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The areca nut is the primary economic source for some farmers in southeast Asia. However, the emergence of areca yellow leaf disease (YLD) has seriously reduced the annual production of areca nuts. There is an urgent need for an effective method to monitor the severity of areca yellow leaf disease (SAYD). This study selected an areca orchard with a high incidence of areca YLD as the study area. An unmanned aerial vehicle (UAV) was used to acquire multispectral and thermal infrared data from the experimental area. The ReliefF algorithm was selected as the feature selection algorithm and ten selected vegetation indices were used as the feature variables to build six machine-learning classification models. The experimental results showed that the combination of ReliefF and the Random Forest algorithm achieved the highest accuracy in the prediction of SAYD. Compared to manually annotated true values, the R2 value, root mean square error, and mean absolute percentage error reached 0.955, 0.049, and 1.958%, respectively. The Pearson correlation coefficient between SAYD and areca canopy temperature (CT) was 0.753 (p value < 0.001). The experimental region was partitioned, and a nonlinear fit was performed using CT versus SAYD. Cross-validation was performed on different regions, and the results showed that the R2 value between the predicted result of SAYD by the CT and actual value reached 0.723. This study proposes a high-precision SAYD prediction method and demonstrates the correlation between the CT and SAYD. The results and methods can also provide new research insights and technical tools for botanical researchers and areca practitioners, and have the potential to be extended to more plants.

S1. BRAFV600E mutation identified in thyroid cancer cell lines analyzed by RNA-seq.S2. STR analysis in thyroid cancer cell lines used in this study.S3. Gene expression of thyroid-specific genes in thyroid cancer cell lines analyzed by RNA-seq.S4. Dose-dependent toxicity of vemurafenib in BRAFV600E thyroidcancer cells.S5. Vemurafenib dose-dependent curves of vemurafenib-resistantBRAFV600E thyroid cancer cells.S6. Vemurafenib induces apoptosis in 8505C cells.S7. Predicted activators and inhibitors in Vem-resistant BRAF mutant thyroid cancer cells.

Supplementary Table 1. Gene expression changes in 8505C after vemurafenib treatment.Supplementary Table 2. Gene expression changes in WRO after vemurafenib treatment.Supplementary Table 3. Gene expression changes in 8505C -Vem-Res 1 relative to parental 8505C.Supplementary Table 4. Gene expression changes in WRO -Vem-Res 6 relative to parental WRO.Supplementary Table 5. Clinical features of thyroid tumors used in Fig. 5.

Purpose: Although gefitinib prolonged the progression-free survival (PFS) of patients with non–small cell lung cancer (NSCLC), unpredictable resistance limited its clinical efficacy. Novel predictive biomarkers with explicit mechanisms are urgently needed. Experimental Design: A total of 282 patients with NSCLC with gefitinib treatment were randomly assigned in a 7:3 ratio to exploratory (n = 192) and validation (n = 90) cohorts. The candidate polymorphisms were selected with Haploview4.2 in Hapmap and genotyped by a MassARRAY system, and the feature variables were identified through Randomforest Survival analysis. Tanswell and clonogenic assays, base editing and cell-derived tumor xenograft model were performed to uncover the underlying mechanism. Results: We found that the germline missense polymorphism rs3742076 (A>G, S628P), located in transactivation domain of FOXM1, was associated with PFS in exploratory (median PFS: GG vs. GA&AA, 9.20 vs. 13.37 months, P = 0.00039, HR = 2.399) and validation (median PFS: GG vs. GA&AA, 8.13 vs. 13.80 months, P = 0.048, HR = 2.628) cohorts. We elucidated that rs3742076_G conferred resistance to gefitinib by increasing protein stability of FOXM1 and facilitating an aggressive phenotype in vitro and in vivo through activating wnt/β-catenin signaling pathway. Meanwhile, FOXM1 level was highly associated with prognosis in patients with EGFR-mutant NSCLC. Mechanistically, FOXM1 rs3742076_G upregulated wnt/β-catenin activity by directly binding to β-catenin in cytoplasm and promoting transcription of β-catenin in nucleus. Remarkably, inhibition of β-catenin markedly reversed rs3742076_G-induced gefitinib resistance and aggressive phenotypes. Conclusions: These findings characterized rs3742076_G as a gain-of-function polymorphism in mediating gefitinib resistance and tumor aggressiveness, and highlighted the variant as a predictive biomarker in guiding gefitinib treatment.

