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Abstract Background C-X-C receptor 4(CXCR4) is widely considered to be a highly conserved G protein-coupled receptor, widely involved in the pathophysiological processes in the human body, including fibrosis. However, its role in regulating macrophage-related inflammation in the fibrotic process of prostatitis has not been confirmed. Here, we aim to describe the role of CXCR4 in modulating macrophage M1 polarization through glycolysis in the development of prostatitis fibrosis. Methods Use inducible experimental chronic prostatitis as a model of prostatic fibrosis. Reduce CXCR4 expression in immortalized bone marrow-derived macrophages using lentivirus. In the fibrotic mouse model, use adenovirus carrying CXCR4 agonists to detect the silencing of CXCR4 and assess the in vivo effects. Results In this study, we demonstrated that reducing CXCR4 expression during LPS treatment of macrophages can alleviate M1 polarization. Silencing CXCR4 can inhibit glycolytic metabolism, enhance mitochondrial function, and promote macrophage transition from M1 to M2. Additionally, in vivo functional experiments using AAV carrying CXCR4 showed that blocking CXCR4 in experimental autoimmune prostatitis (EAP) can alleviate inflammation and experimental prostate fibrosis development. Mechanistically, CXCR4, a chemokine receptor, when silenced, weakens the PI3K/AKT/mTOR pathway as its downstream signal, reducing c-MYC expression. PFKFB3, a key enzyme involved in glucose metabolism, is a target gene of c-MYC, thus impacting macrophage polarization and glycolytic metabolism processes.

Abstract Asymmetric optical transmission (AOT) has been an enduring hot topic of interest in various fields, including optical communication, information processing, and so on. Particularly, the development of reciprocal micro-nanostructures achieving AOT further facilitates and accelerates the miniaturization and integration of traditional optical components. However, most of these optical components merely consider a single AOT band and transmission in a specified direction, limiting the development of their versatile functions. In this paper, we theoretically propose an all-dielectric metamaterial consisting of a nanograting and a defective multilayer photonic crystal, exhibiting multi-band and bidirectional multiplexing AOT. More specifically, the proposed metamaterial demonstrates both narrowband and wideband AOT for incidence from the nanograting to the photonic crystal, and a completely different narrowband AOT for the opposite incidence, namely, from the photonic crystal to the nanograting. These distinctive AOT spectral features are achieved by matching the diffraction effect of the nanograting with the special energy band of the defective multilayer photonic crystal. Remarkably, the device exhibits a transmittance difference of up to 0.974 and a contrast ratio of up to 0.997 (transmittance ratio of up to 673), with a transmission bandwidth of 62.7 nm for incident light with a wavelength of 624 nm illuminating from the nanograting to the defective multilayer photonic crystal. Furthermore, the bandwidth and number of transmission bands can be flexibly tuned by changing the polarization angle of the incident light, showcasing its excellent polarization multiplexing characteristics. The designed metamaterial provides an effective strategy for the realization of versatile AOT devices and is conducive to expanding the application scenarios of AOT devices.

Abstract Objective To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer’s disease (AD). Methods Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically ‘AND’ between different categories (e.g., ‘Alzheimer’s Disease’ AND ‘SSRIs’) and ‘OR’ within the same category (e.g., ‘citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline’), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis. Results Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings. Conclusion This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary.

Abstract Identification of high consequence areas is an important task in pipeline integrity management. However, traditional identification methods are generally characterized by low efficiency, high cost and low accuracy. For this reason, this paper proposes a recognition method based on the improved algorithm Mask Region-based Convolutional Neural Network. Coordinate attention mechanism module is introduced into the traditional Mask R-CNN algorithm to improve the recognition accuracy and reduce the training time. For the identification results, GIS tools are utilized to establish high consequence zones along both sides of the pipeline, and the grade and scope of the high consequence zones are determined according to relevant specifications.In this paper, this method is used to identify the high-consequence area of a pipeline section in Guangdong Province, the results show that: 1, the improved algorithm in the identification of densely populated, geologic hazards, flammable and explosive high consequence zones of the average accuracy of the identification of 1.7%, 3.4%, 3.9%. 2, The method in this paper identifies 8 more building elements and 0.311 more kilometers of pipeline mileage compared to traditional identification methods. The method of this paper can provide a reference for the early identification of high consequence areas of pipelines.

Popularization of medical knowledge plays an important role in promoting effective communication and understanding between doctors and patients. Based on the shortcomings of the model of popularization of traditional medical knowledge, such as unidirectional dissemination, insufficient depth of information and difficulty in understanding, this paper explores the types and advantages of innovative models of popularization of medical knowledge by searching the literature. Currently, the main models of community-based popularization of medical knowledge include traditional media (TV, radio, newspapers), lectures, special report, books, brochures, etc., which are limited in terms of the effectiveness of information dissemination, lack of interaction and personalization, as well as continuity and traceability. In this paper, an in-depth discussion was conducted on the innovative model of popularizing the knowledge of critical care medicine in the community, and many new models of popularizing knowledge, including cartoons, animation, virtual reality, augmented reality, and Internet platforms were proposed, and useful community practice was carried out. The results of the practice showed that the number of reading hits and the satisfaction with popularizing science were significantly increased under the innovative models of popularization of knowledge. The innovative model of popularization of knowledge can improve the efficiency of medical knowledge popularization, enhance patient participation, bridge the gap of medical knowledge, and provide customized health management solutions, which is of a significant advantage, however, it also has limitations such as higher dependence on technology and equipment, and the model of popularization of knowledge still needs to be continuously innovated and explored.

Abstract Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.

