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Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Stingdeficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases.

Multifunctional group compounds, 2-acyl-3-sulfonamidobut-2-enoates, are efficiently constructed using solid calcium carbide as an alkyne source through the simultaneous formation of two bonds in one step. The salient features of this protocol are the use of an inexpensive, abundant, and easy-to-use alkyne source as a substitute for flammable and explosive gaseous acetylene, low-cost catalyst, mild conditions, wide substrate scope, high stereoselectivity, satisfactory yield, and simple manipulation. This method can also be extended to the gram scale.

Byline: Xiaoying. Han, Min. Meng, Tiehong. Zhang, Jiao. Wang, Guanghui. Huang, Yang. Ni, Wenhong. Li, Jianjian. Dai, Xia. Yang, Xin. Ye The programmed cell death 1 (PD-1) inhibitor - camrelizumab [...]

Byline: Jiao. Wang, Likuan. Hu, Xia. Yang, Xin. Ye, Yang. Ni, Min. Meng, Guanghui. Huang, Tiehong. Zhang, Wenhong. Li, Xiaoying. Han, Zhigang. Wei, Jianjian. Dai, Zhigeng. Zou Purpose: To reveal [...]

Background: Epilepsy is a chronic neurological condition with various underlying mechanisms. It is known to affect a multitude of people across the globe, regardless of age and gender. Seizures associated with epilepsy involve the participation of stimulatory glutamatergic mechanisms along with inflammation and oxidative damage.Objectives: In this investigation, the anti-epileptic effect of scutellarein, a phytochemical compound isolated from Erigeron breviscapus(Vant.), has been evaluated in the pentylenetetrazol (PTZ) kindling epilepsy model in mice.Materials and Methods: The experimental mice were categorized into six groups with six animals in each. The first control group was given normal saline. The second group was provided only PTZ through an intraperitoneal route to induce seizures. The third and fourth groups received two oral doses of scutellarein (10 and 20 mg/kg) before 30 min of PTZ induction. Diazepam was intraperitoneally administered to the fifth group as a positive control. The impact of scutellarein on the duration and initiation of clonic and tonic convulsion, mortality, kindling, mobility, and immobility duration in PTZ-induced rodents was estimated. Also, the impact of scutellarein on oxidative stress markers and antioxidant and inflammatory marker levels was also evaluated.Results: Scutellarein treatment was able to reduce PTZ-induced seizures in mice. In PTZ animals, scutellarein lowered the seizure severity by suppressing the onset and duration of convulsions. Scutellarein successfully modulated the PTZ-provoked changes in gamma-aminobutyric acid (GABA), glutamate, and dopamine levels, as well as Ca2+ATPase and Na+K+ATPase activity.Conclusion: Furthermore, it remarkably reduced the oxidative stress markers and decreased the contents of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in PTZ animal brain tissues, confirming its anti-convulsant potential.

In response to climate change, many countries are introducing agricultural insurance. But will farmers buy more agricultural insurance as climate change deepens? The literature has shown that climate change has a significantly positive impact on agricultural insurance. Using data from China over the period 2012–2021, we examine the effects of climate change (CC) on agricultural insurance coverage (AIC). We find that CC does not always have a positive impact on AIC; instead, farmers’ insurance choices depend on the difference between their total costs and earnings. Only when total earnings are greater than total costs will farmers choose agricultural insurance. Compensation and subsidies are components of total earnings and premiums are components of total costs. They are affected by the government's insurance policies and charging standards and insurance companies' compensation schemes. This study examines the factors that affect farmers’ insurance choices and recommends strategies for improving agricultural insurance.

This experiment aimed to discuss and reveal the effect and mechanism of mannanase on intestinal inflammation in broilers triggered by a soybean meal diet. In this experiment, 384 Arbor Acres broilers at 1 d old were randomly divided into 3 treatment groups. The broilers were fed a corn-soybean meal basal diet, a low-energy diet (metabolizable energy reduced by 50 kcal/kg), and a low-energy diet supplemented with 100 mg/kg mannanase for 42 d. The low-energy diet increased feed conversion ratio from 0 to 42 d, reduced ileal villus height and villus height-to-crypt depth ratio and upregulated the expression of nuclear factor kappa B (NF-κB) in the ileum (P < 0.05). It also reduced cecal short-chain fatty acids (SCFA), such as acetic acid (P < 0.05). Compared with low-energy diets, the addition of mannanase increased body weight at 42 d, promoted the digestibility of nutrients, and maintained the morphology and integrity of the intestinal epithelium of broilers (P < 0.05). In addition, mannanase upregulated the expression of claudin-1 (CLDN1) and zonula occludens-1 (ZO-1) in the jejunum at 21 d, downregulated the expression of ileal NF-κB, and increased the content of isobutyric acid in the cecum of broilers (P < 0.05). The results for the ileal microbiota showed that a low-energy diet led to a decrease in the relative abundance of Lactobacillus reuteriin the ileum of broilers. The addition of mannanase increased the relative abundance of Lactobacillus-KC45band Lactobacillus johnsoniiin broilers. Furthermore, a low-energy diet reduced the relative abundance of Butyricicoccusin the intestine of broilers and inhibited oxidative phosphorylation and phosphoinositol metabolism. Mannanase increased the relative abundance of Odoribacter, promoted energy metabolism and N-glycan biosynthesis, and increased the activities of GH3 and GH18. It is concluded that mannanase could improve the growth performance of broilers by reducing the expression of NF-κBin the ileum, increasing the production of SCFA in the cecum, suppressing intestinal inflammation, balancing the intestinal microbiota, reducing damage to the intestinal barrier, and improving the efficiency of nutrient utilization to alleviate the adverse effects caused by the decrease in dietary energy level.

