Photosynthetic capacity and assimilate transport of the lower canopy influence maize yield under high planting density.

Photosynthesis is a major trait of interest for development of high-yield crop plants. However, little is known about the effects of high-density planting on photosynthetic responses at the whole-canopy level. Using the high-yielding maize (Zea mays L.) cultivars 'LY66', 'MC670', and 'JK968', we here conducted a two-year field experiment to assess ear development in addition to leaf characteristics and photosynthetic parameters in each canopy layer at four planting densities. Increased planting density promoted high grain yield and population-scale biomass accumulation despite reduced per-plant productivity. MC670 had the strongest adaptability to high-density planting conditions. Physiological analysis showed that increased planting density primarily led to decreases in the single-leaf area above the ear for LY66 and MC670 and below the ear for JK968. Furthermore, high planting density decreased chlorophyll content and the photosynthetic rate due to decreased canopy transmission, leading to severe decreases in single-plant biomass accumulation in the lower canopy. Moreover, increased planting density improved pre-silking biomass transfer, especially in the lower canopy. Yield showed significant positive relationships with photosynthesis and biomass in the lower canopy, demonstrating the important contributions of these leaves to grain yield under dense planting conditions. Increased planting density led to retarded ear development as a consequence of reduced glucose and fructose contents in the ears, indicating reductions in sugar transport that were associated with limited sink organ development, reduced kernel number, and yield loss. Overall, these findings highlighted the photosynthetic capacities of the lower canopy as promising targets for improving maize yield under dense planting conditions.

Targeting NG2 relieves the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitors.

BRAFV600E represents a constitutively active onco-kinase and stands as the most prevalent genetic alteration in thyroid cancer. However, the clinical efficacy of small-molecule inhibitors targeting BRAFV600E is often limited by acquired resistance. Here, we find that nerve/glial antigen 2 (NG2), also known as chondroitin sulfate proteoglycan 4 (CSPG4), is up-regulated in thyroid cancers, and its expression is increased with tumor progression in a BRAFV600E-driven thyroid cancer mouse model. Functional studies show that NG2 knockout almost does not affect tumor growth, but significantly improves the response of BRAF-mutant thyroid cancer cells to BRAF inhibitor PLX4720. Mechanistically, the blockade of ERK-dependent feedback by BRAF inhibitor can activate receptor tyrosine kinase (RTK) signaling, causing the resistance to this inhibitor. NG2 knockout attenuates the PLX4720-mediated feedback activation of several RTKs, improving the sensitivity of BRAF-mutant thyroid cancer cells to this inhibitor. Based on this finding, we propose and demonstrate an alternative strategy for targeting NG2 to effectively treat BRAF-mutant thyroid cancers by combining multiple kinase inhibitor (MKI) Sorafenib or Lenvatinib with PLX4720. Thus, this study uncovers a new mechanism in which NG2 contributes to the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitor, and provides a promising therapeutic option for BRAF-mutant thyroid cancers.

High expression of RTEL1 predicates worse progression in gliomas and promotes tumorigenesis through JNK/ELK1 cascade.

Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas.

The diagnostic value of [18F]FAPI-42 PET/CT for pulmonary artery masses: comparison with [18F]FDG PET/CT.

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

M6A-induced transcription factor IRF5 contributes to the progression of cervical cancer by upregulating PPP6C.

Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.

Prussian-Blue-Analogue-Derived Ultrathin Co2P-Fe2P Nanosheets for Universal-pH Overall Water Splitting.

The great interest in large-scale electrochemical water splitting toward clean hydrogen has spurred large numbers of studies on developing cost-efficient and high-performance bifunctional electrocatalysts. Here, a Prussian-blue-analogue-derived method is proposed to prepare honeycomb-like ultrathin and heterogeneous Co2P-Fe2P nanosheets on nickel foam, showing low overpotentials of 0.080, 0.088, and 0.109 V for the hydrogen evolution reaction (HER) at 10 mA cm-2 as well as 0.290, 0.370, and 0.730 V for the oxygen evolution reaction (OER) at 50 mA cm-2 in alkaline, acidic, and neutral electrolytes, respectively. When directly applied for universal-pH water electrolysis, excellent performances are achieved especially at ultralow voltages of 1.45 V at 10 mA cm-2, 1.66 V at 100 mA cm-2, and 1.79 V at 500 mA cm-2 under alkaline conditions. In situ Raman spectroscopy measurements demonstrate that the excellent HER performance can be attributed to heterogeneous Co2P-Fe2P while the ultrahigh alkaline OER performance originates from reconstruction-induced oxyhydroxides.

