NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/ß-catenin pathway.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a poor prognosis, yet the underlying mechanism needs further exploration. Non-SMC condensin I complex subunit D2 (NCAPD2) is a widely expressed protein in OSCC, but its role in tumor development is unclear. This study aimed to explore NCAPD2 expression and its biological function in OSCC. NCAPD2 expression in OSCC cell lines and tissue specimens was analyzed using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cancer cell growth was evaluated using cell proliferation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and colony formation assays. Cell migration was evaluated using wound healing and Transwell assays. Apoptosis was detected using flow cytometry. The influence of NCAPD2 on tumor growth in vivo was evaluated in a mouse xenograft model. NCAPD2 expression was significantly higher in OSCC than that in normal oral tissue. In vitro, the knockdown of NCAPD2 inhibited OSCC cell proliferation and promoted apoptosis. NCAPD2 depletion also significantly inhibited the migration of OSCC cells. Moreover, NCAPD2 overexpression induced inverse effects on OSCC cell phenotypes. In vivo, we demonstrated that downregulating NCAPD2 could inhibit the tumorigenicity of OSCC cells. Mechanically, OSCC regulation by NCAPD2 involved the Wnt/ß-catenin signaling pathway. These results suggest NCAPD2 as a novel oncogene with an important role in OSCC development and a candidate therapeutic target for OSCC.

New insights into changes in phosphorus profile at sediment-water interface by microplastics: Role of benthic bioturbation.

Microplastics (MPs) have attracted increasing attention due to their ubiquitous occurrence in freshwater sediments and the detrimental effects on benthic invertebrates. However, a clear understanding of their downstream impacts on ecosystem services is still lacking. This study examines the effects of bio-based polylactic acid (PLA), fuel-based polyethylene terephthalate (PET), and biofilm-covered PET (BPET) MPs on the bioturbator chironomid larvae (Tanypus chinensis), and the influence on phosphorus (P) profiles in microcosms. The changes in biochemical responses and metabolic pathways indicated that MPs disrupted energy synthesis by causing intestinal blockage and oxidative stress in T. chinensis, leading to energy depletion and impaired bioturbation activity. The impairment further resulted in enhanced sedimentary P immobilization. For larval treatments, the internal-P loadings were respectively 11.4%, 8.6%, and 9.0% higher in the PLA, PET, and BPET groups compared to the non-MP control. Furthermore, the influence of bioturbation on P profiles was MP-type dependent. Both BPET and PLA treatments displayed more obvious impacts on P profiles compared to PET due to the changes in MP bioavailability or sediment microenvironment. This study connects individual physiological responses to broader ecosystem services, showing that MPs alter P biogeochemical processes by disrupting the bioturbation activities of chironomid larvae.

Improved PGC demodulation algorithm for fiber optic interferometric sensors.

An improved phase generated carrier arctangent demodulation algorithm based on harmonic mixing and phase quadrature technology (PGC-Arctan-HP) is proposed in this paper, which can eliminate the effects of modulation depth shift, carrier phase delay, and light intensity disturbance (LID) on the demodulation results. The simulation results are consistent with theoretical analysis, and indicate that the PGC-Arctan-HP algorithm can achieve optimal demodulation compared with other demodulation algorithms. The results of interferometric experiments show that the demodulated waveforms of the improved algorithm are relatively stable with an amplitude error of 0.0294%. The total-harmonic-distortion (THD) and the signal-to-noise-and-distortion (SINAD) can reach -60.0286 dB and 59.5388 dB.

Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy.

PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. RESULTS: Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)-positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). CONCLUSION: Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Impact of residual disease biomarkers on the prognosis of HER2-positive breast cancer following neoadjuvant therapy.

BACKGROUND: The changes in prognostic factors and clinicopathological characteristics of residual disease following neoadjuvant therapy (NAT) for breast cancer are important references for postoperative adjuvant therapy. The analyses of the relationship between the clinicopathological characteristics of residual diseases and the prognosis were not comprehensive in most previous studies. This study aimed to determine how prognostic factors changed following NAT and the impact of clinicopathological characteristics of residual disease on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: The study comprised 350 consecutive patients with HER2-positive breast cancer who had residual disease after surgery following NAT. The independent risk factors affecting the prognosis of HER2-positive breast cancer were analyzed using univariate and multivariate Cox regression analyses. Chi-square test and binary logistic regression were used to analyze the influencing factors of HER2 loss following NAT. RESULTS: The expression of prognostic factors changed significantly following NAT. A total of 44 patients (12.6%) had HER2 loss. HER2 status (immunohistochemistry (IHC) 3+ vs. IHC 2+/FISH+, p < 0.001) at baseline was associated with HER2 loss. In this investigation, the HER2 loss did not affect the prognosis. In univariate analysis, the decrease in Ki-67 (p < 0.001) after NAT was associated with improved prognosis, but this influence was lost in the Cox proportional hazards model. The ypN stage (p < 0.001), postoperative ER status (p = 0.020), Miller-Payne grade (p = 0.007), and targeted therapy (p = 0.003) were all independent prognostic factors. CONCLUSIONS: ER, PR, HER2, and Ki-67 changed significantly after NAT, but no impact of these changes on DFS was observed in this study. Postoperative N stage, postoperative ER status, MP grade, and targeted therapy were independent prognostic factors in patients with HER2-positive breast cancer after NAT.