To perform multiplex profiling of single cells and eliminate the risk of potential sample loss caused by centrifugation, we developed a microfluidic flow cytometry and mass spectrometry system (μCytoMS) to evaluate the drug uptake and induced protein expression at the single cell level. It involves a microfluidic chip for the alignment and purification of single cells followed by detection with laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). Biofunctionalized nanoprobes (BioNPs), conjugating ∼3000 6-FAM-Sgc8 aptamers on a single gold nanoparticle (AuNP) (Kd= 0.23 nM), were engineered to selectively bind with protein tyrosine kinase 7 (PTK7) on target cells. PTK7 expression induced by oxaliplatin (OXA) uptake was assayed with LIF, while ICP-MS measurement of 195Pt revealed OXA uptake of the drug in individual cells, which provided further in-depth information about the drug in relation to PTK7 expression. At an ultralow flow of ∼0.043 dyn/cm2(20 μL/min), the chip facilitates the extremely fast focusing of BioNPs labeled single cells without the need for centrifugal purification. It ensures multiplex profiling of single cells at a throughput speed of 500 cells/min as compared to 40 cells/min in previous studies. Using a machine learning algorithm to initially profile drug uptake and marker expression in tumor cell lines, μCytoMS was able to perform in situprofiling of the PTK7 response to the OXA at single-cell resolution for tests done on clinical samples from 10 breast cancer patients. It offers great potential for multiplex single-cell phenotypic analysis and clinical diagnosis.

In vivo sensing of the dynamics of ions with high selectivity is essential for gaining molecular insights into numerous physiological and pathological processes. In this work, we report an ion-selective micropipette sensor (ISMS) through the integration of functional crown ether-encapsulated metal–organic frameworks (MOFs) synthesized in situ within the micropipette tip. The ISMS features distinctive sodium ion (Na+) conduction and high selectivity toward Na+sensing. The selectivity is attributed to the synergistic effects of subnanoconfined space and the specific coordination of 18-crown-6 toward potassium ions (K+), which largely increase the steric hindrance and transport resistance for K+to pass through the ISMS. Furthermore, the ISMS exhibits high stability and sensitivity, facilitating real-time monitoring of Na+dynamics in the living rat brain during spreading of the depression events process. In light of the diversity of crown ethers and MOFs, we believe this study paves the way for a nanofluidic platform for in vivo sensing and neuromorphic electrochemical sensing.

ABSTRACTPARP (poly(ADP-ribose) polymerase) inhibitors have demonstrated promising clinical activity in multiple homologous recombination (HR) deficiency tumors. However, glioblastoma (GBM) patients have obtained little benefit from PARP inhibitors alone. PARP inhibition shows considerable promise when used together with other therapeutic agents. Thus, novel combination therapies may enhance PARP inhibitor efficacy and overcome resistance mechanisms in GBM. Herein, we report that concurrent treatment with the PARP inhibitor olaparib and XPO1 (exportin 1) inhibitor KPT330 showed synergetic anticancer effects on GBM cells. Mechanistically, in the nucleus, we show that KPT330 induced the nuclear retention of SQSTM1 (sequestosome 1) and further inhibited the ubiquitination of the DNA repair signal H2AX (H2A.X variant histone) mediated by olaparib, thus inhibiting DNA damage response and repair in GBM. Moreover, in the cytoplasm, KPT330 blocked the activation of autophagic flux caused by olaparib reagent, downregulated the expression of LAPTM4B (lysosomal protein transmembrane 4 beta) and induced the dysfunction of lysosomes, thereby preventing the degradation of autophagosome, and ultimately promoted cell death. Furthermore, in the LN229-luc mouse orthotopic xenograft model, combination treatment showed significantly increased antitumor efficacy compared to each monotherapy. These data illustrate the application prospects of combined oral administration of olaparib and KPT330 for the treatment of glioblastoma.AbbreviationsAO: acridine orange; ATM: ATM serine/threonine kinase; CHEK1: checkpoint kinase 1; CHEK2: checkpoint kinase 2; CI: combination index; DMSO: dimethyl sulfoxide; DSBs: double-strand breaks; GBM: glioblastoma; HR: homologous recombination; H2AX: H2A.X variant histone; IHC: immunohistochemistry; LAPTM4B: lysosomal protein transmembrane 4 beta; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PARP: poly(ADP-ribose) polymerase; RAD51: RAD51 recombinase; SQSTM1: sequestosome 1; SSBs: single-strand breaks; RNF168: ring finger protein 168; XPO1: exportin 1.

Recent efforts have promoted programmable wireless environments (PWEs) to enhance the reception quality in high-frequency bands via reconfigurable intelligent surfaces (RISs). However, relevant research efforts are limited to setups with stationary users. This paper shows that crowd mobility in indoor PWEs induces spatio-temporal shadows on the surfaces, resulting in spatio-temporal sparsity in channel gains due to signal blockages. This overlooked aspect impacts the operation strategy of PWEs as the shadowed RIS tiles would contribute to the overheads while offering almost no improvement to the reception quality. Hence, this paper proposes an optimal strategy that excludes the shadowed tiles, which maximizes the utilization efficiency of RISs while minimizing the overheads. Since signal blockage is tied with the details of user mobility, a general model does not exist to identify such shadowed tiles for exclusion. Hence, we follow a data-driven approach that capitalizes on a realistic indoor mobility model and ray-tracing to generate the channel data. However, conventional ray-tracing presents high complexity that hinders data generation. So, we propose an approach to identify the shadow regions with a nine-order of magnitude reduction in complexity to efficiently generate the channel data. Furthermore, we present two exclusion strategies that offer guaranteed and best-effort quality-of-service support, and each can identify the tiles to be excluded via a search method with a complexity of $\mathcal {O}(N)$ for $N$ tiles. The results indicate that the proposed strategies reduce the overheads by $45-50\%$ while maintaining optimal service quality in various environments, operation frequencies, and user and access point density.

