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Abstract Background Esophageal Squamous Cell Carcinoma (ESCC) remains a predominant health concern in the world, characterized by high prevalence and mortality rates. Advances in single-cell transcriptomics have revolutionized cancer research by enabling a precise dissection of cellular and molecular diversity within tumors. Objective This study aims to elucidate the cellular dynamics and molecular mechanisms in ESCC, focusing on the transcriptional influence of STAT3 (Signal Transducer and Activator of Transcription 3) and its interaction with LHPP, thereby uncovering potential therapeutic targets. Methods Single-cell RNA sequencing was employed to analyze 44,206 cells from tumor and adjacent normal tissues of ESCC patients, identifying distinct cell types and their transcriptional shifts. We conducted differential gene expression analysis to assess changes within the tumor microenvironment (TME). Validation of key regulatory interactions was performed using qPCR in a cohort of 21 ESCC patients and further substantiated through experimental assays in ESCC cell lines. Results The study revealed critical alterations in cell composition and gene expression across identified cell populations, with a notable shift towards pro-tumorigenic states. A significant regulatory influence of STAT3 on LHPP was discovered, establishing a novel aspect of ESCC pathogenesis. Elevated levels of STAT3 and suppressed LHPP expression were validated in clinical samples. Functional assays confirmed that STAT3 directly represses LHPP at the promoter level, and disruption of this interaction by promoter mutations diminished STAT3's repressive effect. Conclusion This investigation underscores the central role of STAT3 as a regulator in ESCC, directly impacting LHPP expression and suggesting a regulatory loop crucial for tumor behavior. The insights gained from our comprehensive cellular and molecular analysis offer a deeper understanding of the dynamics within the ESCC microenvironment. These findings pave the way for targeted therapeutic interventions focusing on the STAT3-LHPP axis, providing a strategic approach to improve ESCC management and prognosis.

Abstract Tourism carbon offsetting is a crucial pathway to achieving peak carbon and carbon neutrality in the tourism industry. Accurately grasping the collaborative evolutionary mechanisms among local governments, tourism enterprises, and tourists is key to promoting the implementation of tourism carbon offsetting. By constructing an evolutionary game model involving local governments, tourism enterprises, and tourists in carbon offsetting, this study uses MATLAB to simulate the evolutionary stable strategies under various conditions. Additionally, it dynamically simulates the collaborative strategies of the three parties under the influence of local government incentive and constraint mechanisms. The results indicate that under strong governmental constraint mechanisms, there is a promotion of active participation in carbon offsetting by local governments, tourism enterprises, and tourists. Incentive policies at certain levels also play a positive guiding role. As incentives increase, local subsidies and intervention costs also rise, leading to an evolution towards less enthusiastic participation among the three parties. Appropriately balanced government incentives and penalties are beneficial in achieving an equilibrium of benefits among multiple stakeholders involved in carbon offsetting, thus helping to attain carbon neutrality goals.

ABSTRACT Backgroud Cancer‐related cognitive impairment is one of the common complications in children with cancer, but our understanding of their experience with cognitive deficits remains limited. From the perspective of parents, this study aimed to explore the distress and demands faced by children with cancer‐related cognitive impairment, to provide references for developing targeted intervention strategies for cancer children. Methods We used a purposeful sampling method to conduct semi‐structured interviews with the parents of 18 children with cancer‐related cognitive impairment. The transcripts were analyzed using Colaizzi's method. Results Three categories and 11 subcategories were obtained from the data analysis, including diverse levels of cognitive impairment in children (speech communication difficulties, impaired executive function, attention deficit, and intellectual disability), persistent negative emotions (anxiety and worry, complaints and resentment, negative avoidance and positive experiences after psychological adjustment), multiple needs (need for disease information, need for professional management, and an urgent need for more external support). Conclusion Parents of children with cancer‐related cognitive impairment face a significant psychological burden, coupled with confusion and numerous inquiries regarding the symptoms and management of their children's cognitive impairment. It is imperative for medical professionals to strengthen the dissemination of information related to cancer‐associated cognitive impairments, while promptly recognizing and intervening in related symptoms. Rational allocation of resources, establishment of targeted support systems, and enhancement of social acceptance may be the key points that policymakers could consider. These efforts hold immense significance, as they play a pivotal role in elevating cognitive capabilities and enhancing the overall quality of life for children with cancer.

Esophageal cancer is considered one of the most significant challenges to public health worldwide. While various therapeutic options exist for esophageal cancer, including chemotherapy, radiotherapy, and surgery, several adverse effects of these medications have been reported. Therefore, a new generation of therapeutic lines should be applied to minimize complications. In this regard, immunotherapy is a novel approach that aims to kill tumor cells directly by targeting them. Specifically, monoclonal antibodies can target specific markers of esophageal cancer tumor cells, keeping other normal cells safe. Multiple monoclonal antibodies optimized for esophageal cancer, such as pembrolizumab, ramucirumab, trastuzumab, nivolumab, and ipilimumab, are available. On the other hand, esophageal cancer tumor cells express a specific inhibitory ligand and its receptor called programmed cell death, which can suppress T cell immune responses. This receptor provides an inhibitory signal, causing the highest expression of the PD-L1 ligand on tumor cells. The outcomes of this interaction lead to the suppression of the activation and function of T lymphocytes. Therefore, immunotherapy for esophageal cancer targeting the PD-1/PD-L1 pathway has shown a remarkable correlation with cancer care. This study presents a comprehensive review of the latest findings related to immunotherapy in esophageal cancer.

