A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Mussel-Inspired Ligand Clicking and Ion Coordination on 2D Black Phosphorus for Cancer Multimodal Imaging and Therapy.

As a promising 2D nanocarrier, the biggest challenge of bare black phosphorus nanosheets (BP NSs) lies in the inherent instability, while it can be improved by surface modification strategies to a great extent. Considering the existing infirm BP NSs surface modification strategies, A mussels-inspired strong adhesive biomimetic peptide with azide groups for surface modification to increase the stability of BP NSs is synthesized. The azide groups on the peptide can quickly and precisely bind to the targeting ligand through click chemistry, solving the problem of nonspecificity of secondary modification of other mussel-mimicking materials. Besides, a catechol-Gd3+ coordination network is further constructed for magnetic resonance imaging (MRI) and inducing intracellular endo/lysosome escape. The fabricated BP-DOX@Gd/(DOPA)4 -PEG-TL nanoplatform exhibits enhanced antitumor abilities through synergetic chemo/photothermal effects both in vitro and in vivo.

Black phosphorus-Au-thiosugar nanosheets mediated photothermal induced anti-tumor effect enhancement by promoting infiltration of NK cells in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous cancer required combination therapy, such as photothermal therapy and chemotherapy. In recent years, cancer immunotherapies are rapidly evolving and are some of the most promising avenues to approach malignancies. Thus, the combination of the traditional therapies and immunotherapy in one platform may improve the efficacy for HCC treatment. RESULTS: In this work, we have prepared a black phosphorus (BP)-Au-thiosugar nanosheets (BATNS), in which Au-thiosugar coating and functionalization improved the stability of both black phosphorus nanosheets (BPNS) and gold ions in different simulated physiological environments. The compression of the BATNS band gap can convert more photon energy to heat generation compared with BPNS, resulting in higher photothermal conversion efficiency. The in vitro and in vivo results also revealed a stronger reduction on the hepatocellular carcinoma of mice and prolonged survival of disease models compared with BPNS. More importantly, BATNS showed an additional immune effect by increasing local NK cell infiltration but not T cell on the liver cancer treatment, and this immune effect was caused by the thermal effect of BATNS photothermal treatment. CONCLUSIONS: The novel BATNS could improve the stability of BPNS and simultaneously combine the cancer thermotherapy and immunotherapy leaded by local NK cell infiltration, resulting in a better therapeutic efficacy on hepatocellular carcinoma. This work also provided a new path to design BP-based materials for biomedical applications.

A coarse-grained model for mechanical behavior of phosphorene sheets.

The popularity of phosphorene (known as monolayer black phosphorus) in electronic devices relies on not only its superior electrical properties, but also its mechanical stability beyond the nanoscale. However, the mechanical performance of phosphorene beyond the nanoscale remains poorly explored owing to the spatiotemporal limitation of experimental observations, first-principles calculations, and atomistic simulations. To overcome this limitation, here a coarse-grained molecular dynamics (CG-MD) model is developed via a strain energy conservation approach to offer a new computational tool for the investigation of the mechanical properties of phosphorene beyond the nanoscale. The mechanical properties of a single phosphorene sheet are first characterized by all-atom molecular dynamics (AA-MD) simulations, followed by a force-field parameter optimization of the CG-MD model by matching these mechanical properties from AA-MD simulations. The intrinsic out-of-plane puckered feature is conserved in our CG-MD model, rendering mechanical anisotropy and heterogeneity in both the in-plane and out-of-plane directions preserved. The results indicate that our coarse-grained model is able to accurately capture the anisotropic in-plane mechanical performance of phosphorene and quantitatively reproduce Young's modulus, ultimate strength, and fracture strain under various environmental temperatures. Our CG-MD model can also capture the anisotropic out-of-plane bending stiffness of phosphorene. We demonstrate the applicability of our model in capturing the fracture toughness of phosphorene in both the armchair and zigzag directions by comparison with the results from AA-MD simulations. This CG-MD model proposed here offers greater capability to perform mechanical mesoscale simulations for phosphorene-based systems, allowing for a deeper understanding of the mechanical properties of phosphorene beyond the nanoscale, and the potential transferability of the developed force-field can help design hybrid phosphorene devices and structures.

