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Background: Pathogenic BRCA1 or BRCA2 germline mutations contribute to hereditary breast, ovarian, prostate, and pancreatic cancer. Paradoxically, bi-allelic inactivation of BRCA1 or BRCA2 (bBRCA1/2) is embryonically lethal and decreases cellular proliferation. The compensatory mechanisms that facilitate oncogenesis in bBRCA1/2 tumors remain unclear. Methods: We identified recurrent genetic alterations enriched in human bBRCA1/2 tumors and experimentally validated if these improved proliferation in cellular models. We analyzed mutations and copy number alterations (CNAs) in bBRCA1/2 breast and ovarian cancer from the TCGA and ICGC. We used Fisher's exact test to identify CNAs enriched in bBRCA1/2 tumors compared to control tumors that lacked evidence of homologous recombination deficiency. Genes located in CNA regions enriched in bBRCA1/2 tumors were further screened by gene expression and their effects on proliferation in genome-wide CRISPR/Cas9 screens. A set of candidate genes was functionally validated with in vitro clonogenic survival and functional assays to validate their influence on proliferation in the setting of bBRCA1/2 mutations. Results: We found that bBRCA1/2 tumors harbor recurrent large-scale genomic deletions significantly more frequently than histologically matched controls (n = 238 cytobands in breast and ovarian cancers). Within the deleted regions, we identified 277 BRCA1-related genes and 218 BRCA2-related genes that had reduced expression and increased proliferation in bBRCA1/2 but not in wild-type cells in genome-wide CRISPR screens. In vitro validation of 20 candidate genes with clonogenic proliferation assays validated 9 genes, including RIC8A and ATMIN (ATM-Interacting protein). We identified loss of RIC8A, which occurs frequently in both bBRCA1/2 tumors and is synthetically viable with loss of both BRCA1 and BRCA2. Furthermore, we found that metastatic homologous recombination deficient cancers acquire loss-of-function mutations in RIC8A. Lastly, we identified that RIC8A does not rescue homologous recombination deficiency but may influence mitosis in bBRCA1/2 tumors, potentially leading to increased micronuclei formation. Conclusions: This study provides a means to solve the tumor suppressor paradox by identifying synthetic viability interactions and causal driver genes affected by large-scale CNAs in human cancers. [ABSTRACT FROM AUTHOR]

Accurately predicting the price of carbon is an effective way of ensuring the stability of the carbon trading market and reducing carbon emissions. Aiming at the non-smooth and non-linear characteristics of carbon price, this paper proposes a novel hybrid prediction model based on improved feature extraction and non-linear integration, which is built on complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), fuzzy entropy (FuzzyEn), improved random forest using particle swarm optimisation (PSORF), extreme learning machine (ELM), long short-term memory (LSTM), non-linear integration based on multiple linear regression (MLR) and random forest (MLRRF), and error correction with the autoregressive integrated moving average model (ARIMA), named CEEMDAN-FuzzyEn-PSORF-ELM-LSTM-MLRRF-ARIMA. Firstly, CEEMDAN is combined with FuzzyEn in the feature selection process to improve extraction efficiency and reliability. Secondly, at the critical prediction stage, PSORF, ELM, and LSTM are selected to predict high, medium, and low complexity sequences, respectively. Thirdly, the reconstructed sequences are assembled by applying MLRRF, which can effectively improve the prediction accuracy and generalisation ability. Finally, error correction is conducted using ARIMA to obtain the final forecasting results, and the Diebold–Mariano test (DM test) is introduced for a comprehensive evaluation of the models. With respect to carbon prices in the pilot regions of Shenzhen and Hubei, the results indicate that the proposed model has higher prediction accuracy and robustness. The main contributions of this paper are the improved feature extraction and the innovative combination of multiple linear regression and random forests into a non-linear integrated framework for carbon price forecasting. However, further optimisation is still a work in progress. [ABSTRACT FROM AUTHOR]

As a promising alternative electrocatalyst to platinum for the oxygen reduction reaction (ORR), an Fe-N/C electrocatalyst with more active sites was designed by using N-doped porous crumpled graphene as carbon precursor. More defects provided by the edges and cavities of the porous crumpled graphene facilitated the anchoring and inhibited the growth of Fe clusters, and hence introduced more active sites. Furthermore, crumpled structure combined with the pores provided abundant mass transfer channels, and the fast kinetics were ensured. Consequently, the porous crumpled graphene-based catalyst showed better ORR activity and good electrochemical stability. The half-wave potential (E 1/2) of porous crumpled graphene-based catalyst was 0.69 ​V vs. RHE, and the current retention rate was above 97% after 20000s. In addition, the influence of different morphologies, degrees of defect, and compositions on the distribution of active sites and ORR performance of Fe-N/C were systematically studied, and the formation mechanism of Fe-N/C was proposed. This study provided valuable insights into designing more effective non-precious metal based electrocatalysts. [ABSTRACT FROM AUTHOR]

Visible-infrared person re-identification (VI-ReID) is a cross-modality retrieval issue aiming to match the same pedestrian between visible and infrared cameras. Thus, the modality discrepancy presents a significant challenge for this task. Most methods employ different networks to extract features that are invariant between modalities. While we propose a novel channel semantic mutual learning network (CSMN), which attributes the difference in semantics between modalities to the difference at the channel level, it optimises the semantic consistency between channels from two perspectives: the local inter-channel semantics and the global inter-modal semantics. Meanwhile, we design a channel-level auto-guided double metric loss (CADM) to learn modality-invariant features and the sample distribution in a fine-grained manner. We conducted experiments on RegDB and SYSU-MM01, and the experimental results validate the superiority of CSMN. Especially on RegDB datasets, CSMN improves the current best performance by 3.43% and 0.5% on the Rank-1 score and mINP value, respectively. The code is available at https://github.com/013zyj/CSMN. [ABSTRACT FROM AUTHOR]

Objectives: Lung cancer is a major public health concern and represents the most common cause of cancer‐related death worldwide. Among eukaryotes, the G protein‐coupled receptor (GPCR) family stands as the largest group of membrane proteins. Alterations in GPCR gene expression and dysregulation of signal transduction have been recognized as the markers of malignancy. As a member of the GPCR family, G protein‐coupled receptor 37 (GPR37) exhibits unknown functions in tumors, particularly in non‐small‐cell lung cancer (NSCLC) Methods: We explored the expression and prognosis of GPR37 in NSCLC through TCGA, GTEx, GEO, and GEPIA2. We detected the expression of GPR37 in NSCLC tissues and cell lines. The study explored the influence of GPR37 on tumor cell proliferation. Furthermore, we examined the effects of GPR37 on tumor cell apoptosis and invasion. Most importantly, we investigated whether GPR37 affects cisplatin‐induced drug resistance in NSCLC. Furthermore, by conducting animal experiments, we assessed the impact of GPR37 on NSCLC and delved into underlying mechanisms. Results: (1) In NSCLC, the expression of GPR37 is markedly higher than that in corresponding normal tissues. We found that elevated GPR37 expression predicts an unfavorable prognosis. (2) It was demonstrated that GPR37 positively regulates NSCLC cell invasion, migration, and proliferation, suppresses cell apoptosis, heightens resistance to cisplatin, and promotes tumor formation and growth. Conversely, we observed that GPR37 knockdown suppresses NSCLC cell invasion, migration, and proliferation, promotes cell apoptosis, increases sensitivity to cisplatin, and affects tumor formation and growth. (3) GPR37 activates PI3K/Akt/mTOR signal transduction pathways to mediate epithelial‐mesenchymal transition (EMT), thereby promoting the progression of NSCLC. Conclusions: It was suggested that GPR37 acts a crucial role in promoting the occurrence and development of NSCLC. Knockdown of GPR37 significantly inhibits the occurrence and development of NSCLC. Therefore, our findings demonstrated that GPR37 may represent a viable therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

