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Abstract The forward triage characteristic of telemedicine highlights its importance again in the COVID-19 pandemic. Telemedicine can provide timely emergency response in the case of environmental or biological hazards, and the patient’s medical privacy data generated in this process can also accelerate the establishment of models for preventing and treating infectious diseases. However, the reuse process of telemedicine user privacy data based on federated learning also faces significant challenges. Differences in regions, economic levels, and grades lead to heterogeneous data and resource-constrained environments, seriously damaging the federated learning process. Besides, the weak password authentication of medical terminals and eavesdropping attacks on transmission channels may cause illegal access to terminals and platforms and leakage of sensitive data. This paper proposed a telemedicine data secure-sharing scheme based on heterogeneous federated learning. Specifically, we proposed a heterogeneous federated learning scheme with model alignment to guide telemedicine practice through the reuse of telemedicine data; in addition, we designed an SM9 threshold identity authentication scheme to guarantee that the patient’s medical privacy data is protected from leakage during the federated learning process. We evaluated our scheme using two third-party medical datasets. The evaluation results indicate that this scheme can still assist the federated learning process in resisting data heterogeneity and resource constraints with almost no performance cost.

BackgroundAlectinib has demonstrated promising disease-free survival (DFS) benefit for early-stage non-small cell lung cancer (NSCLC) patients with ALK rearrangement positive in phase 3 ALINA trial. However, real-world evidence for the efficacy and safety of alectinib in early-stage ALK-positive NSCLC is limited.Materials and methodsWe retrospectively reviewed 68 patients with stage IB-IIIB ALK-positive NSCLC who underwent complete pulmonary resections from April 2010 to July 2023 at a single institution. 38 (55.9%) enrolled patients had N2 lymph node metastasis, and 17 (24.9%) patients had multi-station N2 metastasis. Patients were stratified into two groups according to the adjuvant treatment regimen, with 19 patients in the alectinib group and 49 patients in the chemotherapy group. There were no significant differences in clinicopathological characteristics between the two groups. After curative resection surgery, patients in alectinib group received oral alectinib at a dose of 600 mg twice daily and patients in chemotherapy group received platinum-based doublet chemotherapy regimen every 3 weeks for 4 cycles. The primary endpoint was 3-year DFS. The Kaplan-Meier method was used to estimate DFS and overall survival (OS). Safety analyses were conducted by comparing the incidence of adverse events between the two groups.ResultsAt the last follow-up date (January 22th, 2024), A total of 1 (5.3%) and 28 (57.1%) DFS events were observed in alectinib group and chemotherapy group respectively. The 3-year DFS showed significant improvement in the alectinib group compared with chemotherapy group (91.7% vs 60.7%, P=0.051). In the IIIAN2 subgroup, the 3-year DFS rate in the alectinib group reached a satisfactory 87.5%. In both groups, the majority of AEs were graded as level 1 or 2, No grade 3-4 AEs were observed in alectinib group.ConclusionAlectinib, as adjuvant therapy, demonstrated favorable efficacy and manageable safety in patients with completely resected ALK-positive stage I B-IIIB non-small cell lung cancer. A limitation of this study is the small sample size, and a larger-scale real-world sample study is needed to further evaluate the efficacy and safety of alectinib as adjuvant therapy.

The application of adjuvant treatment has significantly enhanced the survival of patients with resectable non-small cell lung cancer (NSCLC) carrying driver gene mutations. However, adjuvant-targeted therapy remains controversial for some NSCLC patients carrying rare gene mutations such as RET, as there is currently a lack of confirmed randomized controlled trials demonstrating efficacy. In this report, we describe the case of a 58-year-old man with stage IIIA NSCLC who underwent complete lobectomy with selective lymph node dissection. Postoperative next-generation sequencing revealed that the patient harbored a rare KIF13A-RET fusion. The patient elected to receive adjuvant treatment with pralsetinib monotherapy and underwent serial circulating tumor DNA (ctDNA) monitoring after surgery. During follow-up, despite experiencing dose reduction and irregular medication adherence, the patient still achieved a satisfactory disease-free survival (DFS) of 27 months. Furthermore, ctDNA predicted tumor recurrence 4 months earlier than imaging techniques. The addition of bevacizumab to the original regimen upon recurrence continued to be beneficial. Pralsetinib demonstrated promising efficacy as adjuvant therapy, while ctDNA analysis offered a valuable tool for early detection of tumor recurrence. By leveraging targeted therapies and innovative monitoring techniques, we aim to improve outcomes and quality of life for NSCLC patients in the future.

Abstract Developing mild photocatalytic bromination strategies using sustainable bromo source has been attracting intense interests, but there is still much room for improvement. Full utilization of redox centers of photocatalysts for efficient generation of Br+ species is the key. Herein we report heterogenous organophotocatalytic HBr oxidation coupled with oxygen reduction to furnish Br2 and H2O2 for effective bromination of arenes over Al2O3 supported perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). Mechanism studies suggest that O-vacancy in Al2O3 can provide Lewis-acid-type anchoring sites for O2, enabling unexpected dual-electron transfer from anchored photoexcited PTCDA to chemically bound O2 to produce H2O2. The in-situ generated H2O2 and Br2 over redox centers work together to generate HBrO for bromination of arenes. This work provides new insights that heterogenization of organophotocatalysts can not only help to improve their stability and recyclability, but also endow them with the ability to trigger unusual reaction mode via cooperative catalysis with supports.

