Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis.

Lipid metabolic reprogramming of tumor cells has been proven to play a critical role in tumor initiation and development. However, lipid metabolism in cancer-associated fibroblasts (CAFs) has rarely been studied, particularly in CAFs of oral squamous cell carcinoma (OSCC). Additionally, the molecular mechanism by which tumor cells regulate lipid metabolism in fibroblasts is unclear. In this study, we found that phosphorylated ATP citrate lyase (p-ACLY), a key lipid metabolic enzyme, was upregulated in OSCC CAFs. Compared to paracancerous normal fibroblasts, CAFs showed enhanced lipid synthesis, such as elevated cytosolic acetyl-CoA level and accumulation of lipid droplets. Conversely, reduction of p-ACLY level blocked this biological process. In addition, blocking lipid synthesis in CAFs or inhibiting fatty acid uptake by OSCC cells reduced the promotive effects of CAFs on OSCC cell proliferation, invasion, and migration. These findings suggested that CAFs are one of lipid sources required for OSCC progression. Mechanistically, AKT signaling activation was involved in the upregulation of p-ACLY level and lipid synthesis in CAFs. Interleukin-8 (IL8), an exocrine cytokine of OSCC cells, could activate AKT and then phosphorylate ACLY in fibroblasts. This study suggested that the IL8/AKT/p-ACLY axis could be considered as a potential target for OSCC treatment.

Pt─O Bond Accelerated Cu0/Cu+ Activity for Boosting Low-Energy Bipolar Hydrogen Production.

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

Accessible Tetrathiafulvalene Moieties in a 3D Covalent Organic Framework for Enhanced Near-Infrared Photo-Thermal Conversion and Photo-Electrical Response.

Redox-active tetrathiafulvalene (TTF)-based covalent organic frameworks (COFs) exhibit distinctive electrochemical and photoelectrical properties, but their prevalent two-dimensional (2D) structure with densely packed TTF moieties limits the accessibility of redox center and constrains their potential applications. To overcome this challenge, an 8-connected TTF linker (TTF-8CHO) is designed as a new building block for the construction of three-dimensional (3D) COFs. This approach led to the successful synthesis of a 3D COF with the bcu topology, designated as TTF-8CHO-COF. In comparison to its 2D counterpart employing a 4-connected TTF linker, the 3D COF design enhances access to redox sites, facilitating controlled oxidation by I2 or Au3+ to tune physical properties. When irradiated with a 0.7 W cm-2 808 nm laser, the oxidized 3D COF samples ( I X - ${\mathrm{I}}_{\mathrm{X}}^{-}$ @TTF-8CHO-COF and Au NPs@TTF-8CHO-COF) demonstrated rapid temperature increases of 239.3 and 146.1 °C, respectively, which surpassed those of pristine 3D COF (65.6 °C) and the 2D COF counterpart (6.4 °C increment after I2 treatment). Furthermore, the oxidation of the 3D COF heightened its photoelectrical responsiveness under 808 nm laser irradiation. This augmentation in photothermal and photoelectrical response can be attributed to the higher concentration of TTF·+ radicals generated through the oxidation of well-exposed TTF moieties.

Melatonin inhibits the stemness of head and neck squamous cell carcinoma by modulating HA synthesis via the FOSL1/HAS3 axis.

Hyaluronic acid (HA) is a glycosaminoglycan and the main component of the extracellular matrix (ECM), which has been reported to interact with its receptor CD44 to play critical roles in the self-renewal and maintenance of cancer stem cells (CSCs) of multiple malignancies. Melatonin is a neuroendocrine hormone with pleiotropic antitumor properties. However, whether melatonin could regulate HA accumulation in the ECM to modulate the stemness of head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, we found that melatonin suppressed CSC-related markers, such as CD44, of HNSCC cells and decreased the tumor-initiating frequency of CSCs in vivo. In addition, melatonin modulated HA synthesis of HNSCC cells by downregulating the expression of hyaluronan synthase 3 (HAS3). Further study showed that the Fos-like 1 (FOSL1)/HAS3 axis mediated the inhibitory effects of melatonin on HA accumulation and stemness of HNSCC in a receptor-independent manner. Taken together, melatonin modulated HA synthesis through the FOSL1/HAS3 axis to inhibit the stemness of HNSCC cells, which elucidates the effect of melatonin on the ECM and provides a novel perspective on melatonin in HNSCC treatment.