Time-varying impacts of green credit on carbon productivity in China: New evidence from a non-parametric panel data model.

In the context of global climate change threatening human survival, and in a post-pandemic era that advocates for a global green and low-carbon economic recovery, conducting an in-depth analysis to assess whether green finance can effectively support low-carbon economic development from a dynamic perspective is crucial. Unlike existing research, which focuses solely on the average effects of green credit (GC) on carbon productivity (CP), we introduce a non-parametric panel data model to investigate GC's impact on CP across 30 provinces in China from 2003 to 2021, verifying a significant time-varying effect. Specifically, during the first phase (2003-2008), GC negatively impacted CP. In the second phase (2009-2014), this negative influence gradually diminished and transformed into a positive effect. In the third phase (2015-2021), GC continued to positively influence CP, although this effect became insignificant during the pandemic. Further subgroup analysis reveals that in the regions with low environmental regulations, GC did not significantly boost CP throughout the sample period. In contrast, in the regions with high environmental regulations, GC's positive effect persisted in the mid to late stages of the sample period. Additionally, compared to the regions with low levels of marketization, the impact of GC on CP was more pronounced in highly marketized regions. This indicates that the promoting effect of GC on CP depends on strong support from environmental regulations and well-functioning market mechanisms. By adopting a non-parametric approach, this study reveals variations in the impact of GC on CP across different stages and under the influence of the pandemic shock, offering new insights into the relationship between GC and China's CP.

Construction of TiO2/CuPc Heterojunctions for the Efficient Photocatalytic Reduction of CO2 with Water.

Utilizing solar energy for photocatalytic CO2 reduction is an attractive research field because of its convenience, safety, and practicality. The selection of an appropriate photocatalyst is the key to achieve efficient CO2 reduction. Herein, we report the synthesis of TiO2/CuPc heterojunctions by compositing CuPc with TiO2 microspheres via a hydroxyl-induced self-assembly process. The experimental investigations demonstrated that the optimal TiO2/0.5CuPc photocatalyst exhibited a significantly enhanced CO2 photoreduction rate up to 32.4 µmol·g-1·h-1 under 300 W xenon lamp irradiation, which was 3.7 times that of the TiO2 microspheres alone. The results of photoelectrochemical experiments indicated that the construction of the heterojunctions by introducing CuPc effectively promoted the separation and transport of photogenerated carriers, thus enhancing the catalytic effect of the photocatalyst.

Excellent predictive-performances of photonic reservoir computers for chaotic time-series using the fusion-prediction approach.

In this work, based on two parallel reservoir computers realized by the two polarization components of the optically pumped spin-VCSEL with double optical feedbacks, we propose the fusion-prediction scheme for the Mackey-Glass (MG) and Lorenz (LZ) chaotic time series. Here, the direct prediction and iterative prediction results are fused in a weighted average way. Compared with the direct-prediction errors, the fusion-prediction errors appear great decrease. Their values are far less than the values of the direct-prediction errors when the iteration step-size are no more than 15. By the optimization of the temporal interval and the sampling period, under the iteration step-size of 3, the fusion-prediction errors for the MG and LZ chaotic time-series can be reduced to 0.00178 and 0.004627, which become 8.1% of the corresponding direct-prediction error and 28.68% of one, respectively. Even though the iteration step-size reaches to 15, the fusion-prediction errors for the MG and LZ chaotic time-series can be reduced to 55.61% of the corresponding direct-prediction error and 77.28% of one, respectively. In addition, the fusion-prediction errors have strong robustness on the perturbations of the system parameters. Our studied results can potentially apply in the improvement of prediction accuracy for some complex nonlinear time series.

