The efficacy and safety of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, in patients with advanced head and neck mucosal melanoma harboring CDK4 amplification.

BACKGROUND: Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification. METHODS: The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494-0.957) and 51.6% (95% CI, 0.307-0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue. CONCLUSIONS: Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration. TRIAL REGISTRATION: ChiCTR2000031608.

Bi-directional two-sample Mendelian randomization identifies causal association of depression with temporomandibular disorders.

BACKGROUND: Depression and anxiety have been suggested to be associated with temporomandibular disorders (TMD) in observational studies. However, the causal association and the direction in the relationship between depression/anxiety and TMD remain unknown. OBJECTIVES: This study investigated the potential causal relationship between depression/anxiety and TMD with two-sample bi-directional Mendelian randomization (MR). METHODS: Summary statistics of depression (N = 500 199), anxiety disorder (N = 17 310) and TMD (N = 195 930) were sourced from large-scale genome-wide association studies (GWAS). The primary Mendelian randomization (MR) estimation employed the inverse-variance weighted meta-analysis (IVW). Additional MR sensitivity methods and multivariate MR (MVMR) were applied to address pleiotropy. RESULTS: IVW results indicated a causal effect of genetically predicted depression on TMD (OR = 1.887, 95% CI = 1.504-2.367, p < .001), which was supported by other sensitivity MR approaches. MVMR results suggested that the negative effect of depression on TMD persisted after conditioning on other potential confounders. The association of anxiety disorder with TMD was not supported by our findings. In the reverse direction, we did not find compelling evidence suggesting the causal effect of TMD on depression and anxiety disorder. CONCLUSIONS: The present study suggests a potential causal association between genetic liability for depression and the risk of TMD. Our MR findings align with prior epidemiological research, underscoring the significance of early detection and prevention of depression in the treatment of TMD.

Enhanced light-field image resolution via MLA translation.

This work describes a method that effectively improves the spatial resolution of light-field images without sacrificing angular resolution. The method involves translating the microlens array (MLA) linearly in both x- and y-directions in multiple steps to achieve 4 ×, 9 ×, 16 × and 25 × spatial resolution improvements. Its effectiveness was firstly validated through simulations with synthetic light-field images, demonstrating that distinct spatial resolution increments can be achieved by shifting the MLA. An MLA-translation light-field camera was built based on an industrial light-field camera, with which detailed experimental tests were carried out on a 1951 USAF resolution chart and a calibration plate. Qualitative and quantitative results prove that MLA translations can significantly improve measurement accuracy in x- and y- directions while preserving z-direction accuracy. Finally, the MLA-translation light-field camera was used to image a MEMS chip to demonstrate that finer structures of the chip can be acquired successfully.

Analysis of error propagation: from raw light-field data to depth estimation.

In micro-lens-array-based light-field imaging, the micro-lens centers serve as the origins of local micro-lens coordinate systems. Each micro-lens receives angular/depth information coded according to its center location. Therefore, the errors in positioning the micro-lens centers will lead to errors in depth estimation. This paper proposes a method that resolves error propagation from raw light-field data to depth estimation based on analyzing large amounts of simulated images with various aperture sizes, noise levels, and object distance values. The simulation employs backward ray tracing and Monte Carlo sampling to improve computational efficiency. The errors are counted and accumulated stepwise from center positioning and generation of sub-aperture images to depth estimation. The disparity errors calculated during depth estimation are shown to be more apparent either with more significant center positioning errors or with a greater defocusing distance. An experiment using an industrial light-field camera is conducted, confirming that disparity errors at considerable object distances can be reduced significantly when the micro-lens centers are positioned with higher accuracy.

Apatinib potentiates the therapeutic effect of anti-PD-1 in locally advanced head and neck cancers.

OBJECTIVES: Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. PATIENTS AND METHODS: We investigate the impact of VEGFR2 inhibition on tumor-infiltrating immune cells in vivo and the activity of the combination of apatinib and anti-PD-1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. RESULTS: We found that apatinib increased the infiltration of CD8+ T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+ PD1+ T cells were significantly increased in apatinib-treated tumors. The combined treatment of apatinib and anti-PD-1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. CONCLUSION: Our study demonstrated that apatinib therapy synergized with an anti-PD-1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.