The hemostatic and comforting effects of oral adhesive bandages in tooth extraction: a randomized controlled clinical study.

OBJECTIVES: To compare oral adhesive bandages with the classic compression method and evaluate the clinical efficacy of this wound dressing material in improving postoperative comfort, wound healing, and hemostasis in tooth extraction. MATERIALS AND METHODS: The study was designed as a randomized controlled clinical trial. A total of 120 patients were recruited and randomly assigned to the study group and the control group. In the study group, oral adhesive bandages were used as wound dressing. In the control group, patients bit on cotton balls and gauze, as usual. Hemorrhage, comfort, and healing levels were evaluated at postoperative 1 h, 24 h, and 7 days. The adhesion time of the oral adhesive bandages was also recorded. RESULTS: The average adhesion time of the oral adhesive bandages was 26.6 h. At postoperative 1 and 24 h, the hemostatic levels of the oral adhesive bandage group were significantly higher than those of the control group. The oral adhesive bandage group also reported significantly higher comfort scores than the control group. Both groups had similar healing levels and side effects. But the mean score for wound healing was slightly higher in the oral adhesive bandage group. CONCLUSIONS: Oral adhesive bandages were more effective than cotton balls and gauze in providing hemostatic and comfort effects on extraction wounds. CLINICAL RELEVANCE: Oral adhesive bandages possess clinical value in the management of extraction wounds.

N-Doped Carbon Nanotubes Supported Fe-Mn Dual-Single-Atoms Nanozyme with Synergistically Enhanced Peroxidase Activity for Sensitive Colorimetric Detection of Acetylcholinesterase and Its Inhibitor.

Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe-Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (·OH) in the H2O2 system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB). Besides, the peroxidase-like activity was greatly weakened by thiocholine (derived from AChE), accompanied by making blue ox-TMB fade. Impressively, the highly improved peroxidase-like property is further evidenced by density functional theory (DFT) calculations, where the dual-single atoms show a lower energy barrier (0.079 eV) and their interactions with the N-CNTs played critical roles for producing the oxygen radicals. By virtue of the nanozyme, a low-cost, specific, and sensitive colorimetric sensor was built for detection of AChE with a broader linear range of 0.1-30 U L-1 and a lower limit of detection (LOD, 0.066 U L-1), combined with its feasible analysis in human serum samples. Also, this platform was applied for measuring huperzine A inhibitor with a wide linear scope of 5-500 nM and a LOD down to 4.17 nM. This strategy provides a low-cost and convenient approach for early clinical diagnosis and drug development.

A theoretical study of the NbS2 monolayer as a promising anchoring material for lithium-sulfur batteries.

Developing efficient cathode materials with good conductivity to restrain the shuttle effect and promote the reaction kinetics has been a key scientific issue for the development of lithium-sulfur (Li-S) batteries. Here, by means of first-principles computations, we demonstrate that the NbS2 monolayer is a promising cathode anchoring material for Li-S batteries. It has a metallic feature that improves the conductivity of sulfur and lithium polysulfides (LiPSs) and promotes the electron transfer ability. The discharge products LiPSs are strongly anchored on the NbS2 monolayer without structural distortion, which effectively alleviates the shuttle effect. Remarkably, the reductions of sulfur to soluble LiPSs are spontaneous exothermic reactions while the subsequent reductions to insoluble LiPSs are endothermic reactions with low Gibbs free energy barriers (0.09-0.18 eV) and reaction activation barriers (0.83-0.93 eV), ensuring the rapid discharge process. In addition, the barriers of Li2S decomposition and Li atom diffusion are only 0.64 and 0.18 eV, respectively, which improve the reaction kinetics in the charging process and the cycling life of batteries. These results suggest that the NbS2 monolayer can be utilized as a promising anchoring material for Li-S batteries to achieve high reversible capacity and conversion efficiency.

