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Unsupervised Domain Adaptation aims to leverage a source domain with ample labeled data to tackle tasks on an unlabeled target domain. However, this poses a significant challenge, particularly in scenarios exhibiting significant disparities between the two domains. Prior methods often fall short in challenging domains due to the impact of incorrect pseudo-labeling noise and the limits of handcrafted domain alignment rules. In this paper, we propose a novel method called DCST (Dual Cross-Supervision Transformer), which improves upon existing methods in two key aspects. Firstly, vision transformer is combined with dual cross-supervision learning strategy to enforce consistency learning from different domains. The network accomplishes domain-specific self-training and cross-domain feature alignment in an adaptive manner. Secondly, due to the presence of noise in challenging domain, and the need to reduce the risks of model collapse and overfitting, we propose a Domain Shift Filter. Specifically, this module allows the model to leverage the memory of source domain features to facilitate a smooth transition. It can also improve the effectiveness of knowledge transfer between domains with significant gaps. We conduct extensive experiments on four benchmark datasets and achieved the best classification results, including 94.3% on Office-31, 86.0% on Office-Home, 89.3% on VisDA-2017, and 48.8% on DomainNet. Code is available in https://github.com/Yislight/DCST.

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This study presents the synthesis and evaluation of a magnetic chitosan-modified biochar (M-BC-CS) composite, developed from waste maize straw, for the efficient removal of copper ions (Cu2+) and methylene blue (MB) dye from aqueous solutions. The composite was characterized using advanced techniques such as SEM, BET, FTIR, XPS, and XRD, confirming its enhanced surface area, porosity, and magnetic properties. The study is aimed at investigating the optimal conditions for adsorption of Cu2+ and MB by M-BC-CS through analysis of the influence of diverse adsorbent dosages, pH levels, reaction times, and initial solution concentrations. The findings demonstrated that the equilibrium duration for the adsorption of Cu2+ and MB by M-BC-CS was 60 min, resulting in corresponding equilibrium adsorption quantities of 54.42 mg/g and 67.23 mg/g, respectively. To elucidate the adsorption mechanism, the present investigation applied the pseudo-second-order kinetic model and the Langmuir isotherm. The outcomes suggested that the adsorption process is attributable to single molecular layer chemisorption. XPS and FTIR analysis determined that ion exchange and electrostatic interactions are the predominant mechanisms responsible for the simultaneous adsorption of Cu2+ and MB, and a competitive relationship exists between these mechanisms. In addition, M-BC-CS exhibited exceptional magnetic separation performance, enabling effortless and effective separation when exposed to an external magnetic field. Furthermore, the results demonstrated that M-BC-CS has good reusability and high adsorption capacity also in real wastewater, thus emphasizing its potential as a promising adsorbent for the elimination of Cu2+ and MB from aqueous solutions.

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Providing accurate prediction of the severity of traffic collisions is vital to improve the efficiency of emergencies and reduce casualties, accordingly improving traffic safety and reducing traffic congestion. However, the issue of both the predictive accuracy of the model and the interpretability of predicted outcomes has remained a persistent challenge. We propose a Random Forest optimized by a Meta-heuristic algorithm prediction framework that integrates the spatiotemporal characteristics of crashes. Through predictive analysis of motor vehicle traffic crash data on interstate highways within the United States in 2020, we compared the accuracy of various ensemble models and single-classification prediction models. The results show that the Random Forest (RF) model optimized by the Crown Porcupine Optimizer (CPO) has the best prediction results, and the accuracy, recall, f1 score, and precision can reach more than 90 %. We found that factors such as Temperature and Weather are closely related to vehicle traffic crashes. Closely related indicators were analyzed interpretatively using a geographic information system (GIS) based on the characteristic importance ranking of the results. The framework enables more accurate prediction of motor vehicle traffic crashes and discovers the important factors leading to motor vehicle traffic crashes with an explanation. The study proposes that in some areas consideration should be given to adding measures such as nighttime lighting devices and nighttime fatigue driving alert devices to ensure safe driving. It offers references for policymakers to address traffic management and urban development issues.