Abstract Objective Our study aimed to determine whether there exists an association between low-grade systemic inflammation, as measured by serum C-reactive protein (CRP), and the risk of lower-extremity deep venous thrombosis (LEDVT) in patients with primary intracerebral hemorrhage (ICH). Methods This observational study was retrospectively conducted on patients with primary ICH who were presented to two tertiary medical centers between January 2021 and August 2022. The primary outcome was detecting LEDVT occurrence within 14 days from the onset of the acute ICH episode. Weighted logistic regression and restricted cubic spline models were employed to estimate the association between CRP and LEDVT following 1:1 propensity score matching (PSM). Results Of the 538 patients with primary ICH who met the inclusion criteria, 76 (14.13%) experienced LEDVT. Based on the cut-off levels of CRP measured upon admission from the receiver operating characteristic (ROC) curve, patients with primary ICH were categorized into two groups: (i) CRP

Background Current research on the physical fitness test scores of high school students is more localized within provinces and cities, with few multicenter, large-sample-size, domain-wide research results. The prevalence of blended online and offline teaching in schools of all types has inevitably prolonged the already long sedentary time of high school students. Whether this trend has some impact on the physical health of high school students is an urgent need for a region-wide study. Objective To investigate and analyze the levels of physical fitness test scores and related influencing factors of urban and rural high school first- and second-year students in seven regions of China, and to explore the empowering paths for the balanced improvement of physical fitness levels of first- and second-year high school students. Methods Stratified randomized cluster sampling method was used to conduct stratified sampling according to urban counties and townships and villages in high school schools in seven regions (East China, South China, North China, Central China, Northwest China, Southwest China, Northeast China) of 31 provinces (municipalities directly under the central government and autonomous regions) of China from January to March 2019, and then randomized clusters of 1 high school school in urban counties and 1 high school school in townships and villages in total of 62 schools were selected respectively. A total of 42 523 freshmen and sophomores in high schools were randomly selected to conduct the research, and the data on students' physical fitness test scores were collected at the same time (BMI reflects the level of physical development; lung capacity reflects the level of physical function; sit-and-reach reflects the level of flexibility; pull-up, 50 m run, standing long jump reflects the level of explosive strength of upper and lower limbs; 1 min sit-up reflects the level of core strength of the torso; 800 m run, 1 000 m run reflects the level of cardiorespiratory endurance), and non-parametric tests and multiple linear regression analysis were used to explore the influencing factors of the level of physical fitness test scores. Results The age distribution of 42 523 high school students was 16.0 (16.0, 17.0) years; 20 074 (47.2%) boys and 22 449 (52.8%) girls, 21 725 (51.1%) in cities, counties and districts, and 20 798 (48.9%) in towns and villages. Comparison of the gender and urban-rural distribution of high school students in the seven regions showed statistically significant differences (PNortheast China>Central China), body mass (Northeast China>North China>Central China), BMI (Central China>Northeast China>North China), lung capacity (Northeast China>Central China>South China), 50 m run (South China>Central China>East China), standing long jump (South China>North China>Northwest China), sit-and-reach (South China>Southwest China>Central China), pull-up (South China>Southwest China>Northwest China), and 1 000 m run (South China>Central China>Southwest China). High school boys in the city, county and districts had higher lung capacity scores than those in the town and country, and lower scores than those in the town and country in the 50 m run, standing long jump, sit-and-reach, pull-up, and 1 000 m run (P0.05). The differences in the scores of high school girls in each physical fitness test in the seven regions are statistically significant (PNortheast China>Northwest China), body mass (Northeast China>North China>Northwest China), BMI (Northeast China>North China>Northwest China), lung capacity (Northeast China>South China>Central China), 50 m run (South China>Central China>East China), standing long jump (South China>North China>Central China), sit-and-reach (Northeast China>Central China>South China), 1 min sit-up (North China>Central China>East China=Southwest China), 800 m run (Northeast>Central China>South China). High school girls in the city and county districts had higher height, body mass, and BMI scores than those in the town and country, and lower scores than those in the town and country in lung capacity, 50 m run, standing long jump, sit-and-reach, 1 min sit-up, and 800 m run (P

Abstract GDM, as a metabolic disease during pregnancy, regulates GLUT3 translocation by AMPK, thereby affecting glucose uptake in trophoblasts. It provides a new research idea and therapeutic target for alleviating intrauterine hyperglycemia in GDM. STZ was used to construct GDM mice, inject AICAR into pregnant mice, and observe fetal and placental weight; flow cytometry was employed for the detection of glucose uptake by primary trophoblast cells; immunofluorescence was applied to detect the localization of GLUT3 and AMPK in placental tissue; Cocofal microscope was used to detect the localization of GLUT3 in trophoblast cells;qRT-PCR and Western blot experiments were carried out to detect the expression levels of GLUT3 and AMPK in placental tissue; CO-IP was utilized to detect the interaction of GLUT3 and AMPK. Compared with the normal pregnancy group, the weight of the fetus and placenta of GDM mice increased (P

Abstract Federated learning is a distributed machine learning paradigm where the goal is to collaboratively train a high quality global model while private training data remains local over distributed clients. However, heterogenous data distribution over clients is severely challenging for federated learning system, which severely damage the quality of model. In order to address this challenge, we propose global prototype distillation (FedGPD) for heterogenous federated learning to improve performance of global model. The intuition is to use global class prototypes as knowledge to instruct local training on client side. Eventually, local objectives will be consistent with the global optima so that FedGPD learns an improved global model. Experiments show that FedGPD outperforms previous state-of-art methods by 0.22% ~1.28% in terms of average accuracy on representative benchmark datasets.