Protection of laryngeal mucosa and function in laryngeal burns by heat absorption of perilaryngeal tissue.

OBJECTIVE: The laryngeal tissue carries most of the heat during inhalation injury. This study aims to explore the heat transfer process and the severity of injury inside laryngeal tissue by horizontally studying the temperature rise process at various anatomical layers of the larynx and observing the thermal damage in various parts of the upper respiratory tract. METHODS: The 12 healthy adult beagles were randomly divided into four groups, and inhaled room temperature air (control group), dry hot air of 80 °C (group I), 160 °C (group II), and 320 °C (group III) for 20 min, respectively. The temperature changes of the glottic mucosal surface, the inner surface of the thyroid cartilage, the external surface of the thyroid cartilage, and subcutaneous tissue were measured every minute. All animals were immediately sacrificed after injury, and pathological changes in various parts of laryngeal tissue were observed and evaluated under a microscope. RESULTS: After inhaling hot air of 80 °C, 160 °C and 320 °C, the increase of laryngeal temperature in each group was ΔT = 3.57 ± 0.25 °C, 7.83 ± 0.15 °C, 11.93 ± 0.21 °C. The tissue temperature was approximately uniformly distributed, and the difference was not statistically significant. The average laryngeal temperature-time curve showed that the laryngeal tissue temperature in group I and group II showed a trend of "first decrease and then increase", except that the temperature of group III directly increased with time. The prominent pathological changes after thermal burns mainly concluded necrosis of epithelial cells, loss of the mucosal layer, atrophy of submucosal glands, vasodilatation, erythrocytes exudation, and degeneration of chondrocytes. Mild degeneration of cartilage and muscle layers was also observed in mild thermal injury. Pathological scores indicated that the pathological severity of laryngeal burns increased significantly with the increase of temperature, and all layers of laryngeal tissue were seriously damaged by 320 °C hot air. CONCLUSIONS: The high efficiency of tissue heat conduction enabled the larynx to quickly transfer heat to the laryngeal periphery, and the heat-bearing capacity of perilaryngeal tissue has a certain degree of protective effect on laryngeal mucosa and function in mild to moderate inhalation injury. The laryngeal temperature distribution was in accordance with the pathological severity, and the pathological changes of laryngeal burns provided a theoretical basis for the early clinical manifestations and treatment of inhalation injury.

Redox-Active Mixed-Linker Metal-Organic Frameworks with Switchable Semiconductive Characteristics for Tailorable Chemiresistive Sensing.

Metal-organic frameworks (MOFs), with diverse metal nodes and designable organic linkers, offer unique opportunities for the rational engineering of semiconducting properties. In this work, we report a mixed-linker conductive MOF system with both tetrathiafulvalene and Ni-bis(dithiolene) moieties, which allows the fine-tuning of electronic structures and semiconductive characteristics. By continuously increasing the molar ratio between tetrathiafulvalene and Ni-bis(dithiolene), the switching of the semiconducting behaviors from n-type to p-type was observed along with an increase in electrical conductivity by 3 orders of magnitude (from 2.88×10-7  S m-1 to 9.26×10-5  S m-1 ). Furthermore, mixed-linker MOFs were applied for the chemiresistive detection of volatile organic compounds (VOCs), where the sensing performance was modulated by the corresponding linker ratios, showing synergistic and nonlinear modulation effects.

HSP90/IKK-rich small extracellular vesicles activate pro-angiogenic melanoma-associated fibroblasts via the NF-κB/CXCL1 axis.

Hypoxia is a main feature of most solid tumors, but how melanoma cells under hypoxic conditions exploit tumor microenvironment (TME) to facilitate tumor progression remains poorly understood. In this study, we found that hypoxic melanoma-derived small extracellular vesicles (sEVs) could improve the proangiogenic capability of cancer-associated fibroblasts (CAFs). This improvement was due to the activation of the IKK/IκB/NF-κB signaling pathway and upregulation of CXCL1 expression and secretion in CAFs. By proteomic analysis, we verified that hypoxia could promote enrichment of chaperone HSP90 and client protein phosphorylated IKKα/ß (p-IKKα/ß) in melanoma-derived sEVs. Delivery of the HSP90/p-IKKα/ß complex by sEVs could activate the IKK/IκB/NF-κB/CXCL1 axis in CAFs and promote angiogenesis in vitro and in vivo. Taken together, these findings deepen the understanding of hypoxic response in melanoma progression and provide potential targets for melanoma treatment.