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INTRODUCTION AND OBJECTIVE: His bundle pacing (HBP) could replace failed biventricular pacing (BVP) in guidelines (IIa Indication), but the high capture thresholds and backup lead pacing requirements limit its development. We assessed the efficacy and safety of HBP combined with atrioventricular node ablation (AVNA) for atrial fibrillation (AF) and compared with BVP and left bundle branch pacing (LBBP). METHODS: We reviewed PubMed, Embase, Web of Science, and Cochrane Library databases on left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) score, QRS duration (QRSd), and pacing threshold. RESULTS: Thirteen studies included 1115 patients (639 with HBP, 338 with BVP, and 221 with LBBP). Compared with baseline, HBP improved LVEF (mean difference [MD]: 9.24 [6.10, 12.37]; p < 0.01), reduced NYHA score (MD: -1.12 [-1.34, -0.91]; p < 0.01), increased QRSd (MD: 10.08 [4.45, 15.70]; p < 0.01), and rose pacing threshold (MD: 0.16 [0.05, 0.26]; p < 0.01). HBP had comparable efficacy to BVP and LBBP and lower QRSd (p < 0.05). HBP had a lower success rate (85.97%) and more complications (16.1%). CONCLUSION: HBP combined with AVNA is effective for AF, despite having a lower success rate and more complications. Further trials are required to determine whether HBP is superior to BVP and LBBP.

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Single-atom catalysts (SACs), featuring highly uniform active sites, tunable coordination environments, and synergistic effects with support, have emerged as one of the most efficient catalysts for various reactions, particularly for electrochemical CO2 reduction (ECR). However, the scalability of SACs is restricted due to the limited choice of available support and problems that emerge when preparing SACs by thermal deposition. Here, an in situ reconstruction method for preparing SACs is developed with a variety of atomic sites, including nickel, cadmium, cobalt, and magnesium. Driven by electricity, different oxygen-containing metal precursors, such as MOF-74 and metal oxides, are directly atomized onto nitrogen-doped carbon (NC) supports, yielding SACs with variable metal active sites and coordination structures. The electrochemical force facilitates the in situ generation of bonds between the metal and the supports without the need for additional complex steps. A series of MNxOy (M denotes metal) SACs on NC have been synthesized and utilized for ECR. Among these, NiNxOy SACs using Ni-MOF-74 as a metal precursor exhibit excellent ECR performance. This universal and general SAC synthesis strategy at room temperature is simpler than most reported synthesis methods to date, providing practical guidance for the design of the next generation of high-performance SACs.

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Amyloid-ß (Aß) species (Aß fibrils and Aß plaques), as one of the typical pathological markers of Alzheimer's disease (AD), plays a crucial role in AD diagnosis. Currently, some near-infrared I (NIR I) Aß probes have been reported in AD diagnosis. However, they still face challenges such as strong background interference and the lack of effective probe design. In this study, we propose molecular design strategy that incorporates CN group and amphiphilic modulation to synthesize a series of amphiphilic NIR I Aß probes, surpassing the commercial probe ThT and ThS. Theoretical calculations indicate that these probes exhibit stronger interaction with amino acid residues in the cavities of Aß. Notably, the probes containing CN group display the ability of binding two distinct sites of Aß, which dramatically enhanced the affinity to Aß species. Furthermore, these probes exhibit minimal fluorescence in aqueous solution and offer ultra-high signal-to-noise ratio (SNR) for in vitro labeling, even in wash-free samples. Finally, the optimal probe DM-V2CN-PYC3 was utilized for in vivo imaging of AD mice, demonstrating its rapid penetration through the blood-brain barrier and labelling to Aß species. Moreover, it enabled long-term monitoring for a duration of 120 min. These results highlight the enhanced affinity and superior performance of the designed NIR I Aß probe for AD diagnosis. The molecular design strategy of CN and amphiphilic modulation presents a promising avenue for the development Aß probes with low background in vivo/in vitro imaging for Aß species.

