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With the development of functional genomics studies, a mass of long non‐coding RNAs (LncRNA) were discovered from the human genome. Long non‐coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA–binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma‐associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/β‐catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1–β‐catenin–WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA‐directed diagnostic and therapeutic strategy for this fatal disease. Our data highlighted the pivotal role of UCA1 in the tumorigenesis of oral squamous cell carcinoma, and revealed a novel LncRNA UCA1‐β‐catenin‐Wnt signaling pathway regulatory network, which may contribute to understand the pathogenesis of oral squamous cell carcinoma.

Lightweight aluminum (Al) alloys have been widely used in frontier fields like aerospace and automotive industries, which attracts great interest in additive manufacturing (AM) to process high-value Al parts. As a mainstream AM technique, laser-directed energy deposition (LDED) shows good scalability to meet the requirements for large-format component manufacturing and repair. However, LDED Al alloys are highly challenging due to their inherent poor printability (e.g. low laser absorption, high oxidation sensitivity and cracking tendency). To further promote the development of LDED high-performance Al alloys, this review offers a deep understanding of the challenges and strategies to improve printability in LDED Al alloys. The porosity, cracking, distortion, inclusions, element evaporation and resultant inferior mechanical properties (worse than laser powder bed fusion) are the key challenges in LDED Al alloys. Processing parameter optimizations, in-situ alloy design, reinforcing particle addition and field assistance are the efficient approaches to improving the printability and performance of LDED Al alloys. The underlying correlations between processes, alloy innovation, characteristic microstructures, and achievable performances in LDED Al alloys are discussed. The benchmark mechanical properties and primary strengthening mechanism of LDED Al alloys are summarized. This review aims to provide a critical and in-depth evaluation of current progress in LDED Al alloys. Future opportunities and perspectives in LDED high-performance Al alloys are also outlined. A rigorous review to understand the root causes of poor printability of Al alloys. Practical strategies to improve Al printability for better mechanical performance. Correlations among process-alloy innovation-microstructure-properties. Benchmark achievable mechanical properties in LDED Al alloys. Future opportunities and perspectives in LDED high-performance Al alloys.

The progress of advanced powder metallurgy techniques for manufacturing copper matrix composites and their advantages are reviewed. Influence mechanisms of ceramic particles on mechanical and thermophysical properties of composites are analyzed. The content, size, morphology and interfacial bonding of particles directly determine the comprehensive performance of composites. Research limitations and future perspectives of ceramic particles reinforced copper matrix composites are outlined. Copper matrix composites doped with ceramic particles are known to effectively enhance the mechanical properties, thermal expansion behavior and high-temperature stability of copper while maintaining high thermal and electrical conductivity. This greatly expands the applications of copper as a functional material in thermal and conductive components, including electronic packaging materials and heat sinks, brushes, integrated circuit lead frames. So far, endeavors have been focusing on how to choose suitable ceramic components and fully exert strengthening effect of ceramic particles in the copper matrix. This article reviews and analyzes the effects of preparation techniques and the characteristics of ceramic particles, including ceramic particle content, size, morphology and interfacial bonding, on the diathermancy, electrical conductivity and mechanical behavior of copper matrix composites. The corresponding models and influencing mechanisms are also elaborated in depth. This review contributes to a deep understanding of the strengthening mechanisms and microstructural regulation of ceramic particle reinforced copper matrix composites. By more precise design and manipulation of composite microstructure, the comprehensive properties could be further improved to meet the growing demands of copper matrix composites in a wide range of application fields.

Background Carbonic anhydrases (CAs) are universal metalloenzymes that catalyze the reversible conversion of carbon dioxide (CO 2 ) and bicarbonate (HCO 3 - ). They are involved in various biological processes, including pH control, respiration, and photosynthesis. To date, eight evolutionarily unrelated classes of CA families (α, β, γ, δ, ζ, η, θ, and ι) have been identified. All are characterized by an active site accommodating the binding of a metal cofactor, which is assumed to play a central role in catalysis. This feature is thought to be the result of convergent evolution. Results Here, we report that a previously uncharacterized protein group, named “COG4337,” constitutes metal-independent CAs from the newly discovered ι-class. Genes coding for COG4337 proteins are found in various bacteria and photosynthetic eukaryotic algae. Biochemical assays demonstrated that recombinant COG4337 proteins from a cyanobacterium ( Anabaena sp. PCC7120) and a chlorarachniophyte alga ( Bigelowiella natans ) accelerated CO 2 hydration. Unexpectedly, these proteins exhibited their activity under metal-free conditions. Based on X-ray crystallography and point mutation analysis, we identified a metal-free active site within the cone-shaped α+β barrel structure. Furthermore, subcellular localization experiments revealed that COG4337 proteins are targeted into plastids and mitochondria of B. natans , implicating their involvement in CO 2 metabolism in these organelles. Conclusions COG4337 proteins shared a short sequence motif and overall structure with ι-class CAs, whereas they were characterized by metal independence, unlike any known CAs. Therefore, COG4337 proteins could be treated as a variant type of ι-class CAs. Our findings suggested that this novel type of ι-CAs can function even in metal-poor environments (e.g., the open ocean) without competition with other metalloproteins for trace metals. Considering the widespread prevalence of ι-CAs across microalgae, this class of CAs may play a role in the global carbon cycle.