The temperatures of the heavy ions (T i ) in the solar corona provide critical information about the heating mechanism of the million-degree corona. However, the measurement of T i is usually challenging due to the nonthermal motion, instrumental limitations, and optically thin nature of the coronal emissions. We present the measurement of T i and its dependency on the ion charge-to-mass ratio (Z / A) at the polar coronal hole boundary, only assuming that heavy ions have the same nonthermal velocity. To improve the Z / A coverage and study the influence of the instrumental broadening, we used a coordinated observation from the EUV Imaging Spectrometer on board the Hinode satellite and the Solar Ultraviolet Measurements of Emitted Radiation (SUMER) on board the Solar and Heliospheric Observatory. We found that the T i of ions with Z / A less than 0.20 or greater than 0.33 are much higher than the local electron temperature. We ran the Alfvén Wave Solar Model-realtime to investigate the formation of optically thin emissions along the line of sight (LOS). The simulation suggested that plasma bulk motions along the LOS broaden the widths of hot emission lines in the coronal hole (e.g., Fe xii, Fe xiii). We discussed other factors that might affect the T i measurement, including the non-Gaussian wings in some bright SUMER lines, which can be fitted by a double-Gaussian or a κ distribution. Our study confirms the preferential heating of heavy ions in coronal holes and provides new constraints on coronal heating models. [ABSTRACT FROM AUTHOR]

Bitcoin is one of the most successful cryptocurrencies, and research on price predictions is receiving more attention. To predict Bitcoin price fluctuations better and more effectively, it is necessary to establish a more abundant index system and prediction model with a better prediction effect. In this study, a combined prediction model with twin support vector regression was used as the main model. Twenty-seven factors related to Bitcoin prices were collected. Some of the factors that have the greatest impact on Bitcoin prices were selected by using the XGBoost algorithm and random forest algorithm. The combined prediction model with support vector regression (SVR), least-squares support vector regression (LSSVR), and twin support vector regression (TWSVR) was used to predict the Bitcoin price. Since the model's hyperparameters have a great impact on prediction accuracy and algorithm performance, we used the whale optimization algorithm (WOA) and particle swarm optimization algorithm (PSO) to optimize the hyperparameters of the model. The experimental results show that the combined model, XGBoost-WOA-TWSVR, has the best prediction effect, and the EVS score of this model is significantly better than that of the traditional statistical model. In addition, our study verifies that twin support vector regression has advantages in both prediction effect and computation speed. [ABSTRACT FROM AUTHOR]

In recent years, frequency-modulated continuous wave (FMCW) radar has been widely used in automatic driving, settlement monitoring and other fields. The range accuracy is determined by the estimation of the signal beat frequency. The existing algorithms are unable to distinguish between signal components with similar frequencies. To address this problem, this study proposed an enhanced root-MUSIC algorithm based on matrix reconstruction. Firstly, based on the sparsity of a singular value vector, a convex optimization problem was formulated to identify a singular value vector. Two algorithms were proposed to solve the convex optimization problem according to whether the standard deviation of noise needed to be estimated, from which an optimized singular value vector was obtained. Then, a signal matrix was reconstructed using an optimized singular value vector, and the Hankel structure of the signal matrix was restored by utilizing the properties of the Hankel matrix. Finally, the conventional root-MUSIC algorithm was utilized to estimate the signal beat frequency. The simulation results showed that the proposed algorithm improved the frequency resolution of multi-frequency signals in a noisy environment, which is beneficial to improve the multi-target range accuracy and resolution capabilities of FMCW radar. [ABSTRACT FROM AUTHOR]

This work presented a novel strategy to integrate colorant and stabilizing effects of BSA-crocin I (BC) nanoparticles with gel-like structure of high internal phase Pickering emulsion (HIPPE, φ = 0.75). The BSA was cross-lined with crocin I to obtain BC nanoparticles for stabilizing HIPPE. When pH = 7.4, the particle size of BC nanoparticles was 326.65–366.40 nm with low polydispersity index (PDI) around 0.5 and zeta potential around −8 mV. The three-phase contact angle of BC nanoparticles was approaching 90°, indicating the strong absorptive capacity at the O/W interface. CLSM images showed the BC nanoparticles surrounded the oil droplets in the emulsions. Specifically, BC-1.5 (7.5% BSA and 0.1125% crocin I)-stabilized HIPPE exhibited the highest stability, with a Turbiscan stability index (TSI) value of 1.3. The thixotropic recovery degree of BC-1.5-stabilized HIPPE was the highest, while the G0′ and G0″ were the lowest, which confirmed that BC-1.5 constructed the most compact gel-network structure around emulsion droplets. The color difference of BC-1.5-stabilized HIPPE was much lower than 1 throughout the UV treatment with the lowest oxidation rate of gardenia oil. The colorimetric and oxidative results verified the color-protective and anti-oxidative abilities of BC nanoparticle-stabilized HIPPE, which might be used for the improvement of the meat product. [ABSTRACT FROM AUTHOR]

[Display omitted] • Inhibition of TDP-43 exerts neuroprotective effects in vivo. • TDP-43 knockdown inactivates the cGAS pathway. • TDP-43 is found to be accumulated in microglia with H/R treatment. Microglia are damaged during cerebral ischemia–reperfusion (I/R). This study was performed to investigate the regulatory effect of tAR DNA-binding protein-43 (TDP-43) on microglia after cerebral I/R in vitro and in vivo. The hypoxia/reoxygenation (H/R) treated microglia and rats with middle cerebral artery occlusion surgery were constructed respectively. The TDP-43 expression in brain tissues and microglia of each group was evaluated by qPCR and western blotting methods. Cell viability and cell apoptosis were combined to evaluate the degree of cell injury. As for animal experiments, neurological score and infarct volume were obtained to evaluate neurological injury. The levels of TDP-43 in the brain tissues of I/R group were higher than that in sham group. Both TDP-43 and Iba1, a typical microglia marker, were expressed in the brain tissues. TDP-43 was also elevated in microglia with H/R treatment. Inhibition of TDP-43 significantly down-regulated neurological deficit scores of rats after I/R surgery, and weakened the H/R treatment induced injury by promoting cell viability, inhibiting cell apoptosis, down-regulating IL-6 and iNOS levels, and up-regulating Arg-1 and IL-10 levels. Inactivation of cGAS pathway mediated by TDP-43 knockdown protects microglia from H/R treatment induced injury. The highly expressed TDP-43 level is associated with cerebral I/R, and inhibition of TDP-43 protects microglia from H/R induced injury through cGAS pathway in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Phosphoenolpyruvate (PEP) is an essential intermediate metabolite that is involved in various vital biochemical reactions. However, achieving the direct and accurate quantification of PEP in plasma or serum poses a significant challenge owing to its strong polarity and metal affinity. In this study, a sensitive method for the direct determination of PEP in plasma and serum based on ethylenediaminetetraacetic acid (EDTA)-facilitated hydrophilic interaction liquid chromatography–tandem mass spectrometry was developed. Superior chromatographic retention and peak shapes were achieved using a zwitterionic stationary-phase HILIC column with a metal-inert inner surface. Efficient dechelation of PEP–metal complexes in serum/plasma samples was achieved through the introduction of EDTA, resulting in a significant enhancement of the PEP signal. A PEP isotopically labelled standard was employed as a surrogate analyte for the determination of endogenous PEP, and validation assessments proved the sensitivity, selectivity, and reproducibility of this method. The method was applied to the comparative quantification of PEP in plasma and serum samples from mice and rats, as well as in HepG2 cells, HEK293T cells, and erythrocytes; the results confirmed its applicability in PEP-related biomedical research. The developed method can quantify PEP in diverse biological matrices, providing a feasible opportunity to investigate the role of PEP in relevant biomedical research. [Display omitted] • A novel, facile and accurate method for the direct determination of PEP in complex biological matrices is developed. • EDTA is an indispensable additive to plasma/serum to dechelate PEP-metal adducts and release free PEP molecules. • The developed method provides a feasible way for delving deeper the significance of PEP in relevant biomedical research. [ABSTRACT FROM AUTHOR]