Delayed dynamical system plays a vital role in describing the dynamical phenomenon of neural networks. In this article, we proposed a class of new BAM neural networks involving time delay. The traits of solution and bifurcation behavior of the established BAM neural networks involving time delay were probed into. First, the existence and uniqueness is discussed using a fixed point theorem. Second, the boundedness of solution of the formulated BAM neural networks involving time delay was analyzed by applying an appropriate function and inequality techniques. Third, the stability peculiarity and bifurcation behavior of the addressed delayed BAM neural networks were investigated. Fourth, Hopf bifurcation control theme of the formulated delayed BAM neural networks was explored by virtue of a hybrid controller. By adjusting the parameters of the controller, we could control the stability domain and Hopf bifurcation onset, which was in favor of balancing the states of different neurons in engineering. To verify the correctness of gained major outcomes, computer simulations were performed. The acquired outcomes of this article were new and own enormous theoretical meaning in designing and dominating neural networks.

Recently, delayed dynamical model has witnessed a great interest from many scholars in biological and mathematical areas due to its potential application in describing the interaction of different biological populations. In this article, relying the previous studies, we set up two new predator-prey systems incorporating delay. By virtue of fixed point theory, inequality tactics and an appropriate function, we explore well-posedness (includes existence and uniqueness, boundedness and non-negativeness) of the solution of the two formulated delayed predator-prey systems. With the aid of bifurcation theorem and stability theory of delayed differential equations, we gain the parameter conditions on the emergence of stability and bifurcation phenomenon of the two formulated delayed predator-prey systems. By applying two controllers (hybrid controller and extended delayed feedback controller) we can efficaciously regulate the region of stability and the time of occurrence of bifurcation phenomenon for the two delayed predator-prey systems. The effect of delay on stabilizing the system and adjusting bifurcation is investigated. Computer simulation plots are provided to sustain the acquired prime outcomes. The conclusions of this article are completely new and can provide some momentous instructions in dominating and balancing the densities of predator and prey.

With the rapid development of the Internet of Vehicles, a large amount of vehicle network data is being generated. The large amount of data presents network communication security challenges. Although intrusion detection technology can assist in safeguarding the system from malicious attacks, the substantial data generated within the vehicle network poses time-consuming detection challenges. Thus, we propose an intrusion detection model for the Internet of Vehicles, utilizing Gaussian random incremental principal component analysis (GRIPCA) and optimal weighted extreme learning machine (OWELM). First, we utilize GRIPCA to reduce data redundancy by projecting high-dimensional data into a low-dimensional space, thus reducing storage costs. Then, we utilize the dynamic inertia weight particle swarm optimization (DPSO) to optimize the parameters of the weighted extreme learning machine (WELM) to achieve the best performance. We utilize the NSL-KDD and CIC-IDS-2017 datasets to perform experiments and compare the results with other techniques. The experimental results show the excellence of the proposed model, achieving an accuracy rate of 91.02% on the NSL KDD dataset and 94.67% on the CIC-IDS-2017 dataset.

Highlights Continuous-wave green vertical-cavity surface-emitting lasers based on self-formed quantum dots were realized with the lowest threshold current density of 51.97 A cm−2. A short cavity (~4.0 λ, where λ is the wavelength in the media) was adopted to enhance the interaction between spontaneous emission and lasing mode, with a big coupling factor up to 0.094. AlN current confinement layer and the electroplated supporting copper plate were utilized to improve heat dissipation, with a low thermal resistance of 842 K W−1.

The optical properties of wurtzite violet InGaN/GaN coupled quantum well (QW) structures are experimentally studied using photoluminescence (PL) and electroluminescence (EL) spectroscopy. Two emission peaks, referred to as Peak H and Peak L, are observed in both PL and EL spectra, due to the ground state splitting induced by the well coupling. Experimental PL and EL results reveal that coupled QWs show different optical responses due to the different variation in the electric field inside the QW structure. Since the direction of the polarization electric field of the as-grown well/barrier layers is different, the external electric field applied by electrodes can change the energy band alignment between the well and the barrier layers, thus adjusting the coupling between the wells. Our results provide relevant information to improve our understanding of the optical properties of InGaN/GaN QWs and to develop novel optoelectronic devices.