A preliminary study of proximal realignment combination surgery in the treatment of adolescent habitual patellar dislocation.

OBJECTIVE: A combination of lateral soft tissue release, medial soft tissue contraction, vastus medialis anterior placement, medial patellofemoral ligament reconstruction, and rectus femoris insertion reconstruction are introduced in the treatment of habitual patellar dislocation in adolescents. METHODS: A retrospective analysis was performed on 12 patients (17 knees) with habitual patellar dislocation and unclosed epiphyses who underwent surgical treatment at the First Hospital of Jilin University from May 2017 to November 2021. The Lysholm scores and Q angle were collected preoperatively and at final follow-up and were compared. RESULTS: Twelve patients (4 boys and 8 girls) aged 10-15 years were retrospectively analysed, who followed up for an average of 21 months (5-48 months). The range of motion of the knee joint returned to normal in all patients, and no cases of complications including surgical site infection, joint stiffness, or patellar re-dislocation occurred. The mean Lysholm scores and Q angles improved from 73.9, and 19.6° preoperatively to 91.7, and 13.9° at the final follow-up, respectively. CONCLUSION: The preliminary effect of the combination surgery for habitual patellar dislocation in adolescents was satisfactory.

Sustainable recovery of titanium from secondary resources: A review.

The exploitation and utilization of secondary resources have the social benefits of saving resources, reducing pollution, and reducing production costs. Currently, less than 20% of titanium secondary resources can be recycled, and there are few reviews on titanium secondary resources recovery, which cannot fully reveal the technical information and progress of titanium secondary resources recovery. This work presents the current global distribution of titanium resources and market supply and demand, then focuses on an overview of technical studies on titanium extraction from different titanium-bearing secondary slags. The following types of titanium secondary resources are mainly available: sponge titanium production, the production of titanium ingot, titanium dioxide production, red mud, titanium-bearing blast furnace slag, spent SCR catalyst, and lithium titanate waste. The various methods of secondary resource recovery are compared, including the advantages and disadvantages, and the future development direction of the titanium recycling process is pointed out. On the one hand, recycling companies can classify and recover each type of residual waste according to its characteristics. On the other hand, solvent extraction technology can be the direction of attention due to the increased requirement for the purity of recovered materials. Meanwhile, the attention to lithium titanate waste recycling should also be enhanced.

MF-094 nanodelivery inhibits oral squamous cell carcinoma by targeting USP30.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, and the incidence of OSCC is increasing. As the mortality of OSCC keeps increasing, it is crucial to clarify its pathogenesis and develop new therapeutic strategies. METHODS: Confocal laser scanning microscopy was used to evaluate the uptake of nanoparticles (NPs). The potential functions of USP30 were evaluated by cell counting kit (CCK)-8, flow cytometry, biochemical assay, coimmunoprecipitation, qRT-PCR, and immunoblotting. The antitumor effect of NP-loaded USP30 inhibitor MF-094 was evaluated in vitro and in vivo. RESULTS: In this study, increased USP30 expression was found in OSCC specimens and cell lines through qRT-PCR and immunoblotting. CCK-8, flow cytometry, and biochemical assay revealed that the deubiquitylated catalytic activity of USP30 contributed to cell viability and glutamine consumption of OSCC. Subsequently, USP30 inhibitor MF-094 was loaded in ZIF-8-PDA and PEGTK to fabricate ZIF-8-PDA-PEGTK nanoparticles, which exhibited excellent inhibition of cell viability and glutamine consumption of OSCC, both in vitro and in vivo. CONCLUSION: The results indicated the clinical significance of USP30 and showed that nanocomposites provide a targeted drug delivery system for treating OSCC.

Epithelioid sarcoma: A clinicopathological study of 12 head and neck cases.