ABSTRACT Melioidosis is a severe and often fatal infectious disease caused by Burkholderia pseudomallei, which poses significant challenges due to its high mortality rate and frequent misdiagnosis. To effectively treat infected patients, especially in epidemic regions like Hainan with a high resistance rate to ceftazidime (CAZ), early diagnosis and resistance testing are critical. Here, we designed a strategy that combines RNase-HII-dependent PCR with lateral flow strip assay (LFSA) for simultaneous detection of B. pseudomallei and its CAZ resistance mutation. In this strategy, we utilized rhPCR technology to design specific primers with a C3-spacer modification. These primers target a 115-base pair region within the ORF2 of the B. pseudomallei type III secretion system gene cluster, as well as the P174L mutation in the penA gene, which is a major mutation associated with CAZ resistance in Hainan. The primers contain complementary RNA bases that can be hydrolyzed only in the presence of thermostable RNase-HII enzymes, facilitating subsequent PCR reactions. Additionally, we introduced two pairs of universal probes carrying fluorescein isothiocyanate (FITC) and biotin, as well as digoxin and biotin. The sequences of these universal probes align with specific regions of the primers, resulting in target products labeled with different tags. The resulting amplification products are then subjected to LFSA, where the presence of specific markers is visually interpreted based on color development. These markers flow to test line 1 (T1) and are captured by a fixed anti-FITC antibody, generating a red line that indicates the presence of B. pseudomallei. Similarly, the occurrence of a red line on test line 2 (T2), which is fixed with anti-digoxin antibodies, indicates the presence of the P174L mutation in B. pseudomallei. This protocol serves as an excellent tool for the rapid diagnosis of melioidosis and provides a basis for selecting appropriate antibiotic medication. It has the potential to revolutionize the diagnosis of melioidosis, particularly in resource-limited settings. Furthermore, this technique holds promise as a versatile tool for disease diagnosis in general. IMPORTANCE This study focused on the development of a reaction system using rhPCR to amplify a specific gene, ORF2, of B. pseudomallei and to identify the P174L mutation associated with increased drug resistance to ceftazidime (CAZ). The system incorporated universal primer probes and a simple temperature cycle reaction. The amplified products were then analyzed using lateral flow strip assay (LFSA) for strain identification and mutation interpretation. The developed system provides a reliable basis for diagnosing melioidosis and selecting appropriate drugs. Its potential impact is particularly significant in resource-limited settings where access to advanced diagnostic techniques is limited. This platform stands out for its simplicity, convenience, sensitivity, specificity, and portability. It shows promise as a point-of-care testing method for detecting single nucleotide polymorphism in genes associated with other diseases. By leveraging the advantages of this platform, researchers and healthcare professionals can potentially expand its use beyond melioidosis and apply it to the rapid detection of genetic variations in other disease-related genes.

Abstract Recent years have witnessed a great progress in single-channel speech separation by applying self-attention based networks. Despite the excellent performance in mining relevant long-sequence contextual information, self-attention networks cannot perfectly focus on subtle details in speech signals, such as temporal or spectral continuity, spectral structure, and timbre. To tackle this problem, we proposed a time-domain adaptive attention network (TAANet) with local and global attention network. Channel and spatial attention are introduced in local attention networks to focus on subtle details of the speech signals (frame-level features). In the global attention networks, a self-attention mechanism is used to explore the global associations of the speech contexts (utterance-level features). Moreover, we model the speech signal serially using multiple local and global attention blocks. This cascade structure enables our model to focus on local and global features adaptively, compared with other speech separation feature extraction methods, further boosting the separation performance. Versus other end-to-end speech separation methods, extensive experiments on benchmark datasets demonstrate that our approach obtains a superior result. (20.7 dB of SI-SNRi and 20.9 dB of SDRi on WSJ0-2mix).

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.

This study examined the effects of physical activity(PA) on the quality of life (QOL) of athletes with disabilities using sport and health theory. We administered a paper-based field questionnaire to 118 athletes with disabilities and used structural equation modeling to analyze the mechanisms of physical self-esteem (PSE) and satisfaction with life (SWL) in the role of PA and QOL in athletes with disabilities. Results: 1) PA still had a significant positive effect on the QOL of athletes with disabilities mediated by PSE (β = 0.206, p

Abstract In the cloud manufacturing process, service composition can combine a single service into a complex service to meet the task requirements. An efficient service composition strategy is crucial, as it affects the efficiency of resource and capacity sharing in the cloud manufacturing system. However, in the face of a large-scale environment, the existing methods have the problems of slow convergence and instability. To solve the problems above, we propose an improved optimization method, named improved-TC. Specifically, we are inspired by the horizontal crossover of CSO in the hybrid-TC teaching phase, the Hybrid-TC is proposed in our previous work, which is a hybrid of the teaching-learning-based optimization algorithm (TLBO) and the crisscross optimization algorithm (CSO). Improved-TC is an improvement on the learning phase of hybrid-TC algorithm, we change the search method of hybrid-TC in the learning phase to a one-dimensional search, thereby some dimensions in the population that are trapped in the local optimum have the chance to jump out of the iteration. Experiments show that our proposed method has a faster convergence speed and more stability in the face of service composition in large-scale environments.

