TCF19 promotes cell proliferation and tumor formation in lung cancer by activating the Raf/MEK/ERK signaling pathway.

OBJECTIVE: This study aimed to investigate TCF19's role in lung cancer development, specifically its involvement in the RAF/MEK/ERK signaling pathway. METHODS: Lung cancer tissue analysis revealed significant TCF19 overexpression. In vitro experiments using A549 and Hop62 cells with TCF19 overexpression demonstrated enhanced cell growth. Transgenic mouse models confirmed TCF19's role in primary tumor development. Transcriptome sequencing identified altered gene expression profiles, linking TCF19 to RAF/MEK/ERK pathway activation. Functional assays elucidated underlying mechanisms, revealing increased phosphorylation of Raf1, MEK1/2, and ERK1/2. Inhibiting RAF1 or ERK through shRaf1 or ERK inhibitor reduced cell cycle-related proteins and inhibited TCF19-overexpressing cell growth. RESULTS: TCF19 was identified as an oncogene in lung carcinoma, specifically impacting the RAF/MEK/ERK pathway. Elevated TCF19 levels in lung cancer suggest targeting TCF19 or its associated pathways as a promising strategy for disease management. CONCLUSION: This study unveils TCF19's oncogenic role in lung cancer, emphasizing its modulation of the RAF/MEK/ERK pathway and presenting a potential therapeutic target for TCF19-overexpressing lung cancers.

Breaking Highly Ordered PtPbBi Intermetallic with Disordered Amorphous Phase for Boosting Electrocatalytic Hydrogen Evolution and Alcohol Oxidation.

Constructing amorphous/intermetallic (A/IMC) heterophase structures by breaking the highly ordered IMC phase with disordered amorphous phase is an effective way to improve the electrocatalytic performance of noble metal-based IMC electrocatalysts because of the optimized electronic structure and abundant heterophase boundaries as active sites. In this study, we report the synthesis of ultrathin A/IMC PtPbBi nanosheets (NSs) for boosting hydrogen evolution reaction (HER) and alcohol oxidation reactions. The resulting A/IMC PtPbBi NSs exhibit a remarkably low overpotential of only 25 mV at 10 mA cm-2 for the HER in an acidic electrolyte, together with outstanding stability for 100 h. In addition, the PtPbBi NSs show high mass activities for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR), which are 13.2 and 14.5 times higher than those of commercial Pt/C, respectively. Density functional theory calculations demonstrate that the synergistic effect of amorphous/intermetallic components and multimetallic composition facilitate the electron transfer from the catalyst to key intermediates, thus improving the catalytic activity of MOR. This work establishes a novel pathway for the synthesis of heterophase two-dimensional nanomaterials with high electrocatalytic performance across a wide range of electrochemical applications.

The Extraction of Coupling-of-Modes Parameters in a Layered Piezoelectric Substrate and Its Application to a Double-Mode SAW Filter.

This paper presents an advanced method that combines coupling-of-modes (COM) theory and the finite element method (FEM), which enables the quick extraction of COM parameters and the accurate prediction of the electroacoustic and temperature behavior of surface acoustic wave (SAW) devices. For validation, firstly, the proposed method is performed for a normal SAW resonator. Then, the validated method is applied to analysis of an I.H.P. SAW resonator based on a 29°YX-LT/SiO2/SiC structure. Via optimization, the electromechanical coupling coefficient (K2) is increased up to 13.92% and a high quality (Q) value of 1265 is obtained; meanwhile, the corresponding temperature coefficient of frequency (TCF) is -10.67 ppm/°C. Furthermore, a double-mode SAW (DMS) filter with low insertion loss and excellent temperature stability is also produced. It is demonstrated that the proposed method is effective even for SAW devices with complex structures, providing a useful tool for the design of SAW devices with improved performance.

Factors associated with generalized pustular psoriasis progression among patients with psoriasis vulgaris in Japan: Results from a claims database study.

