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The synthesis of two three-dimensional coordination frameworks [CdX2(TPA)] (X = Br for 1and I for 2) has been achieved through the assembly of tri(pyridine-3-yl)amine (TPA) with cadmium halides. The compounds are isostructural, and both are fabricated from the infinite linkage of Cd2+and TPA molecules, with halide anions serving as the μ2-bridging and terminally coordinated species. Photoluminescence properties of two coordination polymers have been thoroughly examined, revealing room-temperature phosphorescence with unique decay lifetimes. Remarkably, a yellow glow is achieved for the samples owing to the heavy atom effects. A comprehensive structure–property analysis, complemented by theoretical calculations, has been conducted to elucidate the mechanisms underlying fluorescence and phosphorescence. Furthermore, the photochromic behavior of the Cd–Br-based solid, which is based on an electron transfer process, has also been investigated.

Accurate and reliable detection of uracil-DNA glycosylase (UDG) activity is crucial for clinical diagnosis and prognosis assessment. However, current techniques for accurately monitoring UDG activity still face significant challenges due to the single input or output signal modes. Here, we develop a sequentially activated-dumbbell DNA nanodevice (SEAD) that enables precise and reliable evaluation of UDG activity through primer exchange reactions (PER)-based orthogonal signal output. The SEAD incorporates a double-hairpin structure with a stem containing two deoxyuridine (dU) sites for target recognition and two preblocked primer binding regions for target amplification and signal output. Upon UDG recognition of dU, the SEAD can be cleaved by apurinic/apyrimidinic endonuclease 1 (APE1), generating two different hairpins with exposed primer binding regions. These hairpins serve as templates to initiate the parallel PER, enabling the extending of two different amplification products: a long single-stranded DNA (ssDNA) with repetitive sequences and a short ferrocene-labeled ssDNA with complementary sequences. These products further self-assemble into DNA nano-strings in an orthogonal manner that act as an electrochemiluminescence signal switch, enabling precise detection of low-abundance UDG. This work develops a sequential input and orthogonal output strategy for accurately monitoring UDG activity, highlighting the significant potential in cancer diagnosis and treatment.

ABSTRACTDysregulation in protein homeostasis results in accumulation of protein aggregates, which are sequestered into dedicated insoluble compartments so-called inclusion bodies or aggresomes, where they are scavenged through different mechanisms to reduce proteotoxicity. The protein aggregates can be selectively scavenged by macroautophagy/autophagy called aggrephagy, which is mediated by the autophagic receptor SQSTM1. In this study, we have identified PLK2 as an important regulator of SQSTM1-mediated aggregation of polyubiquitinated proteins. PLK2 is upregulated following proteasome inhibition, and then associates with and phosphorylates SQSTM1 at S349. The phosphorylation of SQSTM1 S349 strengthens its binding to KEAP1, which is required for formation of large SQSTM1 aggregates/bodies upon proteasome inhibition. Our findings suggest that PLK2-mediated phosphorylation of SQSTM1 S349 represents a critical regulatory mechanism in SQSTM1-mediated aggregation of polyubiquitinated proteins.

All-solution processed organic solar cells are the ultimate aim of printable photovoltaics, but their electrical losses arising from poor contact of top electrodes greatly limit efficiency improvement. To solve the problem, a solution-processed hybrid top electrode was constructed using silver nanowires (AgNWs) as the skeleton and ZnO nanoparticles (ZnO-NPs) as the matrix. When constructing the skeleton, a spin-rinsing treatment was first used to reduce the amount of the residual insulating polyvinylpyrrolidone wrapped around the AgNWs to promote intimate contact among the AgNWs in the skeleton. Then, the ZnO-NPs matrix was deposited onto the AgNWs skeleton, bridging the AgNWs skeleton with the underlayer ZnO-NPs electron transporting layer (ETL). The underlayer ZnO-NPs ETL can also induce the growth of the ZnO-NPs matrix to minimize lattice mismatch, which creates additional transport channels from the ETL to the AgNWs skeleton for charge collection. As a result, the obtained electrode significantly enhances the electrical contact in the device, thus delivering record power conversion efficiencies of 16.04% and 14.54% for rigid and flexible all-solution processed OSCs, respectively.