Improving the life satisfaction of ecological migrants is important for promoting the construction of an ecological civilisation. Based on using sustainable livelihood theory and social adaptation theory to construct an analytical framework for life satisfaction, we innovatively include livelihood capital, social adaptation, and life satisfaction in the same research framework. Using microscopic research data on Kazakh herders in Kalajun, Xinjiang, we empirically analyse the effects of livelihood capital and social adaptation on herders’ life satisfaction using structural equation modelling and further discuss the direct and indirect effects of livelihood capital on life satisfaction. The results show that, first, the mean value of livelihood capital of the sample herding households is below the medium level overall, the mean value of social adaptation is above the medium level, and the life satisfaction of herders is above the medium level. Thus, the ecological migration policy has enhanced the herders’ life satisfaction to a certain extent. Second, financial and natural capital contribute more to the level of livelihood capital, while cultural, life, and psychological adaptation contribute more to the level of social adaptation. Third, both livelihood capital and social adaptation have a significant positive effect on pastoralists’ life satisfaction, i.e., the higher the level of livelihood capital and social adaptation of pastoralists, the more prominent their livelihood capacity and social relations are, and the higher their life satisfaction will be. Fourth, the direct effect of social adaptation on life satisfaction is significantly greater than that of livelihood capital; this should be used to alleviate psychological stress by enhancing herders’ social adaptation abilities. Fifth, the direct impact of livelihood capital on life satisfaction is greater than its indirect impact, and the improvement in human and financial capital will help herders overcome their current livelihood difficulties. The findings of this study will help the government understand the level of livelihood capital and social adaptation of ecological migrant households and provide a reference for further improving ecological migrants’ wellbeing and promoting sustainable regional development.

In this work, we report a novel quantum state reconstruction process based on the disentanglement algorithm. We propose a sequential disentanglement scheme, which can transform an unknown quantum state into a product of computational zero states. The inverse evolution of the zero states reconstructs the quantum state up to an overall phase. By sequentially disentangling the qubits one by one, we reduce the required measurements with only individual qubit measurement and identify the transformation unitary efficiently. Variational quantum circuit and reinforcement learning methods are used for the quantum circuit design for continuous and discrete quantum gates implementation. Demonstrations with our proposal for the reconstruction of the random states are presented. Our method is universal and imposes no specific ansatz or constraint on the quantum state.

Abstract Although current attention‐based speech enhancement methods have been proven to be capable of significantly improving the noise reduction performance, a bottleneck has arisen in juggling both detailed features and high‐level features: The more attention paid to such performance indicators as speech intelligibility index and articulation index will lead to the loss of subtle features such as syllable continuity and timbre distortion. To tackle such a problem, we divide the speech enhancement model into multiple stages, with a special attention mechanism introduced in each stage so that the detailed speech information is retained and the features of high levels are captured. In this research, a Multi‐Stage Attention Network (MSANet) is implemented in cascade by using three different attention modules: Self Attention, Channel Attention and Spatial Attention. The attention module in each stage needs only to focus on the features of its corresponding stage, thus giving full play to their respective advantages without affecting or damaging the features of other stages, helping decouple the feature extraction process and obtaining the features capable of complementing one another. The comparisons and ablation experiments show that the performance of MSANet is superior to those of current mainstream time domain or time‐frequency domain state‐of‐the‐art methods. Compared to the baseline, PESQ score of their model (3.11) has increased by 5%, CSIG (4.44) has increased by 2.5%, CBAK (3.63) has increased by 2.8% and COVL (3.81) has increased by 3.8%, which demonstrates the potential of MSANet as speech feature extraction backbones. An implementation of the PyTorch version is available here: http://www.msp‐lab.cn:1436/msp/MSANet.

Abstract Background The complications of postoperative pain, such as hypertension, hypermetabolism, irritability, and postoperative cognitive dysfunction, significantly affect the postoperative rehabilitation of elderly patients. Intrathecal morphine prolongs analgesia after surgery, but has been implicated in nausea and vomiting, pruritus, postoperative respiratory depression, or apneic episodes. The present study explored the effect and safety of low-dose morphine used adjunctively with bupivacaine during single spinal anesthesia or sufentanil patient-controlled intravenous analgesia (PCIA) in elderly patients with hip fracture surgery. Since elderly patients often need anticoagulant therapy in the early postoperative period, single spinal anesthesia was involved in completing the operation in this study. Methods Eighty elderly patients aged 70–85 years who underwent elective hip fracture surgery with single spinal anesthesia were divided into two groups, 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of morphine (morphine group, group M) and 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of sufentanil PCIA (sufentanil group, group S). The analgesia scores using the visual analogue scale (VAS), the Brinell comfort scale (BCS) were evaluated at 6, 12, 24, and 48 h after operation, and adverse reactions were recorded such as nausea and vomiting, pruritus, sedation, respiratory depression, and POD (postoperative delirium) with Delirium Rating Scale-r 98. Results Within 24 h after operation, the analgesic and BCS scores of group M were better than those of group S (P

Abstract Growing evidence indicates that lncRNA colon cancer-associated transcript 2 (CCAT2) is associated with cancers. However, the clinical value of CCAT2 in cervical cancer (CC) remains unclear. In this study, serum CCAT2 level was detected by real-time quantitative PCR (RT-qPCR). Carbohydrate antigen 125 (CA125) and squamous-cell carcinoma antigen (SCC) were detected by electrochemiluminescence. A receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CCAT2. Kaplan-Meier survival analysis and univariable and multivariable analyses were performed to assess the prognostic value of CCAT2. The relative expression level of CCAT2 in primary CC patients was significantly higher than that in cervical intraepithelial neoplasias (CIN) patients and healthy controls (both P

Summary: The cerebellum is critical for motor coordination and learning. However, the role of feedback circuitry in this brain region has not been fully explored. Here, we characterize a nucleo-ponto-cortical feedback pathway in classical delayed eyeblink conditioning (dEBC) of rats. We find that the efference copy is conveyed from the interposed cerebellar nucleus (Int) to cerebellar cortex through pontine nucleus (PN). Inhibiting or exciting the projection from the Int to the PN can decelerate or speed up acquisition of dEBC, respectively. Importantly, we identify two subpopulations of PN neurons (PN1 and PN2) that convey and integrate the feedback signals with feedforward sensory signals. We also show that the feedforward and feedback pathways via different types of PN neurons contribute to the plastic changes and cooperate synergistically to the learning of dEBC. Our results suggest that this excitatory nucleo-ponto-cortical feedback plays a significant role in modulating associative motor learning in cerebellum.