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This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, ß4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

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The study aimed to discuss the association between sleep duration and the risk of hyperhomocysteinemia (Hhcy). This cross-sectional study included 4173 adults (≥ 20 years) from the National Health and Nutrition Examination Survey 2005-2006. According to their sleep duration, participants were divided into five subgroups. Multivariate logistic regression analysis models and restrictive cubic spline regressions were used to explore the association between sleep duration and the risk of Hhcy. Compared with the participants who sleep 7 h, sleep deprivation (≤ 5 h) increased the risk of Hhcy, odds ratio (OR) 1.68 (95% confidence interval (CI) 1.06-2.68); Excessive sleep (≥ 9 h) also increased the risk of Hhcy, OR 1.86 (95% CI 1.09-3.14) after adjusting for a series of confounding factors in the entire population. The risk of Hhcy was distributed in a U-shape with sleep duration. Similar results were demonstrated in obese populations. The association between sleep duration and the risk of Hhcy is U-shaped. Both sleep deprivation and excessive sleep can increase the risk of Hhcy.

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Nucleic acid strand displacement is a pivotal concept in dynamic nucleic acid nanotechnologies, which has been extensively investigated and applied across various fields. Compared with DNA systems, the genetically expressed RNA strand displacement technology offers unique advantages for construction of genetic circuits in living cells, where RNA expression and modulation may be seamlessly integrated into the genomic network for long-term and stable regulations of diversified biological functionalities. This Concept paper provides an overview of previous efforts on developments of synthetic gene circuits through utilization of RNA strand displacement, including our endeavors in this field. Moreover, future prospects, potential applications and challenges of the genetically expressed RNA strand displacement technology are also discussed.

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Recombinant adeno-associated viruses (rAAVs) have emerged as an attractive tool for gene delivery, and demonstrated tremendous promise in gene therapy and gene editing-therapeutic modalities with potential "one-and-done" treatment benefits compared to conventional drugs. Given their tropisms for the central nervous system (CNS) across various species including humans, rAAVs have been extensively investigated in both pre-clinical and clinical studies targeting neurodegenerative disease. However, major challenges remain in the application of rAAVs for CNS gene therapy, such as suboptimal vector design, low CNS transduction efficiency and specificity, and therapy-induced immunotoxicity. Therefore, continuing efforts are being made to optimize the rAAV vectors from their "core" genetic payloads to their "coat" or capsid structure. In this review, we describe current approaches for rAAV vector design tailored for transgene expression in the CNS, summarize the development of CNS-targeting AAV serotypes, and highlight recent advancements in AAV capsid engineering, aimed at generating a new generation of rAAVs with improved CNS tropism. Additionally, we discuss various administration routes for delivering rAAVs to the CNS and provide an overview of AAV-mediated gene therapies currently under investigation in clinical trials for the treatment of neurodegenerative diseases.

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BACKGROUND: Coronary Artery Fistulas (CAFs) Patients with aneurysm may face severe complications, necessitating prompt treatment. However, data on the outcomes of transcatheter closure in CAFs patients with aneurysm are notably scarce. METHODS: This retrospective study included all consecutive CAFs patients who underwent transcatheter closure at Fuwai Hospital from January 2010 to December 2023. Patients were divided into two groups based on the presence of aneurysm, and baseline characteristics, anatomical features, and transcatheter closure outcomes were further compared. RESULTS: The study ultimately included 104 patients, consisting of 56 in the aneurysm group and 48 in the non-aneurysm group. Patients in the aneurysm group were younger [39.79 (16.35) versus 50.69 (13.31) years, p < 0.001] and more frequently present with heart murmurs (21.43% vs. 6.25%, p = 0.03). Multivariate logistic regression indicated that a larger fistula diameter and the presence of CCFs are independent risk factors for the presence of aneurysm in CAF patients. The procedural success rate (75% vs. 75%, P = 1), fistula recanalization rate (11.11% vs. 16.67%, p = 0.42), and reintervention rate (3.7% vs. 6.25%, p = 0.89) were similar between the aneurysm and non-aneurysm groups. CONCLUSION: A larger fistula diameters and the presence of coronary-cameral fistulas are independent risk factors for the occurrence of aneurysms in patients with CAFs. The outcomes of transcatheter closure are comparable for CAFs patients with and without aneurysm, though post-closure thrombosis within the fistula appears to be more common in patients with aneurysm.