OBJECTIVES: To determine the clinicopathological features of epithelioid sarcoma presenting in head and neck region (HNES) and elucidate diagnostic key points and treatment options for HNES. MATERIALS AND METHODS: A total of 12 HNES cases were collected in our department from 2010 to 2020. Their clinical information and pathological features were documented, and relevant follow-up was performed. Immunohistochemistry was carried to analyze the protein markers of HNES. RESULTS: Of the 12 HNES cases, 10 were primary tumors and 2 were metastasized from foot and shoulder, respectively. The patients with primary tumors were significantly younger than those with metastasized ones (22.7 vs 41.5, p = .0157), and male patients outnumbered female patients (3:1). Of all HNES cases, 9 were classic subtype, and 3 were proximal subtype. HNES patients had a poor prognosis, with 5-year overall survival of 41.5% and 5-year relapse-free survival of 22.5%. A loss of INI1 was identified as the hallmark of HNES with 83.3% (10/12) of HNES cases presenting as EZH2 positive. CONCLUSIONS: HNES is more prevalent at younger ages and in males, has a poor prognosis, and exhibits a greater proportion of classic subtype than proximal subtype. EZH2 inhibitor has therapeutic potential in HNES.

Strategies for Polysulfide Immobilization in Sulfur Cathodes for Room-Temperature Sodium-Sulfur Batteries.

Room-temperature sodium-sulfur batteries are one of the most attractive energy storage systems due to their low cost and ultrahigh energy density (2600 W h kg-1 ). During the charge/discharge process, the sulfur can react with sodium via a multistep redox reaction to obtain a high specific capacity (1675 mA h g-1 ). However, these batteries face the difficult challenge of the "shuttle effect," which hinders their practical application. Many strategies have been employed to address this issue on sulfur electrodes, such as intact physical confinement, chemical inhibition, and electrocatalysis. In this review, the mechanisms of the abovementioned strategies are summarized, the remaining issues are clarified, and research directions are proposed for developing advanced sodium-sulfur batteries.

Highly-Dispersed Submicrometer Single-Crystal Nickel-Rich Layered Cathode: Spray Synthesis and Accelerated Lithium-Ion Transport.

For conventional polycrystalline Ni-rich cathode material consisting of numerous primary particles in disordered orientation, the crystal anisotropy in charge/discharge process results in the poor rate capability and rapid capacity degradation. In this work, highly-dispersed submicron single-crystal LiNi0.8 Co0.15 Al0.05 O2 (SC-NCA) cathode is efficiently prepared by spray pyrolysis (SP) technique followed by a simple solid-state lithiation reaction. Porous Ni0.8 Co0.15 Al0.05 Ox precursor prepared via SP exhibits high chemical activity for lithiation reaction, enabling the fabrication of single-crystal cathode at a relatively low temperature. In this way, the contradiction between high crystallinity and cation disordering is well balanced. The resulted optimized SC-NCA shows polyhedral single-crystal morphology with moderate grain size (≈1 µm), which are beneficial to shortening the Li+ diffusion path and improving the structural stability. As cathode for lithium ion batteries, SC-NCA delivers a high discharge capacity of 202 and 140 mAh g-1 at 0.1 and 10 C, respectively, and maintains superior capacity retention of 161 mAh g-1 after 200 cycles at 1C. No micro-crack is observed in the cycled SC-NCA particles, indicating such single-crystal morphology can greatly relieve the anisotropic micro-strain. This effective, continuous and adaptable strategy for preparing single-crystal Ni-rich cathode without any additive may accelerate their practical application.

NAT10 as a potential prognostic biomarker and therapeutic target for HNSCC.

