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Sequential recommendation typically utilizes deep neural networks to mine rich information in interaction sequences. However, existing methods often face the issue of insufficient interaction data. To alleviate the sparsity issue, self-supervised learning is introduced into sequential recommendation. Despite its effectiveness, we argue that current self-supervised learning-based (i.e., SSL-based) sequential recommendation models have the following limitations: (1) using only a single self-supervised learning method, either contrastive self-supervised learning or generative self-supervised learning. (2) employing a simple data augmentation strategy in either the graph structure domain or the node feature domain. We believe that they have not fully utilized the capabilities of both self-supervised methods and have not sufficiently explored the advantages of combining graph augmentation schemes. As a result, they often fail to learn better item representations. In light of this, we propose a novel multi-task sequential recommendation framework named Adaptive Self-supervised Learning for sequential Recommendation (ASLRec). Specifically, our framework combines contrastive and generative self-supervised learning methods adaptively, simultaneously applying different perturbations at both the graph topology and node feature levels. This approach constructs diverse augmented graph views and employs multiple loss functions (including contrastive loss, generative loss, mask loss, and prediction loss) for joint training. By encompassing the capabilities of various methods, our model learns item representations across different augmented graph views to achieve better performance and effectively mitigate interaction noise and sparsity. In addition, we add a small proportion of random uniform noise to item representations, making the item representations more uniform and mitigating the inherent popularity bias in interaction records. We conduct extensive experiments on three publicly available benchmark datasets to evaluate our model. The results demonstrate that our approach achieves state-of-the-art performance compared to 14 other competitive methods: the hit rate (HR) improved by over 14.39%, and the normalized discounted cumulative gain (NDCG) increased by over 18.67%.
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This case report details a rare instance of rapid iris metastasis from esophageal cancer in a 59-year-old man. A literature review was conducted to explore recent advances in detecting, diagnosing, and treating intraocular metastatic malignancies. Positron emission tomography-computed tomography played a crucial role in identifying primary sites and systemic metastases. Local treatment combined with systemic therapy effectively reduced tumor size, preserved useful vision, and improved the patient's survival rate. A comparison was made of the characteristics of iris metastases from esophageal cancer and lung cancer, including age, gender, tumor characteristics, and treatment. The challenges associated with diagnosis and treatment are discussed, highlighting the implications for clinical practice.
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Background: Sialyllacto-N-tetraose b (LSTb) is a component of human milk oligosaccharides. Due to its low concentration, the impact of LSTb on neurodevelopment remains largely unexplored. It is worth studying whether LSTb should be added to infant formula to simulate breast milk. This study aimed to investigate the effect of LSTb on the development of motor neurons of the central nervous system using a transgenic zebrafish model. Methods: Transgenic (Tg) zebrafish line (Hb9:GFP) was incubated with LSTb, and the axonal growth of caudal primary (CaP) neurons was assessed. Locomotor behavior was evaluated, and RNA sequencing (RNA-seq) was performed to identify the differentially expressed genes (DEGs). The expression of Slit2 and Slit3, genes involved in axon guidance, was further analyzed through real-time polymerase chain reaction (real-time PCR) and whole-mount in situ hybridization. Results: There was a significant increase in the number and length of CaP axon branches, suggesting that LSTb promotes CaP development. Behavioral analysis revealed enhanced locomotor activity in LSTb-treated larvae, indicating improved motor function. RNA-seq analysis identified 5,847 DEGs related to central nervous system neuron differentiation, including Slit2 and Slit3, which are known to contribute to axon guidance. In situ hybridization confirmed increased Slit2 expression in the central nervous system of LSTb-treated larvae. Conclusions: LSTb significantly influences motor neuron development, potentially through the upregulation of Slit2 and Slit3. This research provides valuable insights into the role of LSTb in neurodevelopment.
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OBJECTIVE: We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension). METHODS: In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs. RESULTS: Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable. CONCLUSION: Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV.