Background: While multiple system atrophy (MSA) presents with high heterogeneous motor and nonmotor symptoms, the associations between clinical phenotypes and prognosis are unclear.Objective: We aimed to evaluate clinical phenotypes of MSA using data-driven approach and measure the impact of phenotypes on survival and bedbound status.Methods: 193 MSA patients were recruited from Xuanwu Hospital Capital Medical University, whose history, motor and non-motor symptoms were examined using cluster analysis. Ninety-five participants were followed-up via telephone after a mean of 31.87 months. We employed Kaplan– Meier analysis to examine survival and performed Cox and logistic regression analyses to identify factors associated with survival and bedbound status.Results: We identified four clinical profiles of MSA: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse. The overall median survival was 7.75 years (95% CI 7.19–8.31). After adjusting for years from symptom onset to diagnosis, age and sex, patients in the malignant diffuse and rigid akinetic-dominant clusters had greater risk of death than sleep and mood disorder-dominant cluster. Furthermore, patients in the malignant diffuse and rigid akinetic-dominant clusters had higher risk of being bedbound than cerebellar symptom-dominant cluster.Conclusions: The malignant diffuse and sleep and mood disorder-dominant were identified besides the two classical subtypes, parkinsonism, and cerebellar symptom-variant. Patients with rigid-akinetic motor profiles have a worse prognosis than cerebellar symptom-dominant profiles in general. Diffuse symptoms, especially postural instability, and cognitive alterations at diagnosis, indicate rapid functional loss and disease progression. The different profiles and prognoses might indicate varied underlying pathological mechanisms.

With the acceleration of urbanisation, the problem of water resource shortage is becoming increasingly serious. Currently, the water use situation in Chinese cities is severe and the contradiction between the supply and demand of water resources is prominent, which has become one of the main factors restricting sustainable development of cities. Traditional research on water-saving landscape design focuses mainly on the analysis of the efficiency of water resource utilisation within a single area or city. The scope of the research is limited and the research methods are individual, which cannot fully meet the current needs of sustainable urban water-saving landscape design. The improved variable scale optimisation algorithm has become an indispensable tool in modern landscape design and would play a more important role in landscape design and ecological environment protection in the future. In response to the shortcomings of traditional variable-scale optimisation algorithms in solving the optimisation problem of water-saving landscape design for ecological sustainable development, this article would use an improved variable-scale optimisation algorithm to study the water-saving landscape design for ecological sustainable development in Community X, City B, Province A. The research results indicated that there were three experts who rated the effect of the water saving landscape design of the first group of designers as good or above, accounting for 37.5 %. The number of people who rated the effectiveness of water-saving landscape design in the second group as good or higher was 8, representing 100 %. The improved variable-scale optimisation algorithm could effectively improve the application of water-saving landscape design in ecological sustainable development.

By aiming at addressing the left-turning problem of an autonomous vehicle considering the oncoming vehicles at an urban unsignallized intersection, a hierarchical reinforcement learning is proposed and a two-layer model is established to study behaviors of left-turning driving. Compared with the conventional decision-making models with a fixed path, the proposed multi-paths decision-making algorithm with horizontal and vertical strategies can improve the efficiency of autonomous vehicles crossing intersections while ensuring safety.

Byline: Yin. Xu, Xiao-yan. Fei, You-hua. Xue, Xue-mei. Wang, Xiao-yan. Wang, Yu-ting. Zheng, Ke. Chen, Jing-jing. He, Xiu-hong. Ren, Lei. Pan, Ling. Wang, Duo. Qian, Wei-feng. Li, Yan. Liang, Yan. [...]

Attitudes are crucial in understanding people’s travel behavior. In this paper, affective and cognitive components are simultaneously considered, where affective attitude refers to feelings and emotions that are evoked from traveling by particular mode, and the cognitive component of an attitude contains the attributes and beliefs associated with that mode. Based on a mobility survey for the Longitudinal Internet Studies for the Social Sciences (LISS) panel, this study endeavors to identify the relative importance of attitude components on travel behavior related to car, public transport, and bike, based on which the nature of mode-specific travel behavior could be determined. Being confined to the psychosocial sphere, the target mode-specific travel behavior will be defined as instrumental if a comparatively strong impact from cognitive attitude is observed and as consummatory if affective attitude has a larger influence on travel behavior. The identified behavioral nature is further examined across people with diverse characteristics. The dominant role of affective attitude suggests car travel behavior to be highly consummatory, which applies for most groups. Public transport travel is performed as an instrumental behavior basically determined by cognitive attitude, and this outcome considerably varies across population groups. Travel by bike is carried out by all the groups firmly as consummatory, and the negative effect of cognitive attitude on bike travel basically reflects people’s motivation to fulfill social desirability, which leads to a behavioral violation. The analysis offers a further understanding of travel behavior, which might provide useful implications for transportation administration.

Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosiscomplex and is highly infectious. Therefore, precautionary measures should be implemented prior to dental treatment to reduce the risk of infection to staff and other patients. Dental history and examination have a role in identification of TB infection. Complex medical history poses a challenge to safe patient management in a dental setting, and close liaison between different disciplines in managing these patients is of paramount importance. This article explores the classical clinical features of pulmonary TB, its oral manifestations and the dental management of patients with active and latent TB.CPD/Clinical Relevance:Clinicians should be aware of the clinical features and dental management of patients with active and latent TB.