Purpose: This study aimed to explore the molecular pathogenesis of Graves’ disease (GD). Methods: The gene expression profile in CD4+T cells from GD patients and healthy controls were analyzed through mRNA-sequencing. The expression of NR4A2 was determined by quantitative real-time PCR and western blot. The levels of Th17 and Treg were determined by flow cytometry. ELISA was employed to detect the levels of IL-10, IL-17A, IL-17F and IL-22. Results: In the CD4+T cells from GD patients, there were 128 up-regulated and 510 down-regulated genes. Subsequently, we focused on the role of nuclear receptor 4 group A member 2 (NR4A2) in GD. NR4A2 was lowly expressed in the CD4+T cells from GD patients. Its expression was negatively correlated with free triiodothyronine and tetraiodothyronine, but positively correlated with thyroid stimulating hormone. NR4A2 knockdown decreased the percentage of Treg cells, with a decreased IL-10 level. While its over-expression augmented the Treg differentiation, with an elevated IL-10 level. In addition, knockdown or over-expression of NR4A2 showed no significant influence on Th17 differentiation. Conclusion: These results indicate that the low level of NR4A2 in GD patients may suppress Treg differentiation, but have no influence on Th17 differentiation, leading to the imbalance of Th17/Treg and contributing to the development of GD. Revealing the role of NR4A2 in GD provides a novel insight for the treatment of GD.

Understanding plant water-use patterns is important for improving water-use efficiency and for sustainable vegetation restoration in arid and semi-arid regions. However, seasonal variations in water sources and their control by different sand-fixing plants in water-limited desert ecosystems remain poorly understood. In this study, stable isotopic ratios of hydrogen (δ2H) and oxygen (δ18O) in precipitation, soil water, groundwater, and xylem water were determined to document seasonal changes in water uptake by three representative plant species (Pinus sylvestrisvar. mongolicaLitv., Amygdalus pedunculataPall., and Salix psammophila) in the northeastern Mu Us sandy land, Northwest China. Based on the depth distribution and temporal variation of measured gravimetric soil water content (SWC), the soil water profile of the three species stands was divided into active (0.01 g g-1< SWC < 0.08 g g-1, 20% < coefficient of variation (CV) < 45%), stable (0.02 g g-1< SWC < 0.05 g g-1, CV < 20%), and moist (0.08 g g-1< SWC < 0.20 g g-1, CV > 45%) layers. Annually, P. sylvestris, A. pedunculata, and S. psammophilaobtained most water from deep (59.2% ± 9.7%, moist layer and groundwater), intermediate (57.4% ± 9.8%, stable and moist layers), and shallow (54.4% ± 10.5%, active and stable layers) sources, respectively. Seasonally, the three plant species absorbed more than 60% of their total water uptake from the moist layer and groundwater in the early (June) dry season; then, they switched to the active and stable layers in the rainy season (July–September) for water resources (50.1%–62.5%). In the late (October–November) dry season, P. sylvestris(54.5%–66.2%) and A. pedunculata(52.9%–63.6%) mainly used water from stable and moist layers, whereas S. psammophila(52.6%–70.7%) still extracted water predominantly from active and stable layers. Variations in the soil water profile induced by seasonal fluctuations in precipitation and groundwater levels and discrepancies in plant phenology, root distribution, and water demand are the main factors affecting the seasonal water-use patterns of artificial sand-fixing plants. Our study addresses the issue of plant water uptake with knowledge of proportional source-water use and reveals important implications for future vegetation restoration and water management in the Mu Us sandy land and similar desert regions around the world.

The energy dissipative features of hydrogen bonds under conditions of mechanical strain have provided an ongoing incentive to explore hydrogen bonding units for the purpose of controlling and customizing the mechanical properties of polymeric materials. However, there remains a need for hydrogen bond units that (1) possess directionality, (2) provide selectivity, (3) dissipate energy effectively, and (4) can be incorporated readily into polymeric materials to regulate their mechanical properties. Here, we report mechanically interlocked hydrogen bond units that incorporate multiple hydrogen bonds within a [2]catenane structure. The conformational flexibility and associated spatial folding characteristics of the [2]catenane units allow for molecular scale motion under external stress, while the interlocked structure serves as a pivot that maintains the directionality and selectivity of the resultant hydrogen bonding units. When incorporated into polymers, these interlocked hydrogen bond motifs serve to strengthen and toughen the resulting materials. This study not only presents a novel hydrogen bond unit for creating polymeric materials with improved mechanical properties but also underscores the unique opportunities that mechanically interlocked hydrogen bond structures may provide across a diverse range of applications.

Ordered mesoporous materials have received great attention due to their well-defined pore structures and potential applications in catalysis, adsorption, separation, drug delivery, etc. Although various compositions of mesoporous solids have been successfully prepared, the preparation of crystalline non-metallic oxyacid salts with ordered mesoporosity remains a major challenge. Herein, we report the synthesis of a mesoporous solid acid crystalline boron phosphate (BPO4) catalyst with a bicontinuous shifted double diamond (SDD) hyperbolic surface structure. The BPO4scaffold was obtained by synergistic self-assembly in a mixed solvent of water and tetrahydrofuran using the diblock copolymer poly(ethylene oxide)-block-polystyrene as template and phosphoric acid and orthoboric acid as inorganic sources. The structure consists of two sets of diamond networks adjacent to each other with a mesostructural scale tetragonal symmetry (space group I41/amd) with unit cell parameters of a= 80 nm and c= 113 nm, which affords the scaffold a specific surface area of 44 m2/g. As a solid acid catalytic material, the SDD BPO4scaffold exhibited excellent catalytic activity at room temperature with a conversion of furfural to 2-(dimethoxymethyl) furan over 70% and can be reused after recovery without serious loss of activity. In the propane oxidative dehydrogenation reaction, SDD BPO4demonstrated high olefin productivity and selectivity while maintaining high reaction rate. This study provides ideas for the preparation of ordered mesoporous crystalline catalytic materials and demonstrates their potential for practical applications.