Optical cascaded reservoir computing for realization of dual-channel high-speed OTDM chaotic secure communication via four optically pumped VCSEL.

In this work, we propose a chaotic secure communication system with optical time division multiplexing (OTDM), using two cascaded reservoir computing systems based on multi beams of chaotic polarization components emitted by four optically pumped VCSELs. Here, each level of reservoir layer includes four parallel reservoirs, and each parallel reservoir contains two sub-reservoirs. When the reservoirs in the first-level reservoir layer are well trained and the training errors are far less than 0.1, each group of chaotic masking signals can be effectively separated. When the reservoirs in the second reservoir layer are effectively trained and the training errors are far less than 0.1, the output for each reservoir can be well synchronized with the corresponding original delay chaotic carrier-wave. Here, the synchronization quality between them can be characterized by the correlation coefficients of more than 0.97 in different parameter spaces of the system. Under these high-quality synchronization conditions, we further discuss the performances of dual-channel OTDM with a rate of 4×60 Gb/s. By observing the eye diagram, bit error rate and time-waveform of each decoded message in detail, we find that there is a large eye-openings in the eye diagrams, low bit error rate and higher quality time-waveform for each decoded message. Except that the bit error rate of one decoded message is lower than 7 × 10-3 in different parameter spaces, and those of the other decoded messages are close to 0, indicating that high-quality data transmissions are expected to be realized in the system. The research results show that the multi-cascaded reservoir computing systems based on multiple optically pumped VCSELs provide an effective method for the realization of multi-channel OTDM chaotic secure communications with high-speed.

Multiphysics-Informed Pharmacokinetic Modeling of Systemic Exposure of Intramuscularly Injected LNPs.

Lipid nanoparticle (LNP) constructs have been widely developed for gene therapy delivery. Understanding local absorption and presystemic clearance kinetics of LNPs, however, remains limited. This subsequently restrains the prediction and assessment of the systemic exposure of locally injected LNPs. As such, a multiscale computational approach was developed by integrating multiphysics simulation of intramuscular absorption kinetics of LNPs with whole-body pharmacokinetics modeling, bridged by a presystemic lymphatic kinetic model. The overall framework was enabled by utilizing physiological parameters obtained from the literature and drug-related parameters derived from experiments. The multiscale modeling and simulation approach predicted the systemic exposure of LNPs administered intramuscularly, with a high degree of agreement between the predicted and the experimental data. Sensitivity analyses revealed that the local absorption rate, pinocytosis presystemic clearance rate, and lymph flow rate of the presystemic lymphatic compartment had the most significant impacts on Cmax. The study yielded refreshing perspectives on estimating systemic exposures of locally injected LNPs and their safety and effectiveness.

Multiphysics Simulation of Local Transport and Absorption Coupled with Pharmacokinetic Modeling of Systemic Exposure of Subcutaneously Injected Drug Solution.

INTRODUCTION: Subcutaneous (SC) injectables have become more acceptable and feasible for administration of biologics and small molecules. However, efficient development of these products is limited to costly and time-consuming techniques, partially because absorption mechanisms and kinetics at the local site of injection remain poorly understood. OBJECTIVE: To bridge formulation critical quality attributes (CQA) of injectables with local physiological conditions to predict systemic exposure of these products. METHODOLOGY: We have previously developed a multiscale, multiphysics computational model to simulate lymphatic absorption and whole-body pharmacokinetics of monoclonal antibodies. The same simulation framework was applied in this study to compute the capillary absorption of solubilized small molecule drugs that are injected subcutaneously. Sensitivity analyses were conducted to probe the impact by key simulation parameters on the local and systemic exposures. RESULTS: This framework was capable of determining which parameters had the biggest impact on small molecule absorption in the SC. Particularly, membrane permeability of a drug was found to have the biggest impact on drug absorption kinetics, followed by capillary density and drug diffusivity. CONCLUSION: Our modelling framework proved feasible in predicting local transport and systemic absorption from the injection site of small molecules. Understanding the effect of these properties and how to model them may help to greatly expedite the development process.