As the capacity of lithium-ion batteries gradually reaches its limit, the high-capacity characteristics of lithium metal batteries (LMBs) make them one of the most promising electrochemical energy storage devices currently. However, uncontrolled lithium dendrite growth can cause poor cell performance and severe safety issues, seriously slowing down the commercialization of LMBs. Transition metals (TMs) are lithiophilic materials that effectively stabilize lithium metal anode (LMA) and inhibit dendrite growth. Herein, the growth of lithium dendrites and the performance of TMs in stabilizing lithium metals are comprehensively discussed in this review. First, we elucidated the formation mechanisms of lithium dendrite, and we put forward several strategies to suppress lithium dendrite formation based on the understanding of these mechanisms. Then, the application of TMs and their compounds to stabilize LMA and their corresponding mechanisms are comprehensively clarified. Last, further research perspectives of TMs in stabilizing LMA are emphasized in detail.

Olanzapine (OLZ) is a widely prescribed antipsychotic drug with a relatively ideal effect in the treatment of schizophrenia (SCZ). However, its severe metabolic side effects often deteriorate clinical therapeutic compliance and mental rehabilitation. The peripheral mechanism of OLZ-induced metabolic disorders remains abstruse for its muti-target activities. Endoplasmic reticulum (ER) stress is implicated in cellular energy metabolism and the progression of psychiatric disorders. In this study, we investigated the role of ER stress in the development of OLZ-induced dyslipidemia. A cohort of 146 SCZ patients receiving OLZ monotherapy was recruited, and blood samples and clinical data were collected at baseline, and in the 4th week, 12th week, and 24th week of the treatment. This case-control study revealed that OLZ treatment significantly elevated serum levels of endoplasmic reticulum (ER) stress markers GRP78, ATF4, and CHOP in SCZ patients with dyslipidemia. In HepG2 cells, treatment with OLZ (25, 50 μM) dose-dependently enhanced hepatic de novo lipogenesis accompanied by SREBPs activation, and simultaneously triggered ER stress. Inhibition of ER stress by tauroursodeoxycholate (TUDCA) and 4-phenyl butyric acid (4-PBA) attenuated OLZ-induced lipid dysregulation in vitro and in vivo. Moreover, we demonstrated that activation of PERK-CHOP signaling during ER stress was a major contributor to OLZ-triggered abnormal lipid metabolism in the liver, suggesting that PERK could be a potential target for ameliorating the development of OLZ-mediated lipid dysfunction. Taken together, ER stress inhibitors could be a potentially effective intervention against OLZ-induced dyslipidemia in SCZ.

C18H12N2O4, monoclinic, P21/c(no. 14), a= 12.3075(7) Å, b= 6.5075(3) Å, c= 18.4929(9) Å, β= 92.883(4)°, V= 1,479.24(13) Å3, Z= 4, Rgt(F) = 0.0394, wRref(F2) = 0.1047, T= 173 K.

Objective: The aim of this study is to create and validate a nomogram model for predicting complications of esophageal injury post-esophagoscopy in patients with esophageal foreign bodies (EFB). Methods: We examined 303 patients who underwent esophagoscopy from January 2019 to December 2022 at a leading hospital in Anhui, known for its expertise in otorhinolaryngology-head and neck surgery. The patients were split into a modeling group and a validation group in a 7:3 ratio. Logistic regression analysis was employed to determine the risk factors for esophageal injury after undergoing esophagoscopy in patients with EFB. Based on these factors, a nomogram risk prediction model was developed and assessed using a goodness of fit test. Results: Logistic regression analysis revealed that the type of foreign body, failure of gastroscopic retrieval, duration of lodgment, lodgment site, and presence of combined cardiovascular and cerebrovascular diseases were significant (p< 0.05) independent risk factors for esophageal injury following esophagoscopy for EFB. The area under the ROC curve for the training set was 0.850, and the Hosmer–Lemeshow goodness of fit test resulted in a pvalue of 0.908. For the validation set, the area under the ROC curve was 0.848, and the Hosmer–Lemeshow test gave a pvalue of 0.665. The calibration curve showed a close alignment between the predicted and observed values. Conclusion: The type of foreign body, duration of lodgment, lodgment site, previous failure of gastroscopic retrieval, and history of combined cardiovascular and cerebrovascular diseases are significant risk factors for esophageal injury following EFB esophagoscopy. This model accurately quantifies the risk of esophageal injury after EFB esophagoscopy.

We evaluated the safety and efficacy of a novel protocol for haploidentical stem cell transplantation (haplo-SCT) in 312 patients with hematologic malignancies. The protocol evolved from the Beijing platform replacing ATG with ATLG; adding Fludarabine and removing cytarabine and Simustine. GVHD prophylaxis combined Basiliximab and low-dose cyclophosphamide post-transplant; overall, the conditioning duration was shortened. Median times to neutrophil and platelet recovery were both 11 days. Graft rejection occurred in 0.96% of patients. Cumulative incidences of grades II–IV and III–IV acute GVHD by day 200 were 35.3% and 8.9%, respectively. Probabilities of total and extensive chronic GVHD at 2 years were 40.7% and 14.7%. CMV viremia was observed in 35.6% of patients, with a 1.9% 100-day CMV pneumonia incidence and no CMV-related mortality. Cumulative incidences of non-relapse mortality at 100 days, 1 year, and 2 years were 2.9, 4.4, and 6.6%. The 4-year OS, RFS, and GRFS rates were 78.9, 70.7, and 47.3%. Older recipient age was associated with higher NRM, while positive pre-transplant MRD predicted worse OS, RFS, and higher relapse incidence. Our novel protocol for haplo-SCT is associated with low infection rates and acceptable risks of graft failure, severe GVHD, and mortality, representing a safe and effective haploidentical transplantation strategy.