Background: To examine the associations of physical activity (PA) and sedentary behavior (SB) with longevity and age acceleration (AA) using observational and Mendelian randomization (MR) studies, and quantify the mediating effects of lipids. Methods: In Guangzhou Biobank Cohort Study (GBCS), PA and SB were assessed by the Chinese Version of the International Physical Activity Questionnaire. Longevity was defined as participants whose age at follow-up or at death was at or above the 90th age percentile. AA was defined as the residual resulting from a linear model that regressed phenotypic age against chronological age. Linear regression and Poisson regression with robust error variance were used to assess the associations of total and specific PA in different intensities, and SB with AA and longevity, yielding βs or relative risks (RRs) and 95% confidence intervals (CIs). Two-sample MR was conducted to examine the causal effects. Mediation analysis was used to assess the mediating effects of lipids. Results: Of 20,924 participants aged 50 + years in GBCS, during an average follow-up of 15.0 years, compared with low PA, moderate and high PA were associated with higher likelihood of longevity (RR (95% CI): 1.56 (1.16, 2.11), 1.66 (1.24, 2.21), respectively), and also cross-sectionally associated with lower AA (β (95% CI): -1.43 (-2.41, -0.45), -2.09 (-3.06, -1.11) years, respectively). Higher levels of moderate PA (MPA) were associated with higher likelihood of longevity and lower AA, whereas vigorous PA (VPA) showed opposite effects. The association of PA with longevity observed in GBCS was mediated by low-density lipoprotein cholesterol (LDL-C) by 8.23% (95% CI: 3.58–39.61%), while the association with AA was mediated through LDL-C, triglycerides and total cholesterol by 5.13% (3.94–7.30%), 7.81% (5.98–11.17%), and 3.37% (2.59–4.80%), respectively. Additionally, in two-sample MR, SB was positively associated with AA (β (95% CI): 1.02 (0.67, 1.36) years). Conclusions: PA showed protective effects on longevity and AA, with the effects being partly mediated through lipids. Conversely, SB had a detrimental impact on AA. MPA was associated with higher likelihood of longevity and reduced AA, whereas VPA showed adverse effects. Our findings reinforce the recommendation of “sit less and move more” to promote healthy longevity, and highlight the potential risks associated with VPA in the elderly.

The aesthetic and practicality of macroscopic fabrics continue to encourage chemists to weave molecules into interlaced patterns with the aim of providing emergent physical and chemical properties when compared with their starting materials. Weaving purely organic molecular threads into flawless two-dimensional patterns remains a formidable challenge, even though its feasibility has been proposed on several occasions. Herein we describe the synthesis of a flawless, purely organic, free-standing two-dimensional woven polymer network driven by dative B−N bonds. Single crystals of this woven polymer network were obtained and its well-defined woven topology was revealed by X-ray diffraction analysis. Free-standing two-dimensional monolayer nanosheets of the woven polymer network were exfoliated from the layered crystals using Scotch Magic Tape. The surface features of the nanosheets were investigated by integrated low-dose and cryogenic electron microscopy imaging techniques. These findings demonstrate the precise construction of purely organic woven polymer networks and highlight the unique opportunities for the application of woven topologies in two-dimensional organic materials.

Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined that an actin-interacting protein, zyxin (ZYX), may involved in GBM invasion. Our own glioma cohort as well as the cancer genome atlas (TCGA), Rembrandt, and Gravendeel databases consistently showed that increased ZYXexpression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYXand demonstrated the role of ZYXin GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYXrevealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1were positively regulated by ZYX. Functionally, STMN1not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYXloss. Taken together, our results indicate that high ZYXexpression was associated with worse prognosis and highlighted that the ZYX-STMN1axis might be a potential therapeutic target for GBM.

Artificial muscles that can convert electrical energy into mechanical energy promise broad scientific and technological applications. However, existing electro-driven artificial muscles have been plagued with problems that hinder their practical applications: large electro-mechanical attenuation during deformation, high-driving voltages, small actuation strain, and low power density. Here, we design and create novel electro-thermal-driven artificial muscles rationally composited by hierarchically structured carbon nanotube (HS-CNT) networks and liquid crystal elastomers (LCEs), which possess adaptive sandwiched nanotube networks with angulated-scissor-like microstructures, thus effectively addressing above problems. These HS-CNT/LCE artificial muscles demonstrate not only large strain (>40%), but also remarkable conductive robustness (R/R0< 1.03 under actuation), excellent Joule heating efficiency ( 233 °C at 4 V), and high load-bearing capacity (R/R0< 1.15 at 4000 times its weight loaded). In addition, our artificial muscles exhibit real-muscle-like morphing intelligence that enables preventing mechanical damage in response to excessively heavyweight loading. These high-performance artificial muscles uniquely combining omnidirectional stretchability, robust electrothermal actuation, low driving voltage, and powerful mechanical output would exert significant technological impacts on engineering applications such as soft robotics and wearable flexible electronics.