Abstract Establishing financial models or economic models to describe economic phenomena in real life has become a heated discussion in society at present. From a mathematical point of view, the exploration on dynamics of financial models or economic models is a valuable work. In this study, we build a new delayed finance model and explore the dynamical behavior containing existence and uniqueness, boundedness of solution, Hopf bifurcation, and Hopf bifurcation control of the considered delayed finance model. By virtue of fixed point theorem, we prove the existence and uniqueness of the solution to the considered delayed finance model. Applying a suitable function, we obtain the boundedness of the solutions for the considered delayed finance model. Taking advantage of the stability criterion and bifurcation argument of delayed differential equation, we establish a delay-independent condition ensuring the stability and generation of Hopf bifurcation of the involved delayed finance model. Exploiting hybrid controller including state feedback and parameter perturbation, we efficaciously adjust the stability region and the time of occurrence of Hopf bifurcation of the involved delayed finance model. The study manifests that time delay is a fundamental parameter in controlling stability region and the time of onset of Hopf bifurcation of the involved delayed finance model. To examine the soundness of established key results, computer simulation figures are concretely displayed. The derived conclusions of this study are perfectly new and has momentous theoretical value in economical operation.

The proliferation of blockchain technology has resulted in diverse token standards, posing challenges for compatibility, security, and performance in existing cross-chain bridges. This paper introduces a novel framework capable of concurrently facilitating fungible token exchange, as well as the processing of both individual and batch non-fungible tokens (NFTs). We deploy token bridges that meet different token standards to support cross-chain staking and unlocking of ERC20, ERC721, and ERC1155. To minimize both waiting times and handling fees, we relocate processes necessitating frequent transactions and verifications to the sidechain. Additionally, we adopt a batch-processing approach for tokens necessitating cross-chain transfers, leveraging payment channels to facilitate efficiency. The system’s reliability is upheld through the validator group. Validators acquire an initial reputation value by making deposits and enhance both their rewards and reputation by successfully completing NFT auction tasks on the sidechain. We use OpenZeppelin’s security library functions to standardize token operations, and carefully design the validator’s reward, punishment, and reputation mechanisms. Our comprehensive contract security audit and system analysis validate our solution’s effectiveness in mitigating common vulnerabilities and internal threats. Implementation and testing with Ethereum and its test network demonstrate substantial reductions in transmission time for key cross-chain token steps by nearly half. Moreover, our framework showcases efficiency and cost-effectiveness with an average gas cost of 693,379.

BackgroundAs the main executor of immunotherapy, T cells significantly affect the efficacy of immunotherapy. However, the contribution of the T cell proliferation regulator to the prognosis of lung adenocarcinoma (LUAD) and immunotherapy is still unclear.MethodsBased on T cell proliferation regulators, LUAD samples from The Cancer Genome Atlas (TCGA) were divided into two different clusters by consensus clustering. Subsequently, the T cell proliferation regulator (TPR) signature was constructed according to the prognostic T cell proliferation regulators. Combined with clinical information, a nomogram for clinical practice was constructed. The predictive ability of the signature was verified by the additional Gene Expression Omnibus (GEO) dataset. We also analyzed the differences of tumor microenvironment (TME) in different subgroups and predicted the response to immunotherapy according to the TIDE algorithm. Finally, we further explored the role of ADA (Adenosine deaminase) in the lung adenocarcinoma cell lines through the knockdown of ADA. ResultsAccording to the consensus clustering, there were differences in survival and tumor microenvironment between two different molecular subtypes. T cell proliferation regulator-related signature could accurately predict the prognosis of LUAD. The low-risk group had a higher level of immune infiltration and more abundant immune-related pathways, and its response to immunotherapy was significantly better than the high-risk group (Chi-square test, p

All the time, differential dynamical models with delay has witness a tremendous application value in characterizing the internal law among diverse biological populations in biology. In the current article, on the basis of the previous publications, we formulate a new Lotka–Volterra commensal symbiosis system accompanying delay. Utilizing fixed point theorem, inequality tactics and an appropriate function, we gain the sufficient criteria on existence and uniqueness, non-negativeness and boundedness of the solution to the formulated delayed Lotka–Volterra commensal symbiosis system. Making use of stability and bifurcation theory of delayed differential equation, we focus on the emergence of bifurcation behavior and stability nature of the formulated delayed Lotka–Volterra commensal symbiosis system. A new delay-independent stability and bifurcation conditions on the model are presented. By constructing a positive definite function, we explore the global stability. By constructing two diverse hybrid delayed feedback controllers, we can adjusted the domain of stability and time of appearance of Hopf bifurcation of the delayed Lotka–Volterra commensal symbiosis system. The effect of time delay on the domain of stability and time of appearance of Hopf bifurcation of the model is given. Matlab experiment diagrams are provided to sustain the acquired key outcomes.

Abstract With the advent of information era, the issues on video copyright continue to emerge. In the grey industrial chain of piracy, the film industry is suffering a major disaster area. The current protection schemes for video copyright are inefficient and costly so that video industry still has to face the infringement. To address poor robustness, weak imperceptibility and difficulty in traceability of the current protection schemes for video copyright, this paper proposes a novel zero-watermarking scheme based on NSCT-SVD and blockchain for video copyright. In addition, we research the feasibility and reason of combining zero-watermarking with blockchain. The designed zero-watermarking algorithm is based on NSCT-SVD, Arnold Transform and key-frames extraction algorithm which is based on distance threshold clustering. The results show the extracted features from video are stable and secure than DWT-SVD based and the past non-blocking. The performance of the blockchain scheme designed for video copyright practices well. Comparatively, the discussion and results showed that the proposed scheme has been verified more credible and efficient in authoritative traceability compared to trusted third party based. The registration information cannot be tampered and be more suitable for copyright protection.