NIR-Light-Activated Combination Therapy with a Precise Ratio of Photosensitizer and Prodrug Using a Host-Guest Strategy.

The co-delivery of photosensitizers with prodrugs sensitive to reactive oxygen species (ROS) for light-triggered ROS generation and cascaded prodrug activation has drawn tremendous attention. However, the absence of a feasible method to deliver the two components at a precise ratio has impaired the application potential. Herein, we report an efficient method to produce a nanosized platform for the delivery of an optimized ratio of the two components by the means of host-guest strategy for maximizing the combination therapy efficacy of cancer treatment. The key features of this host-guest strategy for the combination therapy are that the ratio between photosensitizer and ROS-sensitive prodrug can be easily tuned, near-infrared (NIR) irradiation can sensitize the photosensitizer and activate the paclitaxel prodrug for its release, and the accumulation process can be tracked by NIR imaging to maximize the efficacy of photodynamic and chemotherapy.

Dynamically PEGylated and Borate-Coordination-Polymer-Coated Polydopamine Nanoparticles for Synergetic Tumor-Targeted, Chemo-Photothermal Combination Therapy.

Multifunctional nanomaterials with efficient tumor-targeting and high antitumor activity are highly anticipated in the field of cancer therapy. In this work, a synergetic tumor-targeted, chemo-photothermal combined therapeutic nanoplatform based on a dynamically PEGylated, borate-coordination-polymer-coated polydopamine nanoparticle (PDA@CP-PEG) is developed. PEGylation on the multifunctional nanoparticles is dynamically achieved via the reversible covalent interaction between the surface phenylboronic acid (PBA) group and a catechol-containing poly(ethylene glycol) (PEG) molecule. Due to the acid-labile PBA/catechol complex and the weak-acid-stable PBA/sialic acid (SA) complex, the nanoparticles can exhibit a synergetic targeting property for the SA-overexpressed tumor cells, i.e., the PEG-caused "passive targeting" and PBA-triggered "active targeting" under the weakly acidic tumor microenvironment. In addition, the photothermal effect of the polydopamine core and the doxorubicin-loading capacity of the porous coordination polymer layer endow the nanoparticles with the potential for chemo-photothermal combination therapy. As expected, the in vitro and in vivo studies both verify that the multifunctional nanoparticles possess relatively lower systematic toxicity, efficient tumor targeting ability, and excellent chemo-photothermal activity for tumor inhibition. It is believed that these multifunctional nanoparticles with synergetic tumor targeting property and combined therapeutic strategies would provide an insight into the design of a high-efficiency antitumor nanoplatform for potential clinical applications.

Hnf4α Is Involved in LC-PUFA Biosynthesis by Up-Regulating Gene Transcription of Elongase in Marine Teleost Siganus canaliculatus.

The rabbitfish Siganus canaliculatus is the first marine teleost shown to be able to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors catalyzed by two fatty acyl desaturases (fad) including Δ4 Fad and Δ6/Δ5 Fad as well as two elongases (Elovl4 and Elovl5). Previously, hepatocyte nuclear factor 4α (Hnf4α) was demonstrated to be predominant in the transcriptional regulation of two fads. To clarify the regulatory mechanisms involved in rabbitfish lipogenesis, the present study focused on the regulatory role of Hnf4α to elovl5 expression and LC-PUFA biosynthesis. Bioinformatics analysis predicted two potential Hnf4α elements in elovl5 promoter, one binding site was confirmed to interact with Hnf4α by gel shift assays. Moreover, overexpression of hnf4α caused a remarkable increase both in elovl5 promoter activity and mRNA contents, while knock-down of hnf4α in S. canaliculatus hepatocyte line (SCHL) resulted in a significant decrease of elovl5 gene expression. Meanwhile, hnf4α overexpression enhanced LC-PUFA biosynthesis in SCHL cell, and intraperitoneal injection to rabbitfish juveniles with Hnf4α agonists (Alverine and Benfluorex) increased the expression of hnf4α, elvol5 and Δ4 fad, coupled with an increased proportion of total LC-PUFA in liver. The results demonstrated that Hnf4α is involved in LC-PUFA biosynthesis by up-regulating the transcription of the elovl5 gene in rabbitfish, which is the first report of Hnf4α as a transcription factor of the elovl5 gene in vertebrates.

TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.