Of those patients diagnosed with generalized pustular psoriasis (GPP) in Japan, approximately 30% have a prior psoriasis vulgaris (PsV) diagnosis. Therefore, understanding factors associated with a GPP diagnosis is essential for early diagnosis of GPP in patients with PsV. This retrospective cohort study was conducted to identify associated factors for GPP diagnosis in patients with PsV. Eligible patients with two confirmed diagnoses of PsV with/without a confirmed GPP diagnosis (International Classification of Disease 10th revision codes L40.0 and L40.1, respectively) were identified from the Japanese Medical Data Center database (JMDC) (July 1, 2005-January 31, 2019). Weighted logistic regression was used to identify associated factors (based on recorded comorbidities) between the PsV only and PsV with GPP cohorts. Odds ratios (ORs) of ≥1.5, associated with a high probability of a GPP diagnosis, were reported for factors with ≥5 patients/cohort. The time from event to GPP diagnosis was evaluated. The highest associated factor for GPP diagnosis was psoriatic arthritis (OR 20.2, 95% confidence interval [CI] 17.06-23.92, P < 0.0001), which also had the shortest time from event to GPP diagnosis (median 119 days). Other comorbidities associated with GPP diagnosis were other psoriasis, tonsillitis, and sinusitis. Treatments associated with GPP diagnosis included systemic corticosteroids (OR 2.19, 95% CI 1.98-2.43, P < 0.0001; median time from treatment initiation to GPP diagnosis 180 days). Other associated treatments (other immunosuppressants, interleukin [IL]-17 or IL-23 inhibitors, and phototherapy) had a delay of ≥1 year from treatment initiation to GPP diagnosis. Back pain, headache, and fever were also identified as associated with a GPP diagnosis. Patients with PsV requiring systemic therapies are more likely to receive a GPP diagnosis than those not requiring systemic treatment. These data will help identify patients with PsV at high risk of developing GPP and potentially support early GPP diagnosis.

Compressible, anti-freezing, and ionic conductive cellulose/polyacrylic acid composite hydrogel prepared via AlCl3/ZnCl2 aqueous system as solvent and catalyst.

From the perspective of environmental sustainability, introducing cellulose into ionic conductive hydrogel is an inevitable trend for the development of flexible conductive materials. We report a double-network cellulose/polyacrylic acid (Cel/PAA) composite hydrogel based on the dissolving of cellulose by AlCl3/ZnCl2 aqueous system. The Cel/PAA composite hydrogel consists of rigid cellulose chains and flexible polyacrylic acid, which synergistically realize the improvement of the mechanical properties. The AlCl3/ZnCl2 aqueous system not only serves as the green solvent for cellulose, but also the Al3+ and Zn2+ metal ions can be served as a catalyst to activate the initiator for polymerization of acrylic acid. Compared with pure cellulose hydrogel, the compression strain of the Cel/PAA composite hydrogel was significantly improved to 80 %, and its conductivity increased by 28.1 %. In addition, its compression stress was enhanced over 2 times than pure PAA hydrogel. The Cel/PAA composite hydrogel exhibits excellent anti-freezing (-45 °C), weight retention (90 %), and conductivity (2.70 S/m) properties, still maintaining transparency and storage stability in the extreme environment. This work presents a facile strategy to develop an ionic conductive cellulose-based composite hydrogel with good conductivity and mechanical properties, which shows potential for the application fields of flexible sensors and 3D-printing functional materials.

An analysis of nonlinear thickness vibration frequencies of multi-layered film bulk acoustic resonators.

The fast reduction of the physical size of film bulk acoustic wave resonators as a layered structure implies the intensification of the electric field which can induce large deformation in the functioning state of devices as a circuit element. Consequently, the nonlinear behavior of the resonator and accompanying properties are to be included and evaluated in the development and optimization for performance improvement. With this objective, the nonlinear formulation of a multilayered film bulk acoustic resonator is presented for the analysis of vibration frequencies and mode shapes with the consideration of larger mechanical deformation. The dominantly linear relationship between the voltage or deformation and frequency is obtained to understand the nonlinear behavior and properties which have been subjected to extensive research analytically and experimentally to satisfy the application needs in all modes of communications and network technology.

Macroporous SnO2/MoS2 inverse opal hierarchitecture for highly efficient trace NO2 gas sensing.

The innovation of NO2 gas sensors is highly desirable in environmental monitoring and human safety. Herein, a macroporous SnO2/MoS2 inverse opal hierarchitecture has been constructed with substantial interface charge transfer, which realizes the efficient and stable detection of NO2 with an enhanced response, fast kinetics, and high selectivity at low temperatures.

Synergizing Hydrogen Spillover and Deprotonation by the Internal Polarization Field in a MoS2 /NiPS3 Vertical Heterostructure for Boosted Water Electrolysis.

