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Porcine epidemic diarrhea virus (PEDV) is the pathogen of Porcine epidemic diarrhea (PED) and can mainly cause acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets. The nucleocapsid (N) protein of PEDV is a highly conserved structural protein. In this study, 6-8-week-old BALB/c mice were immunized with purified PEDV, and three monoclonal antibodies (mAbs) against the PEDV N protein were generated, named 3C6,4F8,4C9. Among them, three new B cell epitopes, 235IGENPDKL242, 12KRVPLSLY19, 372DAFKTGNA380 were firstly identified in the viral N-protein. Among them, 4F8 and 4C9 had IgG1 isotype with Kappa light chain, while 3C6 had IgG2a isotype with Kappa light chain. Three monoclonal antibodies (mAbs) demonstrated specific reactivity with PEDV as evidenced by Western blot and indirect immunofluorescence assay. By studying the interaction between the mAbs and the N protein, we can gain insights into the protein's conformation and functional regions. This information will help develop fast and accurate PEDV diagnostic methods.
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Based on the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases, this article analyzes the deductive context, cooperation network, and research hotspots of land development rights (LDR) research in the Chinese and international literature by using CiteSpace software, and it also explores the implications of this research for the theory and practice of national territory spatial planning (NTSP) in China. The results show that (1) the literature on LDR in Chinese and international journal articles initially appeared in 1995 and 1973, respectively, researches in China experienced three stages: embryonic fluctuating development, rapid growth and stable development, and wave development, while international researches experienced two stages: embryonic fluctuating and a gradually increasing development. (2) Among these scholars and research institutions, there is no obvious difference between Chinese and international scholars, while the Renmin University of China and the State University System of Florida are the research institutions with the largest number of Chinese and international journal articles, respectively. (3) In terms of publishing journals, international journals mainly focus on land policy, cities, and resource fields, while Chinese journals mainly focus on the agricultural economy, civil and commercial law, economic systems, and macroeconomic management fields. (4) The direction and scale of thematic research vary greatly, with Chinese research mainly conducted from the perspectives of rights attribution and benefits distribution, while international research mainly focuses on the operation of the right-to-development system and its impact on the environment. In the future, studies focus on China's need to strengthen the research and institutional practice of LDR at the legal level, value level, and extension level following national conditions, formulate a land value-added benefit distribution system with efficiency and fairness, and strengthen the practice of LDR in China's NTSP based on the differences between urban and rural development.
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OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.
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Background: Sarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients. Methods: Patients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA). Results: A total of 480 patients with RA were included in the study (90% female, with the largest number in the 45-59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795-0.9498) and 0.907 (95% CI: 0.8552-0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility. Conclusion: This study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.
Subject(s)
Arthritis, Rheumatoid , Nomograms , Sarcopenia , Humans , Arthritis, Rheumatoid/complications , Sarcopenia/diagnosis , Sarcopenia/etiology , Female , Male , Middle Aged , Aged , Risk Assessment , Risk Factors , Prognosis , Adult , ROC Curve , Reproducibility of ResultsABSTRACT
The development of pure organic room-temperature phosphorescent (RTP) materials greatly facilitates the integrated application of luminescent materials. Herein, a type of photoactivated red RTP material was constructed by simply doping 4-(benzo[c][1,2,5]thiadiazol-5-ylthio)benzonitrile (p-NNS) into a poly(methyl methacrylate) (PMMA) matrix. The obtained film realized a controllable photoactivation process by regulation of diverse solvent levels, demonstrating potential advantages in optical anti-counterfeiting applications. Furthermore, luminescent properties of the doped film were utilized to detect oxygen content from 2.00% to 4.90%, which revealed the exact consumption of ambient oxygen under UV light. Every CIE point of the luminescence corresponds to a certain oxygen content, illustrating the visualization of oxygen content. The remarkable regulation of solvent effect and oxygen content in this work will provide competitive material for further optical applications.