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Visualizing a 3D blood flow velocity field through noninvasive imaging is crucial for analyzing hemodynamic mechanisms in areas prone to disorders. However, traditional correlation-based optical coherence tomography (OCT) velocimetry techniques have a maximum measurable flow velocity depending on the A-line rate. We presented the ergodic speckle contrast OCT (ESCOCT) to break the bottleneck in measuring the rapid blood flow velocity. It achieved a measurement of blood flow velocity ranging from 9.5 to 280 mm/s using a 100 kHz swept-source (SS) OCT based on 100 A-repeats scanning mode. Addressing the non-ergodic problem of temporal OCT signals by integrating more consecutive A-scans, ESCOCT can enable the estimation for lower velocity flows by increasing A-repeats. ESCOCT provided a wide dynamic range with no upper limit on measuring blood flow velocity with an adequate signal-to-noise ratio and improved the sensitivity and accuracy of the hemodynamic assessment.
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Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Velocidade do Fluxo Sanguíneo/fisiologia , Reologia/métodos , Humanos , Razão Sinal-RuídoRESUMO
Background: Orf, also known as contagious ecthyma (CE), is an acute, contagious zoonotic disease caused by the orf virus (ORFV). The F1L protein is a major immunodominant protein on the surface of ORFV and can induce the production of neutralizing antibodies. Methods: The prokaryotic expression system was used to produce the recombinant F1L protein of ORFV, which was subsequently purified and used to immunize mice. Positive hybridoma clones were screened using an indirect enzyme-linked immunosorbent assay (ELISA). The reactivity and specificity of the monoclonal antibody (mAb) were verified through Western blot and indirect immunofluorescence (IFA). The linear antigenic epitope specific to the mAb was identified through Western blot, using truncated F1L proteins expressed in eukaryotic cells. A multiple sequence alignment of the ORFV reference strains was performed to evaluate the degree of conservation of the identified epitope. Results: After three rounds of subcloning, a mAb named Ba-F1L was produced. Ba-F1L was found to react with both the exogenously expressed F1L protein and the native F1L protein from ORFV-infected cells, as confirmed by Western blot and IFA. The mAb recognized the core epitope 103CKSTCPKEM111, which is highly conserved among various ORFV strains, as shown by homologous sequence alignment. Conclusion: The mAb produced in the present study can be used as a diagnostic reagent for detecting ORFV and as a basic tool for exploring the mechanisms of orf pathogenesis. In addition, the identified linear epitope may be valuable for the development of epitope-based vaccines.
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The adsorption behavior of gold thiosulfate ions on the surface of kaolinite was studied using a combination of experimental research and quantum chemical calculations. Under the condition of a stirring time of 30 min, a stirring speed of 500 r·min-1, and a mass ratio of 30% kaolinite in the slurry, when the initial gold concentration of 56.50 mg·L-1,the adsorption rate of gold-thiosulfate ions from a kaolinite-containing solution was 7.44%. The results of Fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS) showed that the physical and chemical adsorption of kaolinite and gold thiosulfate occurred in solution. Quantum chemical calculations were performed using the CASTEP module in Materials Studio. The adsorption energy of gold thiosulfate on the surface of kaolinite (001) was calculated as - 438.01 kJ·mol-1.The calculated H76-O289 distance was 1.615 Å. Mulliken Charge population analysis and bond population analysis showed that gold thiosulfate ions form relatively stable bonds on the kaolinite surface (001). In the process of thiosulfate immersion, part of gold is adsorbed by kaolinite, which affects the extraction of gold. These results indicate that during the leaching process of gold thiosulfate, kaolinite has the ability to "catch" gold, which affects the leaching efficiency.
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Herein, we describe a novel photoinduced iron-catalyzed strategy for multicomponent C-H alkylation of in situ generated imines. By utilizing the alkyl radicals generated through iron-mediated photocatalytic C-H activation, the imines formed in situ are further subjected to addition reactions, resulting in the synthesis of various secondary and tertiary amine products. This method is simple to operate and does not require additional oxidants. It is applicable to inert alkane substrates such as cyclic alkanes, cyclic ethers, toluene, and ketones. The reaction is also compatible with various aromatic amines, alkyl amines, halogenated aromatic amines, as well as aromatic aldehydes, alkyl aldehydes, and cinnamaldehyde, among other different types of aldehydes.