Melatonin inhibits EMT and PD-L1 expression through the ERK1/2/FOSL1 pathway and regulates anti-tumor immunity in HNSCC.

Melatonin is an endogenous hormone with various biological functions and possesses anti-tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death-ligand 1 (PD-L1) expression and inhibited epithelial-mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti-programmed death-1 (PD-1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti-tumor immunity by increasing CD8+ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD-L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti-PD-1 antibody in vivo, which could provide promising strategies for HNSCC treatment.

Efficient and Selective Electroreduction of CO2 to HCOOH over Bismuth-Based Bromide Perovskites in Acidic Electrolytes.

Metal halide perovskites, primarily used as optoelectronic devices, have not been applied for electrochemical conversion due to their insufficient stability in moisture. Herein, two bismuth-based perovskites are introduced as novel electrocatalysts to convert CO2 into HCOOH in aqueous acidic media (pH 2.5), exhibiting a high Faradaic efficiency for HCOOH of >80 % in a wide potential range from -0.75 to -1.25 V. Their structural evolution against water was dynamically monitored by in situ spectra. Theoretical calculations further reveal that the formation of intermediate OCHO* on bismuth sites of Cs3 Bi2 Br9 (111) play a pivotal role toward HCOOH production, which has a lower energy barrier than that on Cs2 AgBiBr6 (001) surfaces. Significantly, CO2 reacts with protons instead of water which can enhance CO2 reduction rate and suppress hydrogen evolution by avoiding carbonate formation in acidic electrolytes. This work paves the way for the extensive investigation of halide perovskites in aqueous systems.

Penta-BCN monolayer: a metal-free photocatalyst with a high carrier mobility for water splitting.

Photocatalytic water splitting has been regarded as a promising strategy to provide clean energy and solve the energy crisis; thus, extensive efforts have been devoted to developing highly efficient photocatalysts. Herein, based on density functional theory computations, we demonstrated that the penta-BCN monolayer is a promising photocatalyst for water splitting. The penta-BCN monolayer is semiconducting with a moderate direct band gap of 2.87 eV, and its band edge positions straddle the redox potentials of water. Remarkably, the penta-BCN monolayer also has a pronounced optical absorption in the ultraviolet and visible light regions and exhibits an ultrahigh hole mobility (∼2 × 105 cm2 V-1 s-1). These desirable properties render the penta-BCN monolayer a promising candidate for photocatalytic water splitting.

Redox-Active Metal-Organic Frameworks with Three-Dimensional Lattice Containing the m-Tetrathiafulvalene-Tetrabenzoate.

Metal-organic frameworks (MOFs) constructed by tetrathiafulvalene-tetrabenzoate (H4TTFTB) have been widely studied in porous materials, while the studies of other TTFTB derivatives are rare. Herein, the meta derivative of the frequently used p-H4TTFTB ligand, m-H4TTFTB, and lanthanide (Ln) metal ions (Tb3+, Er3+, and Gd3+) were assembled into three novel MOFs. Compared with the reported porous Ln-TTFTB, the resulted three-dimensional frameworks, Ln-m-TTFTB ([Ln2(m-TTFTB)(m-H2TTFTB)0.5(HCOO)(DMF)]·2DMF·3H2O), possess a more dense stacking which leads to scarce porosity. The solid-state cyclic voltammetry studies revealed that these MOFs show similar redox activity with two reversible one-electron processes at 0.21 and 0.48 V (vs. Fc/Fc+). The results of magnetic properties suggested Dy-m-TTFTB and Er-m-TTFTB exhibit slow relaxation of the magnetization. Porosity was not found in these materials, which is probably due to the meta-configuration of the m-TTFTB ligand that seems to hinder the formation of pores. However, the m-TTFTB ligand has shown to be promising to construct redox-active or electrically conductive MOFs in future work.