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Background and objectives: Fatigue has been associated with adverse effects on recovery from ischemic stroke based on previous observational research. The purpose of our study was to explore the potential causal association of fatigue with poor functional outcome after ischemic stroke by employing Mendelian randomization (MR). Methods: A set of instrumental variables, comprising 36 single-nucleotide polymorphisms (SNPs) that are only related to fatigue, were derived from a genome-wide association study (GWAS) that included 449,019 general individuals. The functional outcomes after ischemic stroke were derived from a GWAS (Genetics of Ischemic Stroke Functional Outcome Network) involving 6,021 survivors. Two-sample MR methods were used to assess the causal effect, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. In bidirectional MR analysis, the reverse causal association was analyzed using the Wald ratio method. The mediation effects of lipid metabolites were analyzed using two-step MR analysis. Results: Genetic liability to fatigue was causally associated with the poor functional outcome (modified Rankin Scale ≥3 at 3 months) after ischemic stroke (OR = 4.20, 95%CI [1.11-15.99], p < 0.05). However, genetic predicted poor functional outcome after ischemic stroke was not associated with fatigue (OR = 1.00, 95%CI [0.99-1.02], p > 0.05). The results of the two-step MR showed that cholesteryl esters to total lipids ratio in large very low-density lipoprotein (VLDL) (ME = -0.13, p < 0.05); concentration of very large VLDL particles (ME = -0.13, p < 0.05); free cholesterol in large VLDL (ME = -0.13, p < 0.05); free cholesterol to total lipids ratio in very large VLDL (ME = -0.22, p < 0.05); phospholipids in large VLDL (ME = -0.15, p < 0.05); phospholipids in very large VLDL (ME = -0.13, p < 0.05); phospholipids to total lipids ratio in large high-density lipoprotein (HDL) (ME = -0.17, p < 0.05); total lipids in very large VLDL (ME = -0.14, p < 0.05); triglycerides in small VLDL (ME = -0.11, p < 0.05); and triglycerides to total lipids ratio in large HDL (ME = -0.10, p < 0.05) assumed a pivotal role in mediating the association between fatigue and poor functional outcome after ischemic stroke. Conclusion: Our study provides evidence supporting the causal association between fatigue and the poor functional outcome after ischemic stroke, which emphasizes the importance of implementing interventions aimed at addressing fatigue. This could offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context. One potential mechanism by which fatigue affects functional outcomes after ischemic stroke is through the action of lipid metabolites.
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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Abnormal formation of neutrophil extracellular traps (NETs) at the synovial membrane leads to the release of many inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Elastase, histone H3, and myeloperoxidase, which are carried by NETs, damage the soft tissues of the joints and aggravate the progression of RA. The balance of NET formation coordinates the pro-inflammatory and anti-inflammatory effects and plays a key role in the development of RA. Therefore, when NETs are used as effector targets, highly targeted drugs with fewer side effects can be developed to treat RA without damaging the host immune system. Currently, an increasing number of studies have shown that traditional Chinese medicines and natural products can regulate the formation of NETs through multiple pathways to counteract RA, which shows great potential for the treatment of RA and has a promising future for clinical application. In this article, we review the latest biological progress in understanding NET formation, the mechanism of NETs in RA, and the potential targets or pathways related to the modulation of NET formation by Chinese medicines and natural products. This review provides a relevant basis for the use of Chinese medicines and natural products as natural adjuvants in the treatment of RA.
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BACKGROUND: Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM. METHODS: Colonic GM (profiled by 16S ribosomal RNA gene amplicon sequencing) was compared in preterm pigs fed colostrum for 4 days, either before, after, or together with formula feeding for 4 days. Correlations between GM and gut parameters were assessed on day 5 or 9. RESULTS: Both exclusive and partial colostrum feeding induced higher GM diversity, lower Enterococcus abundance, and improved intestinal maturation parameters (villus structure, digestive enzyme activities, permeability), relative to exclusive formula feeding (all p < 0.05). Across feeding regimens, Enterococcus abundance was inversely correlated with intestinal maturation parameters. Conversely, there was no correlation between GM changes and early NEC lesions. CONCLUSION: Bovine colostrum inhibits formula-induced Enterococcus overgrowth and gut dysfunctions just after preterm birth but these effects are not causally linked. Optimising diet-related host responses, not GM, may be critical to prevent NEC in preterm newborn pigs and infants. IMPACT: Supplement of bovine colostrum to formula feeding modified the gut microbiota by increasing species diversity and reducing Enterococcus abundance, while concurrently improving intestinal functions in preterm pigs. Diet-related changes to the gut microbiota were not clearly associated with development of necrotizing enterocolitis (NEC) in preterm pigs, suggesting that diet-related gut microbiota effects are not critical for diet-related NEC protection. The study highlights the potential to use bovine colostrum as a supplement to formula feeding for preterm infants lacking human milk.