The turn of contemporary visual culture has led to the expansion of the connotation and scope of visual communication design (VCD) education, the generation of new artistic concepts and forms, and the great changes in the subject education system. VCD instruction now has an enhanced teaching environment and operational platform because of the rapid advancement of digital technology. Digital technology is expected to break through traditional learning methods in the future and will be more widely integrated into VCD courses. A topic that must be addressed and explored in the reform and growth of VCD education is how to build a fairer and more inclusive college art education subject system. Therefore, it is particularly important to design a complete VCD teaching evaluation system. In this paper, artificial intelligence technology is applied to the teaching quality evaluation (TQE) system, and a scientific and reliable TQE model is obtained. The main works of this paper are as follows: (1) analyze the background and significance of TQE research, and systematically expound the domestic and foreign research status of TQE, genetic algorithm, and neural network. (2) Using an adaptive mutation evolutionary method, this research builds a TQE system for the VCD course and produces a BPNN model. The adaptive mutation genetic algorithm's convergence speed is considerably faster than the regular genetic algorithms, the optimized neural network's performance is also superior, and the model has a faster convergence time and better prediction accuracy. [ABSTRACT FROM AUTHOR]

The MYB family, one of the largest transcription factor (TF) families, plays an important role in plant growth, development, and stress response. Although genome-wide analysis of the MYB family has been performed in many species based on sequence similarity, predicting the potential functions of the MYB genes and classifying the regulators into specific metabolic pathways remains difficult. In this study, using a hidden Markov model search and co-expression regulatory network analysis, we demonstrated a process to screen and identify potential MYB TFs in the anthocyanin biosynthesis pathway of Gossypium hirsutum. As a result, we identified 617 and 784 MYB genes (812 in total) from the previously reported and recently released genomes, respectively. Using 126 structural genes involved in the anthocyanin biosynthesis pathway as targets for several co-expression network analyses, we sorted out 31 R2R3-MYB genes, which are potential regulators in the specific pathway. Phylogenetic and collinearity analyses indicated that 83.9% of the 31 MYB genes originated from whole genome duplication or polyploidization. In addition, we revealed relatively specific regulatory relationships between the MYB TFs and their target structural genes. Approximately, 71% of the MYBs could regulate only a single anthocyanin-related structural gene. Moreover, we found that the A- and D- subgenome homoeologs of MYB TFs in G. hirsutum rarely co-regulate the same target gene. The current study not only demonstrated an easy method to rapidly predict potential TFs in a specific metabolic pathway, but also enhanced our understanding of the evolution, gene characteristics, expression, and regulatory pattern of MYB TFs in G. hirsutum. [ABSTRACT FROM AUTHOR]

The nonthermal broadening of spectral lines formed in the solar corona is often used to seek evidence of Alfvén waves propagating in the corona. To have a better understanding of the variation of line widths at different altitudes, we measured the line widths of the strong Fe xii 192.4, 193.5, and 195.1 Å and Fe xiii 202.0 Å in an off-limb southern coronal hole up to 1.5 R⊙ observed by the Extreme Ultraviolet Spectrometer on board the Hinode satellite. We compared our measurements to the predictions from the Alfvén Wave Solar Model (AWSoM) and the SPECTRUM module. We found that the Fe xii and Fe xiii line widths first increase monotonically below 1.1 R⊙ and then keep fluctuating between 1.1 and 1.5 R⊙. The synthetic line widths of Fe xii and Fe xiii below 1.3 R⊙ are notably lower than the observed ones. We found that the emission from a streamer in the line of sight significantly contaminates the coronal hole line profiles even up to 1.5 R⊙ both in observations and simulations. We suggest that either the discrepancy between the observations and simulations is caused by insufficient nonthermal broadening at the streamer in the AWSoM simulation or the observations are less affected by the streamer. Our results emphasize the importance of identifying the origin of the coronal EUV emission in off-limb observations. [ABSTRACT FROM AUTHOR]

[Display omitted] • A robust method is proposed for determination of multi-class veterinary drugs in animal muscles. • High recovery, simple operation and effective cleanup were achieved in this method. • Application to several animal muscle samples analysis demonstrate its practicality. Excessive use of veterinary drugs in livestock growth poses a threat to food safety. It is, however, challenging to quantify these multi-class veterinary drugs within animal muscles, because of their varied physicochemical properties. In this work, we presented a simple, efficient and sensitive method for the simultaneous determination of multi-class veterinary drugs with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The method involves a highly efficient extraction using a EDTA (pH 7)-ACN (30:70, v/v) solvent system, followed by a one-step solid-phase extraction cleanup approach with PRiME HLB sorbent (Reversed-phase N -vinylpyrrolidone and divinylbenzene copolymer). For all the analytes, over a wide range of polarity, satisfactory recoveries were obtained between 70% and 120%, with relative standard deviations <15%. Excellent sensitivities were achieved with the limits of quantification ranging from 0.2 μg/kg to 3.0 μg/kg. This developed method provides a new targeted strategy for the analysis of multi-class veterinary drugs in muscle matrices. [ABSTRACT FROM AUTHOR]

Graphical abstract The paraventricular thalamic nucleus (PVT) is placed at a key position of neural circuits underlying drug addiction. Elucidating the precise role of PVT pathways in drug-related behaviors could assist the development of effective treatments for drug addiction. Abstract Drug addiction is a chronic relapsing brain disease characterized by compulsive, out-of-control drug use and the appearance of negative somatic and emotional consequences when drug access is prevented. The limited efficacy of treatment urges researchers toward a deeper understanding of the neural mechanism of drug addiction. Brain circuits that regulate reward and motivation are considered to be the neural substrate of drug addiction. An increasing body of literature indicates that the paraventricular thalamic nucleus (PVT) could serve as a key node in the neurocircuits that control goal-directed behaviors. In this review, we summarize the anatomical and functional evidence that the PVT regulates drug-related behaviors. The PVT receives extensive inputs from the brainstem and hypothalamus, and is reciprocally connected with the limbic system. Neurons in the PVT are recruited by drug exposure as well as cues and context associated with drug taking. Pathway-specific perturbation studies have begun to decipher the precise role of PVT circuits in drug-related behaviors. We also highlight recent findings about the involvement of neural plasticity of the PVT pathways in drug addiction and provide perspectives on future studies. [ABSTRACT FROM AUTHOR]