This paper investigate a laser processing parameters effects on the tensile properties and surface roughness of a SLM-manufactured 316L stainless steel sample. A multi-index weight model was established using the orthogonal test and entropy weight method. Then, the model assessed the effect of three process factors (scanning speed v, filling laser power P, and scan spacing s). The influence of different combinations of processing parameters on tensile properties and surface roughness was also analyzed. The results revealed that the level of the effects on the sample’s properties from high to low was P, v, and s (P > v > s), respectively. Tensile properties were influenced by laser power and scanning speed first with an increase, followed by a decrease, while scan spacing affected tensile properties with a decrease followed by an increase; the maximum tensile strength was 693 MPa. Surface roughness was affected by filling laser power and scanning power and scanning speed first with a decrease, followed by an increase, while scan spacing affected surface roughness with an increase followed by a decrease. Under experimental conditions, when the laser energy density (E) was 69.44 J·mm−3, the surface roughness of formed parts was the best; Ra was 2.04 μm.

Background: The electro-hydraulic load simulator is a semi-physical simulation system. It is used to simulate different loads on the bearing capacity object (steering gear system) under working conditions and further test the dynamic and static characteristics of the bearing capacity object. Therefore, it is widely used in important applications such as the simulation of various loads and the development of high-performance steering gear systems. Objective: By analyzing and discussing the electro-hydraulic load simulator equipment and its improvement methods, some useful conclusions have been drawn to predict the development of the electro-hydraulic load simulator and its key technologies. Methods: The current status of research on electro-hydraulic load simulator prototypes is discussed in depth. The electro-hydraulic load simulators are classified according to the loading system applying force (torque). The improvement methods of the electro-hydraulic load simulator, including the method of suppressing the extraneous force, the compensation method of nonlinear factors, and the method of establishing the mathematical model, are analyzed and summarized. Results: By summarizing the literature and patents on electro-hydraulic load simulation technology, the principle, and characteristics of different equipment and improvement methods are analyzed and compared, and future development of electro-hydraulic load simulation equipment and technology is discussed. Conclusion: The research on the characteristics of the prototype, the hardware means and control strategy to suppress the extraneous force, the compensation of nonlinear factors, and the methods of establishing the mathematical model are beneficial to improve the loading accuracy of the electrohydraulic load simulator.

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer.Implications:Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.

A model for ICAM1-CAR T and anti-PD1 antibody activities in advanced thyroid cancers.

Purpose:Although gefitinib prolonged the progression-free survival (PFS) of patients with non–small cell lung cancer (NSCLC), unpredictable resistance limited its clinical efficacy. Novel predictive biomarkers with explicit mechanisms are urgently needed.Experimental Design:A total of 282 patients with NSCLC with gefitinib treatment were randomly assigned in a 7:3 ratio to exploratory (n = 192) and validation (n = 90) cohorts. The candidate polymorphisms were selected with Haploview4.2 in Hapmap and genotyped by a MassARRAY system, and the feature variables were identified through Randomforest Survival analysis. Tanswell and clonogenic assays, base editing and cell-derived tumor xenograft model were performed to uncover the underlying mechanism.Results:We found that the germline missense polymorphism rs3742076 (A>G, S628P), located in transactivation domain of FOXM1, was associated with PFS in exploratory (median PFS: GG vs. GA&AA, 9.20 vs. 13.37 months, P = 0.00039, HR = 2.399) and validation (median PFS: GG vs. GA&AA, 8.13 vs. 13.80 months, P = 0.048, HR = 2.628) cohorts. We elucidated that rs3742076_G conferred resistance to gefitinib by increasing protein stability of FOXM1 and facilitating an aggressive phenotype in vitro and in vivo through activating wnt/β-catenin signaling pathway. Meanwhile, FOXM1 level was highly associated with prognosis in patients with EGFR-mutant NSCLC. Mechanistically, FOXM1 rs3742076_G upregulated wnt/β-catenin activity by directly binding to β-catenin in cytoplasm and promoting transcription of β-catenin in nucleus. Remarkably, inhibition of β-catenin markedly reversed rs3742076_G-induced gefitinib resistance and aggressive phenotypes.Conclusions:These findings characterized rs3742076_G as a gain-of-function polymorphism in mediating gefitinib resistance and tumor aggressiveness, and highlighted the variant as a predictive biomarker in guiding gefitinib treatment.