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Introduction: Echinococcosis is a chronic zoonotic disease caused by tapeworms of the genus Echinococcus. The World Health Organization (WHO) has identified encapsulated disease as one of 17 neglected diseases to be controlled or eliminated by 2050. There is no accurate, early, non-invasive molecular diagnostic method to detect echinococcosis. The feasibility of circulating free DNA as a diagnostic method for echinococcosis has yielded inconclusive results in a number of published studies. However, there has been no systematic evaluation to date assessing the overall performance of these assays. We report here the first meta-analysis assessing the diagnostic accuracy of cfDNA in plasma, serum, and urine for echinococcosis. Methods: We systematically searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WeiPu databases up to 17 January 2024, for relevant studies. All analyses were performed using RevMan 5.3, Meta-DiSc 1.4, Stata 17.0, and R 4.3.1 software. The sensitivity, specificity, and other accuracy indicators of circulating free DNA for the diagnosis of echinococcosis were summarized. Subgroup analyses and meta-regression were performed to identify sources of heterogeneity. Results: A total of 7 studies included 218 patients with echinococcosis and 214 controls (156 healthy controls, 32 other disease controls (non-hydatid patients), and 26 non-study-targeted echinococcosis controls were included). Summary estimates of the diagnostic accuracy of cfDNA in the diagnosis of echinococcosis were as follows: sensitivity (SEN) of 0.51 (95% CI: 0.45-0.56); specificity (SPE) of 0.99 (95% CI: 0.97-0.99); positive likelihood ratio (PLR) of 11.82 (95% CI: 6.74-20.74); negative likelihood ratio (NLR) of 0.57 (95% CI: 0.41-0.80); diagnostic ratio (DOR) of 36.63 (95% CI: 13.75-97.59); and area under the curve (AUC) value of 0.98 (95% CI: 0.96-1.00). Conclusion: Existing evidence indicates that the combined specificity of circulating cfDNA for echinococcosis is high. However, the combined sensitivity performance is unsatisfactory due to significant inter-study heterogeneity. To strengthen the validity and accuracy of our findings, further large-scale prospective studies are required.Systematic review registrationThe systematic review was registered in the International Prospective Register of Systematic Reviews PROSPERO [CRD42023454158]. https://www.crd.york.ac.uk/PROSPERO/.
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OBJECTIVE: This study aimed to investigate the efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted computed tomography (CT)-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of pelvic recurrent cervical carcinoma after external beam radiotherapy. METHODS: From January 2019 to August 2023, 45 eligible patients were enrolled in this prospective cohort. All patients underwent 3D-PNCT-assisted CT-guided HDR-ISBT with a prescribed dose of 4-7 Gy/fraction to the high-risk clinical target volume (HR-CTV) over 3-8 fractions, either for curative or palliative purposes. The primary endpoints were local progression-free survival (LPFS) and tumor response rate (TRR). The secondary outcome measures included overall survival (OS), toxicities, and symptom resolution. RESULTS: Forty-five patients received 261 fractions of 3D-PNCT-assisted HDR-ISBT. Twenty-nine patients had isolated pelvic recurrence, and 16 patients had simultaneous extra-pelvic or distant recurrences. The TRR was 66.7%. The 2- and 5-year LPFS rates were 30.0% and 25.7%, respectively. The median OS was 23.2 months, and 2- and 5-year OS rates were 49.5% and 34.0%, respectively. The multivariate analysis indicated that squamous cell carcinoma, radical surgery, recurrence-free interval≥12 months, tumor diameter, pelvic recurrence type, and HR-CTV D90≥45 Gy were independent factors influencing LPFS (all p<0.05). D100≥21 Gy, V100≥83%, and V150≥45% were associated with better LPFS (all p<0.05). Tumor diameter and metastasis were independent predictive factors for OS (all p<0.05). The pain relief rate was 66.7% (10/15). Grade 3-4 toxicities occurred in 20.0% of patients. CONCLUSION: 3D-PNCT-assisted HDR-ISBT for reirradiation of recurrent cervical cancer proved to be an effective and safe alternative to radical surgery.