BACKGROUND: Increasing evidence has demonstrated the critical roles of mRNA modification regulators on multiple types of cancers. However, it is still poorly known about the prognostic and therapeutic value of mRNA modification regulators in HNSCC. METHODS: The gene expression profile of 36 mRNA modification regulators and their corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Stepwise regression in R with both directions was used to construct a model for the prognosis of HNSCC. Univariate Cox regression survival analysis was performed to identify the most significant risk gene. Gene set enrichment analysis (GSEA) was applied to determine the cancer-associated pathways with NAT10. Immunohistochemistry (IHC) staining was performed to evaluate the expression of NAT10 in formalin fixed paraffin-embedded (FFPE) samples of HNSCC. Univariate and multivariate Cox regression survival analysis performed to identify the independent risk factors associated with the OS of patients with HNSCC. HNSCC cell lines (Cal-27, FaDu, and Detroit-562) were transfected with short interfering RNA (siRNA) targeting NAT10 or treated with Remodelin, a small-molecule inhibitor of NAT10. Knockdown efficiency of siRNA was assessed by quantitative real-time PCR (qRT-PCR) and western blotting. In addition, CCK-8 assay, scratch assay and transwell assay were used to examine the proliferation, migration, and invasion abilities of the three HNSCC cell lines after NAT10 was inhibited genetically and pharmaceutically. Cell cycle and cell apoptosis assays were performed by flow cytometry. Finally, the therapeutic value of Remodelin in HNSCC was evaluated via a patient-derived xenograft (PDX) model. The statistical analysis was performed with SPSS 23.0. RESULTS: A risk prediction model containing 10 mRNA modification regulators was constructed and showed prognostic value in HNSCC. NAT10 was further identified as a key risk gene and independent prognostic factor in TCGA HNSCC dataset. The GSEA analysis suggested that high NAT10 expression was associated with MYC, E2F, G2M checkpoint, mTORC1, DNA repair and oxidative phosphorylation pathways. NAT10 protein expression was significantly up-regulated in tumour cells compared to normal epithelial cells in FFPE samples and increased NAT10 protein expression was correlated with poor overall survival of 267 HNSCC patients. Genetic depletion of NAT10 using siRNA or chemical inhibition of NAT10 using Remodelin resulted in reduced cell proliferation, migration and invasion abilities in Cal-27, FaDu and Detroit-562 cells. Knockdown of NAT10 using siRNA significantly increased cell cycle arrest in S/G2-phase. Remodelin significantly inhibited tumour growth and tumour cell proliferation in the PDX model of HNSCC. CONCLUSIONS: NAT10 could be a potential prognostic marker and a therapeutic target for HNSCC.

The effect of chitosan molecular weight on CO2-triggered switching between emulsification and demulsification.

The role of molecular weight as a key physical property of macromolecules in determining the CO2-triggered switching characteristics of responsive emulsions prepared using CO2-switchable macromolecules has not been studied and is the focus of the current study. In this work, CO2-switchable chitosan of four different molecular weights is used to investigate the effect of molecular weight on CO2-triggered switching of CO2-responsive emulsions. The molecular weight of chitosan is shown to have an opposite effect on emulsification and demulsification by the CO2 trigger. Before bubbling of CO2, chitosan of higher molecular weight forms a more stable three-dimensional network structure in the continuous phase of oil-in-water (O/W) emulsions, which leads to the formation of a more stable emulsion. After bubbling of CO2, the chitosan of higher molecular weight makes the continuous phase more viscous, which leads to an incomplete demulsification as compared with the chitosan of lower molecular weight. Experimental evidence from the measurement of conductivity, interfacial tension and rheological properties is provided to support the proposed mechanism. This work is of great significance in guiding the selection of desirable CO2-switchable polymers for switchable emulsions of desired switching characteristics.

Sulfur in Amorphous Silica for an Advanced Room-Temperature Sodium-Sulfur Battery.

The room-temperature (RT) Na/S battery is a promising energy storage system owing to suitable operating temperature, high theoretical energy density, and low cost. However, it has a poor cycle life and low reversible capacity. In this work, we report a long-life RT-Na/S battery with amorphous porous silica as a sulfur host. The sulfur is loaded into amorphous silica by a dipping method; the optimal sulfur loading is up to 73.48 wt %. Molecular dynamics simulation and first-principles calculations suggest that the complex pores, acting as micro-containers and the formation of Na-O chemical bonds between amorphous silica and sodium polysulfide, give the electrodes a strong ability to inhibit sodium polysulfide shuttle. This would give rise to effectively avoiding the loss of active sulfur, corresponding to a superior capacity and an excellent cyclability even at 10 A gsulfur -1 (nearly 100 % coulomb efficiency and high reversible capacity of 955.8 mAh gsulfur -1 after 1460 cycles).