This paper introduces the demand-driven assembly line rebalancing problem (DDALRP) and proposes a non-linear, multi-objective, combinatorial optimization model to solve it. A DDALRP arises whenever the production output of the assembly line (AL) must be continuously readjusted along a planning horizon in order to satisfy as much as possible a given demand forecast; thus, dealing not with a one-time rebalance, but with a multi-period rebalance, fact that exponentially increases the complexity and combinatorial nature of the problem. Adapting or regulating the production output of the AL to a particular demand forecast or production plan is a relatively new idea in the assembly line balancing (ALB) / rebalancing (ALR) literature; and the novelty of this work is the rebalancing mechanism employed to solve the problem: we address the problem by reallocating workers to stations, taking into consideration their learning and forgetting (L&F) curves. Our proposed model was solved by implementing a genetic algorithm (GA) in 162 cases (three problem instances under 54 scenarios each), which produced useful insights about the dynamics of worker reallocation under different situations: optimistic, most-likely, pessimistic L&F coefficients; experienced and inexperienced workers; and different demand scenarios.

BackgroundZinc is a key mineral element in regulating cell growth, development, and immune system. We constructed the zinc metabolism-related gene signature to predict prognosis and immunotherapy response for lung adenocarcinoma (LUAD).MethodsZinc metabolism-associated gene sets were obtained from Molecular Signature Database. Then, the zinc metabolism-related gene signature (ZMRGS) was constructed and validated. After combining with clinical characteristics, the nomogram for practical application was constructed. The differences in biological pathways, immune molecules, and tumor microenvironment (TME) between the different groups were analyzed. Tumor Immune Dysfunction and Exclusion algorithm (TIDE) and two immunotherapy datasets were used to evaluate the immunotherapy response.ResultsThe signature was constructed according to six key zinc metabolism-related genes, which can well predict the prognosis of LUAD patients. The nomogram also showed excellent prediction performance. Functional analysis showed that the low-risk group was in the status of immune activation. More importantly, the lower risk score of LUAD patients showed a higher response rate to immunotherapy.ConclusionThe state of zinc metabolism is closely connected to prognosis, tumor microenvironment, and response to immunotherapy. The zinc metabolism-related signature can well evaluate the prognosis and immunotherapy response for LUAD patients.

Summary: Background: This phase 2 trial aimed to compare adjuvant icotinib with observation in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage IB non-small cell lung cancer (NSCLC). Methods: We performed a randomised, open-label, phase 2 trial from May 1, 2015 to December 29, 2020 at Sun Yat-sen University Cancer Center in China. Patients with completely resected, EGFR-mutant, stage IB (the 7th edition of TNM staging) NSCLC without adjuvant chemotherapy were randomised (1:1) to receive adjuvant therapy with icotinib (125 mg, three times daily) for 12 months or to undergo observation until disease progression or intolerable toxicity occurred. The primary endpoint was 3-year disease-free survival (DFS). CORIN (GASTO1003) was registered with Clinicaltrials.gov, with the number NCT02264210. Findings: A total of 128 patients were randomised, with 63 patients in the icotinib group and 65 patients in the observation group. The median duration of follow-up was 39.9 months. The three-year DFS was significantly higher in the icotinib group (96.1%, 95% confidence interval [CI], 91.3–99.9) than in the observation group (84.0%, 95% CI, 75.1–92.9; P = 0.041). The DFS was significantly longer in the icotinib group than in the observation group, with a hazard ratio (HR) of 0.23 (95% CI, 0.07–0.81; P = 0.013). The OS data were immature, with three deaths in the observation arm. In the icotinib group, adverse events (AEs) of any grade were reported in 49 patients (77.8%), and grade 3 or greater AEs occurred in four patients (6.3%). No treatment-related deaths occurred. Interpretation: Our findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile. Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

Optically pumped wavelength-tunable vertical-cavity surface-emitting lasers (VCSELs) operating in the ultraviolet A (UVA) spectrum were demonstrated. The VCSELs feature double dielectric distributed brag reflectors and a wedge-shaped cavity fabricated using the substrate transfer technique and laser lift off, resulting in a graded cavity length in one device. A resonant period gain structure is used in the InGaN/GaN multi-quantum well active region to enhance the coupling between the cavity mode field and the active layers. The optical field inside the cavity is modulated by the cavity length; thus, tunable lasing at different wavelengths is realized at different points of a single VCSEL chip. The lasing wavelength extends from 376 to 409 nm, covering most of the UVA band below the band gap of GaN. The threshold pumping power density of the UVA VCSELs at different wavelengths ranges from 383 to 466 kW/cm2, which is among the lowest values for ultraviolet (UV) VCSELs. This study is promising for the development of small-footprint, power-efficient UV light sources.

