIC, HOXC13‐AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC‐AS1, AGAP2‐AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP‐1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2‐AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF‐κB and ERK 1/2 in the TGF‐β signaling pathway. Conclusions A prognostic lncRNA signature of TGF‐β signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2‐AS1 plays an important role in glioma progression. A TGF‐β signaling‐related lncRNA signature has been established in glioma, which can be used for prognostic judgment, immune infiltration status speculation, and immunotherapy response prediction. Furthermore, in vitro experiments confirmed that silencing of TGF‐β signaling‐related lncRNA could inhibit the proliferation of glioma cells. This study provides candidate biomarkers with clinical application value for glioma.

Cadmium (Cd) is a high‐risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd‐induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd‐induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP‐response element binding protein at Ser133(CREBS133) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage‐dependent anion‐selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity. After cadmium (Cd) exposure, the cytosolic Ca2+‐dependent increases and activation of cAMP‐response element binding protein (CREB) orchestrally upregulates mitochondrial calcium uniporter (MCU) gene transcription, and promotes its translocation into mitochondria. The upregulated MCU in mitochondria directly interacts with voltage‐dependent anion‐selective channel protein 1 (VDAC1) and further enhances the dimerization and ubiquitination of VDAC1, which then overactivates mitophagy and leads to hepatocyte death.

Background Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. Methods We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. Results Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p  = 0.002; 69.0% (20/29) vs 40.0% (10/25), p  = 0.033; 69.0% (20/29) vs 46.4% (13/28), p  = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066–2.975; p  = 0.028). All the adverse events were transient and tolerable. Conclusion Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

The lack of a specific targeting strategy against cancer stem cells in current cancer treatment regimens is at least partly responsible for life‐threatening cytotoxicity for patients undergoing traditional chemotherapy. An effective cancer stem cell targeting system is urgently required for the next generation of cancer medicine. Epithelial cell adhesion molecule (EpCAM) is overexpressed in most solid cancers and it has recently been identified as a cancer stem cell marker. In this study, we isolated a 40‐base RNA aptamer that binds to EpCAM from a random oligonucleotide library using systematic evolution of ligands by exponential enrichment. The aptamer was further truncated to 19 bases. This 19‐nt RNA aptamer interacts specifically with a number of live human cancer cells derived from breast, colorectal, and gastric cancers that express EpCAM, but not with those not expressing EpCAM, as analyzed using flow cytometry and confocal microscopy. The binding affinity of the EpCAM RNA aptamer to human cancer cells is approximately 55 nM. Importantly, this EpCAM RNA aptamer is efficiently internalized after binding to cell surface EpCAM. To our knowledge, this is the first RNA aptamer against a cancer stem cell surface marker being developed. Such cancer stem cell aptamers will greatly facilitate the development of novel targeted nanomedicine and molecular imaging agents for cancer theranostics. (Cancer Sci 2011; 102: 991–998)

Monitoring the ecological environment quality is an important task that is often connected to achieving sustainable development. Timely and accurate monitoring can provide a scientific basis for regional land use planning and environmental protection. Based on the Google Earth Engine platform coupled with the greenness, humidity, heat, and dryness identified in remote sensing imagery, this paper constructed a remote sensing ecological index (RSEI) covering northern Anhui and quantitatively analyzed the characteristics of the spatiotemporal changes in the ecological environment quality from 2001 to 2020. Geodetector software was used to explore the mechanism driving the characteristics of spatial differentiation in the ecological environment quality. The main conclusions were as follows. First, the ecological environment quality in northern Anhui declined rapidly from 2001 to 2005, but the rate of decline slowed from 2005 to 2020 and a trend of improvement gradually emerged. The ecological environment quality of Huainan from 2001 to 2020 was better and more stable compared with other regional cities. Bengbu and Suzhou showed a trend of initially declining and then improving. Huaibei, Fuyang, and Bozhou demonstrated a trend of a fluctuating decline over time. Second, vegetation coverage was the main influencing factor of the RSEI, while rainfall was a secondary factor in northern Anhui from 2001 to 2020. Finally, interactions were observed between the factors, and the explanatory power of these factors increased significantly after the interaction. The most apparent interaction was between vegetation coverage and rainfall ( q  = 0.404). In addition, we found that vegetation abundance had a positive impact on ecological environment quality, while population density and urbanization had negative impacts, and the ecological environment quality of wetlands was the highest. Our research will provide a theoretical basis for environmental protection and support the high-quality development of northern Anhui.