Screening protective miRNAs and constructing novel lncRNAs/miRNAs/mRNAs networks and prognostic models for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents 10-20 % of all breast cancer (BC) cases and is characterized by poor prognosis. Given the urgent need to improve prognostication and develop specific therapies for TNBC, the identification of new molecular targets is of great importance. MicroRNA (miRNA) has been reported as a valuable and novel molecular target in the progression of TNBC. However, the expression and function of miRNAs in different tumors are heterogeneous. Herein, we first analyzed miRNA data from The Cancer Genome Atlas (TCGA) and surprisedly found that overexpressed miRNAs were associated with poor survival in all breast cancer patients, but the overexpressed miRNAs were associated with better survival in TNBC patients. Based on the heterogeneity of miRNA expression in TNBC, we conducted further analysis using univariate Cox proportional hazard regression models and identified 17 miRNAs with prognostic potential. Subsequently, a multivariate Cox model was employed to create a 3-miRNA prognostic model for predicting overall survival in TNBC patients. The diagnostic model exhibited an area under the curve (AUC) of 0.727, and multivariable Cox regression indicated that each covariate was associated with survival. These data indicate that this model is relatively accurate and robust for risk assessment, which have a certain value for clinical application. In order to explore the network behind the overexpressed miRNAs in TNBC, we established a novel network consisting of lncRNAs, miRNAs, and mRNAs through complete transcriptome data from matched samples in the TCGA database. In this network, IRS-1 appeared to be the top hub gene. Experimental results demonstrated that miR-15b-5p and miR-148a-3p effectively target IRS-1 in vitro, shedding light on the intricate regulatory mechanisms in TNBC mediated by the heterogeneous miRNAs. Besides, miR-148a-3p significantly inhibited cell migration and viability. Overall, this study may add valuable insights into the molecular landscape of TNBC based on miRNAs and have the potential to contribute to the development of targeted therapies and improved prognostic strategies of TNBC.

Near-infrared molecular sensor for visualizing and tracking ONOO- during the process of anti-tuberculosis drug-induced liver damage.

Isoniazid (INH) and pyrazinamide (PZA) are both the first-line anti-tuberculosis drugs in clinical treatment. It is notable that there are serious side effects of the drugs along with upregulation of reactive nitrogen species, mainly including peripheral neuritis, gastrointestinal reactions, and acute drug-induced liver injury (DILI). Among them, DILI is the most common clinical symptom as well as the basic reason of treatment interruption, protocol change, and drug resistance. As vital reactive nitrogen species (RNS), peroxynitrite (ONOO-) has been demonstrated as a biomarker for evaluation and pre-diagnosis of drug-induced liver injury (DILI). In this work, we developed a red-emitting D-π-A type fluorescence probe DIC-NP which was based on 4'-hydroxy-4-biphenylcarbonitrile modified with dicyanoisophorone as a fluorescent reporter and diphenyl phosphinic chloride group as the reaction site for highly selective and sensitive sensing ONOO-. Probe DIC-NP displayed a low detection limit (14.9 nM) and 60-fold fluorescent enhancement at 669 nm in the sensing of ONOO-. Probe DIC-NP was successfully applied to monitor exogenous and endogenous ONOO- in living HeLa cells and zebrafish. Furthermore, we verified the toxicity of isoniazid (INH) and pyrazinamide (PZA) by taking the oxidative stress induced by APAP as a reference, and successfully imaged anti-tuberculosis drug-induced endogenous ONOO- in HepG2 cells. More importantly, we developed a series of mice models of liver injury and investigated the hepatotoxicity caused by the treatment of anti-tuberculosis drugs. At the same time, H&E of mice organs (heart, liver, spleen, lung, kidney) further confirmed the competence of probe DIC-NP for estimating the degree of drug-induced liver injury, which laid a solid foundation for medical research.

Stictamycin, an Aromatic Polyketide Antibiotic Isolated from a New Zealand Lichen-Sourced Streptomyces Species.