Dislocations as Single Photon Sources in Two-Dimensional Semiconductors.

Single photon sources hold great promise in quantum information technologies and are often materialized by single atoms, quantum dots, and point defects in dielectric materials. Yet, these entities are vulnerable to annealing and chemical passivation, ultimately influencing the stability of photonic devices. Here, we show that topologically stable dislocations in transition metal dichalcogenide monolayers can act as single photon sources, as supported by calculated defect levels, diploe matrix elements for transition, and excitation lifetimes with first-principles. The emission from dislocations can range from 0.48 to 1.29 eV by varying their structure, charge state, and chemical makeup in contrast to the visible range provided by previously reported sources. Since recent experiments have controllably created dislocations in monolayer materials, these results open the door to utilizing robustly stable defects for quantum computing.

Salivary Porphyromonas gingivalis predicts outcome in oral squamous cell carcinomas: a cohort study.

BACKGROUND: Studies suggest Porphyromonas gingivalis (Pg) increased the incidence of oral squamous cell carcinoma (OSCC). However, fimA genotypes distribution of Pg, the origination of Pg in tissue, and its prognostic value are inconclusive. We aimed to investigate the frequency of fimA genotypes in OSCC patients, study the association between Pg and OSCC, and explore the prognostic value of Pg. METHODS: The abundance of Pg in saliva from the OSCC group and the OSCC-free group was analysed by qPCR. The presence of Pg was explored in OSCC tissue and para-cancerous tissue by in situ hybridization. The frequency of fimA genotypes in saliva and OSCC tissue was determined by PCR, then PCR products were sequenced and compared. Clinical data were extracted, and patients followed up for a median period of 23 months. Clinicopathological variables were compared with the abundance of Pg using Pearson Chi-square test or Fisher's exact test. The disease-free survival (DFS) rate was calculated by Kaplan-Meier method with log-rank tests. RESULTS: Comparing the OSCC-free group, 95 patients with OSCC showed a high abundance of Pg in saliva (P = 0.033), and OSCC tissue showed strong in situ expression of Pg compared with paired normal tissue. Patients with OSCC showed a dominant distribution of Pg with genotype I + Ib (21.1%), II (31.6%), and IV (21.1%). FimA genotypes detected in saliva were in accordance with those in OSCC tissue, there was, moreover, a significant similarity in amplified Pg fragments. Of the 94 responsive OSCC patients, the recurrence rate was 26.6% (25/94). Overabundance of Pg in saliva showed advanced pathologic staging (P = 0.008), longer disease-free time (P = 0.029) and lower recurrence rate (P = 0.033). The overabundance of Pg in saliva was associated with improved disease-free survival (P = 0.049). CONCLUSIONS: This study indicated that Pg might involve in the pathogenesis of OSCC, Pg carrying fimA I, Ib, II, and IV were prevalent genotypes in patients with OSCC, the provenance of Pg in OSCC tissue might be from the salivary microbial reservoir, and the abundance of Pg in saliva might consider as a favorable potential prognostic indicator in OSCC.

IGF2BP3 facilitates cell proliferation and tumorigenesis via modulation of JAK/STAT signalling pathway in human bladder cancer.

Insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) has been reported to contribute to tumorigenesis in several human cancers. However, the biological functions of IGF2BP3 in bladder cancer are poorly understood. We investigated the relation between IGF2BP3 expression and prognosis of bladder cancer patients. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGF2BP3 functions. The results showed that IGF2BP3 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its higher expression was closely correlated with poor prognosis in bladder cancer patients. Overexpression of IGF2BP3 markedly promoted cell proliferation and cell cycle progression and inhibited cell apoptosis, while knockdown of IGF2BP3 notably suppressed the proliferation, promoted cell apoptosis and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGF2BP3 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumour-promoting activity of IGF2BP3. Tumour growth in vivo was also suppressed by knocking down of IGF2BP3. Hence, IGF2BP3 facilitated bladder cancer cell proliferation by activating the JAK/STAT signalling pathway. These findings suggest that IGF2BP3 exhibits an oncogenic effect in human bladder cancer progression.