Abstract Parkinson’s disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3–25% of sporadic Parkinson’s patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson’s disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson’s disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson’s disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.

BackgroundOlder adults, a population particularly susceptible to misinformation, may experience attempts at health-related scams or defrauding, and they may unknowingly spread misinformation. Previous research has investigated managing misinformation through media literacy education or supporting users by fact-checking information and cautioning for potential misinformation content, yet studies focusing on older adults are limited. Chatbots have the potential to educate and support older adults in misinformation management. However, many studies focusing on designing technology for older adults use the needs-based approach and consider aging as a deficit, leading to issues in technology adoption. Instead, we adopted the asset-based approach, inviting older adults to be active collaborators in envisioning how intelligent technologies can enhance their misinformation management practices. ObjectiveThis study aims to understand how older adults may use chatbots’ capabilities for misinformation management. MethodsWe conducted 5 participatory design workshops with a total of 17 older adult participants to ideate ways in which chatbots can help them manage misinformation. The workshops included 3 stages: developing scenarios reflecting older adults’ encounters with misinformation in their lives, understanding existing chatbot platforms, and envisioning how chatbots can help intervene in the scenarios from stage 1. ResultsWe found that issues with older adults’ misinformation management arose more from interpersonal relationships than individuals’ ability to detect misinformation in pieces of information. This finding underscored the importance of chatbots to act as mediators that facilitate communication and help resolve conflict. In addition, participants emphasized the importance of autonomy. They desired chatbots to teach them to navigate the information landscape and come to conclusions about misinformation on their own. Finally, we found that older adults’ distrust in IT companies and governments’ ability to regulate the IT industry affected their trust in chatbots. Thus, chatbot designers should consider using well-trusted sources and practicing transparency to increase older adults’ trust in the chatbot-based tools. Overall, our results highlight the need for chatbot-based misinformation tools to go beyond fact checking. ConclusionsThis study provides insights for how chatbots can be designed as part of technological systems for misinformation management among older adults. Our study underscores the importance of inviting older adults to be active co-designers of chatbot-based interventions.

Objectives This study explored the mechanisms by which physical activity was associated with depressive symptoms in multi-ethnic (Han, Yi and Tibetan) adolescents in southwest China. The mediating role of insomnia in the association of physical activity with depressive symptoms, the moderating role of resilience in this mediation model and the moderating role of parental absence in the moderated mediation model were also examined.Design A cross-sectional survey.Setting In southwest China (Sichuan Province and Tibet Autonomous Region).Participants 3195 adolescents from a school-based survey conducted between April and October 2020.Methods There were 3143 valid samples in this study (47.2% males with mean age=12.88±1.68 years). Structural equation models were developed to estimate the direct and mediating effect, and the moderating effect. Multigroup comparison was performed to examine the differences and similarities of the moderated mediation model across three parental absence subgroups: (1) both parents present, (2) one parent absent and (3) both parents absent.Results As hypothesised, physical activity was significantly and positively associated with the reduction of depressive symptoms in adolescents. Insomnia partially mediated the effect of physical activity on depressive symptoms. In addition, resilience moderated the direct and indirect effects of physical activity (through insomnia) on depressive symptoms. Finally, the multigroup comparison indicated the moderating effect of parental absence on the moderated mediation model.Conclusions Physical activity was associated with alleviating insomnia symptoms among adolescents, thus correlating with the improvement of their depressive symptoms. Resilience was associated with enhancing the beneficial effects of physical activity, further improving depressive symptoms among adolescents, especially those with both absent parents. It is evident that physical activity interventions should be further incorporated into public health programmes to foster the physical and mental health of left-behind adolescents in southwest China.

Background: The changes in risk scores of inflammatory markers among patients diagnosed with hepatocellular carcinoma (HCC) remain unknown. Aims: To investigate the relationship between the inflammation risk score and other contributing factors and the prognostic outcomes in patients with moderate and advanced hepatitis B virus (HBV)-related HCC. Study Design: A retrospective cohort study. Methods: A total of 174 patients with moderate and advanced HBV related HCC were recruited to investigate the impact of stratified inflammatory risk scores and other associated risk factors on disease prognosis. Based on the optimal cut-off values calculated by the Youden index, the patients were divided into high-risk and low-risk groups based on their inflammation risk scores. Results: The study found a significant difference in median survival time between the low-risk and high-risk groups based on the inflammation risk score. Furthermore, the inflammation risk score, alpha-fetoprotein levels, transarterial chemoembolization treatment, and Barcelona Clinic Liver Cancer stage were identified as independent prognostic factors. The four variables were used to construct a prognostic nomogram for HCC. Subsequent evaluations using time-dependent receiver operating characteristic analysis and calibration curve tests revealed the nomogram’s commendable discriminatory ability. As a result, the nomogram proved to be an effective tool for predicting survival at 2- to 4-years. Conclusion: The inflammation risk score has been identified as a significant prognostic factor for HBV-related HCC. The development of nomogram models has provided a practical and effective tool for determining the prognosis of patients affected by HBV-related HCC.