The classic sol-gel method for preparing antireflective coatings (ARCs) known for decades often employs an organic liquid as the solvent, so it is necessary to develop an environmental- friendly and feasible procedure for commercial ARC fabrication. Herein, self-cleaning ARCs were prepared from water-based silica hydrosols followed by a chemical vapor deposition process. The average transmittance rose remarkably after the dip-coating of silica hydrosols. Polyethylene glycols (PEGs) with molecular weights of 1000, 2000 and 4000 were adopted as template agents to lower the refractive index of the coatings and thus enhance the antireflective performance. The PEG1000-modified coating has the highest average transmittance of 96.44%. Field-emission scanning electron microscopy and atomic force microscopy showed the surface roughness increased with the rise of molecular weight of PEG and the coating from PEG1000 is relatively smooth. Water contact angle measurement and anti-smudge test showed the chemical vapor deposition endowed the ARCs with hydrophobicity and self-cleaning ability. [ABSTRACT FROM AUTHOR]

The salience of behaviorally relevant stimuli is dynamic and influenced by internal state and external environment. Monitoring such changes is critical for effective learning and flexible behavior, but the neuronal substrate for tracking the dynamics of stimulus salience is obscure. We found that neurons in the paraventricular thalamus (PVT) are robustly activated by a variety of behaviorally relevant events, including novel (“unfamiliar”) stimuli, reinforcing stimuli and their predicting cues, as well as omission of the expected reward. PVT responses are scaled with stimulus intensity and modulated by changes in homeostatic state or behavioral context. Inhibition of the PVT responses suppresses appetitive or aversive associative learning and reward extinction. Our findings demonstrate that the PVT gates associative learning by providing a dynamic representation of stimulus salience. [ABSTRACT FROM AUTHOR]

Abstract: Choline receptor blocker succinylcholine (suxamethonium [SUX]) is a depolarizing neuromuscular blocking agent to relax muscles. It is often used in clinic to conduct auxiliary endotracheal intubation as a surgical anesthetic inducer, which can cause respiratory depression and cardiac arrest. In recent years, SUX was occasionally used for theft and crime by daubing on darts, resulting in intoxication or even death. Regarding the rapid detection demand of SUX in first aid and emergency response, a bit of challenges still existed, especially towards biomedical samples due to its properties of high hydrophilic, alkali‐liable, low onset concentration, and susceptibility to cholinesterase. In this report, we described an on‐site surface‐enhanced Raman spectroscopy (SERS) method on SUX in the first time. We found that key parameters facilitated this SERS method including MgI2‐induced appropriate aggregation and higher pH, in which enhanced electrostatic interaction between analyte and AuNPs occurred, and larger adsorption capacity of AuNPs, which makes the sensitive measurement of alkali‐liable SUX become possible. Coupled with simple and optimized pretreatment procedures, successful measurement of SUX in plasma and urine samples was also achieved. The limit of detection reached 1 μg/L in plasma and 10 μg/L in urine. We regarded acids for precipitating abundant proteins and inhibited cholinesterase activity in plasma and proteins for assisting antiagglomeration of AuNPs when coexisted with plenty of inorganic salts in urine, as the critical parameters in sample pretreatment. We hope this method can find its great potential in forensic and clinical diagnosis in case of SUX poisoning or intoxication. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a malignancy of the bone marrow. The median survival time of patients with MM is only 5 years, with patients frequently experiencing relapse. Currently, there is no effective therapy for recurrent MM. The results of the present study indicated that pyrvinium pamoate (PP), a US Food and Drug Administration-approved oral anthelmintic drug, exhibited potent antitumor activity in MM cells in vitro. It is demonstrated that PP inhibited MM cell proliferation and mediated apoptosis. Notably, PP markedly promoted the degradation of β-catenin and abrogated its phosphorylation. PP triggered apoptosis in MM cells by inducing the release of cytochrome c and downregulating the expression of myeloid leukemia cell differentiation protein. In addition, PP effectively induced cell death in primary MM cells. In conclusion, PP may be a promising agent for the clinical treatment of MM. [ABSTRACT FROM AUTHOR]

Organophosphorous nerve agents (NAs) pose a great threat to nations and people because of their acute and extreme toxicities. The rapid detection of NAs has attracted growing interest in the first emergency response field. In this work, we demonstrate a simple and sensitive surface-enhanced Raman spectroscopic (SERS) method for NAs detection, and G- and V-agents discrimination. The results show that VX (V-agents) can be directly detected at a 20 ng mL level with pinhole shell-isolated gold nanoparticles (pinSHINs) as the substrate. Moreover, combined with a specific and prompt alkaline keto-oxime transformation approach in a full aqueous solution, G-agents can be measured as low as 10 ng mL with excellent discrimination from V-agents and other common organophosphorous pesticides within several minutes. The achieved discriminative detection of G-agents and VX could be significant not only for reducing the false positive and negative signals but also for providing an appropriate recommendation on the effective medical rescue. A decontamination outcome occurred alongside, any highly toxic G-agents were converted to a less toxic phosphate, and the generated cyanide was fully and firmly adsorbed onto the surface of pinSHINs substrate, which may be further used for on-site detection of extremely toxic NA prototypes. [ABSTRACT FROM AUTHOR]

Differentiation of 3T3-L1 cells into adipocytes involves a highly-orchestrated series of events including contact inhibition (CI), clonal expansion, growth arrest, and terminal differentiation. Recent study demonstrated that 3T3-L1 preadipocytes will not be differentiated into mature adipocytes without CI stage, which indicated that CI stage plays an important role during 3T3-L1 adipogenesis. However, the molecular mechanism is not yet fully understood. In the present study, we found that the expression level of miR-29a/b/c was decreased and the expression of DNMT3A was up-regulated during CI stage, respectively. Furthermore, overexpression of miR-29a/b/c during CI stage inhibits adipogenesis significantly but not at other stages. In addition, miR-29a/b/c repressed DNMT3A expression by directly targeting its 3’ untranslated region (3’ UTR). Our data reveal a novel mechanism of miR-29a/b/c in the regulation of adipogenesis. [ABSTRACT FROM AUTHOR]

Most person re-identification methods are researched under various assumptions. However, viewpoint variations or occlusions are often encountered in practical scenarios. These are prone to intra-class variance. In this paper, we propose a multiscale global-aware channel attention (MGCA) model to solve this problem. It imitates the process of human visual perception, which tends to observe things from coarse to fine. The core of our approach is a multiscale structure containing two key elements: the global-aware channel attention (GCA) module for capturing the global structural information and the adaptive selection feature fusion (ASFF) module for highlighting discriminative features. Moreover, we introduce a bidirectional guided pairwise metric triplet (BPM) loss to reduce the effect of outliers. Extensive experiments on Market-1501, DukeMTMC-reID, and MSMT17, and achieve the state-of-the-art results on mAP. Especially, our approach exceeds the current best method by 2.0% on the most challenging MSMT17 dataset. [ABSTRACT FROM AUTHOR]