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Transient ischemic attack (TIA) is an early warning sign of stroke and death, necessitating suitable animal models due to the associated clinical diagnostic challenges. In this study, we developed a TIA model using flexible spatially targeted photothrombosis combined with real-time blood flow imaging feedback. By modulating the excitation light using wavefront technology, we precisely created a square light spot (50 × 250 µm), targeted at the distal middle cerebral artery (dMCA). The use of laser speckle contrast imaging (LSCI) provided real-time feedback on the ischemia, while the excitation light was ceased upon reaching complete occlusion. Our results demonstrated that the photothrombus formed in the dMCA and spontaneously recanalized within 10 min (416.8 ± 96.4 s), with no sensorimotor deficits or infarction 24 h post-TIA. During the acute phase, ischemic spreading depression occurred in the ipsilateral dorsal cortex, leading to more severe ischemia and collateral circulation establishment synchronized with the onset of dMCA narrowing. Post-reperfusion, the thrombi were primarily in the sensorimotor and visual cortex, disappearing within 24 h. The blood flow changes in the dMCA were more indicative of cortical ischemic conditions than diameter changes. Our method successfully establishes a photochemical TIA model based on the dMCA, allowing for the dynamic observation and control of thrombus formation and recanalization and enabling real-time monitoring of the impacts on cerebral blood flow during the acute phase of TIA.
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Circulação Cerebrovascular , Modelos Animais de Doenças , Ataque Isquêmico Transitório , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/fisiopatologia , Animais , Masculino , Trombose/diagnóstico por imagem , Camundongos , Imagem de Contraste de Manchas a Laser/métodos , Artéria Cerebral Média/diagnóstico por imagemRESUMO
OBJECTIVE: Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular multimodal analgesia techniques used during total knee arthroplasty (TKA). This study aimed to explore the efficacy of adding the IPACK technique to ACB and LIA in patients undergoing TKA. METHODS: In this retrospective cohort study, patients who underwent primary unilateral TKA were divided into two groups based on their date of admission. Sixty-three patients underwent IPACK, ACB and LIA (IPACK group) during surgery, while 60 patients underwent ACB and LIA (control group). The primary outcome was the postoperative administration of morphine hydrochloride as a rescue analgesic. Secondary outcomes included time to first rescue analgesia, postoperative pain assessed using the visual analog scale (VAS), functional recovery assessed by knee range of motion and ambulation distance, time until hospital discharge, and complication rates. RESULTS: The two groups were similar in average postoperative 0-to-24-h morphine consumption (11.8 mg for the control group vs 12.7 mg for the IPACK group, p = .428) and average total morphine consumption (18.2 mg vs 18.0 mg, p = .983) during hospitalization. There were also no significant differences in the secondary outcomes. CONCLUSIONS: The addition of IPACK to ACB and LIA did not provide any clinical analgesic benefits. Orthopedic surgeons and anesthesiologists are justified in using ACB and LIA without IPACK for TKA.
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Artroplastia do Joelho , Bloqueio Nervoso , Dor Pós-Operatória , Artéria Poplítea , Humanos , Estudos Retrospectivos , Artroplastia do Joelho/métodos , Masculino , Feminino , Idoso , Artéria Poplítea/cirurgia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Pessoa de Meia-Idade , Analgésicos Opioides/administração & dosagem , Morfina/administração & dosagem , Anestésicos Locais/administração & dosagem , Medição da Dor , Anestesia Local/métodos , Analgesia/métodos , Manejo da Dor/métodosRESUMO
The hippocampus is a critical brain region. Transcriptome data provides valuable insights into the structure and function of the hippocampus at the gene level. However, transcriptome data is often incomplete. To address this issue, we use the convolutional neural network model to repair the missing voxels in the hippocampus region, based on Allen institute coronal slices in situ hybridization (ISH) dataset. Moreover, we analyze the gene expression correlation between coronal and sagittal dataset in the hippocampus region. The results demonstrated that the trend of gene expression correlation between the coronal and sagittal datasets remained consistent following the repair of missing data in the coronal ISH dataset. In the last, we use repaired ISH dataset to identify novel genes specific to hippocampal subregions. Our findings demonstrate the accuracy and effectiveness of using deep learning method to repair ISH missing data. After being repaired, ISH has the potential to improve our comprehension of the hippocampus's structure and function.