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Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

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Electrocatalytic coupling of CO2 and NO3- to urea is a promising way to mitigate greenhouse gas emissions, reduce waste from industrial processes, and store renewable energy. However, the poor selectivity and activity limit its application due to the multistep process involving diverse reactants and reactions. Herein, we report the first work to design heterostructured Cu-Bi bimetallic catalysts for urea electrosynthesis. A high urea Faradaic efficiency (FE) of 23.5% with a production rate of 2180.3 µg h-1 mgcat-1 was achieved in H-cells, which surpassed most reported electrocatalysts in the literature. Moreover, the catalyst had a remarkable recycling stability. Experiments and density functional theory calculations demonstrated that introduction of moderate Bi induced the formation of the Bi-Cu/O-Bi/Cu2O heterostructure with abundant phase boundaries, which are beneficial for NO3-, CO2, and H2O activation and enhance C-N coupling and promote *HONCON intermediate formation. Moreover, favorable *HNCONH2 protonation and urea desorption processes were also validated, further explaining the reason for high activity and selectivity toward urea.

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PDK1 is crucial for PI3K/AKT/mTOR and Ras/MAPK cancer signaling. It phosphorylates AKT in a PIP3-dependent but S6K, SGK, and RSK kinases in a PIP3-independent manner. Unlike its substrates, its autoinhibited monomeric state has been unclear, likely due to its low population time, and phosphorylation in the absence of PIP3 has been puzzling too. Here, guided by experimental data, we constructed models and performed all-atom molecular dynamics simulations. In the autoinhibited PDK1 conformation that resembles autoinhibited AKT, binding of the linker between the kinase and PH domains to the PIF-binding pocket promotes the formation of the Glu130-Lys111 salt bridge and weakens the association of the kinase domain with the PH domain, shifting the population from the autoinhibited state to states accessible to the membrane and its kinase substrates. The interaction of the substrates' hydrophobic motif and the PDK1 PIF-binding pocket facilitates the release of the autoinhibition even in the absence of PIP3. Phosphorylation of the serine-rich motif within the linker further attenuates the association of the PH domain with the kinase domain. These suggest that while the monomeric autoinhibited state is relatively stable, it can readily shift to its active, catalysis-prone state to phosphorylate its diverse substrates. Our findings reveal the PDK1 activation mechanism and discover the regulatory role of PDK1's linker, which lead to two innovative linker-based inhibitor strategies: (i) locking the autoinhibited PDK1 through optimization of the interactions of AKT inhibitors with the PH domain of PDK1 and (ii) analogs (small molecules or peptidomimetics) that mimic the linker interactions with the PIF-binding pocket.

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Currently reported circularly polarized luminescent devices are primarily based on rare earth and noble metal complexes or lead perovskite materials. Reports on electroluminescent devices employing eco-friendly luminescent materials are notably scarce. In this study, we strategically designed and synthesized manganese complexes featuring Binapo as the chiral ligand. The complex structure reveals a tetrahedral coordination configuration, with the R/S configurations exhibiting a mirror relationship. Leveraging the strong ligand field and chiral structural characteristics of Binapo, the enantiomers display red emission and exhibit significant circularly polarized luminescence with a circularly polarized luminescence asymmetric factor (g lum) of 5.1 × 10-3. The circularly polarized electroluminescent performance was investigated by using a solution processing method and host-guest doping strategy. Our efforts resulted in device performance with an external quantum efficiency (EQE) exceeding 4%, and its electroluminescent asymmetric factor (g EL) reached an impressive -8.5 × 10-3. This surpasses the performance of most devices relying on platinum (Pt) and iridium (Ir) metal complexes and perovskite related materials. Our work establishes a pathway for the development of cost-effective and environmentally friendly chiral electroluminescent materials and devices.