PurposeThe dysregulation of copper metabolism is closely related to the occurrence and progression of cancer. This study aims to investigate the prognostic value of copper metabolism-related genes (CMRGs) in lung adenocarcinoma (LUAD) and its characterization in the tumor microenvironment (TME).MethodsThe differentially expressed CMRGs were identified in The Cancer Genome Atlas (TCGA) of LUAD. The least absolute shrinkage and selection operator regression (LASSO) and multivariate Cox regression analysis were used to establish the copper metabolism-related gene signature (CMRGs), which was also validated in Gene Expression Omnibus (GEO) database (GSE72094). The expression of key genes was verified by quantitative real-time PCR (qRT-PCR). Then, the CMRGS was used to develop a nomogram to predict the 1-year, 3-year, and 5-year overall survival (OS). In addition, differences in tumor mutation burden (TMB), biological characteristics and immune cell infiltration between high-risk and low-risk groups were systematically analyzed. Immunophenoscore (IPS) and an anti-PD-L1 immunotherapy cohort (IMvigor210) were used to verify whether CMRGS can predict the response to immunotherapy in LUAD.Results34 differentially expressed CMRGs were identified in the TCGA dataset, 11 of which were associated with OS. The CMRGS composed of 3 key genes (LOXL2, SLC31A2 and SOD3) had showed good clinical value and stratification ability in the prognostic assessment of LUAD patients. The results of qRT-PCR confirmed the expression of key CMRGs in LUAD and normal tissues. Then, all LUAD patients were divided into low-risk and high-risk groups based on median risk score. Those in the low-risk group had a significantly longer OS than those in the high-risk group (P

With the development of technology, Moore's law will come to an end, and scientists are trying to find a new way out in brain-like computing. But we still know very little about how the brain works. At the present stage of research, brain-like models are all structured to mimic the brain in order to achieve some of the brain's functions, and then continue to improve the theories and models. This article summarizes the important progress and status of brain-like computing, summarizes the generally accepted and feasible brain-like computing models, introduces, analyzes, and compares the more mature brain-like computing chips, outlines the attempts and challenges of brain-like computing applications at this stage, and looks forward to the future development of brain-like computing. It is hoped that the summarized results will help relevant researchers and practitioners to quickly grasp the research progress in the field of brain-like computing and acquire the application methods and related knowledge in this field.

Abstract Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16’s involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.

Abstract In the past 10 years, MXene (transition metal carbides, nitrides, and carbonitrides), a 2D nanomaterial, has become one of the research hotspots with its hydrophilic ends, solution machinability, and excellent electronic, mechanical, and optical characteristics. Herein, recent progress on Ti3C2Tx MXene materials is reviewed, analyzed, and evaluated with highlights on their electrical performances and applications. The progress on electrical conductivity enhancement of Ti3C2Tx MXene is carefully reviewed from a number of aspects in Ti3AlC2 MAX phase precursor, synthesis methods, delamination treatment, removal of delamination compounds, surface terminations, thin‐film deposition methods, and storage environment and time. Finally, a summary is provided and the challenges are discussed to further enhance the electrical conductivity.

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain to be elucidated. This study was designed to investigate the impact of hypoxic acclimation (HA) on cardiac I/R injury and the antioxidative mechanism(s). Male adult mice were acclimated in a hypoxic chamber (10% oxygen [O2]) for 8 h/day for 14 days, and then subjected to cardiac I/R injury by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h or 7 days. Our results showed that HA attenuated oxidative stress and reduced infarct size in the I/R hearts. This cardioprotective effect is coupled with an elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification partially due to inflammatory stimulation. Hyperglycosylation activated glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway, resulting in an upregulation of NADPH/NADP+ and GSH/GSSG couples and enhancement of redox homeostasis in the heart. Pharmacological suppression of O-GlcNAcylation totally abolished the influence of HA on the G6PDH activity, redox balance and post-I/R damage in the hearts and cultured cardiomyocytes, whereby augmentation of O-GlcNAcylation further enhanced the benefits, suggesting a central role of O-GlcNAcylation in HA-initiated antioxidative and cardioprotective effects. These findings, therefore, identified HA as a promising anti-I/R strategy for the heart and proposed O-GlcNAc modification of G6PDH as a therapeutic target in ischemic heart disease.