Hydrogen spillover (HSo) has emerged to upgrade the hydrogen evolution reaction (HER) activity of Pt-support electrocatalysts, but it is not applicable to the deprotonated oxygen evolution reaction (OER). Non-precious catalysts that can perform well in both HSo and deprotonation (DeP) are extremely desirable for a sustainable hydrogen economy. Herein, an affordable MoS2 /NiPS3 vertical heterostructure catalyst is presented to synergize HSo and DeP for efficient water electrolysis. The internal polarization field (IPF) is clarified as the driving force of HSo in HER electrocatalysis. The HSo from the MoS2 edge to NiPS3 can activate the NiPS3 basal plane to boost the HER activity of the MoS2 /NiPS3 heterostructure (112 mV vs reversible hydrogen electrode (RHE) at 10 mA cm-2 ), while for OER, the IPF in the heterostructure can facilitate the hydroxyl diffusion and render MoS2 -to-NiPS3 /P-to-S dual-pathways for DeP. As a result, the stacking of OER-inactive MoS2 on the NiPS3 surface still brings intriguing OER enhancements. With them serving as electrode couples, the overall water splitting is attested stably with a cell voltage of 1.64 V at 10 mA cm-2 . This research puts forward the IPF as the criterion in the rational design of HSo/DeP-unified non-precious catalysts for efficient water electrolysis.

Elemental Two-Dimensional Materials for Li/Na-Ion Battery Anode Applications.

Two-dimensional (2D) nanostructure is currently the subject in the fields of new energy storage and devices. During the past years, a broad range of 2D materials represented by graphene have been developed and endow with excellent electrochemical properties. Among them, elemental 2D materials (Xenes) are an emerged material family for Li/Na-ion battery (LIB/SIB) anodes. Compared with other 2D materials and bulk materials, Xenes may exhibit some great superiorities for Li/Na storage, including excellent conductivity, fast ion diffusion and large active sites exposure. In this review, we provide a systematic summary of the recent progress and achievements of Xenes as well as their applications in LIBs/SIBs. The broad categorization of Xenes from group IIIA to VIA has been concisely outlined, and the related details in syntheses, structures and Li/Na-ion storage properties are reviewed. Further, the latest research progress of Xenes in Li/Na ion batteries are summarized, together with mechanism discussions. Finally, the challenges and prospects of Xenes applied to Li/Na ion battery are proposed based on its current developments.

Extracting Lamb wave vibrating modes with convolutional neural network.

In recent years, micro-acoustic devices, such as surface acoustic wave (SAW) devices, and bulk acoustic wave (BAW) devices have been widely used in the areas of Internet of Things and mobile communication. With the increasing demand of information transmission speed, working frequencies of micro-acoustic devices are becoming much higher. To meet the emerging demand, Lamb wave devices with characteristics that are fit for high working frequency come into being. However, Lamb wave devices have more complicated vibrating modes than SAW and BAW devices. Methods used for SAW and BAW devices are no longer suitable for the mode extraction of Lamb wave devices. To solve this difficulty, this paper proposed a method based on machine learning with convolutional neural network to achieve automatic identification. The great ability to handle large amount of images makes it a good option for vibrating mode recognition and extraction. With a pre-trained model, we are able to identify and extract the first two anti-symmetric and symmetric modes of Lamb waves in varisized plate structures. After the successful use of this method in Lamb wave modes automatic extraction, it can be extended to all micro-acoustic devices and all other wave types. The proposed method will further promote the application of the Lamb wave devices.

An Algorithm for Solving the Phase Ambiguity Problem of SAW Delay-Line Sensor Systems.

Solving the phase ambiguity problem is crucial to achieving a wide-range and high-precision measurement for the frequency-domain sampling (FDS)-based surface acoustic wave (SAW) delay-line sensor systems. This study proposes an improved phase estimation algorithm called dual-band phase estimation (DBPE) to solve the problem. By using DBPE, the SAW sensor system can obtain an extensive and alterable measuring range without further requirements for sensor design or transmitted signals. Thus, it can be widely used in various FDS-based SAW delay-line sensor systems. Monte Carlo simulations and temperature measuring experiments, based on a YZ-cut LiNbO3 SAW delay-line sensor and a switched frequency-stepped continuous wave (S-FSCW) reader, are performed to demonstrate the algorithm's validity. The Monte Carlo simulations show that DBPE can effectively solve the phase ambiguity problem and has better performance than frequency estimation in measuring precision at a low signal-to-noise ratio (SNR). The temperature-sensing experiments show that DBPE has a good performance in measuring range and precision, serving as a phase ambiguity solver in the temperature sensor system.

