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Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models. The endosomal pH-responsive NP platform for systemic delivery of si TBCE and DDP for synergistic chemoresistance liver cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Angiogenesis inhibition has become a promising therapeutical strategy for cancer treatment. Current clinical anti-angiogenesis treatment includes antibodies against vascular endothelial growth factor (VEGF) or VEGF receptor, fusion proteins with high affinity to VEGF receptor, and tyrosine kinase inhibitors of VEGF receptor. However, current treatments are prone to systemic toxicity or acquiring drug resistance. A natural bioactive lipid 1,2-dipalmitoyl-sn‑glycero-3-phosphate (dipalmitoyl phosphatidic acid, DPPA) was reported to exhibit anti-angiogenic and anti-tumoral activity. However, the hydrophobic property of DPPA largely restricted its clinical use, while systemic infusion of free DPPA could result in undesirable side effects. Herein, we successfully developed DPPA-based lipid-nanoparticles (DPPA-LNPs) which turns the "therapeutic payload into nanocarrier". This strategy could improve on DPPA's hydrophiliciy, thereby facilitating its systemic administration.. DPPA-LNPs not only retained the therapeutic anti-angiogenic and anti-tumoral bioactivity of parental DPPA, but also greatly improved its tumor targeting ability via enhanced permeability and retention (EPR) effect. This strategy not only eliminates the limitation of drug encapsulation rate, toxicity of the delivery vehicle; but also enhances DPPA bioacvtity in vitro and in vivo. Systemic administration of DPPA-LNPs significantly suppressed the blood vessel formation and tumor growth of triple negative breast cancer and liver cancer growth on both xenograft tumor models. This is the first-in-kind self-therapeutic inherent lipid to be made into a nanocarrier, with inherent anti-angiogenic and anti-tumor properties. DPPA nanocarrier is fully natural, fully compatible with minimal systemic toxicity. DPPA nanocarrier can accumulate at high concentration at tumor via EPR effect, exerting both anti-angiogenic and anti-tumor effects in vivo. DPPA nanocarrier could be used to encapsulate biologics or small molecules for synergistic anti-cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

• Under pronunciation principles, this paper presents a smartphone-based pronunciation training system for practicing monophthong regarding vowel articulation. • Speech and ultrasonic signals are captured and analyzed simultaneously to determine the tongue position and shape of the lips respecting uttering vowels. • The proposed system implementing a commercial smartphone is robust with high accuracy for practical scenarios. • The evaluation for its impact on user experience shows that the proposed system has raised learning engagement and enjoyment. Learning a foreign language pronunciation is the most challenging task for non-native speakers. Improving pronunciation based on feedback on pronunciation error scores is also not easy for learners. Our goal is to develop an alternative approach to pronunciation training that can point out articulation errors at the phoneme level to users through a smartphone-based system. Using self-correction as a means of ensuring learners' engagement, we focus on self-correction of pronunciation by adjusting articulation. In order to identify articulation concerning pronunciation, the system evaluates both audible and inaudible acoustic signals to examine fine-grained frequency-shifting direction of mouth movements and tongue position simultaneously. The result shows that the system can reach an average accuracy of 99.09% and is robust in different scenarios and genders. Additionally, the evaluation of the user study reveals that the proposed system provides positive user experiences and allows learners to improve their pronunciation more efficiently. [ABSTRACT FROM AUTHOR]