The lamin B receptor (LBR) gene is located in chromosome 1q42.12 and encodes the lamin B receptor, an intracellular protein that binds to lamin B. LBR mutations are associated with a broad phenotypic spectrum ranging from non-lethal to lethal skeletal dysplasias. The typical phenotypes include the Pelger−Huet anomaly (PHA) and embryonic lethal Greenberg dysplasia (GRBGD). With the further study of this gene, other phenotypes have been found in different individuals. This retrospective study analyzed recurrent prenatal moderate skeletal dysplasias in Chinese fetuses. Nothing malformed was detected in the fetal karyotype and microarray, while the whole-exome sequencing identified a homozygous variant (NM_002296.4:c.1757G>A, NP_002287.2:p.Arg586His) in exon 14 of the LBR gene in both fetuses. Mutation analysis in the parents confirmed that the c.1757G>A variation is heterozygous by Sanger sequencing. Intensive analysis on bioinformatics and familial co-segregation suggest that the homozygous variation in the LBR gene is responsible for this recurrent prenatal moderate skeletal dysplasia. Moreover, moderate skeletal dysplasias differ from typical GRBGD phenotypes. Our findings are based on the DNA base test and the prenatal diagnosis of skeletal dysplasia, which can be helpful in proper phenotyping and contribute to a better understanding of the correlation between the phenotype and genotype.

Summary: Itch is a complex and unpleasant sensory experience. Recent studies have begun to investigate the neural mechanisms underlying the modulation of sensory and emotional components of itch in the brain. However, the key brain regions and neural mechanism involved in modulating the attentional processing of itch remain elusive. Here, we showed that the prelimbic cortex (PrL) is associated with itch processing and that the manipulation of itch-responsive neurons in the PrL significantly disrupted itch-induced scratching. Interestingly, we found that increasing attentional bias toward a distracting stimulus could disturb itch processing. We also demonstrated the existence of a population of attention-related neurons in the PrL that drive attentional bias to regulate itch processing. Importantly, itch-responsive neurons and attention-related neurons significantly overlapped in the PrL and were mutually interchangeable in the regulation of itch processing at the cellular activity level. Our results revealed that the PrL regulates itch processing by controlling attentional bias.

Abstract Object detection is one of the main tasks in computer vision and has made great progress in recent years. However, the performance of target detectors is significantly dropped by the differences between existing datasets and application scenarios, leading to the so‐called domain shift problem. To address such an issue, a novel co‐teaching based pseudo label refinery framework for cross‐domain object detection is developed, which cooperates with two models to select data from target domain for each other. This strategy can effectively purify the predicted pseudo labels and resist noisy labels. Specifically, the framework consists of two encoders (i.e. structure encoder and global encoder), two classifiers and one discriminator, in which structure encoder is used to extract structural features that are not disturbed by colour, and the global encoder is used to extract the complete discriminant features. The two encoders are each followed by a classifier. In training, the structure and global encoder with labelled source samples are first trained, so that it has the initial recognition ability. Then the samples assigned are used with pseudo labels by the classifier following the structure encoder to fine‐tune the global encoder which pre‐trained on the labelled source domain and obtain the refined labels for the target data. With the refined labels, the structure encoder is further optimised on the target domain. During this process, the proposal is to cross use the two classifiers to promote the mutual transfer of complementary capabilities of the two encoders. Moreover, a novel residual channel attention block (RCA) embedded with salient features is designed to pay more attention to the target regions. Extensive experiments demonstrate that the developed framework can generate clean labels for unlabelled target data and boost the performance of cross domain object detection. The code is available at http://www.msp‐lab.cn:1436/msp/cbplr‐master.

Osteoarthritis (OA) is a multifactorial and chronic degenerative joint disease. Due to the adverse effects of currently used drugs, a safer and more effective therapy for treating OA is needed. Peroxisome proliferator-activated receptor-γ (PPARγ) is a key protein protecting cartilage. DNMT1-mediated hypermethylation of PPARγ promoter leads to its suppression. Therefore, DNMT1 might be an effective target for exerting cartilage protective effects by regulating the epigenetic expression of PPARγ. Dabushen decoction (DD) is a representative prescription of Dunhuang ancient medical prescription, which has a potential therapeutic effect on OA. So far, the research of the efficacy and material basis of DD in the treatment of OA remains unclear. In this study, Micro-CT, HE staining, S-O staining, and immunohistochemistry analysis were used to demonstrate that DD increased the expression of PPARγ and collagen synthesis in an OA rat model. Next, the structure of DNMT1 was used to screen the active constituents of DD by molecular docking method for treatment OA. Seven potential active constituents, including isoliquiritigenin, emodin, taxifolin, catalpol, alisol A, zingerone, and schisandrin C were hited. The protective effect of the potential active constituents to chondrocytes were evaluated by protein capillary electrophoresis, immunofluorescence assays, and ex vivo culture of rat knee cartilage. The five constituents, such as alisol A, emodin, taxifolin, isoliquiritigenin, and schisandrin C could promote the expression of PPARγ and ameliorate IL-1β-induced downregulation of collagen II and the production of MMP-13. Alisol A and Emodin could effectively mitigate cartilage damage. At last, molecular dynamics simulations with MM-GBSA method was applied to investigate the interaction pattern of the active constituents and DNMT1 complexes. The five constituents, such as alisol A, emodin, taxifolin, isoliquiritigenin, and schisandrin C achieved a stable binding pattern with DNMT1, in which alisol A has a relatively high binding free energy. In conclusion, this study elucidates that the active constituents of DD (alisol A, emodin, taxifolin, isoliquiritigenin, and schisandrin C) could ameliorate osteoarthritis via PPARγ preservation by targeting DNMT1.These findings facilitated clinical use of DD and provided a valuable strategy for developing natural epigenetic modulators from Chinese herbal formula.