Background: Lymph node metastasis (LNM) is an important pathological characteristic of bladder cancer (BCa). However, the molecular mechanism underlying LNM was not thoroughly elaborated. Identification for LNM-related biomarkers may contribute to making suitable therapies. So, the current study was aimed to identify key genes and construct a prognostic signature.Methods: Based on the Cancer Genome Atlas (TCGA) database, gene expression and clinical information were obtained. Then, the weighted gene co-expression network analysis (WGCNA) was performed to identify the key modules and hub genes. A function analysis and a gene set enrichment analysis were applied to explore biological functions and pathways of interested genes. Furthermore, a prognostic model based on LNM-related genes was constructed by using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.Results: Finally, nine co-expression modules were constructed, and two modules (turquoise and green) were significantly associated with LNM. Three hub genes were identified as DACT3, TNS1, and MSRB3, which were annotated in actin binding, actin cytoskeleton, adaptive immune response, and cell adhesion molecular binding by the GSEA method. Further analysis demonstrated that three hub genes were associated with the overall survival of BCa patients. In addition, we built a prognostic signature based on the genes from LNM-related modules and evaluated the prognostic value of this signature.Conclusion: In general, this study revealed the key genes related to LNM and prognostic signature, which might provide new insights into therapeutic target of BCa.

Background The efficacy of docetaxel-based chemotherapy is limited by the development of drug resistance. Recent studies demonstrated the efficacy of anti-programmed death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapies in metastatic prostate cancer. The ataxia telangiectasia mutation (ATM) protein plays a crucial role in maintaining genome stability and function of mitosis. Here, we aimed to determine whether PD-1/PD-L1 signaling contributes to the resistance to DTX and to elucidate the mechanism underlying DTX-induced PD-L1 expression.Methods In this retrospective study, PD-L1 expression was analyzed in 33 tumor tissue samples from prostate cancer patients. Prostate cell lines were used to perform functional assays and examine underlying mechanisms in vitro. A fully mouse prostate cancer model and a humanized chimeric mouse bearing human prostate tumors and peripheral blood mononuclear cells were used for in vivo assays.Results We have shown that DTX, a chemotherapeutic drug which causing microtubule interference, could significantly induce the expression of PD-L1 in prostate cancer cells. This effect is blocked by the inhibition of ATM, suggesting that it plays an essential role in PD-L1 expression upregulated by DTX. Mechanistic studies have shown that ATM activity in cancer cells enhances the stability of the NF-κB essential modulator (NEMO), which leading to an increase in the NF-κB activity and PD-L1 expression. Using the mouse model, it was further demonstrated that a combination of ATM and NEMO inhibitors along with DTX augmented the antitumor efficacy of chemotherapy, which are comparable to that of PD-L1 antibody.Conclusions Our findings have revealed that a previously unrecognized ATM-NEMO signaling which induced by DTX is capable of suppressing tumor immunity by activating the expression of PD-L1, suggesting that the ATM-NEMO-NF-κB axis can be exploited to restore the immune balance and overcome cancer resistance triggered by DTX.Graphic Abstract: supplementary file 1

Abstract Background For secondary cavity-nesting bird species that do not add lining materials to nests, the presence of old nest material or organic remains that have accumulated within nest cavities from previous breeding events may be a cue of nest-site quality. These materials potentially contain information about past breeding success in con- and heterospecifics and may improve the thermal insulation of eggs during incubation. However, few studies have addressed whether the presence of old nest materials serves as a cue for cavity-nesting raptors when choosing specific nest sites. Methods We conducted a 9-year nest box experiment to test whether old nest materials from con- and heterospecifics serve as informative cues to the European Kestrel (Falco tinnunculus) when making nest selection decisions, as this species uses nest boxes without adding nesting material. Results The presence of old nest materials and entrance size best discriminated nest boxes occupied by European Kestrels from unoccupied boxes. Nest boxes containing conspecific organic remains, artificial dry leaf and branch material, and material left behind by Great Tits (Parus major) were reused at higher rates, especially those containing conspecific nest material, than nest boxes containing true or simulated nest materials from predators. In 2010, no single nest box was occupied by the same banded individual that occupied the box in the previous year (10 females and 2 males were banded in 2009). Conclusions European Kestrels preferred nest boxes containing old nest material over empty boxes, which is consistent with previous findings that they exploit con- and heterospecific cues when deciding where to settle and breed, as old nest or organic material provides substrate for incubating females. Kestrels may be able to assess the predation risks associated with a specific nest site based on experience or the presence of prey remains. The repeated use of nest boxes across breeding seasons by kestrels cannot be entirely ascribed to philopatry. This study provides evidence that old nest materials are potentially used as informative cues when making nest-site selection decisions in European Kestrels.

Objectives The aim of this work is to explore the association between chronic exposure to nonylphenol (NP), a representative environmental endocrine disruptor (EED), and the risk of depression and its potential mechanism. Methods A hospital-based case control study was conducted from August to December 2018. Forty-one patients with confirmed depression and 47 healthy volunteers were recruited. In vitro, 20 rats were randomly divided into the control group (corn oil) and NP exposure group (n = 10 per group), which were gavaged at a dose of 4 mg/kg w/day for 180 days. Results The depressed patient group had higher Zung Self-Rating Depression Scale (SDS) (P