The classical factors for predicting prognosis currently cannot meet the developing requirements of individualized and accurate prognostic evaluation in lung adenocarcinoma (LUAD). With the rapid development of high-throughput DNA sequencing technologies, genomic changes have been discovered. These sequencing data provide unprecedented opportunities for identifying cancer molecular subtypes. In this article, we classified LUAD into two distinct molecular subtypes (Cluster 1 and Cluster 2) based on Copy Number Variations (CNVs) and mRNA expression data from the Cancer Genome Atlas (TCGA) based on non-negative matrix factorization. Patients in Cluster 1 had worse outcomes than that in Cluster 2. Molecular features in subtypes were assessed to explain this phenomenon by analyzing differential expression genes expression pattern, which involved in cellular processes and environmental information processing. Analysis of immune cell populations suggested different distributions of CD4+ T cells, CD8+ T cells, and dendritic cells in the two subtypes. Subsequently, two novel genes, TROAP and RASGRF1, were discovered to be prognostic biomarkers in TCGA, which were confirmed in GSE31210 and Tianjin Medical University Cancer Institute and Hospital LUAD cohorts. We further proved their crucial roles in cancers by vitro experiments. TROAP mediates tumor cell proliferation, cycle, invasion, and migration, not apoptosis. RASGRF1 has a significant effect on tumor microenvironment. In conclusion, our study provides a novel insight into molecular classification based on CNVs related genes in LUAD, which may contribute to identify new molecular subtypes and target genes. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Wound dressings with multiple functions are required to meet the complexity of the wound healing process. The multifunctionality often leads to an increase in the complexity and difficulty in dressing preparation. To surmount this problem, we used a facile preparation and fabrication process to fabricate a multi-functional dressing by integrating four widely accessible materials: plain gauze, sodium alginate (SA), Ca2+ and Co2+. Firstly, mixed Ca2+/Co2+ ion solutions with different concentration were applied to gauzes. After drying, SA solution was added to ionized gauze and Co2+-Ca2+/Gauze/SA (Ion-GSA) composite dressings were formed easily. In vitro results showed that all Ion-GSA dressings exhibited strong mechanical properties, uniform dispersion and sustained release of Ca2+ and Co2+, and the ability to retain moisture and absorb wound exudate. Besides the above advantages, dressings prepared with 0.25 g/L Co2+ and 4 g/L Ca2+ (Co2+0.25-Ca2+4 GSA composite dressings) exhibited the best overall effect for inducing a hypoxia-like response, and favorable cytocompatibility, hemostatic property and antibacterial activity. In vivo wound healing assays revealed that Co2+0.25-Ca2+4 GSA composite dressings inhibited bacterial growth, increased local Hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) protein expression, and accelerated full-thickness skin wound healing in mouse bacterial-infected wound model. The quick healing wounds had improved angiogenesis, macrophages regulation, re-epithelialization and dense collagen deposition. Collectively, our results indicated that Co2+0.25-Ca2+4 GSA composite dressings promote wound healing. Statement of Significance Wound dressings with integrated functionalities are required to meet complex clinical requirements. However, there is often a trade-off between reducing preparation complexity and increasing the multifunctionality of the dressing's properties. In this study, we prepared multifunctional composite dressings by a facile preparation process using widely accessible materials. The composite dressings possessed the mechanical strength of gauze, had the effective wound exudate absorption, moisture maintenance and hemostatic property capacity of calcium alginate hydrogels, and had the hypoxia-like induction and the antimicrobial effects of Co2+. These functions all together promote bacteria-infected wound healing. Thus, we believed that the composite dressings can be widely applied in skin wound repair duo to their facile preparation method and good therapeutic effect. [ABSTRACT FROM AUTHOR]

Diabetes has been associated with postoperative complications, such as increased risk of tissue infection and impaired tissue repair caused by destabilization of hypoxia-inducible factor-1α (HIF-1α). Consequently, it is imperative to fabricate anti-bacterial and pro-regenerative small-diameter vascular grafts for treating cardiovascular disease in diabetic patients. Herein, we developed electrospun cobalt ion (Co2+)-loaded poly (ε-caprolactone) (PCL) microfiber vascular grafts (PCL-Co grafts). The released Co2+ significantly increased the stabilization of HIF-1α in high-glucose (HG)-treated HUVECs (HG-HUVECs) and macrophages (HG-macrophages). This resulted in enhanced cell migration, nitric oxide production, and secretion of bioactive factors by HG-HUVECs, and polarization of HG-macrophages toward M2 phenotypes in vitro. The Co2+ also conferred anti-bacterial properties to the grafts, while not perturbing the inherent anti-bacterial activities of HG-macrophages. Following abdominal artery implantation into type 2 diabetes mellitus (T2DM) rats, PCL-Co grafts were evaluated for performance in infection (grafts pre-contaminated with Staphylococcus aureus) and prophylaxes models (grafts alone). PCL-Co grafts prevented the incidence of subsequent infection in prophylaxes model and effectively inhibited the bacterial growth in the infection model. PCL-Co grafts also significantly enhanced cellularization, vascularization, endothelialization, contractile SMC regeneration and macrophages polarization in both models. Collectively, PCL-Co grafts exhibited the potential to combat infection and improve tissue regeneration under diabetes conditions. [ABSTRACT FROM AUTHOR]

This study presents a novel approach to enhance methanol synthesis (MS) efficiency through integration with an MEA-based decarbonized biomass direct-fired power plant (BFPP-CCS). The integration optimizes the utilization of chemical energy from feedstocks by combining exothermic MS reactions with diverse thermal energies, which effectively captures chemical energy through synergistic utilization from MS and various thermal inputs. Gradual methanol conversion maximizes both its chemical and fuel properties. Through such integration, the enhancement of waste heat and purge gas utilization in MS and BFPP carbon capture processes results in a 3.42 MW improvement in power generation and a 26.0 % reduction in associated energy penalties from CCS. Analysis of a 150 kton/yr MS facility and a 35 MW BFPP-CCS demonstrates 2.87 % increase in overall efficiency and reduction in CCS heat consumption by 1.03 GJ/tCO 2. Moreover, this integrated approach yields a 33.1 M$ NPV increase and 3.4 years DPP decrease, achieving carbon-neutral power and liquid fuels production. Sensitivity analysis indicates the polygeneration system performs optimally around 250 °C and 60 bar, with a preference for 0.90 MS recycle ratio. Additionally, factors such as carbon recovery rate, electrolysis efficiency, and fixed carbon content in biomass are quantitatively revealed as crucial for maximizing carbon mitigation potential. • An efficient carbon-neutral power and methanol cogeneration is proposed. • Purge gas and waste heat in MS and CCS are recovered more effectively. • Mechanism of irreversible exergy losses in cogeneration system is revealed. • Carbon emissions characteristics of cogeneration is quantitatively demonstrated. • Higher primary energy utilization efficiency and better profitability are attainable. [ABSTRACT FROM AUTHOR]

