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The emerging heterogeneous membranes show unprecedented superiority in harvesting the osmotic energy between ionic solutions of different salinity. However, the power densities are limited by the low interfacial transport efficiency caused by a mismatch of pore alignment and insufficient coupling between channels of different dimensions. Here we demonstrate the use of three-dimensional (3D) gel interface to achieve high-performance osmotic energy conversion through hybridizing polyelectrolyte hydrogel and aramid nanofiber membrane. The ionic diode effect of the heterogeneous membrane facilitates one-way ion diffusion, and the gel layer provides a charged 3D transport network, greatly enhancing the interfacial transport efficiency. When used for harvesting the osmotic energy from the mixing of sea and river water, the heterogeneous membrane outperforms the state-of-the-art membranes, to the best of our knowledge, with power densities of 5.06 W m −2 . The diversity of the polyelectrolyte and gel makes our strategy a potentially universal approach for osmotic energy conversion. Heterogeneous membranes show great promise in harvesting the osmotic energy, but the performance is limited by the low interfacial transport efficiency. Here, the authors report use of a three-dimensional polyelectrolyte gel interface to achieve high-performance osmotic energy conversion.

The salinity gradient between seawater and river water is a clean energy source and an alternative solution for the increasing energy demands. A membrane-based reverse electrodialysis technique is a promising strategy to convert osmotic energy to electricity. To overcome the limits of traditional membranes with low efficiency and high resistance, nanofluidic is an emerging technique to promote osmotic energy harvesting. Here, we engineer a high-performance nanofluidic device with a hybrid membrane composed of a silk nanofibril membrane and an anodic aluminum oxide membrane. The silk nanofibril membrane, as a screening layer with condensed negative surface and nanochannels, dominates the ion transport; the anodic aluminum oxide membrane, as a supporting substrate, offers tunable channels and amphoteric groups. Thus, a nanofluidic membrane with asymmetric geometry and charge polarity is established, showing low resistance, high-performance energy conversion, and long-term stability. The system paves avenues for sustainable power generation, water purification, and desalination. Membrane-based reverse electrodialysis is promising for salinity gradient power generation, but achieving efficiency and stability is challenging. Here the authors design silk nanofibril-based hybrid membranes to realize high-performance capture of osmotic energy from ambient waters.

The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA (pMEG3) in CRPC cells. An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models. The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs. PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.

Background Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. Methods Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. Results We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. Conclusion In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.

Psoriasis is an inflammatory skin disease mediated by the immune system and characterized by an inflammatory ring, also known as an epithelial immune microenvironment (EIME). The interaction between the epithelial tissue of the skin and the immune system has a crucial role in the immune cycle of psoriasis. Although the formation of new blood vessels in skin lesions provides energy support for the proliferation of epidermal keratinocytes, the role of angiogenesis in psoriasis has not been extensively studied. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis that has an important role in the development of psoriasis. VEGFA promotes angiogenesis and directly stimulates epidermal keratinocytes and infiltrating immune cells, thus contributing to the progression of psoriasis. Measuring VEGFA levels to identify angiogenic characteristics in psoriasis patients may be a predictive biomarker for disease severity and response to anti-angiogenic therapy. Clinical data have shown that anti-angiogenic therapy can improve skin lesions in psoriasis patients. Therefore, this study aimed to uncover the underestimated role of blood vessels in psoriasis, explore the relationship between VEGFA and keratinocytes in the EIME, and inspire innovative drug therapies for the treatment of psoriasis.