BackgroundCirculating antioxidants are associated with a lower risk of Alzheimer’s disease (AD) in observational studies, suggesting potential target areas for intervention. However, whether the associations are causal remains unclear. Here, we studied the causality between antioxidants and AD or cognitive function using two-sample Mendelian randomisation (MR).MethodsSingle nucleotide polymorphisms strongly (p<5×10−8) associated with antioxidants (vitamin A, vitamin C, zinc, selenium, β-carotene and urate) and outcomes (AD, cognitive performance and reaction time) were obtained from the largest and most recent genome-wide association studies (GWAS). MR inverse variance weighting (IVW) and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis.ResultsHigher genetically determined selenium level was associated with 5% higher risk of AD (OR 1.047, 95% CI 1.005 to 1.091, p=0.028) using IVW. Higher genetically determined urate level was associated with worse cognitive performance (β=−0.026, 95% CI −0.044 to −0.008, p=0.005) using MR-PRESSO. No association between the other antioxidants and AD, cognitive performance and reaction time was found. Similar results were found in the sensitivity analyses.ConclusionOur results suggest that lifelong exposure to higher selenium may be associated with a higher risk of AD, and higher urate levels could be associated with worse cognitive performance. Further analyses using larger GWAS of antioxidants are warranted to confirm these observations. Our results suggest that caution is needed in the interpretation of traditional observational evidence on the neuroprotective effects of antioxidants.

This study delves into the alterations in resonant frequencies due to bending in flexible sensor applications. We examined the resonant frequencies of four inductor–capacitor (LC) resonant circuits subjected to various bending conditions and assessed the performance of LC temperature sensors under different bending states. Optimization of the sensor coil parameters was achieved through finite element simulations. LC resonant circuits were fabricated on flexible Pi films utilizing an inkjet printing technique, followed by bending tests. Our findings indicate a rise in the circuit’s resonant frequency as the bending radius diminishes. Separate simulations for capacitors and inductors revealed that the factors influencing the shift in resonant frequency after bending vary across LC sensors with different architectures. Additionally, we evaluated two configurations of LC temperature sensors in bending states. Notably, the reel-type LC temperature sensor, designed for direct winding at the temperature measurement site, demonstrated a measurement sensitivity of 89.3 KHz/°C, presenting a pioneering approach for temperature assessment in constrained, enclosed, and curved environments. The insights gleaned from this research are instrumental for the design and optimization of flexible sensors in practical applications.

Communication plays a crucial role in coordinating the behavior of multiple agents. However, unstable communication connections in complex environments may lead to intermittent communication, information delays, and control strategy failures. This study proposes the multiagent cooperative search learning (MACSL) algorithm to achieve efficient search tracking in dynamic, partially observable environments with intermittent communication. First, to enhance the search efficiency when global communication links are unreachable, we propose a cooperative search strategy based on reinforcement learning from the perspective of teammate strategy learning. By designing an environment-aware map to guide agent exploration and learning, an effective distributed coverage search is realized. Second, to mitigate the impact of communication interruptions on shared information loss, we investigate target information prediction based on a recurrent neural network. The update rule of the target probability map and the cooperative model are optimized. Experimental results validate the effectiveness of the MACSL algorithm for cooperative search with intermittent communication.

Automatic brain tumor segmentation using multi-parametric magnetic resonance imaging (mpMRI) holds substantial importance for brain diagnosis, monitoring, and therapeutic strategy planning. Given the constraints inherent to manual segmentation, adopting deep learning networks for accomplishing accurate and automated segmentation emerges as an essential advancement. In this article, we propose a modality fusion diffractive network (MFD-Net) composed of diffractive blocks and modality feature extractors for the automatic and accurate segmentation of brain tumors. The diffractive block, designed based on Fraunhofer's single-slit diffraction principle, emphasizes neighboring high-confidence feature points and suppresses low-quality or isolated feature points, enhancing the interrelation of features. Adopting a global passive reception mode overcomes the issue of fixed receptive fields. Through a self-supervised approach, the modality feature extractor effectively utilizes the inherent generalization information of each modality, enabling the main segmentation branch to focus more on multimodal fusion feature information. We apply the diffractive block on nn-UNet in the MICCAI BraTS 2022 challenge, ranked first in the pediatric population data and third in the BraTS continuous evaluation data, proving the superior generalizability of our network. We also train separately on the BraTS 2018, 2019, and 2021 datasets. Experiments demonstrate that the proposed network outperforms state-of-the-art methods.

Quorum‐sensing (QS) is an essential mechanism of microbial self‐regulation. In this work, the presence of QS in Acetobacter pasteurianuswas demonstrated, and N‐acyl‐homoserine lactones N‐C4‐HSL and N‐C8‐HSL were identified as the signal molecules. The exogenous addition of N‐C4‐HSL, N‐C8‐HSL, N‐C10‐HSL, and N‐C12‐HSL result in the reduction in biomass, and lead to 11.56%, 11.91%, 7.94%, and 4.69% decrease in acetic acid production, respectively, when compared with the control. A hypothetical N‐acylhomoserine lactonase (AHL lactonase) 0046 was overexpressed in A. pasteurianusCGMCC 3089, and the recombinant strain exhibites a 17.38% and 12.75% increase in the biomass and the acetic acid production rate, respectively. Those results prove the negative regulation of QS on acetic acid fermentation, and overexpression of 0046 protein alleviates this negative effect. In this present work, the presence of quorum‐sensing (QS) in Acetobacter pasteurianuswas demonstrated, and N‐acyl‐homoserine lactones N‐C4‐HSL and N‐C8‐HSL were identifying as the signal molecules. And, the effects of QS signal molecules and overexpression of a potential N‐acylhomoserine lactonase 0046 on acetic acid fermentation were analyzed.

