Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1.

BACKGROUND: The clinical response rate to immune checkpoint blockade (ICB) therapy in melanoma remains low, despite its widespread use. Circular non-coding RNAs (circRNAs) are known to play a crucial role in cancer progression and may be a key factor limiting the effectiveness of ICB treatment. METHODS: The circRNAs that were downregulated after coadministration compared with single administration of PD-1 inhibitor administration were identified through RNA-seq and Ribo-seq, and thus the circPIAS1 (mmu_circ_0015773 in mouse, has_circ_0008378 in human) with high protein coding potential was revealed. Fluorescence in situ hybridization (FISH) assays were conducted to determine the localization of circPIAS1 in human and mouse melanoma cells, as well as its presence in tumor and adjacent tissues of patients. Validation through dual-luciferase reporter assay and LC-MS/MS confirmed the ability of circPIAS1 to encode a novel 108 amino acid polypeptide (circPIAS1-108aa). Specific antisense oligonucleotides (ASOs) targeting the junction site of circPIAS1 were developed to reduce its intracellular levels. Proliferation changes in melanoma cells were assessed using CCK8, EdU, and colony formation assays. The impact of circPIAS1-108aa on the ferroptosis process of melanoma cells was studied through GSH, MDA, and C11-BODIPY staining assays. Western Blot, Immunoprecipitation (IP), and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques were employed to investigate the impact of circPIAS1-108aa on the P-STAT1/SLC7A11/GPX4 signaling pathway, as well as its influence on the balance between STAT1 SUMOylation and phosphorylation. Additionally, a melanoma subcutaneous transplanted tumor mouse model was utilized to examine the combined effect of reducing circPIAS1 levels alongside PD-1 inhibitor. RESULTS: Compared with the group treated with PD-1 inhibitor alone, circPIAS1 was significantly down-regulated in the coadministration group and demonstrated higher protein coding potential. CircPIAS1, primarily localized in the nucleus, was notably upregulated in tumor tissues compared to adjacent tissues, where it plays a crucial role in promoting cancer cell proliferation. This circRNA can encode a unique polypeptide consisting of 108 amino acids, through which it exerts its cancer-promoting function and impedes the effectiveness of ICB therapy. Mechanistically, circPIAS1-108aa hinders STAT1 phosphorylation by recruiting SUMO E3 ligase Ranbp2 to enhance STAT1 SUMOylation, thereby reactivating the transduction of the SLC7A11/GPX4 signaling pathway and restricting the immunogenic ferroptosis induced by IFNγ. Furthermore, the combination of ASO-circPIAS1 with PD-1 inhibitor effectively inhibits melanoma growth and significantly enhances the efficacy of immune drugs in vivo. CONCLUSIONS: Our study uncovers a novel mechanism regarding immune evasion in melanoma driven by a unique 108aa peptide encoded by circPIAS1 in melanoma that dramatically hinders immunogenic ferroptosis triggered by ICB therapy via modulating the balance between SUMOylation and phosphorylation of STAT1. This work reveals circPIAS1-108aa as a critical factor limiting the immunotherapeutic effects in melanoma and propose a promising strategy for improving ICB treatment outcomes.

Application of Virtual and Augmented Reality Technology in Hip Surgery: Systematic Review.