Enrichment of nutrients is believed to lead to coastal hypoxia which have become a seasonal phenomenon over large river estuarine areas such as the Mississippi River-Northern Gulf of Mexico and Changjiang-East China Sea. A similar nutrient enrichment process exists in the Pearl River. However, hypoxia occurs only as episodic events over a relatively small area. We hypothesize that frequent wind events play the interruptive mechanism in preventing the seasonal formation of bottom hypoxia. We used 29 years’ time series data of dissolved oxygen (DO) and winds in the Hong Kong coastal waters to test the hypothesis. Our results show that bottom DO at 3 stations in southern waters of Hong Kong occasionally drops below the hypoxic level (2 mg/L), lasting only for less than one month in summer. Episodic hypoxia events appear to occur more frequently in recent years, but bottom DO does not show a significantly decreasing trend. The wind speed of 6 m/s appears to be a threshold, above which a wind event could destroy water column stratification and interrupt the formation of low-oxygen (DO

Gastric hepatoid adenocarcinoma (GHAC) is a highly aggressive histological subtype of gastric cancer (GC) with similar tissue morphology to hepatocellular carcinoma. GHAC frequently produces alpha-fetoprotein (AFP) and has a poor prognosis; however, standardized treatment remains elusive. We report a male patient in his early 60s with GHAC who received immunotherapy, and the curative effect was evaluated. He was admitted because of progressive fatigue and dizziness for 2 months. He had experienced spontaneous epigastric pain with muscular defense of the epigastrium and accompanying tenderness 1 year earlier and underwent radical gastrectomy. Immunohistochemistry showed that hepatocyte-specific marker (Hep) was highly-expressed, indicating probable GHAC. Additionally, imaging suggested GC recurrence or gastric stump cancer. Radioimmunoassay indicated an AFP level of >1210.00 µg/L, and liver biopsy was performed following abdominal contrast-enhanced computed tomography. Pathology showed a few hepatocytes and proliferative fibrous connective tissue. The patient received three cycles of chemotherapy, with no obvious improvement. The possibility of surgical treatment was excluded, and immunotherapy or palliative treatment was selected. He received 11 cycles of a programed death-1 (PD-1) monoclonal antibody, and the effect of treatment was satisfactory. The mechanism of action of immunotherapy in GHAC warrants further investigation.

This paper is devoted to the problem of uncertainty in fractional-order Chaotic systems implemented by means of standard electronic components. The fractional order element (FOE) is typically substituted by one complex impedance network containing a huge number of discrete resistors and capacitors. In order to balance the complexity and accuracy of the circuit, a sparse optimization based parameter selection method is proposed. The random error and the uncertainty of system implementation are analyzed through numerical simulations. The effectiveness of the method is verified by numerical and circuit simulations, tested experimentally with electronic circuit implementations. The simulations and experiments show that the proposed method reduces the order of circuit systems and finds a minimum number for the combination of commercially available standard components.

Abstract Background This study aimed to investigate the clinical characteristics of miR-450b-3p in the patients of gastric cancer (GC), and further explore whether miR-450b-3p could inhibit the proliferation of GC cells via regulating KLF7. Methods Real-time quantitative PCR (qRT-PCR) was performed to detect the expression level of miR-450b-3p in 48 GC patients of tumor tissue and paracancerous tissue specimens collected, and the associations between miR-450b-3p and the clinical characteristics of GC patients were analyzed. Meanwhile, the expression of miR-450b-3p in GC cell lines was verified using qRT-PCR. miR-450b-3p overexpression vectors was constructed in GC cell lines including AGS and BGC-823, and then CCK-8 cell proliferation assay, Plate colony formation assay and EdU assay were applied to analyze the biological function of miR-450b-3p in GC cell lines. Results The results of qRT-PCR showed that the expression level of miR-450b-3p in GC tissues was lower than that in paracancerous tissues, and the difference was statistically significant. Compared with GC patients with high-miR-450b-3p expression, these GC patients with low-miR-450b-3p expression had a higher pathological stage and tumor size. Subsequently, the proliferation ability of GC cells in miR-450b-3p mimic was significantly decreased when comparing with the NC mimic. In addition, qRT-PCR indicated that the expression level of KLF7 significantly decreased after miR-450b-3p mimic. Therefore, it was demonstrated that miR-450b-3p might inhibit the malignant progression of GC via modulating KLF7. Bioinformatics analysis and dual luciferase reporter suggested miR-450b-3p was bound to KLF7. Finally, the results of the reverse experiment confirmed that overexpression of KLF7 could reverse miR-450b-3p mimic induced-inhibition of GC malignant progression. Conclusions Generally, miR-450b-3p significantly down-regulated in GC tissues and cell lines, and was associated with the pathological stage and tumor size of GC patients. Meanwhile, miR-450b-3p inhibited cell proliferation in GC via modulating KLF7.

Real-time acquisition of industrial production data and rapid response to changes in the external environment are key to ensuring the symmetry of a CPS. However, during industrial production, the collected data are inevitably disturbed by environmental noise, which has a huge impact on the subsequent data processing of a CPS. The types of noise vary greatly in different work scenarios in a factory. Meanwhile, barriers such as data privacy protection and copyright restrictions create great difficulties for model synthesis in the information space. A speech enhancement model with teacher–student architecture based on federal knowledge distillation is proposed to alleviate this problem. (1) We pre-train teacher models under different noise conditions to create multiple teacher models with symmetry and excelling in the suppression of a priori noise. (2) We construct a symmetric model–student model of the physical space of the teacher model trained on public data and transfer the knowledge of the teacher model to the student model. The student model can suppress multiple types of noise. Notably, with the TIMIT dataset and the NoiseX92 noise set, the accuracy of the proposed method improved by an average of 1.00% over the randomly specified teacher method in the PESQ metric and 0.17% for STOI.