Here we describe the isolation and characterization of stictamycin, a new aromatic polyketide with activity against Staphylococcus aureus. Stictamycin was identified following metabolic profiling and bioactivity guided fractionation of organic extracts from Streptomyces sp. 438-3, an isolate from the New Zealand lichen Sticta felix. Comprehensive 1D and 2D NMR analyses were performed to determine the planar structure of stictamycin and relative configurations of stereo centers, with subsequent comparison of experimental and theoretical ECD spectra allowing elucidation of the absolute configuration. Whole-genome sequencing and biosynthetic gene cluster (BGC) analysis revealed that the Streptomyces sp. 438-3 strain contains an atypical type II polyketide (T2PKS) BGC capable of assembling polycyclic-aromatic ring skeletons. Cloning and knockout studies of this T2PKS BGC were used to confirm that it is responsible for the biosynthesis of stictamycin and elucidate a plausible biosynthetic scheme.

High-Spatial-Resolution NDVI Reconstruction with GA-ANN.

The normalized differential vegetation index (NDVI) for Landsat is not continuous on the time scale due to the long revisit period and the influence of clouds and cloud shadows, such that the Landsat NDVI needs to be filled in and reconstructed. This study proposed a method based on the genetic algorithm-artificial neural network (GA-ANN) algorithm to reconstruct the Landsat NDVI when it has been affected by clouds, cloud shadows, and uncovered areas by relying on the MODIS characteristics for a wide coverage area. According to the self-validating results of the model test, the RMSE, MAE, and R were 0.0508, 0.0557, and 0.8971, respectively. Compared with the existing research, the reconstruction model based on the GA-ANN algorithm achieved a higher precision than the enhanced spatial and temporal adaptive reflectance fusion model (ESTARFM) and the flexible space-time data fusion algorithm (FSDAF) for complex land use types. The reconstructed method based on the GA-ANN algorithm had a higher root mean square error (RMSE) and mean absolute error (MAE). Then, the Sentinel NDVI data were used to verify the accuracy of the results. The validation results showed that the reconstruction method was superior to other methods in the sample plots with complex land use types. Especially on the time scale, the obtained NDVI results had a strong correlation with the Sentinel NDVI data. The correlation coefficient (R) of the GA-ANN algorithm reconstruction's NDVI and the Sentinel NDVI data was more than 0.97 for the land use types of cropland, forest, and grassland. Therefore, the reconstruction model based on the GA-ANN algorithm could effectively fill in the clouds, cloud shadows, and uncovered areas, and produce NDVI long-series data with a high spatial resolution.

Disulfiram/Cu Kills and Sensitizes BRAF-Mutant Thyroid Cancer Cells to BRAF Kinase Inhibitor by ROS-Dependently Relieving Feedback Activation of MAPK/ERK and PI3K/AKT Pathways.

BRAFV600E, the most common genetic alteration, has become a major therapeutic target in thyroid cancer. Vemurafenib (PLX4032), a specific inhibitor of BRAFV600E kinase, exhibits antitumor activity in patients with BRAFV600E-mutated thyroid cancer. However, the clinical benefit of PLX4032 is often limited by short-term response and acquired resistance via heterogeneous feedback mechanisms. Disulfiram (DSF), an alcohol-aversion drug, shows potent antitumor efficacy in a copper (Cu)-dependent way. However, its antitumor activity in thyroid cancer and its effect on cellular response to BRAF kinase inhibitors remain unclear. Antitumor effects of DSF/Cu on BRAFV600E-mutated thyroid cancer cells and its effect on the response of these cells to BRAF kinase inhibitor PLX4032 were systematically assessed by a series of in vitro and in vivo functional experiments. The molecular mechanism underlying the sensitizing effect of DSF/Cu on PLX4032 was explored by Western blot and flow cytometry assays. DSF/Cu exhibited stronger inhibitory effects on the proliferation and colony formation of BRAFV600E-mutated thyroid cancer cells than DSF treatment alone. Further studies revealed that DSF/Cu killed thyroid cancer cells by ROS-dependent suppression of MAPK/ERK and PI3K/AKT signaling pathways. Our data also showed that DSF/Cu strikingly increased the response of BRAFV600E-mutated thyroid cancer cells to PLX4032. Mechanistically, DSF/Cu sensitizes BRAF-mutant thyroid cancer cells to PLX4032 by inhibiting HER3 and AKT in an ROS-dependent way and subsequently relieving feedback activation of MAPK/ERK and PI3K/AKT pathways. This study not only implies potential clinical use of DSF/Cu in cancer therapy but also provides a new therapeutic strategy for BRAFV600E-mutated thyroid cancers.