Human drivers have excellent perception and reaction abilities in complex environments such as dangerous highways, busy intersections, and harsh weather conditions. To achieve human-level driving performance, autonomous driving systems require powerful environmental perception systems and the ability to make accurate decisions in difficult situations, enabling vehicles to maintain smooth driving. However, making decisions based on visual perception is still a daunting challenge for autonomous vehicles, also current end-to-end networks and modular frameworks have limitations in effectively addressing perception, decision-making, and control, such as a lack of interpretability and weak generalization ability in complex environments. This paper proposes an elaborate modular pipeline for autonomous driving that effectively integrates semantic perception information, multi-level decision tasks, and control modules. The decision-making module comprehensively considers high-level maneuver selection and low-level motion control in both horizontal and vertical directions. The proposed MP framework is trained end-to-end by a novel hierarchical reinforcement learning method with a new action sampling mechanism. To adapt to the experimental scenarios, we use the CARLA simulation platform to collect data to evaluate the proposed autonomous driving framework and its new training method, considering various environmental factors such as sunny, dusk, and rainy weather. The results show that the framework exhibits smooth and effective driving strategies in different environments and can converge quickly and stably. The method improves learning efficiency and reduces unnecessary coupling and error propagation. Overall, the proposed framework and training method provide new ideas for improving existing autonomous driving systems.

CuO-based nanostructures have been widely investigated in catalysis, sensing, and energy conversion and storage in recent years. The unique properties of these nanostructures are largely related to the morphology and crystallinity of CuO. The controlled deposition of conformal CuO thin films by atomic layer deposition (ALD) has remained challenging until now owing to the limited understanding of the nucleation behavior and growth process. Here, a novel ALD process for copper oxide was developed using copper(II) trifluoroacetylacetonate [Cu(tfacac)2] as the metal precursor. The nucleation and initial growth of a CuO film are strongly dependent on the surface OH concentration. A continuous particulate-like CuO film was grown on OH-abundant pristine SiO2particles, whereas the surface of the annealed SiO2particles (presenting mostly isolated OH groups) remained uncoated under the same growth conditions. Moreover, a uniform and conformal CuO film was grown on covalently functionalized CNTs under identical conditions as pristine SiO2particles. This study provides a strategy for tailoring the structure and the properties of thin films via ALD, which is promising for designing well-tailored nanostructures for various applications.

ABSTRACTMacroautophagy/autophagy is an evolutionarily conserved biological process among eukaryotes that degrades unwanted materials such as protein aggregates, damaged mitochondria and even viruses to maintain cell survival. Our previous studies have demonstrated that MoVast1 acts as an autophagy regulator regulating autophagy, membrane tension, and sterol homeostasis in rice blast fungus. However, the detailed regulatory relationships between autophagy and VASt domain proteins remain unsolved. Here, we identified another VASt domain-containing protein, MoVast2, and further uncovered the regulatory mechanism of MoVast2 in M. oryzae. MoVast2 interacted with MoVast1 and MoAtg8, and colocalized at the PAS and deletion of MoVAST2results in inappropriate autophagy progress. Through TOR activity analysis, sterols and sphingolipid content detection, we found high sterol accumulation in the ΔMovast2mutant, whereas this mutant showed low sphingolipids and low activity of both TORC1 and TORC2. In addition, MoVast2 colocalized with MoVast1. The localization of MoVast2 in the MoVAST1deletion mutant was normal; however, deletion of MoVAST2leads to mislocalization of MoVast1. Notably, the wide-target lipidomic analyses revealed significant changes in sterols and sphingolipids, the major PM components, in the ΔMovast2mutant, which was involved in lipid metabolism and autophagic pathways. These findings confirmed that the functions of MoVast1 were regulated by MoVast2, revealing that MoVast2 combined with MoVast1 maintained lipid homeostasis and autophagy balance by regulating TOR activity in M. oryzae.

Accurate segmentation of head and neck organs at risk is crucial in radiotherapy. However, the existing methods suffer from incomplete feature mining, insufficient information utilization, and difficulty in simultaneously improving the performance of small and large organ segmentation. In this paper, a multistage hierarchical learning network is designed to fully extract multidimensional features, combined with anatomical prior information and imaging features, using multistage subnetworks to improve the segmentation performance. First, multilevel subnetworks are constructed for primary segmentation, localization, and fine segmentation by dividing organs into two levels—large and small. Different networks both have their own learning focuses and feature reuse and information sharing among each other, which comprehensively improved the segmentation performance of all organs. Second, an anatomical prior probability map and a boundary contour attention mechanism are developed to address the problem of complex anatomical shapes. Prior information and boundary contour features effectively assist in detecting and segmenting special shapes. Finally, a multidimensional combination attention mechanism is proposed to analyze axial, coronal, and sagittal information, capture spatial and channel features, and maximize the use of structural information and semantic features of 3D medical images. Experimental results on several datasets showed that our method was competitive with state-of-the-art methods and improved the segmentation results for multiscale organs.

Lysine lactylation (kla) as a post-translational modification (PTM) is linked to chromatin remodeling and gene transcription. Nitrogen stress can induce triacylglyceride (TAG) accumulation in most microalgae. To reveal lipid synthesis from another layer, the 4D label-free proteome method was used to track lactylation modifications and protein expression profiles after 3 days of nitrogen deprivation in Nannochloropsis oceanicato analyze the function and prevalence of lactylation. Under nitrogen deprivation (ND) and nitrogen repletion (NR) cultivation conditions, we mapped the proteome and lactylome of proliferating microalgal cells. The results showed that there were 5203 proteins identified and 1245 proteins differentially expressed; among them, 664 were upregulated and 581 were downregulated. The N. oceanicastrain also has a total of 868 lactylation sites, which were found on 379 proteins. The lactylated proteins were linked to biological activities as diverse as lipid metabolism, carbon fixation, photosynthesis, glycolysis, and the tricarboxylic acid (TCA) cycle and were found in various subcellular compartments. Under ND, 414 specific lactylation sites were found in 252 proteins. More interestingly, under ND vs NR, lactylation showed a significantly upregulated trend. This study provides a foundation for the future epigenetic enhancement of microalgal cells by providing the first dataset of lactylome in Nannochloropsis.