Background Chronic Obstructive Pulmonary Disease (COPD) remains a significant public health challenge due to its high morbidity and mortality rates. Emerging research has identified eosinophilic inflammation as a crucial factor in the pathogenesis and exacerbation of COPD, warranting a detailed exploration of its underlying mechanisms and therapeutic implications.Objective This review aims to elucidate the role of eosinophils in COPD, focusing on their contribution to airway remodeling, exacerbation frequency, and the inflammatory cascade.Methods We conducted a comprehensive literature review of recent studies that discuss the pathophysiological role of eosinophils in COPD and the clinical outcomes associated with modulating eosinophilic activity.Results Eosinophils contribute to COPD progression by releasing cytotoxic proteins and cytokines that intensify the inflammatory response and airway alterations. Targeting specific eosinophil-related cytokines with monoclonal antibodies or receptor antagonists may potentially reduce eosinophil counts, mitigate exacerbations, and improve patient outcomes.Conclusion Understanding eosinophilic involvement in COPD can facilitate the development of precision medicine approaches, offering more tailored and effective treatment options. Future research should continue to focus on the integration of eosinophil biomarkers in clinical practice to enhance therapeutic decisions and management strategies for COPD patients.

Abstract Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.

Abstract Background Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. Method Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. Results Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. Conclusion The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

Abstract The effectiveness of sequence-to-sequence (seq2seq) models in natural language processing has been well-established over time, and recent studies have extended their utility by treating mathematical computing tasks as instances of machine translation and achieving remarkable results. However, our exploratory experiments have revealed that the seq2seq model, when employing a generic sorting strategy, is incapable of inferring on matrices of unseen rank, resulting in suboptimal performance. This paper aims to address this limitation by focusing on the matrix-to-sequence process and proposing a novel diagonal-based sorting. The method constructs a stable ordering structure of elements for the shared leading principal submatrix sections in matrices with varying ranks. We conduct experiments involving maximal independent sets and Sudoku laws, comparing seq2seq models utilizing different sorting methods. Our findings demonstrate the advantages of the proposed diagonal-based sorting in inference, particularly when dealing with matrices of unseen ranks. By introducing and advocating for this method, we enhance the suitability of seq2seq models for investigating the laws of matrix inclusion and exploring their potential in solving matrix-related tasks.

The deployment of large language models (LLMs) within the healthcare sector has sparked both enthusiasm and apprehension. These models exhibit the remarkable ability to provide proficient responses to free-text queries, demonstrating a nuanced understanding of professional medical knowledge. This comprehensive survey delves into the functionalities of existing LLMs designed for healthcare applications and elucidates the trajectory of their development, starting with traditional Pretrained Language Models (PLMs) and then moving to the present state of LLMs in the healthcare sector. First, we explore the potential of LLMs to amplify the efficiency and effectiveness of diverse healthcare applications, particularly focusing on clinical language understanding tasks. These tasks encompass a wide spectrum, ranging from named entity recognition and relation extraction to natural language inference, multimodal medical applications, document classification, and question-answering. Additionally, we conduct an extensive comparison of the most recent state-of-the-art LLMs in the healthcare domain, while also assessing the utilization of various open-source LLMs and highlighting their significance in healthcare applications. Furthermore, we present the essential performance metrics employed to evaluate LLMs in the biomedical domain, shedding light on their effectiveness and limitations. Finally, we summarize the prominent challenges and constraints faced by large language models in the healthcare sector by offering a holistic perspective on their potential benefits and shortcomings. This review provides a comprehensive exploration of the current landscape of LLMs in healthcare, addressing their role in transforming medical applications and the areas that warrant further research and development.

Abstract The color and texture characteristics of crops can reflect their nitrogen (N) nutrient status and help optimize N fertilizer management. This study conducted a one-year field experiment to collect sugarcane leaf images at tillering and elongation stages using a commercial digital camera and extract leaf image color feature (CF) and texture feature (TF) parameters using digital image processing techniques. By analyzing the correlation between leaf N content and feature parameters, feature dimensionality reduction was performed using principal component analysis (PCA), and three regression methods (multiple linear regression; MLR, random forest regression; RF, stacking fusion model; SFM) were used to construct N content estimation models based on different image feature parameters. All models were built using five-fold cross-validation and grid search to verify the model performance and stability. The results showed that the models based on color-texture integrated principal component features (C-T-PCA) outperformed the single-feature models based on CF or TF. Among them, SFM had the highest accuracy for the validation dataset with the model coefficient of determination (R2) of 0.9264 for the tillering stage and 0.9111 for the elongation stage, with the maximum improvement of 9.85% and 8.91%, respectively, compared with the other tested models. In conclusion, the SFM framework based on C-T-PCA combines the advantages of multiple models to enhance the model performance while enhancing the anti-interference and generalization capabilities. Combining digital image processing techniques and machine learning facilitates fast and nondestructive estimation of crop N-substance nutrition.

Jingzhi Guanxin Oral Liquids (JZGX), a traditional Chinese medicine formulation prepared from the decoction of five herbs, has been utilized to relieve chest pain with coronary artery disease (CAD). However, the chemical composition and therapeutic mechanisms of JZGX remain obscured. In this research, the potential targets and pathways of JZGX against CAD were anticipated through network pharmacology based on analyzing its chemical constituents using UPLC-Q-TOF-MS/MS. One hundred seven ingredients in JZGX were identified. The 39 active chemicals and 37 key targets were screened, and CAD-related signaling pathways were clustered, mainly associated with lipid metabolism. Subsequently, the atherosclerotic CAD animal model employing 24 weeks of high-fat diet (HFD) ApoE−/− mice was constructed to investigate the JZGX efficacy and underlying mechanisms validating network forecasts. The histological staining examination and cardiovascular biomarker tests confirmed that JZGX reduced plaque formation in the aorta and decreased blood lipids in vivo. It featured anti-inflammatory, anti-thrombotic, and myocardial protective effects. JZGX prevented excessive lipid deposits and inflammation within the liver and exhibited hepatoprotective properties. Serum untargeted metabolomics analysis indicated that JZGX ameliorated metabolic abnormalities in atherosclerotic CAD mice and prompted lipid metabolism, especially linoleic acid. The PPARs and attached critical targets (SREBP1, FASN, PTGS2, and CYP3A), filtered from the networks and connected with lipid metabolism, were dramatically modulated through JZGX administration, as revealed by western blotting. The molecular docking outcomes showed that all 39 active ingredients in JZGX had good binding activity with PPARα and PPARγ. These findings illustrate that JZGX alleviates atherosclerotic CAD progression by remodeling the lipid metabolism and regulating PPAR-related proteins.