Fracture mechanisms in multilayer phosphorene assemblies: from brittle to ductile.

The outstanding mechanical performance of nacre has stimulated numerous studies on the design of artificial nacres. Phosphorene, a new two-dimensional (2D) material, has a crystalline in-plane structure and non-bonded interaction between adjacent flakes. Therefore, multi-layer phosphorene assemblies (MLPs), in which phosphorene flakes are piled up in a staggered manner, may exhibit outstanding mechanical performance, especially exceptional toughness. Therefore, molecular dynamics simulations are performed to study the dependence of the mechanical properties on the overlap distance between adjacent phosphorene layers and the number of phosphorene flakes per layer. The results indicate that when the flake number is equal to 1, a transition of fracture patterns is observed by increasing the overlap distance, from a ductile failure controlled by interfacial friction to a brittle failure dominated by the breakage of covalent bonds inside phosphorene flakes. Moreover, the failure pattern can be tuned by changing the number of flakes in each phosphorene layer. The results imply that the ultimate strength follows a power law with the exponent -0.5 in terms of the flake number, which is in good agreement with our analytical model. Furthermore, the flake number in each phosphorene layer is optimized as 2 when the temperature is 1 K in order to potentially achieve both high toughness and strength. Moreover, our results regarding the relations between mechanical performance and overlap distance can be explained well using a shear-lag model. However, it should be pointed out that increasing the temperature of MLPs could cause the transition of fracture patterns from ductile to brittle. Therefore, the optimal flake number depends heavily on temperature to achieve both its outstanding strength and toughness. Overall, our findings unveil the fundamental mechanism at the nanoscale for MLPs as well as provide a method to design phosphorene-based structures with targeted properties via tunable overlap distance and flake number in phosphorene layers.

Nannochloropsis genomes reveal evolution of microalgal oleaginous traits.

Oleaginous microalgae are promising feedstock for biofuels, yet the genetic diversity, origin and evolution of oleaginous traits remain largely unknown. Here we present a detailed phylogenomic analysis of five oleaginous Nannochloropsis species (a total of six strains) and one time-series transcriptome dataset for triacylglycerol (TAG) synthesis on one representative strain. Despite small genome sizes, high coding potential and relative paucity of mobile elements, the genomes feature small cores of ca. 2,700 protein-coding genes and a large pan-genome of >38,000 genes. The six genomes share key oleaginous traits, such as the enrichment of selected lipid biosynthesis genes and certain glycoside hydrolase genes that potentially shift carbon flux from chrysolaminaran to TAG synthesis. The eleven type II diacylglycerol acyltransferase genes (DGAT-2) in every strain, each expressed during TAG synthesis, likely originated from three ancient genomes, including the secondary endosymbiosis host and the engulfed green and red algae. Horizontal gene transfers were inferred in most lipid synthesis nodes with expanded gene doses and many glycoside hydrolase genes. Thus multiple genome pooling and horizontal genetic exchange, together with selective inheritance of lipid synthesis genes and species-specific gene loss, have led to the enormous genetic apparatus for oleaginousness and the wide genomic divergence among present-day Nannochloropsis. These findings have important implications in the screening and genetic engineering of microalgae for biofuels.

Computational Modeling of Interfacial Behaviors in Nanocomposite Materials.

Towards understanding the bulk material response in nanocomposites, an interfacial zone model was proposed to define a variety of material interface behaviors (e.g. brittle, ductile, rubber-like, elastic-perfectly plastic behavior etc.). It also has the capability to predict bulk material response though independently control of the interface properties (e.g. stiffness, strength, toughness). The mechanical response of granular nanocomposite (i.e. nacre) was investigated through modeling the "relatively soft" organic interface as an interfacial zone among "hard" mineral tablets and simulation results were compared with experimental measurements of stress-strain curves in tension and compression tests. Through modeling varies material interfaces, we found out that the bulk material response of granular nanocomposite was regulated by the interfacial behaviors. This interfacial zone model provides a possible numerical tool for qualitatively understanding of structure-property relationships through material interface design.

An improved interfacial bonding model for material interface modeling.