Pyrite-driven autotrophic denitrification (PAD) represents a cheap and promising way for nitrogen removal from organic-limited wastewater, which has obtained increasing attention in recent years. However, the limited denitrification rate and unclear mechanism underlying the process have hindered the engineered application of PAD. This study aims to shed light on the impacts of different pretreatments (i.e., ultrasonication, acid-washing and calcination) on micron-pyrite surface characteristics, denitrification performance and biofilm formation during PAD in batch reactors. A series of solid-phase analyses revealed that all pretreatments could significantly promote biofilm attachment on pyrite granules, but impacted the proportion, distribution and chemical oxidation state of sulfur (S) and iron (Fe) at varying degrees. Batch tests showed that ultrasonication and acid-washing could enhance the total nitrogen reduction rate by 14% and 99%, and decrease the sulfate production rate by 51% and 42%, respectively, when compared with untreated pyrite. Microbial community analysis indicated that Thiobacillus and Rhodanobacter dominated in PAD systems. Two types of indirect mechanisms (i.e., contact and non-contact) for pyrite leaching may co-occur in PAD system, resulting in ferrous iron (Fe2+), thiosulfate (S 2 O 3 2−) and sulfide (S2−) as the main electron donors for denitrification. A PAD mechanism model was proposed to describe the PAD electron transfer pathway with the aim to optimize the engineered application of PAD for nitrogen removal. [Display omitted] • Pretreatments modified pyrite surface and promoted biofilm development. • Acid-washing could enhance the nitrate nitrogen reduction rate by 99%. • A mechanism model was proposed for pyrite-driven autotrophic denitrification (PAD). • Fe2+, S 2 O 3 2− and S2− were identified as the main electron donors for PAD. • Thiobacillus and Rhodanobacter dominated in PAD systems. [ABSTRACT FROM AUTHOR]

This paper concerns the approximate controllability of a class systems governed by coupled degenerate equations. The equations may be weakly degenerate and strongly degenerate on the boundary. It is shown that the systems are approximately controllable by constructing the controls via the conjugate problems. [ABSTRACT FROM AUTHOR]

• Automated SPE UPLC-MS/MS was used to analyze QNs at low concentration levels in environmental water. • Attempts were made to correct for the matrix effects with 15 ILISs for QNs. • The factors that influence the sensitivity are discussed. • The comparison with other reported results was summarized. • This method is simple, rapid, convenient, high sensitivity, and efficient. The widespread use of quinolones in humans and animals has become a major threat to public health. In this study, a simple, rapid, sensitive, and high throughput method based on automatic solid-phase extraction and isotope dilution ultra-performance liquid chromatography tandem mass spectrometry was described for the determination of trace quinolones in environmental water. The proposed automated solid-phase extraction method was initially optimized, and the optimum experimental conditions found were 1 L water sample with 0.5 g/L Na 2 EDTA (pH 3) extracted and enriched by CNW Poly-Sery HLB cartridge at a flow rate of 50 mL/min and eluted by 8 mL of methanol. The linearity of the method ranged from 0.05 to 100 μg/L for 15 quinolones, with correlation coefficients ranging from 0.9993 to 0.9999. The limits of detection were in the low ng/L level, ranging from 0.005 to 0.051 ng/L. Finally, the optimized method was applied for determining trace levels of 15 quinolones in Wahaha pure water, tap water, river water, and seawater samples with good recoveries of 93 %–119 % and satisfactory relative standard deviations of 0.1 %–13.9 %. Fourteen quinolones were detected, and ofloxacin was the predominant congener in river water and seawater. [ABSTRACT FROM AUTHOR]

New double perovskite Sr 3 LiNbO 6 : x %Mn4+ and Sr 3 LiNbO 6 : x %Mn4+, 1.25 x %Zn2+ far-red-emitting phosphors were reported for the first time. The phosphors were characterized by XRD, SEM, PL, PLE, UV–vis spectroscopy, CIE color coordinate and internal quantum efficiency (IQE) measurements. Under the excitation of 365 nm light, Sr 3 LiNbO 6 : x %Mn4+ phosphors show a strong far-red emission peak at 695 nm, which is suitable for use in indoor plant application. Furthermore, by co-doping of Zn2+ ions, a more homogeneous particle size distribution was obtained and the emission intensity can raise up to 1.29 times that of Mn4+ single-doped samples. The Sr 3 LiNbO 6 :0.6%Mn4+, 0.75%Zn2+ phosphor can obtain an IQE of 78.4% and an emission intensity of 80.6% at 423 K from that at 284 K, showing a high luminous efficiency and thermal stability. Finally, a LED lamp was fabricated with the use of far-red-emitting optimized phosphor, which shows an effective promotion on growth rate and content of photosynthesis pigments of wheat. The results show that Sr 3 LiNbO 6 :Mn4+, Zn2+ phosphors may have a promising future in the field of agriculture cultivations. [Display omitted] • A new Sr 3 LiNbO 6 :Mn4+ red-emitting phosphor was synthesized for the first time. • The particle size homogeneity was obviously improved by Zn2+ doping. • A quantum efficiency of 78.4% was achieved by Sr 3 LiSbO 6 :Mn4+, Zn2+ phosphor. • The emission intensity of Sr 3 LiNbO 6 :Mn4+, Zn2+ phosphor retained 80.6% at 423 K. • The fabricated LED device can accelerate the growth of hydroponic wheat. [ABSTRACT FROM AUTHOR]

This paper deals with the global existence of solutions to a strongly coupled parabolic-parabolic system of chemotaxis arising from the theory of reinforced random walks. More specifically, we investigate the attraction-repulsion chemotaxis model with fast diffusive term and nonlinear source subject to the Neumann boundary conditions. Such fast diffusion guarantees the global existence of solutions for any given initial value in a bounded domain. Our main results are based on the method of energy estimates, where the key estimates are obtained by a technique originating from Moser’s iterations. Moreover, we notice that the cell density goes to the maximum value when the diffusion coefficient of the cell density tends to infinity. [ABSTRACT FROM AUTHOR]

This paper is devoted to studying the long time behavior of solutions to a bipolar quantum hydrodynamic in one-dimensional space for general pressure functions. The model is usually applied to simulate some quantum effects in semiconductor devices. The decay rate for time variable is obtained by the entropy functional method and semidiscrete technique. [ABSTRACT FROM AUTHOR]

• Maackiain exerts potent anti-oxidant and anti-inflammatory capacities against sepsis-associated organ injury. • Activation of AMP-activated protein kinase (AMPK)/Nrf2/HO-1 pathway by MA contributes to its anti-oxidant and anti-inflammatory properties. • PRKAA1 is a potential pharmacological target of Maackiain. Sepsis is a life-threatening medical condition caused by infection-triggered aberrant immune responses, leading to host tissue and organ injury. Despite advances in medical interventions, the mortality rate for septic shock remains high. Recent studies highlight the role of oxidative stress in the occurrence and development of sepsis, providing a potential therapeutic target for preventing sepsis-associated organ injury. In this study, we showed that Maackiain, a natural compound isolated from Sophora flavescens , exerted a protective role in a cecal ligation and puncture (CLP)-induced murine model of sepsis. Maackiain treatment reduced organ injury, and mitigated systematic inflammation and oxidative stress in septic mice. Maackiain also reduced the levels of inflammatory cytokines and reactive oxygen species (ROS) in RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS). We further demonstrated that Maackiain initiated activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in RAW264.7 cells in an AMP-activated protein kinase (AMPK)-dependent way. Moreover, inhibition of AMPK/Nrf2 axis abrogated the anti-inflammatory and anti-oxidant effects of Maackiain both in vitro and in vivo. Collectively, our study indicates that Maackiain treatment inhibits inflammatory response and oxidative stress via activation of AMPK/Nrf2/HO-1 pathway, thus exerting a protective effect against sepsis, providing an alternative option for sepsis prevention. [ABSTRACT FROM AUTHOR]