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescensand Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-β1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 μM) dose-dependently decreased TGF-β1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg–1·d–1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.

Aminoacyl-tRNA synthetases (aaRSs) are ubiquitously expressed, essential enzymes, synthesizing aminoacyl-tRNAs for protein synthesis. Functional defects of aaRSs frequently cause various human disorders. Human KARSencodes both cytosolic and mitochondrial lysyl-tRNA synthetases (LysRSs). Previously, two mutations (c.1129G>A and c.517T>C) were identified that led to hearing impairment; however, the underlying biochemical mechanism is unclear. In the present study, we found that the two mutations have no impact on the incorporation of LysRS into the multiple-synthetase complex in the cytosol, but affect the cytosolic LysRS level, its tertiary structure, and cytosolic tRNA aminoacylation in vitro. As for mitochondrial translation, the two mutations have little effect on the steady-state level, mitochondrial targeting, and tRNA binding affinity of mitochondrial LysRS. However, they exhibit striking differences in charging mitochondrial tRNALys, with the c.517T>C mutant being completely deficient in vitroand in vivo.We constructed two yeast genetic models, which are powerful tools to test the in vivoaminoacylation activity of KARSmutations at both the cytosolic and mitochondrial levels. Overall, our data provided biochemical insights into the potentially molecular pathological mechanism of KARSc.1129G>A and c.517T>C mutations and provided yeast genetic bases to investigate other KARSmutations in the future.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situexcitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+and Mn2+released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

Crack-based flexible strain sensors with ultra-high sensitivity under tiny strain are highly desired for environmental perception and motion detection of novel flexible and miniature robots. However, previously reported methods for fabricating crack patterns have often sacrificed the cyclic stability of the sensor, leading to a trade-off relationship between the sensitivity and the cyclic stability. Here, a universal and simple strategy based on fatigue loading with an ultra-large cumulative strain of up to ∼1.2 × 107%, rather than the traditionally quasi-static pre-overloading methods, is proposed to introduce channel cracks in the sensing layer without sacrificing the cyclic stability. The developed flexible strain sensors exhibit high strain-sensitivity (gauge factor = 5798) under tiny strain (< 3%), high cyclic stability (15 000 cycles) and a low strain detecting limit (0.02%). Furthermore, a leaf-like mechanosensor is developed using the fatigue crack-based strain sensor for the realization of multifunctional applications in environment perception and micro-motion detection. Brilliant airflow sensing performance with a wide sensing range (0.93–11.93 m s−1) and a fast response time (0.28 s) for amphibious applications is demonstrated. This work provides a new strategy for overcoming limits of crack-based flexible strain sensors and the developed leaf-like mechanosensor shows great application potential in miniature and flexible reconnaissance robots.

MADS-boxgenes play a vital role in the vegetative and reproductive growth of plants. In this study, a MiAGL1gene was cloned and identified from mango (Mangifera indicaL.). The DNA sequence of AGAMOUS-LIKE1(MiAGL1) was 8741 bp in length, including a 723 bp open reading frame and encoding 241 amino acids. MiAGL1belongs to the MADS-box family. This gene was expressed not only in vegetative tissues but also in floral organs, and the highest expression level was found in flowers. MiAGL1was expressed in leaves at different floral developmental stages, but the peak appeared at the floral organ differentiation stage. MiAGL1was present in the cell membrane and nucleus. Ectopic expression of MiAGL1in Arabidopsisresulted in significant early flowering under long-day conditions. Overexpression of MiAGL1resulted in abnormal flowering and silique morphology, such as a decrease or absence of petals, smaller petals, and shorter, bent or distorted capsules. The endogenous Arabidopsis thalianaflowering-related genes FT, AP1, and SEPwere significantly upregulated, and AtSVPwas downregulated in the transgenic lines. Therefore, our data showed that the MiAGL1gene may play a crucial role in flowering time regulation and floral organ identity.