Purpose:Advanced thyroid cancers, including poorly differentiated and anaplastic thyroid cancer (ATC), are lethal malignancies with limited treatment options. The majority of patients with ATC have responded poorly to programmed death 1 (PD1) blockade in early clinical trials. There is a need to explore new treatment options.Experimental Design:We examined the expression of PD-L1 (a ligand of PD1) and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lines, and investigated the PD1 expression level in peripheral T cells of patients with thyroid cancer. Next, we studied the tumor-targeting efficacy and T-cell dynamics of monotherapy and combination treatments of ICAM1-targeting chimeric antigen receptor (CAR) T cells and anti-PD1 antibody in a xenograft model of ATC.Results:Advanced thyroid cancers were associated with increased expression of both ICAM1 and PD-L1 in tumors, and elevated PD1 expression in CD8+ T cells of circulating blood. The expression of ICAM1 and PD-L1 in ATC lines was regulated by the IFNγ–JAK2 signaling pathway. ICAM1-targeted CAR T cells, produced from either healthy donor or patient T cells, in combination with PD1 blockade demonstrated an improved ability to eradicate ICAM1-expressing target tumor cells compared with CAR T treatment alone. PD1 blockade facilitated clearance of PD-L1 high tumor colonies and curtailed excessive CAR T expansion, resulting in rapid tumor clearance and prolonged survival in a mouse model.Conclusions:Targeting two IFNγ-inducible, tumor-associated antigens—ICAM1 and PD-L1—in a complementary manner might be an effective treatment strategy to control advanced thyroid cancers in vivo.

Expression of ICAM1 and PD-L1 in anaplastic thyroid tumor cell lines.

Supplementary Figure from FOXM1 Variant Contributes to Gefitinib Resistance via Activating Wnt/β-Catenin Signal Pathway in Patients with Non–Small Cell Lung Cancer

PD1 inhibition enhances survival benefit of CAR T treatment in KHM-5M xenografts.

Supplementary Table from FOXM1 Variant Contributes to Gefitinib Resistance via Activating Wnt/β-Catenin Signal Pathway in Patients with Non–Small Cell Lung Cancer

Background Proportional-integral-differential (PID) controller is widely used in the engineering field because of its simple structure, high control accuracy, and easy operation. Various kinds of PID controllers have their own advantages, disadvantages, and application scenarios. Objective By analyzing and discussing the improved PID control techniques in the electro-hydraulic servo system, some valuable conclusions have been drawn to predict the future research and development of PID control techniques. Methods The improved PID control techniques applied to electro-hydraulic servo systems are classified into three categories: PID parameter tuning technology, PID parameter online adjustment strategy and compound control strategy combined with PID algorithm. Results By comparing the principles and characteristics of the above techniques, the advantages, disadvantages and application scenarios of each are analyzed, and the further development of PID control technology is discussed. Conclusion Based on the characteristics of electro-hydraulic servo systems, the further combination of the three types of technology can make up for the shortcomings of PID algorithms to form a control strategy with high control accuracy, high robustness, and fast response speed.