[Display omitted] • Natural deep eutectic solvent was tailor-made for extraction of target crocins. • Correlation between physical properties and extraction efficiency was established. • Pulse-ultrasonication-assisted extraction showed synergistic extraction efficiency. • The integration of affinity-dissolution and cavitation-mass transfer was verified. • Extracted crocins showed antiglycative effect and protective effect on DNA damage. This study proposed natural deep eutectic solvent (NADES) based pulse-ultrasonication-assisted extraction (P-UAE) for green recovery of crocins from gardenia fruits (Gardenia jasminoides Ellis). Choline chloride-1,2-propylene glycol (ChCl-PG, 1:2.5, mol/mol) with 35 % (v/v) water content was tailor-made to obtain the highest extraction efficiency with high surface tension, polarity, conductivity, pH, and low viscosity, density for affinity-based extraction of crocins. The optimized P-UAE conditions (extraction time 120 s, ultrasonic power 400 W, solvent-to-solid ratio 40 mL g−1, extraction temperature 35 ℃) led to the maximum yield of crocins (36.97 mg g−1 DW). The second-order kinetic model was fitted to the extraction process and the synergistic effect was verified by SEM and FTIR. The crocetin was identified as the main compound by UPLC-Triple-TOF/MS. The antiglycative effect and protective effect on DNA indicated the bioactive activities of crocins. Therefore, the ChCl-PG based P-UAE could serve as a green strategy to effectively extract crocins from gardenia fruits. [ABSTRACT FROM AUTHOR]

Fungicides are often used to extend the storage time of postharvest satsuma mandarin fruit. In recent years, fungicide residue has become an issue of food safety. This study aimed to investigate the distribution and migration of three typical fungicides (imazalil, prochloraz, thiophanate-methyl) in postharvest satsuma mandarins using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three fungicides could quickly penetrate satsuma mandarins and their gradient concentrations of residues in the fruit were: carpopodium > mesocarp > epicarp > pulp. However, the residues of three fungicides in the edible pulp were obviously lower than the maximum residue limit (MRL = 5.0 mg/kg in China). Residues of the three fungicides decreased in epicarp and carpopodium but increased in mesocarp and pulp during storage. Fungicides could quickly penetrate the fruit, settling primarily in the carpopodium but little in the pulp. Both epicarp and carpopodium were the breakthrough pathways for the fungicides entering the fruit, while epicarp was the main route for the penetration of fungicides. These findings shed new information on the behavior of fungicides and the safety issue of satsuma mandarins. [ABSTRACT FROM AUTHOR]

Here we report a case of a 34-year-old patient with psoriasis who developed uveitis induced by adalimumab. After receiving two subcutaneous injections of adalimumab, the patient suffered from a sudden onset of ocular pain and blurred vision in her left eye, which was diagnosed with acute anterior uveitis. Adalimumab therapy was discontinued and the patient was hospitalised for the treatment of acute anterior uveitis with systemic corticosteroids. This paradoxical adverse event was alleviated after timely interventions and went into remission during a 6-month follow-up period. To the best of our knowledge, this is the first case of uveitis occurring in patients with psoriasis under adalimumab treatment. It indicates that paradoxical uveitis, although rare, is one of the adverse events of adalimumab therapy. Early recognition and prompt intervention would lead to a good outcome. [ABSTRACT FROM AUTHOR]

A two-step method has been used to fabricate nano-particles of layer-structured bismuth chalcogenide compounds, including BiTe, BiSe, and BiSeTe, through a nano-scaled top-down route. In the first step, lithium (Li) atoms are intercalated between the van der Waals bonded quintuple layers of bismuth chalcogenide compounds by controllable electrochemical process inside self-designed lithium ion batteries. And in the second step, the Li intercalated bismuth chalcogenides are subsequently exposed to ethanol, in which process the intercalated Li atoms would explode like atom-scaled bombs to exfoliate original microscaled powder into nano-scaled particles with size around 10 nm. The influence of lithium intercalation speed and amount to three types of bismuth chalcogenide compounds are compared and the optimized intercalation conditions are explored. As to maintain the phase purity of the final nano-particle product, the intercalation lithium amount should be well controlled in Se contained bismuth chalcogenide compounds. Besides, compared with binary bismuth chalcogenide compound, lower lithium intercalation speed should be applied in ternary bismuth chalcogenide compound. [ABSTRACT FROM AUTHOR]

Abstract: Bi2Te3 nanosheets and nanotubes have been prepared via a microwave-assisted method using ethylene glycol as solvent and reducing agent at 180°C, 190°C and 195°C. X-ray diffraction, transmission electron microscopy, electron diffraction, X-ray energy dispersive spectrometry and high-resolution transmission electron microscopy were employed to characterize the products. It is found that both the nanosheets and nanotubes are well-crystallized single crystals and morphologies of the products are greatly affected by the reaction temperature. A possible formation mechanism related to layer structure rolling was also proposed. [Copyright &y& Elsevier]

[Display omitted] • Bixin treatment significantly reduces the airway inflammatory response, as well as improves the airway hyperresponsiveness in a murine asthma model mimicking an acute asthma attack in human. • Bixin treatment ameliorates chronic airway inflammation and AHR, as well as prevents airway remodeling in a chronic asthmatic mouse model. In vitro experiments indicated that Bixin suppressed the epithelial mesenchymal transition induced by TGF-β. • In addition, we found that administration of Bixin also restored the steroids sensitivity in a mouse asthma model resistance to the glucocorticoids treatment. • We demonstrate that Bixin functions to inhibit PI3K/Akt activation. The inhibitory capacity of Bixin on PI3K/Akt activation may contribute to the protective effects of Bixin in murine asthma models. Accumulating evidence has implicated the potential of natural compounds in treatment of asthma. Bixin is a natural food coloring isolated from the seeds of Bixa Orellana , which possesses anti-tumor, anti-inflammatory and antioxidative properties. Nevertheless, its therapeutic effect in asthma has not been elucidated. Our present study demonstrated that administration of Bixin suppressed allergic airway inflammation and reversed glucocorticoids resistance, as well as alleviated airway remodeling and airway hyperresponsiveness (AHR) in asthmatic mice. In vitro studies showed that Bixin treatment could inhibit the development of epithelial-mesenchymal transition (EMT) mediated by transforming growth factor beta (TGF-β) signaling. Importantly, Bixin antagonized activation of phosphatidylinositol 3–kinase/protein kinase B (PI3K/Akt) pathway both in vitro and in vivo. Above all, our findings reveal that Bixin functions as a potent antagonist of PI3K/Akt signaling to protect against allergic asthma, highlighting a novel strategy for asthma treatment based on natural products. [ABSTRACT FROM AUTHOR]