In this work, we address the question whether a sufficiently deep quantum neural network can approximate a target function as accurate as possible. We start with typical physical situations that the target functions are physical observables, and then we extend our discussion to situations that the learning targets are not directly physical observables, but can be expressed as physical observables in an enlarged Hilbert space with multiple replicas, such as the Loschmidt echo and the Rényi entropy. The main finding is that an accurate approximation is possible only when all the input wave functions in the dataset do not span the entire Hilbert space that the quantum circuit acts on, and more precisely, the Hilbert space dimension of the former has to be less than half of the Hilbert space dimension of the latter. In some cases, this requirement can be satisfied automatically because of the intrinsic properties of the dataset, for instance, when the input wave function has to be symmetric between different replicas. And if this requirement cannot be satisfied by the dataset, we show that the expressivity capabilities can be restored by adding one ancillary qubit at which the wave function is always fixed at input. Our studies point toward establishing a quantum neural network analogy of the universal approximation theorem that lays the foundation for expressivity of classical neural networks.

Abstract. Background:. Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods:. The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results:. Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios+ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion:. Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

Prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR) are considered to be effective neurobiological measures of sensorimotor gating and information processing. The deficit of PPI and habituation of ASR has been proposed to be candidate endophenotypes of schizophrenia spectrum disorders. However, there has been little information on PPI and ASR measures in Chinese. The present study aimed to provide more information about the characteristics of PPI and ASR in young healthy Chinese and investigate their sensitivity to experimental parameters and characteristics of population. In this study, we examined the PPI and habituation of ASR in 41 young healthy adults (21 males and 20 females), using an acoustic startle stimulus of 115 dB and a prepulse of 75 dB at a lead interval (LI) of 60 ms and 120 ms, respectively. The behavioral performance demonstrated that the PPI and habituation of ASR in all the young participants were robust. The significant difference was not observed in PPI and habituation between male and female. The block effect on PPI was significant; PPI reduces with increasing training. Latency facilitation was observed under prepulse conditions, with a significant effect of LI. Compared to previous studies in Caucasians, Chinese in this study shows a higher habituation and PPI. In conclusion, this research provides more data of behavioral characteristics of PPI and ASR in young healthy Chinese. Chinese in this study shows a higher habituation and PPI than Caucasians in previous studies.

In the field of Differential Evolution (DE), a number of measures have been used to enhance algorithm. However, most of the measures need revision for fitting ensemble of different combinations of DE operators-ensemble DE algorithm. Meanwhile, although ensemble DE algorithm may show better performance than each of its constituent algorithms, there still exists the possibility of further improvement on performance with the help of revised measures. In this paper, we manage to implement measures into Ensemble of Differential Evolution Variants (EDEV). Firstly, we extend the collecting range of optional external archive of JADE-one of the constituent algorithm in EDEV. Then, we revise and implement the Event-Triggered Impulsive (ETI) control. Finally, Linear Population Size Reduction (LPSR) is used by us. Then, we obtain Improved Ensemble of Differential Evolution Variants (IEDEV). In our experiments, good performers in the CEC competitions on real parameter single objective optimization among population-based metaheuristics, state-of-the-art DE algorithms, or up-to-date DE algorithms are involved. Experiments show that our IEDEV is very competitive.

Background: Advances in treatment and supportive care have significantly improved the overall survival (OS) of pediatric patients with acute lymphoblastic leukemia (ALL). However, there is a large number of these patients who continue to relapse after receiving standard treatment. Accurate identification of patients at high risk of relapse and targeted therapy may significantly improve their prognosis. Therefore, the aim of this study was to identify significant prognostic factors for pediatric ALL and establish a novel nomogram for the prediction of survival.Methods: The ALL clinical data of Phases I and II of the Therapeutic Applicable Research to Generate Effective Treatments (TARGET) project were merged and randomly divided into training and validation groups. The LASSO regression model was used to select the specific factors related to the OS of the training group and generate prognostic nomograms according to the selected characteristics. The predictive accuracy of the nomogram for OS was verified using the concordance index of the training and validation groups, the area under the receiver operating characteristic curve for prognostic diagnosis, and the calibration curve.Results: A total of 1,000 children with ALL were included in the TARGET project. Of those, 489 patients had complete follow-up data for further analysis. The data were randomly divided into the training group (n = 345) and the validation group (n = 144). Seven clinical characteristics, namely age at diagnosis, peripheral white blood cells, bone marrow and CNS site of relapse, ETV6/RUNX1 fusion, TCF3/PBX1, and BCR/ABL1 status, were selected to construct the nomogram. The concordance indices of the training and validation groups were 0.809 (95% confidence interval: 0.766–0.852) and 0.826 (95% confidence interval: 0.767–0.885), respectively. The areas under the receiver operating characteristic curve of the 3-year, 5-year, and 10-year OS in the training group were 0.804, 0.848, and 0.885, respectively, while that of the validation group were 0.777, 0.825, and 0.863, respectively. Moreover, the calibration curves demonstrated a favorable consistency between the predicted and actual survival probabilities.Conclusions: Independent predictors of OS in children with ALL included age at diagnosis, white blood cells, bone marrow site of relapse, CNS site of relapse, ETV6/RUNX1 fusion, TCF3/PBX1, and BCR/ABL1 status. The nomograms developed using these high-risk factors can more simply, accurately, and quantitatively predict the survival of children, and improve treatment and prognosis.