Byline: Min. Meng, Wenhong. Li, Xia. Yang, Guanghui. Huang, Zhigang. Wei, Yang. Ni, Xiaoying. Han, Jiao. Wang, Xin. Ye Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. [...]

Byline: Zhigang. Wei, Xia. Yang, Xin. Ye, Guanghui. Huang, Wenhong. Li, Xiaoying. Han, Jiao. Wang, Min. Meng, Yang. Ni, Zhigeng. Zou, Qiang. Wen Aim: The present study evaluated the safety [...]

Byline: Wenhong. Li, Zhigang. Wei, Xia. Yang, Guanghui. Huang, Xiaoying. Han, Yang. Ni, Jiao. Wang, Min. Meng, Zhigeng. Zou, Qiang. Wen, Xin. Ye Background: Camrelizumab is a promising anti-programmed cell [...]

Byline: Jiao. Wang, Yang. Ni, Xia. Yang, Guanghui. Huang, Zhigang. Wei, Wenhong. Li, Xiaoying. Han, Min. Meng, Xin. Ye, Jiayun. Lei Objectives: The objective of this study is to determine [...]

The accuracy and efficiency tuning the local electronic structure of catalyst active sites are pre-requisites for achieving high selectivity CO2reduction reaction on a wide potential window, whereas remain a great challenge. Here, a B-doped CuIn alloy catalyst with tunable electronic structure for the highly effective electrochemical conversion of CO2to CO has been exploited. The obtained B-doped CuIn alloy performs an optimal CO Faraday efficiency of 99% at –0.6 V (vs. the reversible hydrogen electrode) and particularly keeps outstanding CO Faraday efficiency (> 90%) over a wide cathodic electrochemical window (400 mV). Density functional theory theoretical calculation manifests that the enhanced performance is primarily ascribed to the electron-capturing ability of high valence state B atom, which optimizes the local electronic structure of adjacent metal active sites and adjusts the binding energy between catalyst and intermediates. A foundation of designing advanced electrochemical CO2reduction reaction catalysts can be served by the insights gained though this research.

The loss of organic components from perovskites has inevitably triggered a series of undesirable results, including ion migration, increased defects, and organic vapors, which severely limit the performance of perovskite solar cells (PSCs) and impede their progress toward commercial applications. To circumvent this issue, we report a novel covalent bonding strategy by employing bis-diazirine (BD) molecules to covalently bond organic cations of perovskites. Experimental and ab initiosimulation results confirmed the efficacy of BD molecules to strongly immobilize the organic cations and eventually enhance the thermal, illumination, and electrical bias resistance properties of perovskites. Consequently, highly efficient (24.36% efficiency, certified 24.02%) and ultra-stable PSCs were realized, which retained 98.6% of their initial efficiency even after 1,000 h of operational tests.

Herein, an NHC (N-heterocyclic carbene)-catalyzed radical coupling reaction between aldehydes and azobis(isobutyronitrile) (AIBN) has been developed. This method provides an efficient and convenient approach for the synthesis of β-ketonitriles containing a quaternary carbon center (31 examples, up to >99% yield) utilizing commercially available substrates. This protocol features broad substrate scope, good functional group tolerance, and high efficiency under metal-free and mild reaction conditions.

This two-sample Mendelian randomization analysis shows that sleep apnea (SA) and snoring increased the risk of hypertension and coronary artery diseases, and these associations may partly be driven by the body mass index.Further studies clarifying the role of adiposity in the effect of SA and snoring on cardiovascular diseases (CVDs) are needed.No evidence of CVDs causally influencing SA or snoring was found.Graphical Abstract

The impacts of climate change on the relationship between fluvial processes and dune landform evolution have been studied. However, the chronology data used to examine this relationship are deficient. The Keriya River has a glacial origin in the Kunlun Mountains on the south margin of the Tarim Basin. The river flows into the Taklimakan Desert, the second largest shifting-dune desert in the world. The dry channels and shifting dunes in this area provide an ideal opportunity to investigate fluvial and aeolian landform evolution processes and their relationship with climate change. We investigated this area during 2008–2011 and obtained 18 fluvial sediment samples from 16 sections for optically stimulated luminescence (OSL) dating. The results show that the ages ranged from 3.4–44.1 ka. Most of the samples (13) were Holocene in age, around 11 ka, 8–9 ka, 5–6.5 ka, 4.6 ka, and 3.4–3.7 ka and were distributed along ancient river channels around sites of Yuansha and Karadun. Two samples close to the Hotan River (38–47 ka) fall within the Marine Isotope Stage 3 (MIS3). Three samples (from one section) were located near ancient channels flowing towards the Yuansha Site and had ages of around 14.5 ka, i.e., during the Last Glacial Maximum (LGM). The analyses of the sediment samples and OSL ages suggest that the Keriya River flooded in the Holocene, the LGM, and MIS3. Fluvial sediments provided the source material for the dunes, and fluvial processes affected the landform evolution in the lower Keriya River. Our results suggest that most of the dunes covered in fluvial sediments in the lower reaches and the area west of the Keriya River developed since the Holocene. This differs from the results of previous studies, which suggested that they developed since the Han (202BC–220AD) and Tang (618–907AD) dynasties. The OSL ages of the fluvial sediments are consistent with the reported deglaciation (after glacial advance) ages in the alpine mountains surrounding the Tarim Basin. This suggests that climate fluctuations may have affected the occurrence of floods and the formation of dunes in the Taklimakan Desert.

The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB2A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB2A2-BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.