Biomarker subset analysis of a phase IIIb, open-label study of afatinib in EGFR tyrosine kinase inhibitor-naive patients with EGFRm+ non-small-cell lung cancer.

Aim: To explore the relationship between mutations in cfDNA and response to afatinib. Patients & methods: In total, 64 patients from one Chinese site with locally advanced/metastatic EGFRm+ non-small-cell lung cancer, who received afatinib 40 mg once daily, were included. Results: Overall, 33 (82.5%) patients became EGFRm- by visit 3; median progression-free survival was longer in these patients vs those who did not (11.0 vs 5.5 months). Progression-free survival was shorter in 42 (45.2%) patients with non-EGFR co-mutations at baseline vs those without (8.1 vs 12.5 months). Neither difference was significant. Conclusion: Afatinib provided clinical benefit for patients with EGFRm+ non-small-cell lung cancer across all subgroups. EGFRm status assessment in plasma cfDNA is a useful method of monitoring treatment.

We conducted a study in 64 Chinese patients with non-small-cell lung cancer to investigate the relationship between cancer mutations detected in the blood and the response to treatment with afatinib, which is known to be effective against EGFR mutations. Technology is now available to detect these mutations in the blood, as an alternative to obtaining and testing lung tissue samples. All 64 patients had EGFR mutations (and some patients had additional types of mutations) when afatinib was started (visit 1 in the study). By visit 3, most patients (82.5%) no longer had EGFR mutations detected in their blood, and these patients responded better to afatinib than those who still had EGFR mutations in their blood. Patients with additional types of mutations generally did not respond as well as those who had only EGFR mutations. Although results showed clinical benefit with afatinib using assessment of mutation status in the blood, statistical significance could not be shown due to the small size of the study. Clinical Trial Registration: NCT01953913 (ClinicalTrials.gov).

A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: Final Analysis, with a Focus on Patients Enrolled at Sites in China.

BACKGROUND: Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies. OBJECTIVE: To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, "near real-world" study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC. PATIENTS AND METHODS: NCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS). RESULTS: 541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9-15.9), and median PFS was 12.1 months (95% CI 11.0-13.6). Median TTSP (13.8 months, 95% CI 12.7-16.1) and PFS (11.4 months, 95% CI 10.9-13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075). CONCLUSIONS: Safety data for afatinib when used in a "near real-world" setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT01953913 (1 October 2013).

Vertically grown CeO2 and TiO2 nanoparticles over the MIL53Fe MOF as proper band alignments for efficient H2 generation and 2,4-DCP degradation.

The design of highly efficient photoca talysts for clean energy production and environmental remediation are the grand challenges of scientific research. Herein, TiO2@MIL53Fe and CeO2@MIL53Fe composite photocatalysts are synthesized via solvothermal technique. The SEM and TEM micrographs reveal that TiO2 and CeO2 nanoparticles are vertically grown onto the surface of MIL53Fe MOF. Further, HRTEM micrograph confirmed the formation of heterojunction. It has been investigated that the resultant TiO2@MIL53Fe and CeO2@MIL53Fe photocatalysts exhibit remarkably improved visible light activities for H2 production and 2,4-dichlorophenol (2,4-DCP) degradation in comparison to the bare MIL53Fe photocatalyst. The enhanced photoactivities of the fabricated TiO2@MIL53Fe and CeO2@MIL53Fe photocatalysts are attributed to significantly promoted charge separation as confirmed via the surface photo voltage (SPV) and photoluminescence (PL) results. Further, the photocatalysts exhibit high stability and reusability as confirmed via the recyclable tests. This work will promote the design of MOF-based efficient photocatalysts for clean energy production and environment purification.

Research in Nonlinearity of Surface Acoustic Wave Devices.

Surface acoustic wave (SAW) devices are one of the indispensable components in the radio frequency (RF) front-end of mobile phones. With the development of mobile communication technology, the requirements for linear specification of devices are more and more strict. Nonlinear distortions of SAW devices have a serious influence on the application of mobile RF modules. To satisfy the strict requirement of linearity of communication system, it is necessary to understand the generation mechanism of nonlinearity and study the accurate modeling, appropriate measurement methods, and nonlinear response elimination technology. In this paper, we summarize the research progress on the nonlinearity of SAW devices in recent years from four aspects: the generation mechanism, simulation methods, measurement system, and suppression technology. The nonlinear harmonics with the nonlinear Mason equivalent circuit model are simulated. Furthermore, harmonics and intermodulation signals of SAW filters are tested by the authors. Thanks to these research studies, it is of great significance to the development of future RF front-end modules with high linear SAW devices.