As an important byproduct of rice bran in the rice milling industry, rice bran oil (RBO) has become increasingly popular in daily diets in recent years. Cadmium (Cd) is a toxic element and easily accumulates in rice bran; thus, it is of great significance to investigate Cd occurrence in RBOs for the sake of public health. In this study, an ultrasound-assisted extraction procedure method using diluted acid followed by inductively coupled plasma mass spectrometry was developed for the determination of Cd in RBOs. Key parameters that affect the ultrasound-assisted extraction of Cd, namely, ultrasonic power, acid extractant, extractant/oil ratio and sonication time, were investigated in detail. Under the optimized extraction conditions with inductively coupled plasma mass spectrometry (ICP-MS) determination, a limit of detection of 0.08 ng g−1, a precision of 5.1%, and recoveries in the range of 97–102% were achieved for the determination of Cd in RBOs. The proposed method is simple, fast and accurate and was applied to analyze RBOs available on the market. The survey showed that the Cd residue was very low, so consumption of RBOs does not pose a risk regarding Cd exposure.

For two nondecreasing sequences d=(d1,d2,⋯,dn)and d′=(d1′,d2′,⋯,dn′)of nonnegative integers, we say that d′majorizes d, denoted by d′⩾d, if di′⩾difor 1⩽i⩽n. An r-uniform hypergraphic sequence d=(d1,d2,⋯,dn)is forcibly k-connected if every r-uniform hypergraph with degree sequence dis k-connected. In this paper, we give a sufficient condition for an r-uniform hypergraphic sequence to be forcibly k-connected and observe that if an r-uniform hypergraphic sequence dsatisfies the condition (which implies dis forcibly k-connected); then, any r-uniform hypergraphic sequence d′⩾dalso satisfies the condition. As a corollary, we obtain the condition of Bondy for forcibly k-connected graphic sequences.

Chemodynamic therapy (CDT) is a promising cancer treatment strategy. However, mild acidic pH, insufficient H2O2content, and overexpressed glutathione (GSH) in the tumor microenvironment (TME) severely impair CDT efficiency. In this study, a novel therapeutic nanosystem (Cu/ZIF-8/Vc-Ca/HA) was constructed for H2O2self-supply and GSH depletion co-enhanced CDT. Typically, calcium ascorbate (Vc-Ca) loaded on the surface of Cu2+-doped ZIF-8 (Cu/ZIF-8) was designed as an original source for H2O2generation, and a hyaluronic acid (HA) shell was subsequently coated to act as a tumor-targeted “guide” and protective layer. Along with the HA shell disintegrated in the TME, exposed Cu/ZIF-8/Vc-Ca dissociated in the tumor acidic microenvironment, thus triggering the release of Vc-Ca and Cu2+. Vc-Ca selectively produced H2O2in tumor cells, which provided abundant H2O2for boosting Fenton-like reactions. Meanwhile, the released Cu2+could get converted into Cu+by consuming excess intracellular GSH, which could reduce the tumor antioxidant capability of the nanosystem. Moreover, byproduct Cu+reacted with abundant H2O2by a highly efficient Fenton-like reaction to generate toxic OH. Biological assays indicated that the Cu/ZIF-8/HA@Vc-Ca nanosystem showed significant anticancer activity by enhancing the CDT process. This study may provide a new strategy for improving the effectiveness of CDT.

Currently, deep learning (DL) methods represented by convolutional neural networks (CNNs) or Transformers are of great interest in hyperspectral image (HSI) classification. And recent works show that hybrid models using CNN and Transformer modules are expected to achieve better performance than when they are used alone. However, these hybrid models applied to HSI classification consider the combination of 2-D CNN and Transformer, which makes the models have high computational complexity. And the information of multiple spectral dimensions different from ordinary RGB images has not been fully excavated. Based on this, we propose, a double branch Convolution-Transformer network (DBCTNet). Specifically, a MSpeFE module is used for multiscale spectral feature extraction at the early stage of the proposed network. Then, a ConvTE block is designed to improve the original Transformer encoder (TE), where a Conv spectral projection unit and a convolutional multihead self-attention (CMHSA) unit are proposed to extract spatial and global spectral features. A double branch module is further built based on 3-D CNN and ConvTE. This module can fully integrate spatial and local–global spectral features, while also having low computational complexity. Experiment results on four public datasets, Pavia University, Houston, WHU-Hi-LongKou, and HuangHeKou, show that DBCTNet achieves satisfactory performance with a small number of parameters and relatively excellent efficiency compared to nine other networks. The implement of DBCTNet will be available publicly at (https://github.com/xurui-joei/DBCTNet).

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ABSTRACTIntroductionComputer-aided drug design (CADD) is a computational approach used to discover, develop, and analyze drugs and active molecules with similar biochemical properties. Molecular simulation technology has significantly accelerated drug research and reduced manufacturing costs. It is an optimized drug discovery method that greatly improves the efficiency of novel drug development processes.AreascoveredThis review discusses the development of molecular simulations of effective cancer inhibitors and traces the main outcomes of in silicostudies by introducing representative categories of six important anticancer targets. The authors provide views on this topic from the perspective of both medicinal chemistry and artificial intelligence, indicating the major challenges and predicting trends.Expert opinionThe goal of introducing CADD into cancer treatment is to realize a highly efficient, accurate, and desired approach with a high success rate for identifying potent drug candidates. However, the major challenge is the lack of a sophisticated data-filtering mechanism to verify bottom data from mixed-quality references. Consequently, despite the continuous development of algorithms, computer power, and interface optimization, specific data filtering mechanisms will become an urgent and crucial issue in the future.