Atherosclerosis is the main pathological basis of cardiovascular diseases (CVDs). Fufang Danshen Tablet (FDT) is a traditional Chinese medicine that has been clinically used to treat CVDs for more than 40 years. Nevertheless, owing to the complexity of the ingredients, the pharmacological mechanism of FDT in the treatment of CVDs has not been fully elucidated. In this study, an integrated strategy of UFLC-Q-TOF-MS/MS, network pharmacology, molecular biology, and transcriptomics was used to elucidate the mechanisms of action of FDT in the treatment of atherosclerosis. In total, 22 absorbed constituents were identified in rat serum after oral administration of FDT. In silico, network pharmacology studies have shown that FDT regulates four key biological functional modules for the treatment of atherosclerosis: oxidative stress, cell apoptosis, energy metabolism, and immune/inflammation. In animal experiments, FDT exerted protective effects against atherosclerosis by reducing the plaque area and lipid levels in ApoE−/− mice. Furthermore, we found that FDT inhibited inflammatory macrophage accumulation by regulating the expression of Selp and Ccl2, which are both involved in monocyte adhesion and migration. The inhibition of monocyte recruitment by FDT is a new perspective to elucidate the anti-atherosclerotic mechanism of FDT, which has not been adopted in previous studies on FDT. Our results may help to elucidate the therapeutic mechanism of FDT against CVDs and provide potential therapeutic targets.

Abstract Background Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated. Methods Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression. Results We identified a SNP rs2678907 located in the 5’ upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lower VRK2 mRNA expression, which is consistent with the observations of reduced VRK2 level in the patients with major depression compared with controls. Notably, Vrk2 −/− mice exhibited depressive-like behaviors compared to Vrk2 +/+ mice and specifically repressing Vrk2 in the ventral hippocampus using adeno-associated virus (AAV) lead to consistent and even stronger depressive-like behaviors in mice. Compared with Vrk2 +/+ mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered in Vrk2 −/− mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways in Vrk2 −/− mice. Conclusions Vrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression.

Online health misinformation commonly includes persuasive strategies that can easily deceive lay people. Yet, it is not well understood how individuals respond to misinformation with persuasive strategies at the moment of exposure. This study aims to address the research gap by exploring how and why older adults fall into the persuasive trap of online health misinformation and how they manage their encounters of online health misinformation. Using a think-aloud protocol, semi-structured interviews were conducted with twenty-nine older adults who were exposed to articles employing twelve groups of common persuasive strategies in online health misinformation. Thematic analysis of the transcripts revealed that some participants fell for the persuasive strategies, yet the same strategies were detected by others as cues to pin down misinformation. Based on the participants' own words, informational and individual factors as well as the interplay of these factors were identified as contributors to susceptibility to misinformation. Participants' strategies to manage misinformation for themselves and others were categorized. Implications of the findings are discussed.

Various injectants are available for the treatment of carpal tunnel syndrome. This systematic review and network meta-analysis was conducted to investigate the effectiveness of different injection therapies in alleviating the symptoms of carpal tunnel syndrome. Various databases were searched for relevant studies from inception until May 10, 2023. Eligible studies were identified using the patient (P), intervention (I), comparison (C), and outcomes (O) model, which involved (P) participants with carpal tunnel syndrome, (I) an intervention based on injection therapy, (C) the use of placebo or another injectant as a control treatment, and (O) the measurement of clinical and electrodiagnostic outcomes of interest. A total of 18 studies were included in the analysis. The network meta-analysis revealed that platelet-rich plasma is effective in the treatment of carpal tunnel syndrome in terms of symptom and pain relief and functional improvement in both the short and long term, whereas steroids are effective only in the short term. Additionally, injections of dextrose solution may offer long-term pain relief as well as short- and long-term symptom alleviation and functional improvement. The study findings suggest that platelet-rich plasma should be used as the first-line treatment for carpal tunnel syndrome, with dextrose and steroids serving as alternative treatment options.

Abstract Background Circular RNAs (circRNAs) may regulate the onset and progression of human malignancies by competitively binding to microRNA (miRNA) sponges, thus regulating the downstream genes. However, aberrant circRNA expression patterns and their biological functions in prostate cancer (PCa) warrant further studies. Our research sought to shed further light on the possible role and molecular mechanism of circEPHA3 action in controlling the growth and metastasis of PCa cells. Materials and methods circEPHA3 (has_circ_0066596) was initially screened from a previous circRNA microarray and identified following Actinomycin D and RNase R assays. Fluorescence in situ hybridization, biotin-coupled probe RNA pulldown, and dual-luciferase reporter gene assays were performed to examine the relationship between circEPHA3 and miR-513a-3p. The biological role of circEPHA3 in PCa was assessed by CCK8, wound healing, Transwell assays, and animal experiments. Results We identified a novel circular RNA, circEPHA3 (has_circ_0066596), which was down-regulated in high-grade PCa tissues and cell lines. The outcomes of CCK8, wound healing, Transwell assays, and animal experiments revealed that circEPHA3 prohibited the progression and metastasis of PCa in vivo and in vitro. Mechanistically, circEPHA3 was directly bound to miR-513a-3p and regulated the downstream gene, BMP2, thereby serving as a tumor suppressor in PCa. Conclusions As a tumor suppressor, circEPHA3 inhibited the proliferation and metastasis of PCa cells through the miR-513a-3p/BMP2 axis, suggesting that circEPHA3 might be a potential therapeutic target for PCa.

