Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

Tunable Nanoparticles with Aggregation-Induced Emission Heater for Precise Synergistic Photothermal and Thermodynamic Oral Cancer Therapy of Patient-Derived Tumor Xenograft.

The fluorophores in the second near-infrared (NIR-II) biological window (1000 - 1700 nm) show great application prospects in the fields of biology and optical communications. However, both excellent radiative transition and nonradiative transition cannot be achieved simultaneously for the majority of traditional fluorophores. Herein, tunable nanoparticles formulated with aggregation-induced emission (AIE) heater are developed rationally. The system can be implemented via the development of an ideal synergistic system that can not only produce photothermal from nonspecific triggers but also trigger carbon radical release. Once accumulating in tumors and subsequently being irradiated with 808 nm laser, the nanoparticles (NMB@NPs) encapsulated with NMDPA-MT-BBTD (NMB) are splitted due to the photothermal effect of NMB, leading to the decomposition of azo bonds in the nanoparticle matrix to generate carbon radical. Accompanied by second near-infrared (NIR-II) window emission from the NMB, fluorescence image-guided thermodynamic therapy (TDT) and photothermal therapy (PTT) which significantly inhibited the growth of oral cancer and negligible systemic toxicity is achieved synergistically. Taken together, this AIE luminogens-based synergistic photothermal-thermodynamic strategy brings a new insight into the design of superior versatile fluorescent NPs for precise biomedical applications and holds great promise to enhance the therapeutic efficacy of cancer therapy.

Serum DSG2 as a potential biomarker for diagnosis of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma.

BACKGROUND: Exploration of serum biomarkers for early detection of upper gastrointestinal cancer is required. Here, we aimed to evaluate the diagnostic potential of serum desmoglein-2 (DSG2) in patients with esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA). METHODS: Serum DSG2 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 459 participants including 151 patients with ESCC, 96 with EJA, and 212 healthy controls. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS: Levels of serum DSG2 were significantly higher in patients with ESCC and EJA than those in healthy controls (P<0.001). Detection of serum DSG2 demonstrated an area under the ROC curve (AUC) value of 0.724, sensitivity of 38.1%, and specificity of 84.8% for the diagnosis of ESCC in the training cohort, and AUC 0.736, sensitivity 58.2%, and specificity 84.7% in the validation cohort. For diagnosis of EJA, measurement of DSG2 provided a sensitivity of 29.2%, a specificity of 90.2%, and AUC of 0.698. Similar results were observed for the diagnosis of early-stage ESCC (AUC 0.715 and 0.722, sensitivity 36.3 and 50%, and specificity 84.8 and 84.7%, for training and validation cohorts, respectively) and early-stage EJA (AUC 0.704, sensitivity 44.4%, and specificity 86.9%). Analysis of clinical data indicated that DSG2 levels were significantly associated with patient age and histological grade in ESCC (P<0.05). CONCLUSION: Serum DSG2 may be a diagnostic biomarker for ESCC and EJA.

A valence balancing rule for the design of bimetallic phosphides targeting high thermoelectric performance.

Two-dimensional (2D) materials with outstanding electronic and mechanical properties have attracted considerable attention as efficient thermoelectric materials. Here, we propose a generalized eight-valence electron rule for designing 2D semiconductor materials, i.e., metal-shrouded bimetallic phosphides ABP (A: group IA element, B: group IIA element). Following this rule, we screen out ten stable semiconductors (LiMgP, LiCaP, LiSrP, NaBeP, NaMgP, KMgP, KCaP, RbMgP, RbCaP and RbSrP) with tunable bandgaps in the range of 0.35-2.40 eV by comprehensive first-principles calculations. Among them, the electron mobility of RbMgP can be as high as 2.3 × 104 cm2 V-1 s-1, and the hole mobility of KMgP is estimated to be 9.9 × 103 cm2 V-1 s-1. Moreover, KMgP, KCaP, RbCaP and RbSrP exhibit an ultralow thermal conductivity of 0.02, 0.14, 0.08 and 0.14 W m-1 K-1, respectively. As a result, KMgP and RbCaP monolayers are p-type or n-type thermoelectric materials with a figure of merit of 2.25 and 1.13 at room temperature, respectively. The underlying mechanism of high electron conductivity and low thermal conductivity has been correlated with their unique bonding characteristics, narrow phonon band gap and the scattering from low-frequency phonons. This work demonstrates not only a guiding electron principle to design stable 2D semiconductors, but also a powerful metal-shrouded strategy for discovering high performance thermoelectric materials by decoupling electronic and thermal transport properties.