CCL21/CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway.

Chemokines and their receptors show a strong relationship with poor clinical outcomes in various cancers. However, their underlying mechanisms remain to be fully elucidated. In our research, we found C-C chemokine receptor 7 (CCR7) and its ligand chemokine ligand 21 (CCL21) were abnormally abundant in oral squamous cell carcinoma (OSCC) tissues, and CCR7 expression was correlated with poor prognosis of OSCC. After exogenous CCL21 stimulation, epithelial-mesenchymal transition (EMT) was promoted in OSCC cells, and cancer stem cell-related markers CD133, CD44, BMI1, ALDH1A1, and OCT4 increased. The migration, invasion, tumorsphere formation, and colony formation abilities of OSCC cells were enhanced, indicating that the stemness of OSCC cells was also improved. The knockdown and overexpression of CCR7 efficiently affected the CCL21-induced EMT and stemness of OSCC cells. When treated with CCL21, the phospho-JAK2 and phospho-STAT3 markedly increased. The inhibitor of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) significantly suppressed CCL21-induced EMT and stemness of OSCC cells. In conclusion, CCL21/CCR7 axis regulated EMT progress and promoted the stemness of OSCC by activating the JAK2/STAT3 signaling pathway. CCL21/CCR7 might be an effective target for OSCC prevention and treatment.

Tumoral microvesicle-activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma.

Metabolic reprogramming is a hallmark of cancer. Stromal cells could function as providers of energy metabolites for tumor cells by undergoing the "reverse Warburg effect," but the mechanism has not been fully elucidated. The interaction between the tumoral microvesicles (TMVs) and stroma in the tumor microenvironment plays a critical role in facilitating cancer progression. In this study, we demonstrated a novel mechanism for the TMV-mediated glycometabolic reprogramming of stromal cells. After being incubated with TMVs, normal human gingival fibroblasts exhibited a phenotype switch to cancer-associated fibroblasts and underwent a degradation of caveolin 1 (CAV1) through the ERK1/2-activation pathway. CAV1 degradation further induced the metabolic switch to aerobic glycolysis in the fibroblasts. The microvesicle-activated fibroblasts absorbed more glucose and produced more lactate. The migration and invasion of oral squamous cell carcinoma (OSCC) were promoted after being cocultured with the activated fibroblasts. Fibroblast-cancer cell glycometabolic coupling ring mediated by monocarboxylate transporter (MCT) 4 and MCT1 was then proved in the tumor microenvironment. Results indicated a mechanism for tumor progression by the crosstalk between tumor cells and stromal cells through the reverse Warburg effect via TMVs, thereby identifying potential targets for OSCC prevention and treatment.-Jiang, E., Xu, Z., Wang, M., Yan, T., Huang, C., Zhou, X., Liu, Q., Wang, L., Chen, Y., Wang, H., Liu, K., Shao, Z., Shang, Z. Tumoral microvesicle-activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma.

A Large Family of Synthetic Two-Dimensional Metal Hydrides.

Synthetic two-dimensional (2D) materials without layered bulk allotropes are approaching a new frontier of materials flatland, one with properties richer than those of graphene-like materials. This is the case even as only a few chemical elements and blends have shown synthetic 2D forms. While hydrogen and metals are earth-abundant and form numerous compounds, rarely are 2D materials with only robust metal-hydrogen bonds. Here, a large new family of 2D materials is found from metal hydrides by high-throughput computational search augmented with first-principles calculations. There are 110 thermally and dynamically stable 2D materials that range from metallic materials to wide-gap semiconductors. A subgroup of these materials even varies from topological insulators to nodal-loop semimetals as well as from antiferromagnetic semiconductors to ferromagnetic half-metals. Unexpectedly, these monolayers resemble graphene in an ability to form weak interlayer interaction due to the variable multicenter bonding of hydrogen that eliminates the otherwise prevalent dangling bonds, rather than the covalent bonds between stacked layers as in previously reported synthetic 2D materials. This feature will favor potential experimental synthesis of these metal hydride monolayers.