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

Visceral adiposity index (VAI) is a new metric for evaluating visceral adiposity dysfunction. The aim of the present study was to explore the association between VAI and incident chronic kidney disease (CKD) in the American elderly population. We included 6085 participants aged 60 years or older with available data on renal function and VAI from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 and divided them into four groups according to the VAI quartiles. VAI values were ln-transformed to reduce skewness. We conducted multivariable logistic regression analyses and spline smoothing plot analyses to evaluate the association between VAI and CKD. After fully adjusting for confounding factors, higher lnVAI was associated with a higher risk of CKD (OR, 1.23; 95 %CI, 1.02, 1.48). Compared to the Q1 group (VAI 3.0). The adjusted ORs (95% CI) in Q3 and Q4 were 1.74 (1.24, 2.42) and 1.59 (1.08, 2.33). Adjusted smoothed plots suggested a nonlinear relationship between lnVAI and CKD. The development of CKD increased with increasing VAI among participants with a lnVAI between −0.6 and 1.6 (VAI: 0.5–5.0). In conclusion, VAI is significantly associated with the risk of CKD in the US elderly population aged 60 years or older.

Abstract Purpose The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of simultaneous and staged resection of SCLM to provide a reference for clinical selection. Methods A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS). Results This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI [0.66–1.19], P = 0.409), gastrointestinal (OR = 1.19, 95% CI [0.89–1.59], P = 0.241) and hepatic (OR = 1.04, 95% CI [0.83–1.31], P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI [0.88–3.64], P = 0.108), 5-year DFS (HR = 1.26, 95% CI [0.96–1.66], P = 0.098) and 5-year OS (HR = 1.13, 95% CI [0.95–1.34], P = 0.164). Lower intraoperative blood loss (SMD = − 0.39, 95% CI [− 0.60 to − 0.18], P

Abstract Lung Squamous Cell Carcinoma (LUSC) is an aggressive malignancy with limited therapeutic options. The response to immune therapy is a determining factor for the prognosis of LUSC patients. This study aimed to develop a reliable immune-related prognostic signature in LUSC. We extracted gene expression and clinical data of LUSC from The Cancer Genome Atlas (TCGA). A total of 502 patients enrolled and were divided into respond and non-responder groups by the TIDE algorithm. The CIBERSORT algorithm and the LM22 gene signature were used to analyze the distribution of immune cells in LUSC. Efficacy and response strength of immunotherapy are calculated by the tumor mutation burden (TMB) and ESTIMATE Score. Differentially expressed genes (DEGs) between the two groups were analyzed. The differential expression genes related to overall survival were pointed as hub DEGs, and a prognostic signature was constructed with lasso regression analysis. LUSC patients were divided into responder and non-responder groups based on the response to immunotherapy. The distribution of immune cells was significantly different between the two groups. Forty-four DGEs were considered as overall survival-related genes. A prognostic signature was constructed, consisting of 11 hub-DGEs, including MMP20, C18orf26, CASP14, FAM71E2, OPN4, CGB5, DIRC1, C9orf11, SPATA8, C9orf144B, and ZCCHC5. The signature can accurately distinguish LUSC patients into high and low-risk groups. Moreover, the high-risk group had a shorter survival time than the low-risk group. The area under the ROC curve was 0.67. The multivariate Cox regression showed that the risk score calculated by the constructed signature was an independent prognostic predictor for LUSC patients. In short, we established a novel immune-related prognostic signature in LUCS, which has significant sensitivity and accuracy in predicting the prognosis of patients. Our research can guide the evaluation of the prognosis of LUSC patients in clinical, and the discovered immune-related genes can provide a theoretical basis for the discovery of new therapeutic targets.

Abstract The present cross-sectional survey was performed to assess the prevalence and factors associated with fear of hypoglycemia (FoH) in hospitalized patients with type 2 diabetes (T2D). Between July and December 2020, 494 patients with T2D were evaluated via structured questionnaires containing sociodemographic information, clinical information, and the Fear of Hypoglycemia-15 scale (FH-15). Patients were divided into the FoH and non-FoH groups according to the FH-15 score. Univariate and multivariate logistic regression analyses were performed to determine factors associated with FoH. Variables with P values

Abstract We report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets: a kinase (hematopoietic progenitor kinase 1), protease (SARS‐CoV‐2 main protease), and nuclear receptor (vitamin D receptor), and evaluated with a reference dataset composed of over 8000 compounds that have their activities reported in the literature. The evaluation considered the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can generate molecules with similar structures to classical active compounds and novel compounds sharing similar binding modes with active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. The ligand ED generated can also be used to support fragment-based drug design. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create .