Paradoxical Roles of Desmosomal Components in Head and Neck Cancer.

Desmosomes are intercellular adhesion complexes involved in various aspects of epithelial pathophysiology, including tissue homeostasis, morphogenesis, and disease development. Recent studies have reported that the abnormal expression of various desmosomal components correlates with tumor progression and poor survival. In addition, desmosomes have been shown to act as a signaling platform to regulate the proliferation, invasion, migration, morphogenesis, and apoptosis of cancer cells. The occurrence and progression of head and neck cancer (HNC) is accompanied by abnormal expression of desmosomal components and loss of desmosome structure. However, the role of desmosomal components in the progression of HNC remains controversial. This review aims to provide an overview of recent developments showing the paradoxical roles of desmosomal components in tumor suppression and promotion. It offers valuable insights for HNC diagnosis and therapeutics development.

Effects of spin-phonon coupling on two-dimensional ferromagnetic semiconductors: a case study of iron and ruthenium trihalides.

The contributions of spin-phonon coupling (SPC) to spin and thermal transport properties are important in emerging two-dimensional (2D) magnetic semiconductors and are relevant to the data security and working stability of spin-based devices. By evaluating the dynamical stability of both ferromagnetic (FM) and paramagnetic (PM) states at 0 K, six transition-metal trihalides, namely FeCl3, FeBr3, FeI3, RuCl3, RuBr3, and RuI3, are identified as ideal 2D magnetic semiconductors for investigating SPC. For these compounds, we perform first-principles calculations to evaluate the spin-relative lattice constants, bond angles, phonon dispersions, lattice thermal conductivity, as well as phonon-relative magnetic coupling parameters, magnetic moment, and Curie temperature. Our results suggest weaker SPC effects on Ru trihalides and stronger SPC effects on Fe trihalides. To explain these observations, we further analyze the SPC induced heat capacity, group velocity, scattering possibility, phonon anharmonicity, and phonon-magnon scattering. More importantly, we also provide a unified explanation for the SPC role in causing anomalous lattice thermal conductivity and stabilizing the ferromagnetic/antiferromagnetic ordering. The present study offers not only in-depth knowledge about the mechanisms of SPC regarding the spin and thermal transport behavior of 2D FM semiconductors, but also a better understanding of thermal management and control in magnetic quantum materials.

New refractory MAB phases and their 2D derivatives: insight into the effects of valence electron concentration and chemical composition.

Since MAB (where M is a transition metal, A is an groups 13-16 element, and B is boron) phases possess good electrical conductivity, high-temperature oxidation and shock resistance, it is meaningful to develop a database to help us figure out optimal compositions and further promote their applications. In this paper, we screened and studied all the available MABs with the M-site being one of the 3d, 4d, or 5d transition metals by using an ab initio method. Among them, 23 MAB phases of M2Al2B2 (222-MAB phases with M = Ti, V, Nb, Ta, Cr, Mo, W, Mn, and Tc) and M2AlB2 (212-MAB phases with M = Sc, Ti, Zr, Hf, V, Nb, Cr, Mo, W, Mn, Tc, Fe, Co, and Ni) stand out in terms of structural stability and their electronic, mechanical, optical and thermodynamic properties have been investigated. For both types of MAB phases early transition elements are more feasible to synthesize than post transition elements, because of the lower number of valence electrons and lower formation energy. The effect of valence electron concentration and composition of MAB compounds could also enable fine tuning of their mechanical properties. The bulk modulus, shear modulus, and Young's modulus of the 222-MAB phases are in the range of 145-233 GPa, 101-145 GPa, and 252-361 GPa, respectively, while they are 152-262 GPa, 91-177 GPa, and 237-422 GPa for the 212-MAB phases, respectively. Their mechanical ductilities also show strong valence electron number dependency, with their maximum value occurring at Ni2AlB2 and Co2AlB2, respectively. More interestingly, a low thermal expansion coefficient and good high temperature strength have also been found in those MAB phases, which are favorable for their potential applications as refractory materials. In addition, the possibility of forming new two-dimensional (2D) materials from layered MAB phases, termed MBenes, is predicted by investigating the interplay of the tensile strain, complex chemical bonding and exfoliation energy.