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Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor, with its biological characteristics intricately linked to the activation of oncogenes. This research specifically explored CCDC137, a molecule within the CCDC family exhibiting the closest association with HCC. Our investigation aimed to unravel the role, underlying mechanisms, and potential therapeutic implications of CCDC137 in the context of HCC. We observed a close correlation between elevated CCDC137 expression and poor prognosis in HCC patients, along with a promotive effect on HCC progression in vitro and in vivo. Mechanistically, we identified LZTS2, a negative regulator of ß-catenin, as the binding protein of CCDC137. CCDC137 facilitated K48-linked poly-ubiquitination of LZTS2 at lysine 467 via recruiting E3 ubiquitin ligase ß-TrCP in the nucleus, triggering AKT phosphorylation and activation of ß-catenin pathway. Moreover, the 1-75 domain of CCDC137 was responsible for the formation of the CCDC137-LZTS2-ß-TrCP complex. Subsequently, designed peptides targeting the 1-75 domain of CCDC137 to disrupt CCDC137-LZTS2 interaction demonstrated efficacy in inhibiting HCC progression. This promising outcome was further supported by HCC organoids and patient-derived xenograft (PDX) models, underscoring the potential clinical utility of the peptides. This study elucidated the mechanism of the CCDC137-LZTS2-ß-TrCP protein complex in HCC and offered clinically significant therapeutic strategies targeting this complex.
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Chitin oligosaccharides have garnered significant attention due to their biological activities, particularly their immunomodulatory properties. However, O-acetylation in chemically preparing chitin oligosaccharides seems inevitable and leads to some uncertainty on the bioactivity of chitin oligosaccharides. In this study, an O-acetyl-free chitin oligosaccharides and three different O-acetylated chitin oligosaccharides with degree of polymerization ranging from 2 to 6 were prepared using ammonia hydrolysis, and their structures and detailed components were further characterized with FTIR, NMR and MS. Subsequently, the effects of O-acetylation on the immunomodulatory activity of chitin oligosaccharides were investigated in vitro and in vivo. The results suggested that the chitin oligosaccharides with O-acetylation exhibited better inflammatory inhibition than pure chitin oligosaccharides, significantly reducing the expression of inflammatory factors, such as IL-6 and iNOS, in the LPS-induced RAW264.7 macrophage. The chitin oligosaccharides with a degree of O-acetylation of 93 % was found to effectively alleviate LPS-induced endotoxemia in mice, including serum inflammation indices reduction and damage repairment of the intestinal liver, and kidney tissues.
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Quitina , Lipopolissacarídeos , Oligossacarídeos , Animais , Camundongos , Acetilação , Lipopolissacarídeos/farmacologia , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Quitina/química , Quitina/farmacologia , Células RAW 264.7 , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismoRESUMO
OBJECTIVES: Ceftolozane-tazobactam (C/T) is a combination of a cephalosporin and a ß-lactamase inhibitor with activity against Gram-negative bacilli (GNB). The study aims were to evaluate the activity of C/T in vitro vs. comparators against clinical GNB isolated from Chinese paediatric patients. METHODS: From 2017-2021, 660 GNB isolates were collected from 20 hospitals across China. The minimum inhibitory concentrations were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and the results were interpreted according to CLSI M100 (2021) breakpoints. RESULTS: GNB isolates were obtained from paediatric patients < 18 years old, mainly from the bloodstream (n = 146), intraperitoneal cavity (n = 138), lower respiratory (n = 278) and urinary tract (n = 96). Overall, C/T was active against 76.6% of 436 Enterobacterales, with a descending susceptibility rate of 100.0% to S. marcescens, 92.2% to E. coli, 83.3% to K. oxytoca, 66.7% to K. aerogenes, 66.7% to P. mirabilis, 58.6% to K. pneumoniae and 57.1% to E. cloacae. The susceptibility of P. aeruginosa to C/T was 89.4%, which was the highest among the ß-lactam antibiotics and was second only to amikacin (92.9%). Isolates of respiratory tract infection (RTI) derived P. aeruginosa were highly susceptible (93.8%) to C/T, while <75% of isolates of RTI derived P. aeruginosa were susceptible to the other ß-lactam antibiotics tested, except for ceftazidime-avibactam (91.2%). CONCLUSION: GNBs collected from paediatric patients in China showed a high susceptibility to C/T making this drug combination an effective choice for treating the paediatric population, especially those infected with P. aeruginosa.