A series of Alx(CoCrNi)100-x(x= 0–21 at.%) medium-entropy alloys (MEAs) were designed and prepared to investigate the effects of Al addition on the microstructures and tensile properties. The results reveal that the lattice structure changes from the initial single FCC structure (x< 10 at.%), to the FCC and disordered BCC structures (x= 10 and 11 at.%), then to the FCC and BCC/B2 structures (11 < x< 21 at.%), finally to the duplex BCC/B2 structures (x≥ 21 at.%) with increasing Al addition. Consistent with microstructures, significant changes also occur in the corresponding tensile properties with Al addition, showing that the strength increases and the ductility decreases with increasing Al addition. Especially, the Al-15 MEA exhibits an acceptable balance of strength and ductility. Furthermore, the mechanism of microstructure evolution and the correlation between microstructures and tensile properties were also discussed and clarified.

Endobronchial ultrasound bronchoscopy (EBUS) and needle confocal laser endomicroscopy (nCLE) are techniques for screening benign and malignant lesions of the hilar and mediastinal lymph node (HMLN). This study investigated the diagnostic potential of EBUS, nCLE, and combined EBUS and nCLE in HMLN lesions. We recruited 107 patients with HMLN lesions who were examined by EBUS and nCLE. A pathological examination was performed, and the diagnostic potential of EBUS, nCLE, and combined EBUS‐nCLE approach was analyzed according to the results. Among the 107 cases of HMLN lesions, 43 cases were benign and 64 cases were malignant on pathological examination, 41 cases were benign and 66 cases were malignant on EBUS examination; 42 cases were benign and 65 cases were malignant on nCLE examination; 43 cases were benign and 64 cases were malignant on combined EBUS‐nCLE examination. The combination approach had 93.8% sensitivity, 90.7% specificity, and 0.922 area under the curve, which was higher than those of EBUS (84.4%, 72.1%, and 0.782, respectively) and nCLE diagnosis (90.6%, 83.7%, and 0.872, respectively). The combination approach had a higher positive predictive value (0.908), negative predictive value (0.881), and positive likelihood ratio (10.09) than that of EBUS (0.813, 0.721, and 3.03, respectively) and nCLE (0.892, 0.857, and 5.56, respectively), whereas, the negative likelihood ratio was lower than that for EBUS (0.22) and nCLE (0.11). No serious complications occurred in patients with HMLN lesions. To summarize, the diagnostic efficacy of nCLE was better than EBUS. The EBUS‐nCLE combination is a suitable approach for diagnosing HMLN lesions.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, and lacks effective treatment. The aberration of WNT pathway underlies many pathological processes including cardiac fibrosis and hypertrophy, while porcupine is an acyltransferase essential for the secretion of WNT ligands. In this study we investigated the role of WNT signaling pathway in HFpEF as well as whether blocking WNT signaling by a novel porcupine inhibitor CGX1321 alleviated HFpEF. We established two experimental HFpEF mouse models, namely the UNX/DOCA model and high fat diet/L-NAME (“two-hit”) model. The UNX/DOCA and “two-hit” mice were treated with CGX1321 (3 mg·kg−1·d−1) for 4 and 10 weeks, respectively. We showed that CGX1321 treatment significantly alleviated cardiac hypertrophy and fibrosis, thereby improving cardiac diastolic function and exercise performance in both models. Furthermore, both canonical and non-canonical WNT signaling pathways were activated, and most WNT proteins, especially WNT3a and WNT5a, were upregulated during the development of HEpEF in mice. CGX1321 treatment inhibited the secretion of WNT ligands and repressed both canonical and non-canonical WNT pathways, evidenced by the reduced phosphorylation of c-Jun and the nuclear translocation of β-catenin and NFATc3. In an in vitro HFpEF model, MCM and ISO-treated cardiomyocytes, knockdown of porcupine by siRNA leads to a similar inhibitory effect on WNT pathways, cardiomyocyte hypertrophy and cardiac fibroblast activation as CGX1321 did, whereas supplementation of WNT3a and WNT5a reversed the anti-hypertrophy and anti-fibrosis effect of CGX1321. We conclude that WNT signaling activation plays an essential role in the pathogenesis of HFpEF, and porcupine inhibitor CGX1321 exerts a therapeutic effect on HFpEF in mice by attenuating cardiac hypertrophy, alleviating cardiac fibrosis and improving cardiac diastolic function.