Bioimaging and Sensing Thiols In Vivo and in Tumor Tissues Based on a Near-Infrared Fluorescent Probe with Large Stokes Shift.

The well-known small-molecule biothiols have been used to maintain the normal metabolism of peroxy radicals, forming protein structures, resisting cell apoptosis, regulating metabolism, and protecting the homeostasis of cells in the organism. A large amount of research has found that abnormal levels of the above biothiols can cause some adverse diseases, such as changes in hair pigmentation, a slower growth rate, delayed response, excessive sleep and skin diseases. In order to further investigate the exact intracellular molecular mechanism of biothiols, it is imperative to explore effective strategies for real-time biothiol detection in living systems. In this work, a new near-infrared (NIR) emission fluorescence probe (probe 1) for sensitive and selective detection of biothiols was devised by combining dicyanoisophorone derivatives with the dinitrobenzenesulfonyl (DNBS) group. As expected, probe 1 could specifically detect biothiols (Cys, Hcy and GSH) through the dinitrobenzenesulfonyl group to form dye 2, which works as a signaling molecule for sensing biothiols in real samples. Surprisingly, probe 1 showed superior sensing characteristics and low-limit detection towards biothiols (36.0 nM for Cys, 39.0 nM for Hcy and 48.0 nM for GSH) with a large Stokes shift (134 nm). Additionally, the function of probe 1 as a platform for detecting biothiols was confirmed by confocal fluorescence imaging of biothiols in MCF-7 cells and zebrafish. More importantly, the capability of probe 1 in vivo has been further evaluated by imaging the overexpressed biothiols in tumor tissue. It is reasonable to believe that probe 1 can provide a valuable method to explore the relationship between biothiols and the genesis of tumor.

Improving maize quality from mechanical grain harvesting by matching maize varieties with accumulated temperature in northeast China.

BACKGROUND: Global warming has led to methods of planting late-maturing maize varieties in northeast China that have hindered the development of physiological maturity (PM) at harvest and the use of mechanical grain harvesting (MGH). Under these conditions it is difficult to balance the drying characteristics of maize varieties and to make full use of accumulated temperature resources in such a way as to reduce grain moisture content (GMC) at harvest. RESULTS: The effective accumulated temperature (AcT) and the drying rates of different varieties vary. In northeast China, with a GMC of 25%, the growth periods of a fast-drying variety (FDV) and a slow-drying variety (SDV) were 114-192 days and 110-188 days respectively. After PM, the FDV needed 47 days and the SDV needed 51 days to reduce the GMC to be ready for MGH. Harvested with a GMC of 20%, the growth period for the FDV was 97-175 days and for the SDV it was 90-171 days. After PM, the FDV required 64 days and the SDV needed 70 days to reduce the GMC to be ready for MGH. CONCLUSION: Matching cultivars with AcT can help farmers to choose suitable varieties. Promoting MGH may boost maize production, thus ensuring China's food security. © 2023 Society of Chemical Industry.

Cohesin RAD21 Gene Promoter Methylation Correlated with Better Prognosis in Breast Cancer Patients.

RAD21 plays multiple roles in numerous cancers. In breast cancer (BC), a high level of RAD21 correlates with poor disease outcomes and resistance to chemotherapy. However, data regarding RAD21 promoter methylation in BC tissue and its correlation with clinical outcomes in patients with BC remain limited. Here, we investigated the clinicopathological features associated with the methylation status of RAD21 in BC to figure out its possible role in pathogenesis and the formation of breast carcinogenesis. The methylation status of the RAD21 gene was significantly associated with better clinical outcomes in patients with BC.