Glioma is the most common tumor of the central nervous system (CNS), with a 5-year survival rate of

Abstract This systematic review and meta-analysis investigated the effect of phonophoresis when various gel types were used. Medline (using PubMed), EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were used to search for relevant studies from the date of their inception to June 28, 2021. We included studies that were randomized controlled trials (RCTs), included patients with a diagnosis of knee osteoarthritis, included treatment with either phonophoresis or therapeutic ultrasound with placebo gel, and reported clinical and functional outcomes. Continuous variables are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Statistical analysis was performed using RevMan 5.3 software. We initially retrieved 2176 studies and finally analyzed nine RCTs including 423 patients. The intervention group significantly outperformed the control group in pain scores with NSAID gel (SMD = − 0.53, 95% CI [− 1.02, − 0.05], I 2 = 73%) and in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) function score with corticosteroid gel (SMD = − 0.96, 95% CI [− 1.47, − 0.44], I 2 = 20%). Phonophoresis alleviated pain and improved functional performance. Because of some limitations of this study, additional high-quality, large-scale RCTs are required to confirm the benefits.

Abstract This study aimed to investigate the epidemiologic, clinical, pathological characteristics, and treatment of patients with Castleman disease (CD) in a single center in China. We retrospectively analyzed the data of 65 Chinese CD patients, divided into unicentric CD (UCD) and multicentric CD (MCD) groups, and also microscopic subtypes as hypervascular (HV), plasmacytic (PC) and Mixed. Based on whether HHV-8 infection existed, MCD was subdivided into HHV-8-associated MCD and idiopathic Castleman disease (iMCD). Detailed epidemiologic, clinicopathological, and treatment data were analyzed and discussed. Of total 65 patients (UCD 33, MCD 32), HV (81.8%) accounted for the most of UCD and total. More females in UCD (60.6%) and more males in MCD (65.6%) were observed. CD occurred in all age groups, most commonly in 40–49 years. The mean age of onset of total was 38.5 years with PC higher than HV (45.5 vs. 35.1 years, P = 0.0413). The median diagnosis delay of MCD was longer than that of UCD (3.00 vs. 1.25 months, P = 0.0436). Abdomen (39.4%) and neck (30.3%) were the most-seen locations of lymphadenopathy in UCD, with neck (65.6%) being predominant in MCD. Mean major diameter of specimens of UCD was greater than MCD (6.4 vs. 3.1 cm, P

Abstract Multiple three-dimensional (3D) tumour organoid models assisted by multi-omics and Artificial Intelligence (AI) have contributed greatly to preclinical drug development and precision medicine. The intrinsic ability to maintain genetic and phenotypic heterogeneity of tumours allows for the reconciliation of shortcomings in traditional cancer models. While their utility in preclinical studies have been well established, little progress has been made in translational research and clinical trials. In this review, we identify the major bottlenecks preventing patient-derived tumour organoids (PDTOs) from being used in clinical setting. Unsuitable methods of tissue acquisition, disparities in establishment rates and a lengthy timeline are the limiting factors for use of PDTOs in clinical application. Potential strategies to overcome this include liquid biopsies via circulating tumour cells (CTCs), an automated organoid platform and optical metabolic imaging (OMI). These proposed solutions accelerate and optimize the workflow of a clinical organoid drug screening. As such, PDTOs have the potential for potential applications in clinical oncology to improve patient outcomes. If remarkable progress is made, cancer patients can finally benefit from this revolutionary technology.

Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics.

Superficial infantile hemangiomas (IH) are benign vascular tumors common in children characterized by bright red "strawberry" lesions on the skin. In order to optimize the treatment for this disease, there is a need to develop objective tools to assess treatment response. Since a color change in the lesion is a good indicator of treatment response, we have developed a digital imaging system to quantify the values of red, green, and blue (RGB) difference and RGB ratio between the tumor and normal tissue to take into account the variations in color between different skin types. The efficacy of the proposed system in assessing treatment response in superficial IH was evaluated in relation to established visual and biochemical tools used to grade hemangiomas. As the treatment progressed, the RGB ratio was almost 1, while the RGB difference was close to 0, which indicates a good response to treatment. There was a strong correlation between the RGB score and the other visual grading systems. However, the correlation between the RGB scoring system and the biochemical method was weak. These findings suggest that the system can be used clinically to objectively and accurately evaluate disease progression and treatment response in patients diagnosed with superficial IH.

Abstract A recent genome-wide copy number variations (CNVs) scan identified a 16q12.2 deletion that included the carboxylesterase 1 (CES1) gene, which is important in the metabolism of fatty acids and cholesterol. We aimed to investigate whether CES1 CNVs was associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in a Chinese Han population. A case–control study was conducted among 303 patients diagnosed with NAFLD and 303 age (± 5) and sex-matched controls from the Affiliated Nanping First Hospital of Fujian Medical University in China. The copy numbers of CES1 were measured using TaqMan quantitative real-time polymerase chain reaction (qPCR) and serum CES1 was measured using enzyme-linked immunosorbent assays. The Chi-squared test and a logistic regression model were used to evaluate the association between CES1 CNVs and NAFLD susceptibility. The distribution of CES1 CNVs showed a higher frequency of CNVs loss ( 2) was not. There was a suggestion of an association between increased CES1 serum protein levels and CNVs losses among cases, although this was not statistically significant (P = 0.07). Copy number losses (

Abstract Myofascial pelvic pain (MFPP) of pelvic floor muscles is a common cause of chronic pelvic pain (CPP). The pathological mechanisms and treatments of MFPP are complex and still unclear until now. The levator ani muscle (LAM) is the major pelvic floor muscle. The purpose of this study was to examine the fascia and attachment of LAM through the electromyogram (EMG) and cadaver dissection. Electrophysiological stimulation of the obturator fascia above the arcus tendinous levator ani (ATLA) could trigger contraction and electrophysiological changes in LAM insertion. The LAM of embalmed adult cadavers was examined especially in the area above the ATLA. Some skeletal muscle fibers were found above the ATLA within the obturator fascia and were confirmed by Masson’s trichrome section staining. Our electromyography (EMG) and anatomical data implied that the attachment of LAM aponeurosis extended beyond ATLA to the inferior border of the superior ramus of the pubic bone. The new discovered attachment of LAM could provide a reference position for clinical diagnosis and treatment of MFPP or CPP.