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Orf is a zoonosis caused by the Orf virus (ORFV), which is endemic in goats, sheep, and wild ruminants worldwide. Orf infection is prevalent in China, with outbreaks reported in several provinces. Currently, there is limited information available regarding the characterization of ORFV strains in Jiangxi province. This study investigated an acute outbreak of Orf that occurred in 2021 in a goat herd in the Jiangxi province of China. Clinical signs in this case included lesions on the lips, nose, and inside the mouth. The presence of ORFV was confirmed from tissue samples by polymerase chain reaction (PCR). The nucleotide sequences of the B2L and F1L genes were fully sequenced and used to construct phylogenetic trees. The results of this investigation identified the ORFV JXxy2021 as the cause of the outbreak. The phylogenetic analysis revealed that the ORFV strain JXxy2021 had the highest similarity to the ORFV strains GO and FJ-SL from the neighboring province of Fujian. This suggests that JXxy2021 was likely transmitted from Fujian province. The results have provided valuable information on the genetic characteristics of JXxy2021 and the endemic situations of Orf in China.
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The recent discovery of superconductivity in La3Ni2O7-δ under high pressure with a transition temperature around 80 K (ref. 1) has sparked extensive experimental2-6 and theoretical efforts7-12. Several key questions regarding the pairing mechanism remain to be answered, such as the most relevant atomic orbitals and the role of atomic deficiencies. Here we develop a new, energy-filtered, multislice electron ptychography technique, assisted by electron energy-loss spectroscopy, to address these critical issues. Oxygen vacancies are directly visualized and are found to primarily occupy the inner apical sites, which have been proposed to be crucial to superconductivity13,14. We precisely determine the nanoscale stoichiometry and its correlation to the oxygen K-edge spectra, which reveals a significant inhomogeneity in the oxygen content and electronic structure within the sample. The spectroscopic results also reveal that stoichiometric La3Ni2O7 has strong charge-transfer characteristics, with holes that are self-doped from Ni sites into O sites. The ligand holes mainly reside on the inner apical O and the planar O, whereas the density on the outer apical O is negligible. As the concentration of O vacancies increases, ligand holes on both sites are simultaneously annihilated. These observations will assist in further development and understanding of superconducting nickelate materials. Our imaging technique for quantifying atomic deficiencies can also be widely applied in materials science and condensed-matter physics.
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Tooth instance segmentation of dental panoramic X-ray images represents a task of significant clinical importance. Teeth demonstrate symmetry within the upper and lower jawbones and are arranged in a specific order. However, previous studies frequently overlook this crucial spatial prior information, resulting in misidentifications of tooth categories for adjacent or similarly shaped teeth. In this paper, we propose SPGTNet, a spatial prior-guided transformer method, designed to both the extracted tooth positional features from CNNs and the long-range contextual information from vision transformers for dental panoramic X-ray image segmentation. Initially, a center-based spatial prior perception module is employed to identify each tooth's centroid, thereby enhancing the spatial prior information for the CNN sequence features. Subsequently, a bi-directional cross-attention module is designed to facilitate the interaction between the spatial prior information of the CNN sequence features and the long-distance contextual features of the vision transformer sequence features. Finally, an instance identification head is employed to derive the tooth segmentation results. Extensive experiments on three public benchmark datasets have demonstrated the effectiveness and superiority of our proposed method in comparison with other state-of-the-art approaches. The proposed method demonstrates the capability to accurately identify and analyze tooth structures, thereby providing crucial information for dental diagnosis, treatment planning, and research.
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Traffic state classification and relevance calculation at intersections are both difficult problems in traffic control. In this paper, we propose an intersection relevance model based on a temporal graph attention network, which can solve the above two problems at the same time. First, the intersection features and interaction time of the intersections are regarded as input quantities together with the initial labels of the traffic data. Then, they are inputted into the temporal graph attention (TGAT) model to obtain the classification accuracy of the target intersections in four states-free, stable, slow moving, and congested-and the obtained neighbouring intersection weights are used as the correlation between the intersections. Finally, it is validated by VISSIM simulation experiments. In terms of classification accuracy, the TGAT model has a higher classification accuracy than the three traditional classification models and can cope well with the uneven distribution of the number of samples. The information gain algorithm from the information entropy theory was used to derive the average delay as the most influential factor on intersection status. The correlation from the TGAT model positively correlates with traffic flow, making it interpretable. Using this correlation to control the division of subareas improves the road network's operational efficiency more than the traditional correlation model does. This demonstrates the effectiveness of the TGAT model's correlation.
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The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nemopilema nomurai Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds' ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A2, showcasing the viability of small-molecule compounds in managing toxin-induced injuries.