This paper examines the development of the Chinese Sentiment Lexicon for Internet (CSLI), a sentiment lexicon for capturing the valence and arousal in Chinese online social media texts. We first review the current sentiment lexicons and their building process, including the collection of words, judging the emotionality of words, and testing reliability and validity. In Study 1, we develop CSLI and test its initial reliability and validity. In Study 2, we further test the convergent validity of CSLI by examining its correlations with human judgment in 429 aggregated Weibo comments. In Study 3, the predictive validity of CSLI is examined by linking its results to personality traits among 52 undergraduates. Two replication studies are also conducted to verify the findings in Study 2 and 3. The results have generally supported the reliability and validity of CSLI. Therefore, CSLI can be used as a research tool to capture the degree of valence and arousal in Chinese online social media texts. Its potential to promote human well-being is also discussed.

Differential Evolution (DE) is powerful for global optimization problems. Among DE algorithms, JADE and its variants, whose mutation strategy is DE/current-to-pbest/1 with optional archive, have good performance. A significant feature of the above mutation strategy is that one individual for difference operation comes from the union of the optional external archive and the population. In existing DE algorithms based on the mutation strategy-JADE and its variants, individuals eliminated from the population are send to the archive. In this paper, we propose a scheme for managing the optional external archive. According to our scheme, two subpopulations are maintained in the population. Each of them regards the other as the archive. In experiments, our scheme is applied in JADE and two of its variants-SHADE and L-SHADE. Experimental results show that our scheme can enhance JADE and its variants. Moreover, it can be seen that L-SHADE with our scheme performs significantly better than four DE algorithms, CoBiDE, MPEDE, EDEV, and MLCCDE.

Schizophrenia (SZ) is a serious and incurable mental disorder characterized by clinical manifestations of positive and negative symptoms and cognitive dysfunction. High-frequency deep brain stimulation (DBS) of the ventral hippocampus (VHP) has been recently applied as a therapeutic approach for SZ in both experimental and clinical studies. However, little is known about the precise mechanism of VHP-DBS treatment for SZ and the role of hippocampal cell activation in the pathogenesis of SZ. With optogenetic technology in this study, we tried to inhibit neuronal activity in the VHP which has dense projections to the prefrontal cortex, before measuring long stumulus-induced delay eyeblink conditioning (long-dEBC) in a rodent model of SZ. Rats were administrated with phencyclidine (PCP, 3 mg/kg, 1/d, ip) for successive 7 days before optogenetic intervention. The current data show that PCP administration causes significant impairment in the acquisition and timing of long-dEBC; the inhibition of bilateral VHP neurons alleviates the decreased acquisition and impaired timing of longd-dEBC in PCP-administered rats. The results provide direct evidence at the cellular level that the inhibition of VHP neuronal cells may be a prominent effect of hippocampal DBS intervention, and increased activity in the hippocampal network play a pivotal role in SZ.

In large-scale computations of physical problems, one often encounters the situation of having to determine a multidimensional function, which can be numerically costly when computing each point in this multidimensional space is already time-demanding. In the work, we propose that the active learning algorithm can speed up such calculations. The basic idea is to fit a multidimensional function by neural networks, and the key point is to make the query of labeled data more economical by using a strategy called “query by committee.” We present the general protocol of this fitting scheme, as well as the procedure of how to further compute physical observables with the fitted functions. We show that this method can work well with two examples, which are the quantum three-body problem in atomic physics and the anomalous Hall conductivity in condensed matter physics, respectively. In these examples, we show that one reaches an accuracy of a few percent error in computing physical observables, all the while using fewer than 10% of total data points compared with uniform sampling. With these two examples, we also visualize that by using the active learning algorithm, the required amount of data points are added mostly in the regime where the function varies most rapidly, which explains the mechanism for the efficiency of the algorithm. We expect broad applications of our method to various kinds of computational physical problems.

The medial prefrontal cortex (mPFC) has been widely investigated for its roles in learning and memory. The present study investigated the time-limited involvement of the caudal anterior cingulate cortex (cACC) of the mPFC in the retrieval process for a simple associative motor learning, trace eyeblink conditioning (tEBC), using a 75 dB or 100 dB tone as the conditioned stimulus (CS). The GABAA receptor agonist muscimol was injected into the cACC of guinea pigs at 1 day or 4 weeks after tEBC acquisition. When muscimol was administered 1 day after tEBC acquisition, the conditioned response (CR) of the 75 dB group was severely impaired, whereas the CR of the 100 dB group exhibited no significant change relative to the control. When muscimol was administered 4 weeks after tEBC acquisition, the CR was impaired in both the 75 dB and 100 dB groups. This study indicate that the cACC of the mPFC is necessary for recent retrieval of tEBC with a low-intensity CS but not of tEBC with a high-intensity CS, whereas for remote retrieval of tEBC, the cACC of the mPFC is essential regardless of whether the CS intensity is high or low. These results support a conditional role for the mPFC in modulating recent retrieval of tEBC and a persistent role for its involvement in remote retrieval of tEBC.