BACKGROUND: Virtual and augmented reality (VAR) represents a combination of current state-of-the-art computer and imaging technologies and has the potential to be a revolutionary technology in many surgical fields. An increasing number of investigators have developed and applied VAR in hip-related surgery with the aim of using this technology to reduce hip surgery-related complications, improve surgical success rates, and reduce surgical risks. These technologies are beginning to be widely used in hip-related preoperative operation simulation and training, intraoperative navigation tools in the operating room, and postoperative rehabilitation. OBJECTIVE: With the aim of reviewing the current status of virtual reality (VR) and augmented reality (AR) in hip-related surgery and summarizing its benefits, we discussed and briefly described the applicability, advantages, limitations, and future perspectives of VR and AR techniques in hip-related surgery, such as preoperative operation simulation and training; explored the possible future applications of AR in the operating room; and discussed the bright prospects of VR and AR technologies in postoperative rehabilitation after hip surgery. METHODS: We searched the PubMed and Web of Science databases using the following key search terms: ("virtual reality" OR "augmented reality") AND ("pelvis" OR "hip"). The literature on basic and clinical research related to the aforementioned key search terms, that is, studies evaluating the key factors, challenges, or problems of using of VAR technology in hip-related surgery, was collected. RESULTS: A total of 40 studies and reports were included and classified into the following categories: total hip arthroplasty, hip resurfacing, femoral neck fracture, pelvic fracture, acetabular fracture, tumor, arthroscopy, and postoperative rehabilitation. Quality assessment could be performed in 30 studies. Among the clinical studies, there were 16 case series with an average score of 89 out of 100 points (89%) and 1 case report that scored 81 (SD 10.11) out of 100 points (81%) according to the Joanna Briggs Institute Critical Appraisal Checklist. Two cadaveric studies scored 85 of 100 points (85%) and 92 of 100 points (92%) according to the Quality Appraisal for Cadaveric Studies scale. CONCLUSIONS: VR and AR technologies hold great promise for hip-related surgeries, especially for preoperative operation simulation and training, feasibility applications in the operating room, and postoperative rehabilitation, and have the potential to assist orthopedic surgeons in operating more accurately and safely. More comparative studies are necessary, including studies focusing on clinical outcomes and cost-effectiveness.

A tartrate-EDTA-Fe complex mediates electron transfer and enhances ammonia recovery in a bioelectrochemical-stripping system.

Traditional bioelectrochemical systems (BESs) coupled with stripping units for ammonia recovery suffer from an insufficient supply of electron acceptors due to the low solubility of oxygen. In this study, we proposed a novel strategy to efficiently transport the oxidizing equivalent provided at the stripping unit to the cathode by introducing a highly soluble electron mediator (EM) into the catholyte. To validate this strategy, we developed a new kind of iron complex system (tartrate-EDTA-Fe) as the EM. EDTA-Fe contributed to the redox property with a midpoint potential of -0.075 V (vs. standard hydrogen electrode, SHE) at pH 10, whereas tartrate acted as a stabilizer to avoid iron precipitation under alkaline conditions. At a ratio of the catholyte recirculation rate to the anolyte flow rate (RC-A) of 12, the NH4 +-N recovery rate in the system with 50 mM tartrate-EDTA-Fe complex reached 6.9 ±â€¯0.2 g N m-2 d-1, approximately 3.8 times higher than that in the non-EM control. With the help of the complex, our system showed an NH4 +-N recovery performance comparable to that previously reported but with an extremely low RC-A (0.5 vs. 288). The strategy proposed here may guide the future of ammonia recovery BES scale-up because the introduction of an EM allows aeration to be performed only at the stripping unit instead of at every cathode, which is beneficial for the system design due to its simplicity and reliability.

Wire-drawing process with graphite lubricant as an industrializable approach to prepare graphite coated stainless-steel anode for bioelectrochemical systems.

Carbon coated stainless-steel (SS) electrode has been suggested to be a powerful composite electrode with high conductivity, excellent biocompatibility and good mechanical strength, which is promising for scaling up the bioelectrochemical systems (BESs). However, the already reported carbon coating methods were independent on the production of SS material. Additional steps and investment of equipment for carbon coating are costly, and the industrialization of these carbon coating processes remains challenging. In this study, we report an industrializable carbon coating approach that was embedded into the production line of the SS wire, which was realized through a wire-drawing process with graphite emulsion as the lubricant and carbon source. We found the slide of SS wire through the dies was essential for the graphite coating in terms of loading amount and stability. When the graphite coated SS wire was prepared as the anode and operated in a BESs, the current density reached 1.761 ± 0.231 mA cm-2, which was 20 times higher than that without graphite coating. Biomass analysis was then conducted, confirming the superior bioelectrochemical performance was attributed to the improvement of biocompatibility by the graphite coating layer. Furthermore, graphite coating by the wire-drawing process was systematically compared with the existing methods, which showed a comparable or even better bioelectrochemical performance but with extremely low cost (0.036 $·m-2) and seconds level of the time consumption. Overall, this study offers a cost-effective and industrializable approach to preparing graphite coated SS electrode, which may open up great opportunities to promote the development of BESs at large scale.