In this paper, we study a three-dimensional full hydrodynamic model in a bounded domain with insulating and adiabatic boundary. The model takes the form of nonisentropic Euler-Poisson system and incorporates recombination/generation terms, describing the bipolar transport of hot carriers in semiconductor optoelectronic devices. Of particular concern are the existence, uniqueness and exponential stability of thermal equilibrium states to the model, since these mathematical results are rendered useful in numerical simulation and physical theory of semiconductors. They are rigorously proved by the perturbation argument and energy method. [ABSTRACT FROM AUTHOR]

Although the brain can discriminate between various sweet substances, the underlying neural mechanisms of this complex behavior remain elusive. This study examines the role of the anterior paraventricular nucleus of the thalamus (aPVT) in governing sweet preference in mice. We fed the mice six different diets with equal sweetness for six weeks: control diet (CD), high sucrose diet (HSD), high stevioside diet (HSSD), high xylitol diet (HXD), high glycyrrhizin diet (HGD), and high mogroside diet (HMD). The mice exhibited a marked preference specifically for the HSD and HSSD. Following consumption of these diets, c-Fos expression levels in the aPVT were significantly higher in these two groups compared to the others. Utilizing fiber photometry calcium imaging, we observed rapid activation of aPVT neurons in response to sucrose and stevioside intake, but not to xylitol or water. Our findings suggest that aPVT activity aligns with sweet preference in mice, and notably, stevioside is the sole plant-based sweetener that elicits an aPVT response comparable to that of sucrose. • Mice preferred stevioside over other plant-based sweeteners as much as sucrose. • Sucrose and stevioside intake activated neurons in the paraventricular nucleus of thalamus (PVT) of mice. • Neuronal activity in the PVT positively correlated with preference behaviors for various sweeteners. [ABSTRACT FROM AUTHOR]

Discusses the importance of nanocrystalline nickel in magnetic materials and the development of the ...-radiation method to prepare nanocrystalline materials. How to prepare nanocrystalline nickel powder; Increase of nickel particles and radiation-chemistry yield of nickel in irradiated solutions; Process of reducing Ni2+ ions in solution.

Reduced glutathione (GSH) and the oxidized glutathione (GSSG) are well-known biomolecules in the main constituents of intracellular redox homeostasis system. A rapid, accurate measurement of cellular GSH and GSSG is quite needed in investigating important biochemical events. In this work, we present a novel and sensitive method to monitor intracellular GSH and GSSG concentrations by a portable surface-enhanced Raman spectroscopy (SERS) technique. We introduced a reduction-sensitive reaction-type Raman probe, 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) to initiate GSH reduction, itself concomitantly converts to 2-nitro-5-thiobenzoic acid (TNB) to release a strong SERS signal. In a convenient way of inorganic salt MgSO 4 induced aggregation of silver nanoparticles substrate, we easily implemented a good discrimination between DTNB and TNB, and a quantitative measurement of GSH and GSSG with a high sensitivity of 10 nM. This SERS method proved its feasible applicability in rapidly and sensitively monitoring GSH depletion behaviors of some notorious alkylating agents, i.e. , sulfur mustard and nitrogen mustards in ex vitro or in vitro (cellular response). This SERS method may be very worthwhile in cellular detoxication event via the GSH approach and other GSH involved biomedical researches. Image 1 • A reduction-sensitive reaction-type SERS sensor is developed for detection of GSH and GSSG in cells. • This method reaches a high sensitivity of 10 nM for GSH and GSSG, so that cellular determination can be readily achieved. • Rapid monitoring of GSH depletion behaviors of typical alkylating agents in ex vitro or in vitro is realized. • This SERS-based method shows potential applicability in GSH involved biomedical researches. [ABSTRACT FROM AUTHOR]

Gaillardia plants have been widely cultivated in China and have become an important component of garden landscaping. Different from the common ligulate ray floret, the cornflower-like (funnel-shaped) ray floret is a special phenotype variation in Gaillardia species. Previous studies revealed that CYC-like genes could shape the floret phenotype in Compositae. To reveal the molecular mechanism of the cornflower-like phenotype, we checked the capitulum transcriptomes of several cultivars of Gaillardia that possess different ray florets. As a result, we identified 11 CYC-like genes, of which five included complete coding region sequences. Phylogenetic analysis revealed that all five genes were CYC2-like genes. Relative expression analysis of RNA-resequencing reads, qRT-PCR comparison, and gene-silencing treatment all showed that the CYC2c gene is the main genetic mechanism responsible for the shaping of the cornflower-like ray floret phenotype in Gaillardia cultivars. This study expounded our understanding of flower morphology evolution and provides useful insights for improving Compositae breeding. [ABSTRACT FROM AUTHOR]

A novel nano-silicon oxides (SiOx)/chitosan complex film was prepared using ultrasonic assistant in the process of dissolving chitosan and silicon oxides (SiOx), and characterized by transmission electron microscopy. Its effect on quality preservation of tomatoes (Solanum lycopersicum L. cv. Zheza 205) was investigated under ambient temperature. The results revealed that the nano-SiOx/chitosan complex (NSCC) film retarded weight loss and softness, delayed the titratable acids and total soluble solids loss, and thus markedly extended shelf life of green tomatoes. The antimicrobial activity of tomatoes coated with NSCC film was also recorded higher compared to chitosan (Ch) films and control. In addition, the NSCC film-coated tomatoes prevent the increase of malondialdehyde content and total polyphenol content. Moreover, the peroxidase activity, phenylalanine ammonia-lyase activity, and polyphenoloxidase activity of tomatoes coated with NSCC film were found lower than that in other treatments. These data indicated that the beneficial effects of nano-SiOx/chitosan complex coating on postharvest quality were possibly associated with the lower rate of O2/CO2 transmission coefficient, limiting food-borne pathogenic bacterial growth, higher antioxidant activities, and also higher reactive oxygen species (ROS) scavenging and anti-browning activities of related enzymes in the tomatoes. Further, the results of the study could be used to successfully develop a novel nano-SiOx/chitosan complex film for improving the postharvested quality of tomatoes and thus effectively utilized by the food packaging industry. [ABSTRACT FROM AUTHOR]

The optimal control problems of degenerate parabolic equations have many applications in economics, physics, climatology, and so on. Motivated by the applications, we consider the optimal control problems of a class of nonlinear degenerate parabolic equations in this paper. The main result is that we deduce the first order necessary condition for the optimal control problem of nonlinear degenerate parabolic equations by variation method. Moreover, we investigate the uniqueness of the solutions to the optimal control problems. For the linear equations, we obtain the global uniqueness, while for the nonlinear equations, we obtain only the local uniqueness. Finally, we give a numerical example to validate the theoretical results. [ABSTRACT FROM AUTHOR]