The crosstalk between AXL and YAP promotes tumor progression through STAT3 activation in head and neck squamous cell carcinoma.

Receptor tyrosine kinases (RTKs) and Yes-associated protein (YAP) are critical driving factors in tumors. Currently, the regulation of RTKs in the Hippo-YAP pathway has been recognized as an important issue. However, the relationship between AXL, one of the RTKs, and YAP in head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, the crosstalk between AXL and YAP was thoroughly investigated in vitro and in vivo. We determined that there was a positive correlation between AXL and YAP in the HNSCC tissue samples and the Cancer Genome Atlas (TCGA) dataset, and high co-expression was associated with poor prognosis. Inhibiting YAP decreased AXL expression in HNSCC cells, while YAP overexpression increased AXL. Moreover, ectopic expression of AXL reversed tumor suppressor phenotypes mediated by YAP silencing. This reversal effect was also confirmed in vivo. In addition, AXL overexpression and Gas6, a ligand of AXL, stimulated YAP dephosphorylation, nuclear translocation, and target gene transcription. AXL inhibition decreased YAP dephosphorylation and nuclear translocation. Mechanistically, Gas6 induced a competitive binding to phosphorylated signal transducers and activators of transcription 3 (STAT3) with large tumor suppressor kinase 1 (LATS1) and inhibited the Hippo pathway. This study revealed a novel non-transcriptional effect of STAT3 in Gas6/AXL-induced YAP activity, suggesting that STAT3 acted as a critical "molecular switch" during the mutual promotion between AXL and YAP, which might be a promising therapeutic target in HNSCC.

Fewer tumour-specific PD-1+CD8+ TILs in high-risk "Infiltrating" HPV- HNSCC.

BACKGROUND: The prognosis of HPV- HNSCC was worse than that of HPV+ HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV- HNSCC. METHODS: The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV- tumours were classified into "Infiltrating" and "Pushing" subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. HNSCC data from the Cancer Genome Atlas (n = 263) were analysed for CD8α, HPV and overall survival (OS). A murine HNSCC model was used to verify the antitumour role of PD-1+CD8+ TILs. RESULTS: The "Infiltrating" HPV- subtype showed shorter OS than the "Pushing" subtype. Moreover, there is a tendency from "Pushing" to "Infiltrating" subtype from the primary to the recurrent lesion. Different from total CD8+ TILs, tumour-specific PD-1+CD8+ TILs were fewer in invasive margin (IM) of "Infiltrating" HPV- tumours. PD-1+CD8+ TILs recognised autologous HNSCC cells and showed stronger inhibition of tumour growth in a murine HNSCC model resistant to PD-1 blockade. CONCLUSIONS: Coevolution of HPV- HNSCC and TILs is characterised by an "Infiltrating" phenotype and less tumour-specific PD-1+CD8+ TILs, which may provide a framework for further translational studies and patient stratification.

Structural Reorganization-Based Nanomaterials as Anodes for Lithium-Ion Batteries: Design, Preparation, and Performance.

In recent years, with the growing demand for higher capacity, longer cycling life, and higher power and energy density of lithium ion batteries (LIBs), the traditional insertion-based anodes are increasingly considered out of their depth. Herein, attention is paid to the structural reorganization electrode, which is the general term for conversion-based and alloying-based materials according to their common characteristics during the lithiation/delithiation process. This Review summarizes the recent achievements in improving and understanding the lithium storage performance of conversion-based anodes (especially the most widely studied transition metal oxides like Mn-, Fe-, Co-, Ni-, and Cu-based oxides) and alloying-based anodes (mainly including Si-, Sn-, Ge-, and Sb-based materials). The synthesis schemes, morphological control and reaction mechanism of these materials are also included. Finally, viewpoints about the challenges and feasible improvement measures for future development in this direction are given. The aim of this Review is to shed some light on future electrode design trends of structural reorganization anode materials for LIBs.