Secondary fracture healing is a complex multi‐stage process in which the mechanical environment plays a key role. The use of an appropriate mechanical stimulation such as strain is conducive to tissue formation between fracture ends, thus aiding the healing process. However, if the strain is too large or too small, the biological behavior of the cells involved in bone healing will be affected, resulting in non‐union or delayed healing. In this review, we summarize the current state of knowledge regarding the effect of strain on cells that play a role in the fracture‐healing process. Overall, the related literature suggests that selection of an adequate strain promotes fracture healing through the stimulation of angiogenesis and osteogenesis, along with inhibition of osteoclast differentiation and bone resorption. However, standardized methods for the application of mechanical stimulation are lacking, and a unified consensus on the mechanism by which strain promotes cell differentiation has not yet been reached. These issues, therefore, deserve further investigation. This article summarizes the state of knowledge regarding the effect of strain on cells involved in the fracture‐healing process.

Aim Rapid anthropogenic warming coupled with changes in land use is altering the distributions of species, with consequences for ecosystem functioning and services. It is crucial to evaluate species range shifts based on understanding of the interaction of temperature with non‐climatic factors such as habitat availability and dispersal potential. Here, we aim to investigate roles of environmental temperature, habitat availability and population connectivity on the distributions of hard‐shore intertidal animals. We further examine potential roles of extensive artificial seawall construction in enabling poleward expansion of species in China, thus reshaping coastal biogeography. Location Chinese coast. Time period 2013–2017. Major taxa studied Intertidal invertebrates. Methods We took an integrative approach encompassing distributional ecology, thermal physiology, molecular genetics, heat budget modelling and larval dispersal to elucidate how interacting multiple drivers, including temperature, habitat availability and larval dispersal, determine distributions of hard‐shore invertebrates, focusing on what sets their range edges at a boundary between biogeographic provinces. Results Our results untangle the complex interactions of global climate change with the impacts of regional scale coastal development. Temperature, larval transport and habitat availability are the major proximate factors controlling the range limits of coastal marine species. The artificial shorelines provide suitable habitats for hard‐shore species on the Yangtze River Delta, and minimum temperature in winter is an important factor setting the new northern range limit of these hard‐shore species along the Chinese coast. Main conclusions In the face of global warming and global sprawl of marine hard infrastructure, species distributions, community structures and biogeographic patterns are experiencing dramatic changes. The combined influence of multiple human stressors including climate change and artificial shorelines can be evaluated by using a multidisciplinary framework, including ecological distribution, physiological sensitivity of species to these stressors, and the role of dispersal in maintaining population connectivity.

The type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system (CRISPR/Cas9) has been successfully applied to edit target genes in multiple plant species. However, it remains unknown whether this system can be used for genome editing in grape. In this study, we described genome editing and targeted gene mutation in ‘Chardonnay’ suspension cells and plants via the CRISPR/Cas9 system. Two single guide RNAs (sgRNAs) were designed to target distinct sites of the L-idonate dehydrogenase gene ( IdnDH ). CEL I endonuclease assay and sequencing results revealed the expected indel mutations at the target site, and a mutation frequency of 100% was observed in the transgenic cell mass (CM) as well as corresponding regenerated plants with expression of sgRNA1/Cas9. The majority of the detected mutations in transgenic CM were 1-bp insertions, followed by 1- to 3-nucleotide deletions. Off-target activities were also evaluated by sequencing the potential off-target sites, and no obvious off-target events were detected. Our results demonstrated that the CRISPR/Cas9 system is an efficient and specific tool for precise genome editing in grape.

Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

Cities are commonly recognized as the immediate hinterland of ports and play a crucial role in fostering the sustainable development of ports. Therefore, it is imperative to investigate the influence of cities on ports. By employing panel data from 2001 to 2021 for both ports and cities in the Bohai Rim region, this study examines the spatial spillover effect of urban economy on port efficiency using the spatial error model (SEM). The findings show that urban economies have a significant spatial spillover effect on port efficiency, but this effect diminishes across different spatial matrices. In particular, the geographical matrix demonstrates a stronger spatial spillover effect of the urban economy on port efficiency. These research findings help to establish a collaborative mechanism for port-city development and provide useful insights for government management decision-making.