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (AdCC) of the Bartholin's gland (AdCC-BG) is a very rare gynecologic vulvar malignancy. AdCC-BGs are slow-growing but locally aggressive and are associated with high recurrence rates. Here we sought to characterize the molecular underpinning of AdCC-BGs. AdCC-BGs (n = 6) were subjected to a combination of RNA-sequencing, targeted DNA-sequencing, reverse-transcription PCR, fluorescence in situ hybridization (FISH) and MYB immunohistochemistry (IHC). Clinicopathologic variables, somatic mutations, copy number alterations and chimeric transcripts were assessed. All six AdCC-BGs were biphasic, composed of ductal and myoepithelial cells. Akin to salivary gland and breast AdCCs, three AdCC-BGs had the MYB :: NFIB fusion gene with varying breakpoints, all of which were associated with MYB overexpression by IHC. Two AdCC-BGs were underpinned by MYBL1 fusion genes with different gene partners, including MYBL1 :: RAD51B and MYBL1 :: EWSR1 gene fusions, and showed MYB protein expression. Although the final AdCC-BG studied had MYB protein overexpression, no gene fusion was identified. AdCC-BGs harbored few additional somatic genetic alterations, and only few mutations in cancer-related genes were identified, including GNAQ , GNAS , KDM6A , AKT1 and BCL2 , none of which were recurrent. Two AdCC-BGs, both with a MYB :: NFIB fusion gene, developed metastatic disease. AdCC-BGs constitute a convergent phenotype, whereby activation of MYB or MYBL1 can be driven by the MYB :: NFIB fusion gene or MYBL1 rearrangements. Our observations further support the notion that AdCCs, irrespective of organ site, constitute a genotypic–phenotypic correlation. Assessment of MYB or MYBL1 rearrangements may be used as an ancillary marker for the diagnosis of AdCC-BGs. • Adenoid cystic carcinoma of the Bartholin's gland (AdCC-BG) is underpinned by MYB or MYBL1 fusion genes. • AdCC-BGs have few somatic genetic alterations in addition to the MYB/ MYBL1 fusion gene. • AdCC-BG constitutes a genotypic–phenotypic correlation. • MYB/ MYBL1 rearrangement assessment may be used as an ancillary marker for AdCC-BG diagnosis. [ABSTRACT FROM AUTHOR]

Objective • To investigate the potential causal relationship between type 1 diabetes and colorectal cancer by using Mendelian randomization (MR). Methods • Two-sample bidirectional MR was used to investigate the causal relationship between type 1 diabetes and colorectal cancer. All research data were collected from the IEU Open GWAS Project database. The dataset of type 1 diabetes included 9 266 cases and 15 574 controls, with correlation analysis in 12 783 129 single nucleotide polymorphisms (SNPs); the dataset of colorectal cancer included 5 657 cases and 372 016 controls, with correlation analysis in 29 999 696 SNPs. The instrumental variables SNPs were screened. The results derived from the inverse-variance weighted (IVW) method were used as the main indicator of effect. The results derived from other four methods, namely MR-Egger regression, weighted median, simple mode, and weighted mode, were used as reference. Sensitivity was analyzed with the leave-one-out method. Heterogeneity was analyzed with Cochran's Q test by using both IVW and MR-Egger methods. Pleiotropy was analyzed with MR-pleiotropy function, and Steiger test was used for directional research. The colocation analysis was used to find out whether the causal relationship between type 1 diabetes and colorectal cancer was caused by the same SNP. The genetic correlation between 2 diseases was analyzed by using the linkage disequilibrium score regression (LDSC). All tests were analyzed by using R language software (version 4.3.1). Results • After being screened, a total of 33 instrumental variables (SNPs) were used. The heterogeneity test results showed that there was heterogeneity among the SNPs (IVW and MR-Egger: P<0.05), so the effect evaluation was based on the results of the random effect model. MR analysis showed that type 1 diabetes had a significant causal effect on colorectal cancer (P< 0.05) by using IVW, MR-Egger, weighted median and weighted mode. Sensitivity analysis showed that the results were stable. Pleiotropy was not detected in pleiotropy test (P>0.05). Steiger test showed that the effect of type 1 diabetes on colorectal cancer was not interfered with by the reverse effect. Reverse MR analysis showed no causal effect of colorectal cancer on type 1 diabetes (P>0.05). The results of colocalization analysis showed that the probability of H4 hypothesis was 45.7%, and the causal relationship between the 2 diseases was not caused by the same SNP in the gene sequences. LDSC analysis demonstrated that there was no genetic correlation between the two diseases. Conclusion • Type 1 diabetes may promote colorectal cancer, but colorectal cancer has no effect on type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Frailty not only affects disease survival but also impacts the long-term function and quality life of all adults diagnosed with and/or treated for cancer.The American Heart Association has introduced Life's Essential 8 (LE8) as a novel metric for assessing cardiovascular health. Currently, LE8's application in evaluating the frailty of cancer survivors remains unreported. This research seeks to explore the connection between LE8 scores and frailty levels in cancer survivors across the United States, thereby addressing a significant void in existing studies. Methods: This study analyzed data from cancer survivors enrolled in the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2005 to 2018, providing a comprehensive dataset. Multivariable logistic regression models were used to examine the linkage between LE8 rankings and frailty condition in cancer survivors. Furthermore, the study delved deeper into this correlation using restricted cubic spline (RCS) curves and subgroup analyses. Results: In the fully adjusted model, an increased LE8 level was closely associated with a reduced odds ratio of frailty among cancer survivors, with an OR of 0.95 (95% CI: 0.94–0.96, p < 0.0001).This pattern persisted across different categorizations of LE8 into low, moderate, and high groups, demonstrating a consistent trend. The analysis revealed a non-linear relationship between LE8 scores and frailty status, further supporting a straightforward association (p-value for non-linearity = 0.0729). Conclusion: Studies have found that the higher the LE8 score, the less likely a cancer patient is to develop debilitating symptoms.This indicates that the LE8 scores may provide an opportunity for interventions aimed at improving the prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

Herein, we found ARHGAP25 was down-regulated in colon biopsies of patients with colorectal cancer (CRC). Gene set enrichment analysis (GSEA) also showed that ARHGAP25 was negatively correlated with Wnt/β-catenin activation. To study the role of ARHGAP25 in CRC and its possible mechanism, we established lentiviral-mediated ARHGAP25 overexpression in HCT116 and RKO cells along with siRNA-mediated ARHGAP25 knockdown in SW620 cells. The metastatic capacity of the CRC cell lines in vitro was assessed by measuring cell proliferation, migration and invasion. Additionally, expression of matrix metalloproteinases (MMP2, MMP7 and MMP9), EMT-associated factors (E-cadherin, ZEB1, Snail and Twist1) and β-catenin (a core part of Wnt/β-catenin signaling) was determined. XAV939, a Wnt/β-catenin inhibitor, was used for treatment. Our data suggests that ARHGAP25 overexpression significantly inhibits CRC cell growth, suppresses cell migration and invasion, and reduces expression of MMPs, EMT-associated factors and β-catenin. Our results suggest not only that ARHGAP25 has an anti-metastatic role in CRC cells, but also that the inactivation of the Wnt/β-catenin pathway is important in this process. Accordingly, siRNA-ARHGAP25 resulted in the opposite effect, favoring CRC metastasis in vitro, and activating the Wnt/β-catenin pathway in CRC cells. In addition, the siRNA-ARHGAP25 induced changes on cell proliferation, migration, and invasion were significantly reversed with XAV939 treatment. Importantly, the anti-metastatic effects of ARHGAP25 were further substantiated in a CRC lung metastasis xenograft model. We conclude that ARHGAP25 negatively regulates the metastatic potential of CRC cells via the Wnt/β-catenin pathway. Thus, our findings implicate ARHGAP25 as a potential therapeutic target in CRC metastasis. [ABSTRACT FROM AUTHOR]