We use high-resolution maps of the molecular interstellar medium (ISM) in the centres of eighty-six nearby galaxies from the millimetre-Wave Interferometric Survey of Dark Object Masses (WISDOM) and Physics at High Angular Resolution in Nearby GalaxieS (PHANGS) surveys to investigate the physical mechanisms setting the morphology of the ISM at molecular cloud scales. We show that early-type galaxies tend to have smooth, regular molecular gas morphologies, while the ISM in spiral galaxy bulges is much more asymmetric and clumpy when observed at the same spatial scales. We quantify these differences using non-parametric morphology measures (Asymmetry, Smoothness and Gini), and compare these measurements with those extracted from idealised galaxy simulations. We show that the morphology of the molecular ISM changes systematically as a function of various large-scale galaxy parameters, including galaxy morphological type, stellar mass, stellar velocity dispersion, effective stellar mass surface density, molecular gas surface density, star formation efficiency and the presence of a bar. We perform a statistical analysis to determine which of these correlated parameters best predicts the morphology of the ISM. We find the effective stellar mass surface (or volume) density to be the strongest predictor of the morphology of the molecular gas, while star formation and bars maybe be important secondary drivers. We find that gas self-gravity is not the dominant process shaping the morphology of the molecular gas in galaxy centres. Instead effects caused by the depth of the potential well such as shear, suppression of stellar spiral density waves and/or inflow affect the ability of the gas to fragment., Comment: 20 pages, 9 figures. Accepted for publication in MNRAS

In this study, Co2P/CoP hybrid nanoparticles (NPs) imbedded on the surface of core-shell metal-organic frameworks (MOFs) derived three-dimensional N, P co-doped graphitized carbon (Co2P/CoP@NPGC) are prepared via direct pyrolysis of P-containing MOF precursors. P dopant dosage is tailored to adjust active sites and crystalline phases of Co2P/CoP@NPGC. The active Co2P and CoP NPs and the synergistic effect from the Co-Nx/C and Co-P/C active sites and porous NPGC make the dominant contributions to the ORR/OER. For ORR, the half-wave potential of Co2P/CoP@NPGC-1 is 0.93V, which is superior to that of Pt/C (E1/2 = 0.875 V). As for OER, Co2P/CoP@NPGC-1 displays a lower overpotential (ƞ = 340 mV) compared to RuO2 (ƞ = 380 mV, at 10 mA cm-2). The Co2P@CoOOH heterojunction guarantees intrinsic conductivity. Furthermore, doping with N and P can modify the surface electronic structure of catalyst to lower the energy of oxygen adsorption and dissociation, which are beneficial to enhance the ORR and OER activity. Additionally, its bifunctional activity parameter (ΔE) for ORR and OER is only 0.64 V, which is lower than that of Pt/C and RuO2 (0.76 V). Therefore, this work proposes a new sight into constructing a competitive core-shell MOFs derived electrocatalyst for ORR/OER.

Compared with oxide-based NIR phosphors, fluoride phosphors have received great attention recently due to their good thermal resistance and high photoelectric efficiency. In this work, novel LiBAlF6:Cr3+ (B = Ca, Sr) with low phonon energy and relatively weak electron-phonon coupling were synthesized through a facile hydrothermal approach. Benefiting from low Dq/B, an ultra-broad NIR emission extending from 650 nm to 1100 nm can be achieved in these phosphors under excitation of blue light. Among them, LiSrAlF6:Cr3+ presents a FWHM of 155 nm. At 423 K, LiCaAl0.4F6: 0.6Cr3+ and LiSrAl0.4F6: 0.6Cr3+ maintain 66.63% and 55.47% of their initial intensities, respectively. Better thermal stability of LiCaAlF6: Cr3+ could be attributed to the broad band gap and weak electron-phonon coupling effect. Photoelectric conversion efficiencies of 5.002% and 5.468% at 300 mA could be obtained for NIR pc-LEDs packaged with LiCaAl0.4F6: 0.6Cr3+ and LiSrAl0.4F6: 0.6Cr3+, respectively. A slightly internal bruise inside apple and water level behind trademark in bottle could be clearly detected, revealing that LiBAlF6:Cr3+ (B = Ca, Sr) phosphors have great application potential in infrared inspection.