The present experiment was designed to determine whether classical eyeblink conditioning (EBC) can be established by using electrical microstimulation of the hippocampus as a conditioned stimulus (CS) paired with an air-puff unconditioned stimulus (US). We intended to examine whether EBC transfer could occur when a CS was shifted between microstimulation of the hippocampus as a CS (Hip-CS) and tone as a CS (tone-CS) and to compare the difference in transfer effectiveness between delay EBC (dEBC) and trace EBC (tEBC). Eight groups of guinea pigs, including 4 experimental groups and 4 control groups, were included in the study. First, the experimental groups received either a Hip-CS or a tone-CS paired with a US; then, these groups were exposed to a shifted CS (tone-CS or Hip-CS) paired with the US. The control groups received the corresponding Hip-CS or tone-CS, which was, however, pseudo-paired with the US. The control groups were then shifted to the tone-CS (or Hip-CS) paired with the US. The results show that EBC can be successfully established when using microstimulation of the hippocampus as a CS paired with an air-puff US, and that the acquisition rates of EBC are higher in the experimental groups than in the control groups after switching from the Hip-CS to the tone-CS or vice versa, indicating the occurrence of learning transfer between EBC established with the Hip-CS and tone-CS. The present study also demonstrated that the EBC re-acquisition rates were remarkably higher in dEBC than in tEBC with both types of transfer, which suggests that the saving effect was more evident in dEBC than tEBC. These results significantly expand our knowledge of EBC transfer as well as the functional neural circuit underlying EBC transfer.

This paper examines changes in returns and trading volumes around earnings announcements for firms which have both A-shares (traditionally for local investors only) and B-shares (traditionally for foreign investors only) in China. It considers the impact of regulatory changes which reduced the segmentation of local and foreign investors across the two classes of shares. We find that both the A- and B-markets experience significant price changes around earning announcements. When the two markets are fully segmented, the magnitude of price changes in the A-share market are significantly smaller than the B-market which lends empirical support to the previous claim that the B-market is less informed. The changes in trading volume indicate that the B-market investors have less divergent expectations and interpretations of the pre-disclosure information compared to the A-market investors.However, when regulatory changes reduced the level of segmentation, the price and volume reactions in the two markets became more consistent. The results suggest that the A- and Bmarkets are more integrated as a result of the regulatory changes.

Background. The pathogenesis of allergic conjunctivitis has not been clearly established. Moreover, previous studies fail to consider human models of allergic conjunctivitis. This study investigated the expression of thymic stromal lymphopoiet in TSLP and its downstream molecules in conjunctival scrappings and tear. Methods. This cross-sectional study compares patients with vernal keratoconjunctivitis (VKC), seasonal allergic conjunctivitis (SAC), and perennial allergic conjunctivitis (PAC) with normal controls. There are 80 people recorded in Shanxi Eye Hospital. Increasingly, 20 are with VKC, 20 are with SAC, 20 are with PAC, and the remaining 20 are normal controls. Conjunctiva were harvested for total RNA extraction and gene expression by real-time polymerase chain reaction. Epithelial cells were collected to make pathological sections for immunohistochemical staining. Human tears were evaluated by Luminex microbead assay. A P value less than 0.05 from Dunnett’s post hoc test in SPSS means a statistical significant distinction. Results. Positive expression in conjunctival cells of patients with allergic conjunctivitis. The expression of TSLP and IL-4, IL-5, and IL-13 mRNA shows a statistically significant difference (P

Zinc-enriched yeast (ZnY) and zinc sulfate (ZnSO4) are considered zinc (Zn) supplements currently available. The purpose of the investigation was to compare and evaluate pharmacokinetics and biodistribution of ZnY and ZnSO4 in rats. ZnY or ZnSO4 were orally administered to rats at a single dose of 4 mg Zn/kg and Zn levels in plasma and various tissues were determined using inductively coupled plasma-optical emission spectrometry. Maximum plasma concentration values were 3.87 and 2.81 μg/mL for ZnY and ZnSO4, respectively. Both ZnY and ZnSO4 were slowly eliminated with a half-life of over 7 h and bone had the highest Zn level in all tissues. Compared to ZnSO4, the relative bioavailability of ZnY was 138.4%, indicating that ZnY had a significantly higher bioavailability than ZnSO4.

The role of the hippocampus in delay eyeblink conditioning (DEC) remains controversial. Here, we investigated the involvement of the hippocampus in DEC with a soft tone as the conditioned stimulus (CS) by using electrolytic lesions or muscimol inactivation of guinea pig dorsal hippocampus. Interestingly, when a soft tone was used as a CS, electrolytic lesions of the hippocampus significantly retarded acquisition of the conditioned response (CR), and muscimol infusions into hippocampus distinctly inhibited the acquisition and expression of CR, but had no significant effect on consolidation of well-learned CR. In contrast, both electrolytic lesions and muscimol inactivation of hippocampus produced no significant deficits in the CR when a loud tone was used as the CS. These results demonstrate that the hippocampus is essential for the DEC when the delay task was rendered more difficult.

Organic anion transporting polypeptides (OATPs) have been extensively recognized as key determinants of absorption, distribution, metabolism and excretion (ADME) of various drugs, xenobiotics and toxins. Putative N-glycosylation sites located in the extracellular loops 2 and 5 is considered a common feature of all OATPs and some members have been demonstrated to be glycosylated proteins. However, experimental evidence is still lacking on how such a post-translational modification affect the transport activity of OATPs and which of the putative glycosylation sites are utilized in these transporter proteins. In the present study, we substituted asparagine residues that are possibly involved in N-glycosylation with glutamine residues and identified three glycosylation sites (Asn134, Asn503 and Asn516) within the structure of OATP1B1, an OATP member that is mainly expressed in the human liver. Our results showed that Asn134 and Asn516 are used for glycosylation under normal conditions; however, when Asn134 was mutagenized, an additional asparagine at position 503 is involved in the glycosylation process. Simultaneously replacement of all three asparagines with glutamines led to significantly reduced protein level as well as loss of transport activity. Further studies revealed that glycosylation affected stability of the transporter protein and the unglycosylated mutant was retained within endoplasmic reticulum.