Background Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer and lacks effective biomarkers. This study seeks to unravel the expression status and the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC tissue samples. Moreover, another objective of this study is to reveal the prognostic molecular signatures for risk stratification in TNBC patients. Methods To determine the expression status of EZH1/EZH2 in TNBC tissue samples, microarray analysis and immunohistochemistry were performed on in house breast cancer tissue samples. External mRNA expression matrices were used to verify its expression patterns. Furthermore, the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC were explored by performing differential expression analysis, co-expression analysis, and chromatin immunoprecipitation sequencing analysis. Kaplan–Meier survival analysis and univariate Cox regression analysis were utilized to detect the prognostic molecular signatures in TNBC patients. Nomogram and time-dependent receiver operating characteristic curves were plotted to predict the risk stratification ability of the prognostic-signatures-based Cox model. Results In-house TMAs (66 TNBC vs. 106 non-TNBC) and external gene microarrays, as well as RNA-seq datasets (1,135 TNBC vs. 6,198 non-TNBC) results, confirmed the downregulation of EZH1 at both the protein and mRNA levels (SMD = −0.59 [−0.80, −0.37]), as is opposite to that of EZH2 (SMD = 0.74 [0.40, 1.08]). The upregulated transcriptional target genes of EZH1 were significantly aggregated in the cell cycle pathway, where CCNA2, CCNB1, MAD2L1, and PKMYT1 were determined as key transcriptional targets. Additionally, the downregulated transcriptional targets of EZH2 were enriched in response to the hormone, where ESR1 was identified as the hub gene. The six-signature-based prognostic model produced an impressive performance in this study, with a training AUC of 0.753, 0.981, and 0.977 at 3-, 5-, and 10-year survival probability, respectively. Conclusion EZH1 downregulation may be a key modulator in the progression of TNBC through negative transcriptional regulation by targeting CCNA2, CCNB1, MAD2L1, and PKMYT1.

Abstract Stroke leads to both regional brain functional disruptions and network reorganization. However, how brain functional networks reconfigure as task demand increases in stroke patients and whether such reorganization at baseline would facilitate post-stroke motor recovery are largely unknown. To address this gap, brain functional connectivity (FC) were examined at rest and motor tasks in eighteen chronic subcortical stroke patients and eleven age-matched healthy controls. Stroke patients underwent a 2-week intervention using a motor imagery-assisted brain computer interface-based (MI-BCI) training with or without transcranial direct current stimulation (tDCS). Motor recovery was determined by calculating the changes of the upper extremity component of the Fugl–Meyer Assessment (FMA) score between pre- and post-intervention divided by the pre-intervention FMA score. The results suggested that as task demand increased (i.e., from resting to passive unaffected hand gripping and to active affected hand gripping), patients showed greater FC disruptions in cognitive networks including the default and dorsal attention networks. Compared to controls, patients had lower task-related spatial similarity in the somatomotor–subcortical, default–somatomotor, salience/ventral attention–subcortical and subcortical–subcortical connections, suggesting greater inefficiency in motor execution. Importantly, higher baseline network-specific FC strength (e.g., dorsal attention and somatomotor) and more efficient brain network reconfigurations (e.g., somatomotor and subcortical) from rest to active affected hand gripping at baseline were related to better future motor recovery. Our findings underscore the importance of studying functional network reorganization during task-free and task conditions for motor recovery prediction in stroke.

Abstract Strong electromagnetic coupling among plasmonic nanostructures paves a new route toward efficient manipulation of photons. Particularly, plasmon-waveguide systems exhibit remarkable optical properties by simply tailoring the interaction among elementary elements. In this paper, we propose and demonstrate a freestanding bilayer plasmonic-waveguide structure exhibiting an extremely narrow transmission peak with efficiency up to 92%, the linewidth of only 0.14 nm and an excellent out of band rejection. The unexpected optical behavior considering metal loss is consistent with that of electromagnetic induced transparency, arising from the destructive interference of super-radiative nanowire dipolar mode and transversal magnetic waveguide mode. Furthermore, for slow light application, the designed plasmonic-waveguide structure has a high group index of approximately 1.2 × 105 at the maximum of the transmission band. In sensing application, its lowest sensing figure of merit is achieved up to 8500 due to the ultra-narrow linewidth of the transmission band. This work provides a valuable photonics design for developing high performance nano-photonic devices.

AbstractBackground The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality.Methods and Patients Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality.Results A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p

Objective To explore the molecular mechanism of anti-glioma by clofoctol targeting on RNA-binding proteins. Methods Biotin pull-down experiments were used to detect the binding of RNA-binding protein UNR (upstream of N-ras) to the target gene Krüppel-like factor 13(KLF13) mRNA fragments, and the effect of clofoctol on the binding to UNR to KLF13 mRNA fragments; The results of clofoctol DARTS sample's mass spectrometry combined with transcriptome chip analysis were used to screen other RNA-binding protein targets and to predict other downstream target genes. Results Clofoctol enhanced the interaction between UNR and the fragment of KLF13 mRNA; Clofoctol also acted on other RNA-binding proteins, and functioned in mTOR signaling pathway and TNF-related apoptosis-inducing ligand (TRAIL)-activated apoptotic signaling pathway. Conclusions Clofoctol can resist gliomas by acting on RNA-binding proteins.