An improved interfacial bonding model was proposed from potential function point of view to investigate interfacial interactions in polycrystalline materials. It characterizes both attractive and repulsive interfacial interactions and can be applied to model different material interfaces. The path dependence of work-of-separation study indicates that the transformation of separation work is smooth in normal and tangential direction and the proposed model guarantees the consistency of the cohesive constitutive model. The improved interfacial bonding model was verified through a simple compression test in a standard hexagonal structure. The error between analytical solutions and numerical results from the proposed model is reasonable in linear elastic region. Ultimately, we investigated the mechanical behavior of extrafibrillar matrix in bone and the simulation results agreed well with experimental observations of bone fracture.

Genomic Foundation of Starch-to-Lipid Switch in Oleaginous Chlorella spp.

The ability to rapidly switch the intracellular energy storage form from starch to lipids is an advantageous trait for microalgae feedstock. To probe this mechanism, we sequenced the 56.8-Mbp genome of Chlorella pyrenoidosa FACHB-9, an industrial production strain for protein, starch, and lipids. The genome exhibits positive selection and gene family expansion in lipid and carbohydrate metabolism and genes related to cell cycle and stress response. Moreover, 10 lipid metabolism genes might be originated from bacteria via horizontal gene transfer. Transcriptomic dynamics tracked via messenger RNA sequencing over six time points during metabolic switch from starch-rich heterotrophy to lipid-rich photoautotrophy revealed that under heterotrophy, genes most strongly expressed were from the tricarboxylic acid cycle, respiratory chain, oxidative phosphorylation, gluconeogenesis, glyoxylate cycle, and amino acid metabolisms, whereas those most down-regulated were from fatty acid and oxidative pentose phosphate metabolism. The shift from heterotrophy into photoautotrophy highlights up-regulation of genes from carbon fixation, photosynthesis, fatty acid biosynthesis, the oxidative pentose phosphate pathway, and starch catabolism, which resulted in a marked redirection of metabolism, where the primary carbon source of glycine is no longer supplied to cell building blocks by the tricarboxylic acid cycle and gluconeogenesis, whereas carbon skeletons from photosynthesis and starch degradation may be directly channeled into fatty acid and protein biosynthesis. By establishing the first genetic transformation in industrial oleaginous C. pyrenoidosa, we further showed that overexpression of an NAD(H) kinase from Arabidopsis (Arabidopsis thaliana) increased cellular lipid content by 110.4%, yet without reducing growth rate. These findings provide a foundation for exploiting the metabolic switch in microalgae for improved photosynthetic production of food and fuels.

Iron Oxide Nanoparticles Induce Autophagosome Accumulation through Multiple Mechanisms: Lysosome Impairment, Mitochondrial Damage, and ER Stress.

Magnetite (iron oxide, Fe3O4) nanoparticles have been widely used for drug delivery and magnetic resonance imaging (MRI). Previous studies have shown that many metal-based nanoparticles including Fe3O4 nanoparticles can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. To investigate the biosafety of Fe3O4 and PLGA-coated Fe3O4 nanoparticles, some experiments related to the mechanism of autophagy induction by these nanoparticles have been investigated. In this study, the results showed that Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticles could be taken up by the cells through cellular endocytosis. Fe3O4 nanoparticles extensively impair lysosomes and lead to the accumulation of LC3-positive autophagosomes, while PLGA-coated Fe3O4 nanoparticles reduce this destructive effect on lysosomes. Moreover, Fe3O4 nanoparticles could also cause mitochondrial damage and ER and Golgi body stresses, which induce autophagy, while PLGA-coated Fe3O4 nanoparticles reduce the destructive effect on these organelles. Thus, the Fe3O4 nanoparticle-induced autophagosome accumulation may be caused by multiple mechanisms. The autophagosome accumulation induced by Fe3O4 was also investigated. The Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticle-treated mice were sacrificed to evaluate the toxicity of these nanoparticles on the mice. The data showed that Fe3O4 nanoparticle treated mice would lead to the extensive accumulation of autophagosomes in the kidney and spleen in comparison to the PLGA-coated Fe3O4 and PLGA nanoparticles. Our data clarifies the mechanism by which Fe3O4 induces autophagosome accumulation and the mechanism of its toxicity on cell organelles and mice organs. These findings may have an important impact on the clinical application of Fe3O4 based nanoparticles.

The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. FROM THE CLINICAL EDITOR: Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect.

Progress on the autophagic regulators and receptors in plants.