BackgroundAlthough adjuvant chemotherapy is established for patients with non-small-cell lung cancer (NSCLC), the long-term survival remains to be improved. Postsurgical circulating tumor DNA (ctDNA) analysis of resectable NSCLC may identify patients at high risk of recurrence after adjuvant chemotherapy and facilitate personalized therapy.MethodsThis analysis included 38 patients who underwent curative-intent resection and received adjuvant chemotherapy for NSCLC. ctDNA analyses of tumor tissue, and pre- and post-operative plasma samples were performed with next-generation sequencing targeting 425 cancer-relevant genes. We define a ctDNA positive event as at least one shared mutation identified simultaneously in the plasma and tumor specimens. The primary endpoint was recurrence-free survival (RFS).ResultsAt least one somatic mutation was identified in the tumor tissue of all 38 patients. Tumor tissue-specific mutated ctDNA was detected in the preoperative plasma samples of 19 (50%) patients. ctDNA in preoperative plasma was in good accordance with that in tissue. ctDNA was detectable in the first post-operative pre-chemotherapy samples of 8 of 35 (22.9%) patients and was associated with inferior RFS (HR, 3.69; P = 0.033). ctDNA was detected in the first post-chemotherapy samples of 8 of 36 (22.2%) patients and was also associated with inferior RFS (HR, 8.76; P < 0.001).ConclusionsPostoperative and post-chemotherapy ctDNA is a promising prognostic marker for resected NSCLC. ctDNA analyses may define a subgroup that remains at high risk of relapse despite standard adjuvant chemotherapy, and may help to inform intensified therapeutic strategies.

Background: Hypersensitivity to general anesthetics may predict poor postoperative outcomes, especially among the older subjects. Therefore, it is essential to elucidate the mechanism underlying hypersensitivity to volatile anesthetics in the aging population. Given the fact that isoflurane sensitivity increases with aging, we hypothesized that deficiencies of mitochondrial function and elevated oxidative levels in the frontoparietal cortex may contribute to the enhanced sensitivity to isoflurane in aging mice.Methods: Isoflurane sensitivity in aging mice was determined by the concentration of isoflurane that is required for loss of righting reflex (LORR). Mitochondrial bioenergetics of the frontoparietal cortex was measured using a Seahorse XFp analyzer. Protein oxidation and lipid oxidation in the frontoparietal cortex were assessed using the Oxyblot protein oxidation detection kit and thiobarbituric acid reactive substance (TBARS) assay, respectively. Contributions of mitochondrial complex II inhibition by malonate and peroxidation by ozone to isoflurane sensitivity were tested in vivo. Besides, effects of antioxidative therapy on mitochondrial function and isoflurane sensitivity in mice were also measured.Results: The mean concentration of isoflurane that is required for LORR in aging mice (14–16 months old) was 0.83% ± 0.13% (mean ± SD, n = 80). Then, the mice were divided into three groups as sensitive group (S group, mean − SD), medium group (M group), and resistant group (R group, mean + SD) based on individual concentrations of isoflurane required for LORR. Activities of mitochondrial complex II and complex IV in mice of the S group were significantly lower than those of the R group, while frontoparietal cortical malondialdehyde (MDA) levels were higher in the mice of S group. Both inhibition of mitochondrial complexes and peroxidation significantly decreased the concentration of isoflurane that is required for LORR in vivo. After treatment with idebenone, the levels of lipid oxidation were alleviated and mitochondrial function was restored in aging mice. The concentration of isoflurane that required for LORR was also elevated after idebenone treatment.Conclusions: Decreased mitochondrial functions and higher oxidative stress levels in the frontoparietal cortex may contribute to the hypersensitivity to isoflurane in aging mice.

Densely populated edge-terminated vertically aligned two-dimensional MoS2 nanosheets (NSs) with thicknesses ranging from 5 to 20 nm were directly synthesized on Mo films deposited on SiO2 by sulfurization. The quality of the obtained NSs was analyzed by scanning electron and transmission electron microscopy, and Raman and X-ray photoelectron spectroscopy. The as-grown NSs were then successfully transferred to the substrates using a wet chemical etching method. The transferred NSs sample showed excellent field-emission properties. A low turn-on field of 3.1 V/μm at a current density of 10 µA/cm2 was measured. The low turn-on field is attributed to the morphology of the NSs exhibiting vertically aligned sheets of MoS2 with sharp and exposed edges. Our findings show that the fabricated MoS2 NSs could have a great potential as robust high-performance electron-emitter material for various applications such as microelectronics and nanoelectronics, flat-panel displays and electron-microscopy emitter tips.

Spatial priority areas for individual and multiple hydrological ecosystem services with economic costs across watershed through systematic conservation model represent a significant step toward cost-effective, transparent allocation of resources for ecosystem conservation and socio-economic development. However, current studies demonstrated that few economic costs derived from natural resources into hydrological ecosystem services reserve networks were involved into spatial conservation of hydrological ecosystem services. Therefore, there is a need for more challenging and integrated testing of economic costs to systematic conservation of hydrological ecosystem services across real-world watershed in order to build effective and reliable priority areas for hydrological ecosystem services. Here though systematic conservation model, we constructed spatial priority areas for multiple hydrological ecosystem services with different economic costs in Teshio watershed, northernmost of Japan. We demonstrated that economic costs impacted on the changes in spatial priority areas under a set of conservation targets and can obviously shift spatial patterns of priority areas for individual and multiple hydrological ecosystem services, which can increase the cost-effectiveness success of ecosystem service conservation for different stakeholders. Additionally, we examined how spatial correlations between priority areas for individual and multiple hydrological services under different economic cost scenarios, which can be recognized as surrogates to measure the ecosystem services tradeoffs from economic and ecological standpoint in the reserve networks designs. Therefore, integrating economic costs into ecosystem-based conservation in watershed is more-comprehensive ecological-economic conservation framework. Keywords: Spatial priority areas, Individual and multiple hydrological ecosystem services, Systematic conservation model, Economic cost scenarios