The mechanical behavior of VCoNi medium-entropy alloys with five different grain sizes at three different temperatures was investigated. The VCoNi alloys with different grain sizes exhibit a traditional strength–ductility trade-off at 77 K, 194 K and 293 K. Both the yield strength and the uniform elongation of the VCoNi alloys with similar grain size increase with decreasing the deformation temperature from 293 to 77 K. Obvious strain hardening rate recovery characterized by an evident up-turn behavior at stage II is observed in VCoNi alloys with the grain size above 11.1 μm. It is found that the extent of the strain hardening rate recovery increases with increasing grain size or decreasing deformation temperature. This may mainly result from the faster increase in the dislocation multiplication rate caused by the decrease in the dislocation mean free path, the decrease in the absorption of dislocations by grain boundaries and the dynamic recovery from the cross-slip with increasing grain size, as well as the suppressed dynamic recovery at cryogenic temperatures. The critical grain sizes for the occurrence of the recovery of strain hardening rate are determined to be around 9.5 μm, 8.3 μm and 3 μm for alloys deformed at 293 K, 194 K and 77 K, respectively. The basic mechanism for the strain hardening behavior of the VCoNi alloys associated with grain size and deformation temperature is analyzed.

Objective: Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. Methods: The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/β-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and β-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. Results: Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/β-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. Conclusion: LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

ZrO2catalysts with different crystal structures show different catalytic performance in isobutene synthesis from CO hydrogenation reaction. Although monoclinic ZrO2has the best catalytic performance in isobutene synthesis from syngas, its isosynthesis active sites are still not well understood. To better understand the critical parameters that influence syngas to isobutene reactions over ZrO2catalysts, we prepared a series of ZrO2catalysts with distinct crystal structures and investigated their catalytic performance of CO hydrogenation to isobutene. Compared with tetragonal and amorphous ZrO2catalysts, there are more coordinatively unsaturated Zr and O sites on the surface of monoclinic ZrO2catalyst. The coordinatively unsaturated Zr sites are the active sites of CO adsorption and activation, which is beneficial to CO conversion. The coordinatively unsaturated O sites provide more basic sites for isobutene formation. Furthermore, the coordinatively unsaturated Zr and O sites on monoclinic ZrO2catalyst surface may inhibit electron transfer to formate species formed during reaction, resulting in weak adsorption on catalyst surface of formate species. The weakly adsorbed formate species on the surface of monoclinic ZrO2catalyst is favorable for the synthesis of isobutene from CO hydrogenation reaction.

Objective: Contact precautions, especially the initiation of isolation, are important measures to prevent and control multidrug-resistant organisms (MDROs). However, the implementation in clinical practice remains weak. This study aimed to analyze the impact of multidisciplinary collaborative intervention on isolation implementation in multidrug-resistant infection, and determine the factors that affect the implementation of isolation measures. Methods: A multidisciplinary collaborative intervention related to isolation was conducted at a teaching tertiary hospital in central China on November 1, 2018. The information of 1338 patients with MDRO infection and colonization at 10 months before and after the intervention was collected. Then, the issuance of isolation orders was retrospectively analyzed. Univariate analysis and multivariate logistic regression analysis were performed to analyze the factors that affected the isolation implementation. Results: The overall issuance rate of isolation orders was 61.21%, which increased from 33.12% to 75.88% (P&lt;0.001) after the implementation of the multidisciplinary collaborative intervention. The intervention (P&lt;0.001, OR=0.166) was a promoting factor for the issuance of isolation orders, in addition to the length of stay (P=0.004, OR=0.991), department (P=0.004), and microorganism (P=0.038). Conclusion: The isolation implementation remains far lower than policy standards. Multidisciplinary collaborative interventions can effectively improve the compliance to isolation measures implemented by doctors, thereby promoting the standardized management of MDROs, and providing reference for further improving the quality of hospital infection management.

Th aim of this study was to analyze acute exacerbation of chronic obstructive pulmonary disease (AECOPD) readmission events and to determine whether neutrophil-to-lymphocyte ratio (NLR) and bilirubin levels were associated with readmission after discharge due to AECOPD.

To explore the active metabolites from Aspergillus, we have discovered five undescribed tricyclic or tetracyclic indole alkaloids aspergillines K–O (1–5) and four known analogues (6–9) from the strain of Nicotiana tabacum-derived Aspergillus versicolorYNCA0363. The α-amino group derived from tryptophan in isolates 1–6was changed to an oxygen atom, which is uncommon in the reported analogues. To the best of our knowledge, 4and 5represent the first examples of indole alkaloids possessing an isochromene moiety. Compounds 1and 3showed obvious anti-tobacco mosaic virus (TMV) activities with inhibition rates of 43.6% ± 2.2 and 58.5% ± 2.8 at the concentration of 20 μM, respectively, which were significantly higher than that of the positive control. Compound 3also showed excellent potential of inducing systemic acquired resistance. Furthermore, compound 3can increase the activities of two reactive oxygen species-scavenging enzymes, peroxidase and superoxide dismutase, and enhance tobacco resistance to TMV. Molecular docking results showed that compound 3exhibits a stronger interaction with TMV-helicase, and showed higher antiviral activities than others. This work revealed that the above indole alkaloids, especially 3, could induce resistance in tobacco plants against the viral pathogen TMV.