ELOVL2-AS1 inhibits migration of triple negative breast cancer.

In this study, we identified a key enhancer RNA (eRNA) region in breast cancer (BRCA) by applying an integrated analysis method. Reported eRNA region and genes affected by them were selected as presumed target pairs. Kaplan-Meier (KM) survival and correlation analyses were performed to screen valuable eRNA region. Based on the KM value and its correlation with the paired target genes, we carefully selected ELOVL2-AS1 as a potential key eRNA region in BRCA. Subsequently, we analyzed the expression of ELOVL2-AS1 and ELOVL2 in four BRCA subtypes and in different BRCA cell lines. The expression of ELOVL2-AS1 and ELOVL2 in triple negative breast cancer (TNBC) was significantly lower than those in Luminal A. After that, we analyzed the function of genes that are positively correlated with ELOVL2-AS1. We found that the co-expression gene mainly related to cilia and cilia characteristics of TNBC is significantly weaker than that of Luminal A. Considering the stronger invasion and metastasis of TNBC (compared with Luminal A) and the close relationship between decreased cilia and metastasis, we overexpressed ELOVL2-AS1 in TNBC and observed its effect on cell migration. The results show that it can inhibit the migration of TNBC. Finally, we analyzed the assay for transposase-accessible chromatin sequencing data, chromatin interaction analysis with paired-end tag sequencing data, and chromatin immunoprecipitation sequencing data and identified the chromatin interaction between ELOVL2-AS1 and ELOVL2, suggesting a direct regulatory interaction.

Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma.

OBJECTIVES: Targeting the deubiquitinases (DUBs) has become a promising avenue for anti-cancer drug development. However, the effect and mechanism of pan-DUB inhibitor, PR-619, on oesophageal squamous cell carcinoma (ESCC) cells remain to be investigated. MATERIALS AND METHODS: The effect of PR-619 on ESCC cell growth and cell cycle was evaluated by CCK-8 and PI staining. Annexin V-FITC/PI double staining was performed to detect apoptosis. LC3 immunofluorescence and acridine orange staining were applied to examine autophagy. Intercellular Ca2+ concentration was monitored by Fluo-3AM fluorescence. The accumulation of ubi-proteins and the expression of the endoplasmic reticulum (ER) stress-related protein and CaMKKß-AMPK signalling were determined by immunoblotting. RESULTS: PR-619 could inhibit ESCC cell growth and induce G2/M cell cycle arrest by downregulating cyclin B1 and upregulating p21. Meanwhile, PR-619 led to the accumulation of ubiquitylated proteins, induced ER stress and triggered apoptosis by the ATF4-Noxa axis. Moreover, the ER stress increased cytoplasmic Ca2+ and then stimulated autophagy through Ca2+ -CaMKKß-AMPK signalling pathway. Ubiquitin E1 inhibitor, PYR-41, could reduce the accumulation of ubi-proteins and alleviate ER stress, G2/M cell cycle arrest, apoptosis and autophagy in PR-619-treated ESCC cells. Furthermore, blocking autophagy by chloroquine or bafilomycin A1 enhanced the cell growth inhibition effect and apoptosis induced by PR-619. CONCLUSIONS: Our findings reveal an unrecognized mechanism for the cytotoxic effects of general DUBs inhibitor (PR-619) and imply that targeting DUBs may be a potential anti-ESCC strategy.

A comparative study among machine learning and numerical models for simulating groundwater dynamics in the Heihe River Basin, northwestern China.

Groundwater is unique resource for agriculture, domestic use, industry and environment in the Heihe River Basin, northwestern China. Numerical models are effective approaches to simulate and analyze the groundwater dynamics under changeable conditions and have been widely used all over the world. In this paper, the groundwater dynamics of the middle reaches of the Heihe River Basin was simulated using one numerical model and three machine learning algorithms (multi-layer perceptron (MLP); radial basis function network (RBF); support vector machine (SVM)). Historical groundwater levels and streamflow rates were used to calibrate/train and verify the different methods. The root mean square error and R2 were used to evaluate the accuracy of the simulation/training and verification results. The results showed that the accuracy of machine learning models was significantly better than that of numerical model in both stages. The SVM and RBF performed the best in training and verification stages, respectively. However, it should be noted that the generalization ability of numerical model is superior to the machine learning models because of the inclusion of physical mechanism. This study provides a feasible and accurate approach for simulating groundwater dynamics and a reference for model selection.

Terahertz imaging employing graphene modulator arrays.

In this paper we propose and experimentally demonstrate arrays of graphene electro-absorption modulators as electrically reconfigurable patterns for terahertz cameras. The active element of these modulators consists of only single-atom-thick graphene, achieving a modulation of the THz wave reflectance > 50% with a potential modulation depth approaching 100%. Although the prototype presented here only contains 4x4 pixels, it reveals the possibility of developing reliable low-cost video-rate THz imaging systems employing single detector.

Extraordinary control of terahertz beam reflectance in graphene electro-absorption modulators.

We demonstrate a graphene-based electro-absorption modulator achieving extraordinary control of terahertz reflectance. By concentrating the electric field intensity in an active layer of graphene, an extraordinary modulation depth of 64% is achieved while simultaneously exhibiting low insertion loss (∼2 dB), which is remarkable since the active region of the device is atomically thin. This modulator performance, among the best reported to date, indicates the enormous potential of graphene for terahertz reconfigurable optoelectronic devices.