In recent years, the frequently occurring contamination accidents in the chemical industry parks in China has posed great threats to the healthy development of the national economy and social stability. For this purpose, this paper conceives a set of dynamic surveillance system against such accidents, which, on the premise of rapidity, simplicity, and reliability principles, revamps and redesign the HYSPLIT air pollution model for the interface, architecture, and functions, wholly integrates with air pollution diffusion model, numerical meteorology forecasting model, and the Geographic Information System (GIS). With the business operation mode, this system can effectively warn against the “uncertainty” of atmospheric pollution events in the chemical industry park, timely access the information about whether any pollutant exceeds allowable limits when an accident occurs. In the response to the emergency accident, it enables quantitative analysis and visual expression on chemical pollutant concentration limits, development trends and health risks, so as to provide an effective business and information support for decision commanders.

Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev) plus pemetrexed/carboplatin (PC) were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients), neutropenia (3 patients), hypertension (1 patient). The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1) and hypertension in 3 patients (grade 1: 2; grade 3: 1). Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

Background and objective Epidermal growth factor receptor (EGFR) gene mutation assay has been applied to select the chemosensitive patients for tyrosine kinase inhibitor (TKI) treatment widely. The aim of this study is to determine the discordance of EGFR mutations between primary and corresponding metastatic tumors in non-small cell lung cancer (NSCLC). Methods Thirty five paired primary tumors and corresponding metastases from Cancer Center of Sun Yatsen University were evaluated for the EGFR mutations by TaqMan RT-PCR analysis. Results EGFR mutations were detected in 29 of 35 primary tumors and in 18 of 35 corresponding metastases. 31.43% (11 of 35, P=0.008) showed discordance in EGFR mutations between primary tumors and corresponding metastases. The EGFR mutation status was consistent in 68.57% (24 of 35) patients. Conclusion EGFR mutations were discordant between the primary tumor and the corresponding metastases in NSCLC.

Background and objective Lung cancer is one of the leading cause of cancer-related death around the world. Surgery is the primary treatment for patients with stage I, II, or IIIA non-small cell lung cancer (NSCLC). However, longterm survival of NSCLC patients after surgery alone is largely unsatisfactory. We undertook to determine whether adjuvant vinorelbine/paclitaxel plus carboplatin prolong overall survival among patients with completely resected stage IIIA-N2 nonsmall cell lung cancer. Methods We randomly assigned patients with completely resected stage IIIA-N2 non-small cell lung cancer to vinorelbine/paclitaxel plus carboplatin or to observation. Results A total of 150 patients (1999-2003) underwent randomization to vinorelbine/paclitaxel plus carboplatin (79 patients) or observation. In both groups, the median age was 57 years, 73 percent were male, and 28 percents had squamous carcinoma. Chemotherapy caused neutropenia in 82 percents of patients (including grade 3 and 4 neutropenia in 42 percent) and there was no treatment-related death observed in this trial. After median follow-up of 39 months (range 1-110), overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (33 months versus 24 months, χ2=4.363, P=0.037), as was disease-free survival (32 months versus 20 months, χ2=5.413, P=0.020). Five-year overall survival rates were 31.1 percent and 19.1 percent, respectively. Conclusion Adjuvant vinorelbine/paclitaxel plus carboplatin have an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected stage IIIA-N2 non-small cell lung cancer.

The stable operation of transistors under a positive bias stress (PBS) is achieved using Hf incorporated into InOx-based thin films processed at relatively low temperatures (150 to 250 °C). The mobilities of the Hf-InOx thin-film transistors (TFTs) are higher than 8 cm2/Vs. The TFTs not only have negligible degradation in the mobility and a small shift in the threshold voltage under PBS for 60 h, but they are also thermally stable at 85 °C in air, without the need for a passivation layer. The Hf-InOx TFT can be stable even annealed at 150 °C for positive bias temperature stability (PBTS). A higher stability is achieved by annealing the TFTs at 250 °C, originating from a reduction in the trap density at the Hf-InOx/gate insulator interface. The knowledge obtained here will aid in the realization of stable TFTs processed at low temperatures.

Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC) remain controversial, we performed a meta-analysis to compare them.An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3-4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M+) and EGFR mutation-negative (EGFR M-) subgroups were pooled. The pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated on the STATA software.Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87-1.21; P = 0.73; I2 = 78.7%, Pheterogeneity