High-fidelity acoustic signal enhancement for phase-OTDR using supervised learning.

Phase-measuring phase-sensitive optical time-domain reflectometry (OTDR) has been widely used for the distributed acoustic sensing. However, the demodulated phase signals are generally noisy due to the laser frequency drift, laser phase noise, and interference fading. These issues are usually addressed individually. In this paper, we propose to address them simultaneously using supervised learning. We first use numerical simulations to generate the corresponding noisy differential phase signals for the given acoustic signals. Then we use the generated acoustic signals and noises together with some real noise data to train an end-to-end convolutional neutral network (CNN) for the acoustic signal enhancement. Three experiments are conduct to evaluate the performance of the proposed signal enhancement method. After enhancement, the average signal-to-noise ratio (SNR) of the recovered PZT vibration signals is improved from 13.4 dB to 42.8 dB, while the average scale-invariant signal-to-distortion ratio (SI-SDR) of the recovered speech signals is improved by 7.7 dB. The results show that, the proposed method can well suppress the noise and signal distortion caused by the laser frequency drift, laser phase noise, and interference fading, while recover the acoustic signals with high fidelity.

Numerical Analysis of Viscous Dissipation in Microchannel Sensor Based on Phononic Crystal.

Phononic crystals with phononic band gaps varying in different parameters represent a promising structure for sensing. Equipping microchannel sensors with phononic crystals has also become a great area of interest in research. For building a microchannels system compatible with conventional micro-electro-mechanical system (MEMS) technology, SU-8 is an optimal choice, because it has been used in both fields for a long time. However, its mechanical properties are greatly affected by temperature, as this affects the phononic bands of the phononic crystal. With this in mind, the viscous dissipation in microchannels of flowing liquid is required for application. To solve the problem of viscous dissipation, this article proposes a simulation model that considers the heat transfer between fluid and microchannel and analyzes the frequency domain properties of phononic crystals. The results show that when the channel length reaches 1 mm, the frequency shift caused by viscous dissipation will significantly affect detecting accuracy. Furthermore, the temperature gradient also introduces some weak passbands into the band gap. This article proves that viscous dissipation does influence the band gap of phononic crystal chemical sensors and highlights the necessity of temperature compensation in calibration. This work may promote the application of microchannel chemical sensors in the future.

A rational design of g-C3N4-based ternary composite for highly efficient H2 generation and 2,4-DCP degradation.

In this work, g-C3N4 based ternary composite (CeO2/CN/NH2-MIL-101(Fe)) has been fabricated via hydrothermal and wet-chemical methods. The composite showed superior photoactivities for H2O reduction to produce H2 and 2,4-dichlorophenol (2,4-DCP) degradation. The amount of H2 evolved over the composite under visible and UV-visible irradiations is 147.4 µmol·g-1·h-1 and 556.2 µmol·g-1·h-1, respectively. Further, the photocatalyst degraded 87% of 2,4-DCP in 2 hrs under visible light irradiations. The improved photoactivities are accredited to the synergistic-effects caused by the proper band alignment with close interfacial contact of the three components that significantly promoted charge transfer and separation. The 2,4-DCP degradation over the composite is dominated by OH radical rather than h+ and O2- as investigated by scavenger trapping experiments. This is further supported by the electron para-magnetic resonance (EPR) study. This work provides new directions for the development of g-C3N4 based highly efficient ternary composite materials for clean energy generation and pollution control.

GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes (TSGs) play a critical role in restricting tumorigenesis and impact the therapeutic effect of various treatments. However, TSGs remain to be systemically determined in lung cancer. Here, we identified GATA6 as a potent lung cancer TSG. GATA6 inhibited lung cancer cell growth in vitro and tumorigenesis in vivo. Mechanistically, GATA6 upregulated p53 and p21 mRNA while it inhibited AKT activation to stabilize p21 protein, thus inducing lung cancer cell senescence. Furthermore, we showed that ectopic expression of GATA6 led to dramatic slowdown of growth rate of established lung tumor xenograft in vivo.