Two-dimensional (2D) nanofluidic channels with confined transport pathways and abundant surface functional groups have been extensively investigated to achieve osmotic energy harvesting. However, solely relying on intrinsic interlayer channels results in insufficient permeability, thereby limiting the output power densities, which poses a significant challenge to the widespread application of these materials. Herein, we present a nanoconfined sacrificial template (NST) strategy to create a crafted channel structure, termed as Turing-type nanochannels, within the membrane. Extrinsic interlaced channels are formed between the lamellae using copper hydroxide nanowires as sacrificial templates. These Turing-type nanochannels significantly increase transport pathways and functional areas, resulting in a 23% enhancement in ionic current while maintaining a cation selectivity of 0.91. The output power density of the Turing-type nanochannel membrane increases from 3.9 to 5.9 W m −2 and remains stable for at least 120 hours. This membrane exhibits enhanced applicability in real saltwater environments across China, achieving output power densities of 7.7 W m −2 in natural seawater and 9.8 W m −2 in salt-lake brine. This work demonstrates the promising potential of the Turing-channel design for nanoconfined ionic transport in the energy conversion field. High permselectivity of nanofluidics remains a challenge in osmotic energy conversion. Here, authors construct two dimensional nanofluidics with Turing-type nanochannels, which provide extrinsic pathways to improve both ion selectivity and flux, thereby achieving efficient osmotic energy harvesting.

Cuproptosis, or copper-induced cell death, has been reported as a novel noncanonical form of cell death in recent times. However, the potential roles of cuproptosis in the alteration of tumor clinicopathological features and the formation of a tumor microenvironment (TME) remain unclear. In this study, we comprehensively analyzed the cuproptosis-related molecular patterns of 1,274 colorectal cancer samples based on 16 cuproptosis regulators. The consensus clustering algorithm was conducted to identify cuproptosis-related molecular patterns and gene signatures. The ssGSEA and ESTIMATE algorithms were used to evaluate the enrichment levels of the infiltrated immune cells and tumor immune scores, respectively. The cuproptosis score was established to assess the cuproptosis patterns of individuals with principal component analysis algorithms based on the expression of cuproptosis-related genes. Three distinct cuproptosis patterns were confirmed and demonstrated to be associated with distinguishable biological processes and clinical prognosis. Interestingly, the three cuproptosis patterns were revealed to be consistent with three immune infiltration characterizations: immune-desert, immune-inflamed, and immune-excluded. Enhanced survival, activation of immune cells, and high tumor purity were presented in patients with low cuproptosisScore, implicating the immune-inflamed phenotype. In addition, low scores were linked to high tumor mutation burden, MSI-H and high CTLA4 expression, showing a higher immune cell proportion score (IPS). Taken together, our study revealed a novel cuproptosis-related molecular pattern associated with the TME phenotype. The formation of cuproptosisScore will further strengthen our understanding of the TME feature and instruct a more personalized immunotherapy schedule in colorectal cancer.

To alleviate the traffic congestion caused by the sharp increase in the number of private cars and save commuting costs, taxi carpooling service has become the choice of many people. Current research on taxi carpooling services has focused on shortening the detour distances. While with the development of intelligent cities, efficiently match passengers and vehicles and planning routes become urgent. And the privacy between passengers in the taxi carpooling service also needs to be considered. In this paper, we propose a time-optimal and privacy-preserving carpool route planning system via deep reinforcement learning. This system uses the traffic information around the carpooling vehicle to optimize passengers’ travel time, not only to efficiently match passengers and vehicles but also to generate detailed route planning for carpooling vehicles. We conducted experiments on an Internet of Vehicles simulator CARLA, and the results demonstrate that our method is better than other advanced methods and has better performance in complex environments.

UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.

Mechanisms underlying the protective effect of apolipoprotein E (APOE) ε2 against Alzheimer disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers. Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ɛ2/ɛ3 AD cases and controls. We also identified an APOE ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes and oligodendrocyte progenitor cells containing the genes C4A, C4B, and HSPA2. These genes were significantly associated with the ratio of phosphorylated tau at position 231 to total Tau but not with amyloid-β 42 level, suggesting this APOE ɛ2 related co-expression network may primarily be involved with tau pathology. HSPA2 expression was oligodendrocyte-specific and significantly associated with C4B protein. Our findings provide the first evidence of a crucial role of the complement pathway in the protective effect of APOE ε2 for AD.