Objectives: To develop and validate the 4-year risk of type 2 diabetes mellitus among adults with metabolic syndrome. Design: Retrospective cohort study of a large multicenter cohort with broad validation. Settings: The derivation cohort was from 32 sites in China and the geographic validation cohort was from Henan population-based cohort study. Results: 568 (17.63) and 53 (18.67%) participants diagnosed diabetes during 4-year follow-up in the developing and validation cohort, separately. Age, gender, body mass index, diastolic blood pressure, fasting plasma glucose and alanine aminotransferase were included in the final model. The area under curve for the training and external validation cohort was 0.824 (95% CI, 0.759–0.889) and 0.732 (95% CI, 0.594–0.871), respectively. Both the internal and external validation have good calibration plot. A nomogram was constructed to predict the probability of diabetes during 4-year follow-up, and on online calculator is also available for a more convenient usage (https://lucky0708.shinyapps.io/dynnomapp/). Conclusion: We developed a simple diagnostic model to predict 4-year risk of type 2 diabetes mellitus among adults with metabolic syndrome, which is also available as web-based tools (https://lucky0708.shinyapps.io/dynnomapp/).

Resveratrol (RSV) has been shown to have a neuroprotective effect in various central nervous system disorders, although the role of RSV in diabetes‐induced cognitive dysfunction is still not fully elucidated. Here, we investigated whether RSV improved diabetes‐related cognitive dysfunction in vivo and in vitro. We induced a rat diabetic model with a high‐fat and high‐sucrose diet followed by intraperitoneal injection of streptozotocin and a diabetic neuron cell model by stimulation with high levels of glucose. We observed that RSV improved impairment in spatial learning and memory in the Morris water maze test (MWM) and novel object recognition test (ORT) in diabetic rats. RSV reversed the reduced miR‐146a‐5p and upregulated thioredoxin‐interacting protein (TXNIP) and inhibited the diabetes‐induced increase in interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α levels in vivo and in vitro. RSV also inhibited diabetes‐induced endoplasmic reticulum stress (ESR) by reducing ESR‐related protein expression in vivo and in vitro. Moreover, inhibition of miR‐146a‐5p partially abolished the protective effects of RSV in HG‐treated primary neurons. Additionally, we used starBase to predict that miR‐146a‐5p interacts with TXNIP, which we then verified using a luciferase reporter gene assay. We further observed that miR‐146a‐5p regulates the mRNA and protein expression of TXNIP in vitro, indicating that the miR‐146a‐5p/TXNIP axis is involved in the regulation of cognitive dysfunction in a rat diabetic model. Collectively, these results demonstrate that RSV plays a neuroprotective role in diabetes‐associated cognitive dysfunction at least in part through regulation of the miR‐146a‐5p/TXNIP axis.

Byline: Min. Meng, Xin. Ye, Xia. Yang, Guanghui. Huang, Zhigang. Wei, Yang. Ni, Wenhong. Li, Xiaoying. Han, Jiao. Wang Apatinib, one of the novel oral antiangiogenic agents, shows survival benefits [...]

Byline: Guanghui. Huang, Xin. Ye, Xia. Yang, Aimin. Zheng, Wenhong. Li, Jiao. Wang, Xiaoying. Han, Zhigang. Wei, Min. Meng, Yang. Ni, Chengkun. Qin, Xingbo. Fei, Liulin. Xiong Objective: The objective [...]

ABSTRACT This paper presents the time-dependent probability of chloride-induced corrosion of reinforced concrete (RC) structures in marine environments. By using the third-moment (TM) method with improved analytical solutions, the stochastic [...]

ABSTRACTBackgroundPapillary thyroid carcinoma (PTC) commonly presents with lymph node metastasis, which may be associated with worsened prognosis. This study aimed to comprehensively evaluate the risk factors of lymph node metastasis in PTC based on preoperative clinical and imaging data and to construct a nomogram model to predict the risk of lymph node metastasis.MethodsA total of 989 patients with PTC were enrolled and randomly divided into training and validation cohorts in an 8:2 ratio. Independent risk factors for lymph node metastasis in PTC were analyzed using univariate and stepwise multivariate logistic regression. An importance analysis of independent risk factors affecting lymph node metastasis was performed according to the random forest method. Subsequently, a nomogram to predict lymph node metastasis was constructed, and the predictive effect of the nomogram was evaluated using receiver operating characteristic analysis and calibration curves.ResultsUnivariate regression analysis revealed that age, sex, body weight, systolic blood pressure, free triiodothyronine, nodule location, nodule number, Thyroid Imaging Reporting and Data System (TI-RADS) grade on color Doppler ultrasound, enlarged lymph node present on imaging, and nodule diameter could affect lymph node metastasis in PTC. Stepwise multivariate regression analysis showed that sex, age, enlarged lymph node present on imaging, nodule diameter, and color Doppler TI-RADS grade were independent risk factors for lymph node metastasis in PTC. Combining these five independent risk factors, a nomogram prediction model was constructed. The area under the curve (AUC) of the nomogram in the training and validation cohorts was 0.742 and 0.765, respectively, with a well-fitted calibration curve.ConclusionOur study showed that independent risk factors for lymph node metastasis in PTC were sex, age, enlarged lymph node present on imaging, nodule diameter, and color Doppler TI-RADS grade. The nomogram constructed based on these independent risk factors can better predict the risk of lymph node metastasis.

By loading a small amount of cadmium acetate dihydrate on the zeolitic imidazolate framework-8 (ZIF-8), a hollow CdS–ZnS–ZIF-8 composite was facilely synthesized by rapid solid-phase grinding with thioacetamide. The evolution of the structure, composition, and photoelectrochemical properties was studied by a series of methods. When it was used as a photocatalyst, the hollow CdS–ZnS–ZIF-8 composite demonstrated a highly visible light response as well as a robust ability and reusability for Cr(VI) reduction, which could be ascribed to the hollow structure and ultrasmall CdS nanoparticles. Notably, the presence of ZIF-8-S (ZIF-8 ground with thioacetamide) could also obviously enhance the stability of CdS by promoting the separation of the photogenerated charge during light irradiation.