[Display omitted] • High performing hollow CuO-NiCo 2 O 4 catalysts for NH 3 BH 3 methanolysis were prepared. • TOF for the hollow CuO-NiCo 2 O 4 in NH 3 BH 3 methanolysis is up to 23.2 min−1. • The Co center in CuO-NiCo 2 O 4 is recognized as active sites by DFT calculations. • Synergistic effect between CuO and NiCo 2 O 4 results from the electrons migration. Rational construction of cost-efficient catalysts with high activity and durability for hydrogen production from ammonia borane (AB) methanolysis is highly desirable but remains a substantial challenge. In this work, we constructed a series of non-noble-metal based hollow CuO-NiCo 2 O 4 nanospheres composite, in which the CuO-NiCo 2 O 4 -0.8 nanospheres exhibit robust catalytic activity with a high turnover frequency (TOF) of 23.2 mol H2 mol cat. −1 min−1 towards AB methanolysis. Systemic experimental and computational studies reveal the promotion of activity results from the synergistic effect between CuO and NiCo 2 O 4. It is revealed the combination of CuO with NiCo 2 O 4 caused the electrons migration among Cu, Ni and Co sites and the change of d-band centers of catalyst, thus enhancing the adsorption process of CH 3 OH and AB molecules on catalyst and subsequently promoting the catalytic activity. Moreover, the Co center in CuO-NiCo 2 O 4 composite is recognized as active sites by DFT calculations. Mechanistically, the rate determining step is the dissociation of O H bond in CH 3 OH, which is confirmed by kinetic isotopic effect experiment. A plausible mechanism of methanolytic dehydrogenation of AB on CuO-NiCo 2 O 4 was proposed based on experiment and DFT calculations. These findings should shed light on the rational construction of cost-efficient catalysts with high performance for hydrogen production from AB methanolysis. [ABSTRACT FROM AUTHOR]

Mechanistic understanding of the topological cues delivered by biomaterials in promotion of oriented tissue regeneration (e.g., peripheral nerve regrowth) remains largely elusive. Here, we engineered nerve conduits composed of oriented microfiber-bundle cores and randomly organized nanofiber sheaths to particularly interrogate the regulatory mechanism of microfiber orientation on promoted peripheral nerve regeneration. With comprehensive yet systematic analyses, we were able to elucidate the intricate cascade of biological responses associated with conduit-assisted nerve regrowth, i.e., oriented microfibers facilitated macrophage recruitment and subsequent polarization toward a pro-healing phenotype, which in turn promoted Schwann cell (SC) migration, myelinization and axonal extension. Pronounced improvement of nerve regeneration in rat sciatic nerve injury was evidenced with enhanced electrophysiologic function, sciatic functional index and alleviated muscle atrophy 3 months post-implantation. The obtained results offer essential insights on the topological regulation of biomaterials in functional nerve tissue regeneration via immune modulation. [ABSTRACT FROM AUTHOR]

Cellular transition to hypoxia following tissue injury, has been shown to improve angiogenesis and regeneration in multiple tissues. To take advantage of this, many hypoxia-mimicking scaffolds have been prepared, yet the oxygen access state of implanted artificial small-diameter vascular grafts (SDVGs) has not been investigated. Therefore, the oxygen access state of electrospun PCL grafts implanted into rat abdominal arteries was assessed. The regions proximal to the lumen and abluminal surfaces of the graft walls were normoxic and only the interior of the graft walls was hypoxic. In light of this differential oxygen access state of the implanted grafts and the critical role of vascular regeneration on SDVG implantation success, we investigated whether modification of SDVGs with HIF-1α stabilizer dimethyloxalylglycine (DMOG) could achieve hypoxia-mimicking responses resulting in improving vascular regeneration throughout the entirety of the graft wall. Therefore, DMOG-loaded PCL grafts were fabricated by electrospinning, to support the sustained release of DMOG over two weeks. In vitro experiments indicated that DMOG-loaded PCL mats had significant biological advantages, including: promotion of human umbilical vein endothelial cells (HUVECs) proliferation, migration and production of pro-angiogenic factors; and the stimulation of M2 macrophage polarization, which in-turn promoted macrophage regulation of HUVECs migration and smooth muscle cells (SMCs) contractile phenotype. These beneficial effects were downstream of HIF-1α stabilization in HUVECs and macrophages in normoxic conditions. Our results indicated that DMOG-loaded PCL grafts improved endothelialization, contractile SMCs regeneration, vascularization and modulated the inflammatory reaction of grafts in abdominal artery replacement models, thus promoting vascular regeneration. [ABSTRACT FROM AUTHOR]