Paenibacillus polymyxa biofertilizer application in a tea plantation reduces soil N2O by changing denitrifier communities.

Increasing the use of nitrogen fertilizers in tea orchards has led to intense nitrous oxide (N2O) emissions. Foliar application of Paenibacillus polymyxa biofertilizer has been proven to be beneficial for organic tea production. In this study, tea yield and quality were significantly improved after application of P. polymyxa biofertilizer compared with the control but were not significantly different from chemical fertilizer treatments. However, the average N2O fluxes in tea fields treated with chemical fertilizers and biofertilizers (225 kg N·ha-1·year-1 for both) were 50.6-973.7 and 0.6-29.1 times higher than those in the control treatment, respectively. Pot experiments conducted to explore the mechanism of N2O reduction induced by P. polymyxa biofertilizer showed that applying P. polymyxa in addition to urea could reduce N2O fluxes by 36.5%-73.1%. Quantitative PCR analysis suggested that a significant increase in the quantity of nirK and nosZ genes was linked to the reduction of N2O, and high-throughput sequencing of nosZ revealed active and potentially efficient denitrifiers in different treatments. Our findings suggest that P. polymyxa biofertilizer is in line with the requirements of modern agriculture, which aims to increase product yield and quality while reducing negative environmental impacts.

Yes-associated protein promotes cell migration via activating Wiskott-Aldrich syndrome protein family member 1 in oral squamous cell carcinoma.

BACKGROUND: Yes-associated protein (YAP) is a candidate oncogene in various cancers including oral squamous cell carcinoma (OSCC). Our previous study demonstrated that TNF-alpha could inhibit cell proliferation and invasion by YAP phosphorylation in OSCC. However, the role of YAP in OSCC is not yet clear. The objective of the present study was to elucidate the function of YAP in promoting migration in OSCC and to explore the possible mechanism with a novel YAP inhibitor CA3. METHODS: A total of 68 OSCC patients were enrolled, and the expression levels of YAP were investigated in tissue specimens by immunohistochemical staining. The inhibitory effects of CA3, a novel inhibitor of YAP, were demonstrated by immunofluorescence, Western blotting, and transwell assays. A human PCR motility array was performed to screen the changes in the gene expression profiles of the cells. In addition, shRNA interference, YAP re-expression, and WAVE1 overexpression plasmids were used to detect the regulatory mechanism of YAP and its relationship with cell migration. RESULTS: Yes-associated protein nuclear expression levels were associated with metastasis and 5-year overall survival rate. CA3 exhibited potent inhibitory effects on OSCC migration. YAP knockdown significantly suppressed tumor cell migration in OSCC. These effects were rescued when YAP was re-expressed and during WAVE1 overexpression in YAP-shRNA stable cells. CONCLUSIONS: The present study revealed that YAP was associated with cell migration and that this process was regulated by YAP/WAVE1. We also demonstrated that CA3 exhibited marked inhibitory effects on YAP expression and that it could be considered a potential therapeutic target for the treatment of OSCC.

Theoretical Study of pKa Values for Trivalent Rare-Earth Metal Cations in Aqueous Solution.

Molecular acidity of trivalent rare-earth metal cations in aqueous solution is an important factor dedicated to the efficiency of their extraction and separation processes. In this work, the aqueous acidity of these metal ions has been quantitatively investigated using a few theoretical approaches. Our computational results expressed in terms of pKa values agree well with the tetrad effect of trivalent rare-earth ions extensively reported in the extraction and separation of these elements. Strong linear relationships have been observed between the acidity and quantum electronic descriptors such as the molecular electrostatic potential on the acidic nucleus and the sum of the valence natural atomic orbitals energies of the dissociating proton. Making use of the predicted pKa values, we have also predicted the major ionic forms of these species in the aqueous environment with different pH values, which can be employed to rationalize the behavior difference of different rare-earth metal cations during the extraction process. Our present results should provide needed insights not only for the qualitatively understanding about the extraction and separation between yttrium and lanthanide elements but also for the prediction of novel and more efficient rare-earth metal extractants in the future.