Autophagy is an evolutionarily highly conserved catabolic pathway among eukaryotic cells that protects the organisms against environmental stress. Normally, autophagy is mainly involved with autophagy-related proteins(ATGs) and autophagic regulators including a series of cytoplasmic proteins and small molecules. Besides, the selective autophagy, which targets damaged organalles or protein aggregates, is mediated by the additional receptors to help the ATGs recognize different substrates. In this review, we summarize recent advances in autophagic regulators like ROS(Reactive oxygen species), TOR(Target of rapamycin) and receptors like NBR1(Neighbor of BRCA1 gene protein), RPN10(Regulatory particle non-ATPase 10) as well as their functional mechanisms mainly in Arabidopsis thaliana.

Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy.

A doxorubicin-loaded mannitol-functionalized poly(lactide-co-glycolide)-b-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (DOX-loaded M-PLGA-b-TPGS NPs) were prepared by a modified nanoprecipitation method. The NPs were characterized by the particle size, surface morphology, particle stability, in vitro drug release and cellular uptake efficiency. The NPs were near-spherical with narrow size distribution. The size of M-PLGA-b-TPGS NPs was ~110.9 nm (much smaller than ~143.7 nm of PLGA NPs) and the zeta potential was -35.8 mV (higher than -42.6 mV of PLGA NPs). The NPs exhibited a good redispersion since the particle size and surface charge hardly changed during 3-month storage period. In the release medium (phosphate buffer solution vs. fetal bovine serum), the cumulative drug release of DOX-loaded M-PLGA-b-TPGS, PLGA-b-TPGS, and PLGA NPs were 76.41 versus 83.11 %, 58.94 versus 73.44 % and 45.14 versus 53.12 %, respectively. Compared with PLGA-b-TPGS NPs and PLGA NPs, the M-PLGA-b-TPGS NPs possessed the highest cellular uptake efficiency in A549 and H1975 cells (lung cancer cells). Ultimately, both in vitro and in vivo antitumor activities were evaluated. The results showed that M-PLGA-b-TPGS NPs could achieve a significantly higher level of cytotoxicity in cancer cells and a better antitumor efficiency on xenograft BALB/c nude mice tumor model than free DOX. In conclusion, the DOX-loaded M-PLGA-b-TPGS could be used as a potential DOX-loaded nanoformulation in lung cancer chemotherapy.

Computational modeling and simulation of spall fracture in polycrystalline solids by an atomistic-based interfacial zone model.

The focus of this work is to investigate spall fracture in polycrystalline materials under high-speed impact loading by using an atomistic-based interfacial zone model. We illustrate that for polycrystalline materials, increases in the potential energy ratio between grain boundaries and grains could cause a fracture transition from intergranular to transgranular mode. We also found out that the spall strength increases when there is a fracture transition from intergranular to transgranular. In addition, analysis of grain size, crystal lattice orientation and impact speed reveals that the spall strength increases as grain size or impact speed increases.

Validation and identification of anoikis-related lncRNA signatures for improving prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell carcinoma (ccRCC) usually has a high metastasis rate and high mortality rate. To enable precise risk stratification, there is a need for novel biomarkers. As one form of apoptosis, anoikis results from the disruption of cell-cell connection or cell-ECM attachment. However, the impact of anoikis-related lncRNAs on ccRCC has not yet received adequate attention. METHODS: The study utilized univariate Cox regression analysis in order to identify the overall survival (OS) associated anoikis-related lncRNAs (ARLs), followed by the LASSO algorithm for selection. On this basis, a risk model was subsequently established using five anoikis-related lncRNAs. To dig the inner molecular mechanism, KEGG, GO, and GSVA analyses were conducted. Additionally, the immune infiltration landscape was estimated using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. RESULTS: The study constructed a novel risk model based on five ARLs (AC092611.2, AC027601.2, AC103809.1, AL133215.2, and AL162586.1). Patients categorized as low-risk exhibited significantly better OS. Notably, the study observed marked different immune infiltration landscapes and drug sensitivity by risk stratification. Additionally, the study preliminarily explored potential signal pathways associated with risk stratification. CONCLUSION: The study exhibited the crucial role of ARLs in the carcinogenesis of ccRCC, potentially through differential immune infiltration. Furthermore, the established risk model could serve as a valuable stratification factor for predicting OS prognosis.