This study investigates the influence of RE elements on the room- and high-temperature properties of magnesium alloys. The effects of RE type, addition level, and multi-element alloying strategies were systematically analyzed to clarify the underlying strengthening mechanisms and processing pathways for optimizing Mg–RE alloys. RE elements enhance the mechanical and thermal properties of Mg alloys through crystal structure modification, formation of thermally stable dispersed phases, precipitation strengthening, and solid-solution strengthening. Compared with conventional alloying elements, RE additions offer distinct advantages in strengthening efficiency and overall performance. To fully exploit these benefits, new research paradigms that integrate machine learning and other advanced techniques are required, enabling the intelligent design of multicomponent alloy systems tailored to specific application requirements.

It is widely known that the special performances and extensive applications of the nanoscale materials are determined by their as-synthesized structures, especially their growth sizes and morphologies. Hereinto, titanium carbides, which show brilliant comprehensive properties, have attracted considerable attention from researchers. How to give full play to their potentials in the light-weight manufacture, microwave absorption, electromagnetic protection, energy conversion and catalyst areas has been widely studied. In this summarized article, the synthesis methods and mechanisms, corresponding growth morphologies of titanium carbides and their further applications were briefly reviewed and analyzed according to their different morphological dimensions, including one-dimensional nanostructures, two-dimensional nanosheets and three-dimensional nanoparticles. It is believed that through the investigation of the crystal structures, synthesis methods, growth mechanisms, and morphology characterizations of those titanium carbides, new lights could be shed on the regulation and control of the ceramic phase specific morphologies to meet with their excellent properties and applications. In addition, the corresponding development prospects and challenges of titanium carbides with various growth morphologies were also summarized.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80 + I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity. Immune checkpoint inhibition is a successful form of immune therapy; however response rates vary widely among individual patients. Here authors show that circulating small extracellular vesicles might contribute to poor response to anti-PD-1 treatment by carrying PD-1 and CD80 which results in higher level of vesicular PD-L1 expression in the circulation at the expense of expression on tumour cell membranes, causing immunosuppression.

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase‐activating protein (GAP) and modulate integrin‐mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling.

As an important part of die steels, hot-work die steels are mainly used to manufacture molds made of solid metal or high-temperature liquid metal from heating to recrystallization temperature. In view of the requirements for mechanical properties and service life for hot-work die steel, it is conducive to improve the thermal fatigue resistance, wear resistance, and oxidation resistance of hot work die steel. In this review, the main failure modes of hot-work die steel were analyzed. Four traditional methods of strengthening and toughening die steel were summarized, including optimizing alloying elements, electroslag remelting, increasing the forging ratio, and heat treatment process enhancement. A new nano-strengthening method was introduced that aimed to refine the microstructure of hot-work abrasive steel and improve its service performance by adding nanoparticles into molten steel to achieve uniform dispersion. This review provides an overview to improve the service performance and service life of hot work die steel.

Background The study explores the value of a model constructed by integrating CTA-based carotid plaque radiomic features, clinical risk factors, and plaque imaging characteristics for prognosticating the risk of ischemic stroke. Methods Data from 123 patients with carotid atherosclerosis were analyzed and divided into stroke and asymptomatic groups based on DWI findings. Clinical information was collected, and plaque imaging characteristics were assessed to construct a traditional model. Radiomic features of carotid plaques were extracted using 3D-Slicer software to build a radiomics model. Logistic regression was applied in the training set to establish the traditional model, the radiomics model, and a combined model, which were then tested in the validation set. The prognostic ability of the three models for ischemic stroke was evaluated using ROC curves, while calibration curves, decision curve analysis, and clinical impact curves were used to assess the clinical utility of the models. Differences in AUC values between models were compared using the DeLong test. Results Hypertension, diabetes, elevated homocysteine (Hcy) concentrations, and plaque burden are independent risk factors for ischemic stroke and were used to establish the traditional model. Through Lasso regression, nine optimal features were selected to construct the radiomics model. ROC curve analysis showed that the AUC values of the three Logistic regression models were 0.766, 0.766, and 0.878 in the training set, and 0.798, 0.801, and 0.847 in the validation set. Calibration curves and decision curve analysis showed that the radiomics model and the combined model had higher accuracy and better fit in prognosticating the risk of ischemic stroke. Conclusions The radiomics model is slightly better than the traditional model in evaluating the risk of ischemic stroke, while the combined model has the best prognostic performance.