Solvothermal synthesis of wire-like SnxSb2Te3+x with an enhanced thermoelectric performance.

Nanostructured tellurides have attracted increasing attention in thermoelectric applications for waste heat recovery and cooling devices. Here, we report on the synthesis of wire-like SnxSb2Te3+x (x = 0, 0.02 and 0.05) nanoparticles using elemental precursors in EG. The enhanced thermoelectric performance was achieved in alloyed samples due to the increase of carrier population in heavy valence band valleys by incorporating Sn(2+) at the Sb(3+) sublattice, enabling the simultaneous realization of low electrical resistivity along with a high Seebeck coefficient as well as the decline of thermal conductivity. Thus a boosted power factor and low thermal conductivity lead to the highest ZT value of 0.58 at 150 °C in the Sn0.02Sb2Te3.02 sample. Our research offers a general wet-chemical route for the preparation of one-dimensional nanomaterials and probably promotes the practical thermoelectric applications of Sb2Te3-based materials at low temperatures.

A Facile Surfactant-Assisted Reflux Method for the Synthesis of Single-Crystalline Sb2Te3 Nanostructures with Enhanced Thermoelectric Performance.

Antimony telluride (Sb2Te3) and its based alloys are of importance to p-type semiconductors for thermoelectric applications near room temperature. Herein, we report a simple, low-energy intensive, and scalable surfactant-assisted reflux method for the synthesis of Sb2Te3 nanoparticles in the solvent ethylene glycol (EG) at low temperatures (120-180 °C). The formation mechanism of platelike Sb2Te3 nanoparticles is proposed. Also, it is found that the size, shape, and chemical composition of the products could be controlled by the introduction of organic surfactants (CTAB, PVP, etc.) or inorganic salts (EDTA-Na2, NaOH, etc.). Additionally, the collected Sb2Te3 nanoparticles were further fabricated into nanostructured pellets using cold-compaction and annealing techniques. Low resistivity [(7.37-19.4) × 10(-6) Ω m], moderate Seebeck coefficient (103-141 µV K(-1)), and high power factor (10-16 × 10(-4) W m(-1) K(-2)) have been achieved in our Sb2Te3-nanostructured bulk materials. The relatively low thermal conductivity (1.32-1.55 W m(-1) K(-1)) is attained in the nanobulk made of PVP-modified nanoparticles, and values of ZT in the range of 0.24-0.37 are realized at temperatures ranging from 50 to 200 °C. Our researches set forth a new avenue in promoting practical applications of Sb2Te3-based thermoelectric power generation or cooling devices.

Enhanced Thermochromic Properties and Solar-Heat Shielding Ability of W(x)V(1-x)O2 Thin Films with Ag Nanowires Capping Layers.

Considerable efforts have been made to shift the phase transition temperature of metal-doped vanadium dioxide (VO2) films nearer the ambient temperature while maintain the excellent thermochromic properties simultaneously. Here, we describe a facile and economic solution-based method to fabricate W-doped VO2 (V(1-x)W(x)O2) thin films with excellent thermochromic properties for the application of smart windows. The substitutional doping of tungsten atoms notably reduces the phase transition temperature to the ambient temperature and retains the excellent thermochromic property. Furthermore, Ag nanowires (NWs) are employed as capping layers to effectively decrease the thermal emissivity from 0.833 to 0.603, while the original near infrared region (NIR) modulation ability is not severely affected. Besides, the Ag NWs layers further depress the phase transition temperature as well as the hysteresis loop width, which is important to the fenestration application. These solution-grown Ag NWs/V(1-x)W(x)O2 thin films exhibit excellent solar modulation ability, narrowed hysteresis loop width as well as low thermal emissivity, which provide a promising perspective into the practical application of VO2-based smart windows.