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Skeletal muscle development is spotlighted in mammals since it closely relates to animal health and economic benefits to the breeding industry. Researchers have successfully unveiled many regulatory factors and mechanisms involving myogenesis. However, the effect of N6-methyladenosine (m6A) modification, especially demethylase and its regulated genes, on muscle development remains to be further explored. Here, we found that the typical demethylase FTO (fat mass- and obesity-associated protein) was highly enriched in goats' longissimus dorsi (LD) muscles. In addition, the level of m6A modification on transcripts was negatively regulated by FTO during the proliferation of goat skeletal muscle satellite cells (MuSCs). Moreover, a deficiency of FTO in MuSCs significantly retarded their proliferation and promoted the expression of dystrophin-associated protein 1 (DAG1). m6A modifications of DAG1 mRNA were efficiently altered by FTO. Intriguingly, the results of DAG1 levels and its m6A enrichment from FB23-2 (FTO demethylase inhibitor)-treated cells were consistent with those of the FTO knockdown, indicating that the regulation of FTO on DAG1 depended on m6A modification. Further experiments showed that interfering FTO improved m6A modification at site DAG1-122, recognized by Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and consequently stabilized DAG1 transcripts. Our study suggests that FTO promotes the proliferation of MuSCs by regulating the expression of DAG1 through m6A modification. This will extend our knowledge of the m6A-related mechanism of skeletal muscle development in animals.

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The formation of a hexagonal diamond represents one of the most intriguing questions in materials science. Under shock conditions, the graphite basal plane tends to slide and pucker to form diamond. However, how the shock strength determines the phase selectivity remains unclear. In this work, using a DFT-trained carbon global neural network model, we studied the shock-induced graphite transition. The poor sliding caused by scarce sliding time under high-strength shock leads to metastable hexagonal diamond with an orientation relationship of (001)G//(100)HD+[010]G//[010]HD, while under low-strength shock due to long sliding distance cubic diamond forms with the orientation (001)G//(111)CD+[100]G//[110]CD, unveiling the strength-dependent graphite transition mechanism. We for the first time provide computational evidence of the strength-dependent graphite transition from first-principles, clarifying the long-term unresolved shock-induced hexagonal diamond formation mechanism and the structural source of the strength-dependent trend, which facilitates the hexagonal diamond synthesis via controlled experiment.

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Liquidambar formosana Hance is renowned for its rich leaf color and possesses notable advantages, such as robust adaptability, strong resistance to diseases and pests, and rapid growth, making it a preferred choice for urban greening and carbon sequestration forest initiatives. The completion of whole-genome sequencing of L. formosana has spurred an increased interest in exploring the molecular mechanisms underlying seasonal changes in leaf color, marking a significant focus in L. formosana breeding research. However, there is currently a lack of stable reference genes suitable for analyzing the expression patterns of functional genes in L. formosana exhibiting varying leaf colors. This study selected five L. formosana varieties with significant differences in leaf colors. Through the RT-qPCR analysis, and evaluation using BestKeeper, geNorm, NormFinder, Delta Ct, and RefFinder, the expression stability of 14 candidate reference genes was examined. Consequently, two reference genes (LifEF1-α and LifACT) with stable expression, suitable for RT-qPCR of L. formosana with diverse leaf colors, were identified. The stability of these selected reference genes was further validated by examining the LifbHLH137 gene, which promoted the biosynthesis of anthocyanins. This advancement facilitated molecular biology and genetic breeding investigations of L. formosana, providing essential data for the precise quantification of functional genes associated with leaf color variation.

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Natural deep eutectic solvents (NADESs) showing higher cryoprotective effects are attracting concerns, because during the storage, system browning always occurs in aldose/amino acid-based NADESs, which generated brown substances remarkably weaken the cryoprotective effects. In this study, proline/glucose-based (PG) and proline/sorbitol-based (PS) NADESs were prepared, of which storage stability, browning profile, brown substance, and cryoprotective effects were investigated. Results showed that PG at molar ratios of 1:1, 2:1, and 3:1, as well as PS at 1:1, and 2:1 can form NADESs, among which only the PG-based ones could get browning after storage. The predominant brown substance was identified as 1-deoxy-1-L-proline-d-fructose (C11H19O7N, 278 m/z), which was subsequently verified to show cytotoxicity and decrease Saccharomyces cerevisiae cells viability after cryopreservation, suggesting that the brown substance could take a negative effect on cryopreservation. This study may help to attract more concerns to the storage and cryopreservation stabilities of the NADESs in food-related applications.

Assuntos