This article investigates the event-triggered model predictive control (ETMPC) problem for nonlinear systems with the bounded disturbance. First, a novel adaptive event-triggered mechanism without Zeno behaviors, in which the triggering threshold can constantly be adjusted with the change of the system state, is proposed for computational load reduction. Then, an adaptive prediction horizon update strategy is proposed to further reduce the computational complexity of the optimization problem at each triggering instant. Moreover, a dual-mode ETMPC algorithm is developed, and sufficient conditions on the algorithm feasibility and the system robust stability are provided. Through a simulation example, the results show that the proposed scheme can use fewer computational resources and a shorter calculation time for solving the optimization problem while ensuring satisfactory system performances than the existing ones.

Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolorunder the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A–C (1–3) and asperheptatides A–D (4–7) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A (8). The structure of 8was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey’s method. The semisynthetic transformation of 1into 8was successfully achieved and the reaction conditions were optimized. Additionally, a series of new derivatives (10−19) of asperversiamide A (1) was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosisH37Ra. The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.

Although great efforts have been made to elucidate the pathological mechanisms of renal diseases and potential prevention and treatment targets that would allow us to retard kidney disease progression, we still lack specific and effective management methods. Epigenetic mechanisms are able to alter gene expression without requiring DNA mutations. Accumulating evidence suggests the critical roles of epigenetic events and processes in a variety of renal diseases, involving functionally relevant alterations in DNA methylation, histone methylation, RNA methylation, and expression of various non-coding RNAs. In this review, we highlight recent advances in the impact of methylation events (especially RNA m6A methylation, DNA methylation, and histone methylation) on renal disease progression, and their impact on treatments of renal diseases. We believe that a better understanding of methylation modification changes in kidneys may contribute to the development of novel strategies for the prevention and management of renal diseases.

The application of blockchain to trace product information has received extensive attention when consumers purchase products through E-commerce platforms. By combining two selling modes (i.e., reselling and agency selling modes) with blockchain, four models are found to analyse the impact of blockchain on the decisions and selling mode selection in a platform supply chain (PSC). Our conclusions show that: when the fixed fee is low, the manufacturer would introduce blockchain, which increases the demand and benefits the retailer and the platform. The manufacturer will choose agency selling mode when the commission rate is low with or without blockchain; otherwise, he prefers reselling mode, which will hurt the benefits of the retailer and the platform. This is opposite to that of the platform. In general, when the fixed fee of blockchain introduction and commission rate satisfy some conditions, the agency selling mode with blockchain can achieve win-win outcomes for PSC and consumers.

Small specimens are increasingly being used in getting mechanical properties directly when there are limited materials to facilitate standard specimens, which play a great role in the rapid measurement of mechanical properties and residual life assessment of in-service reactor components. Although tensile and fatigue properties of the small specimens are investigated extensively, theoretical models for describing the mechanical properties of small specimens need to be established. Here, we conduct a systematic investigation of tensile and fatigue properties of pure Cu specimens with thicknesses ranging from 3 to 0.2 mm. The results show that the decrease in uniform elongation of the 0.2 mm-thick specimens is mainly due to the effects of grain boundary and free surface on the strain hardening rate. A modified theoretical model correlated with the ratio of the surface grain layer thickness to the grain size is proposed to predict variation in yield strength of the small specimens more accurately. Furthermore, the mechanism for the difference in fatigue life between the 0.2 mm-thick specimen and other thicker specimens is elucidated. The Basquin equation-based model is presented as a potential way to evaluate the fatigue life of metals using small specimens.

Hybrid battery thermal management system (BTMS) coupling phase change material (PCM) with liquid cooling channels (LCCs) is promising for battery temperature control. However, the contact modes of PCM and LCC with the batteries are critical for battery thermal management but they are rarely studied. In this work, three contact modes of PCM and LCCs with batteries are studied, where only PCM directly contact with batteries in Type 1, PCM and LCCs contact with batteries alternatively in Type 2, while PCM and LCCs contact with batteries separately in Type 3. Merits and demerits of the different contact modes are systematically analyzed. Insertion of ultrathin PCM layer between LCCs and batteries is proposed to alleviate the temperature non-uniformity resulted from low temperature zone at battery and channel interface in Type 2 and 3. The improved BTMSs with suitable PCM layer thickness (0.2 mm) could control Tmaxand ∆Tmaxat 36.12 °C and 2.91 °C in Type 2 and 36.09 °C and 3.19 °C in Type 3 even under a high discharge rate of 5C. Environmental adaptabilities of the hybrid BTMSs are also compared under various ambient temperatures and convection conditions. The results highlight the significance of hybrid BTMS, especially in the design of improved Type 2 with ultrathin PCM layer, for the development of advanced cooling systems.

Byline: Tao. Jia, Qing-Qing. Cao, Xue-Mei. Chen, Feng-Lei. Xu Objective: The aim of this study was to investigate the effect of the Akt inhibitor Src-homology 5 (SH-5) on the proliferation [...]

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