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The effective management of water and nitrogen is crucial in the artificial cultivation of medicinal plants. Sophora alopecuroides, a perennial herbaceous plant in the Fabaceae family, is extensively used in medicine, with alkaloids as its primary bioactive constituents. Nevertheless, there remains a significant knowledge gap regarding how rhizospheric microbial communities respond to varying water and nitrogen conditions and their intricate relationships with soil environments and the growth of S. alopecuroides. In this study, two-year-old S. alopecuroides were used in a two-factor, three-level water-nitrogen interaction experiment. The irrigation levels included W1 (30-35% of maximum water holding capacity), W2 (50-55%), and W3 (70-75%), while nitrogen levels comprised N1 (32 mg/kg), N2 (64 mg/kg), and N3 (128 mg/kg). The study assessed plant growth indicators, total alkaloid content, and rhizospheric soil physicochemical parameters of S. alopecuroides. High-throughput sequencing (16S rRNA and ITS) was employed to analyze variations in rhizospheric microbial community composition and structure. The results showed that Proteobacteria and Ascomycota are the predominant bacterial and fungal phyla in the rhizosphere microbial community of S. alopecuroides. The highest biomass and alkaloid accumulation of S. alopecuroides were observed under the N1W3 treatment (50% nitrogen application and 70-75% of maximum water holding capacity). Specifically, six bacterial genus-level biomarkers (TRA3_20, MND1, env_OPS_17, SBR1031, Haliangium, S0134_terrestrial_group) and six fungal genus-level biomarkers (Pseudeurotium, Rhizophagus, Patinella, Pseudeurotium, Patinella, Rhizophagus) were identified under the N1W3 treatment condition. In the partial least squares path modeling (PLS-PM), water and nitrogen treatments demonstrated markedly positive direct effects on soil physicochemical parameters (p < 0.01), while showing significant negative direct impacts on alkaloid accumulation and plant growth indicators (p < 0.05). Soil physicochemical parameters, in turn, significantly negatively affected the rhizosphere fungal community (p < 0.05). Additionally, the rhizosphere fungal community exhibited highly significant negative direct effects on both the plant growth indicators and total alkaloid content of S. alopecuroides (p < 0.01). This study provides new insights into the interactions among rhizosphere soil environment, rhizosphere microbiota, plant growth, and alkaloid accumulation under water and nitrogen regulation, offering a scientific basis for the water and nitrogen management in the cultivation of S. alopecuroides.
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BACKGROUND: Lung ischemia reperfusion injury (IRI) is the principal cause of primary graft dysfunction (PGD) after lung transplantation, affecting short-term and long-term mortality post-transplantation. PANoptosis, a newly identified form of regulated cell death involving apoptosis, necroptosis, and pyroptosis, is now considered a possible cause of organ damage and IRI. However, the specific role of PANoptosis to the development of lung IRI following lung transplantation is still not fully understood. METHODS: In this study, we identified differentially expressed genes (DEGs) by analyzing the gene expression data from the GEO database related to lung IRI following lung transplantation. PANoptosis-IRI DEGs were determined based on the intersection of PANoptosis-related genes and screened DEGs. Hub genes associated with lung IRI were further screened using Lasso regression and the SVM-RFE algorithm. Additionally, the Cibersort algorithm was employed to assess immune cell infiltration and investigate the interaction between immune cells and hub genes. The upstream miRNAs that may regulate hub genes and compounds that may interact with hub genes were also analyzed. Moreover, an external dataset was utilized to validate the differential expression analysis of hub genes. Finally, the expressions of hub genes were ultimately confirmed using quantitative real-time PCR, western blotting, and immunohistochemistry in both animal models of lung IRI and lung transplant patients. RESULTS: PANoptosis-related genes, specifically interferon regulatory factor 1 (IRF1) and interleukin 1 alpha (IL1A), have been identified as potential biomarkers for lung IRI following lung transplantation. In mouse models of lung IRI, both the mRNA and protein expression levels of IRF1 and IL1A were significantly elevated in lung tissues of the IRI group compared to the control group. Moreover, lung transplant recipients exhibited significantly higher protein levels of IRF1 and IL1A in PBMCs when compared to healthy controls. Patients who experienced PGD showed elevated levels of IRF1 and IL1A proteins in their blood samples. Furthermore, in patients undergoing lung transplantation, the protein levels of IRF1 and IL1A were notably increased in peripheral blood mononuclear cells (PBMCs) compared to healthy controls. In addition, patients who developed primary graft dysfunction (PGD) exhibited even higher protein levels of IRF1 and IL1A than those without PGD. Furthermore, PANoptosis was observed in the lung tissues of mouse models of lung IRI and in the PBMCs of patients who underwent lung transplantation. CONCLUSIONS: Our research identified IRF1 and IL1A as biomarkers associated with PANoptosis in lung IRI, suggesting their potential utility as targets for diagnosing and therapeutically intervening in lung IRI and PGD following lung transplantation.
Subject(s)
Interferon Regulatory Factor-1 , Interleukin-1alpha , Lung Transplantation , Lung , Reperfusion Injury , Lung Transplantation/adverse effects , Reperfusion Injury/immunology , Reperfusion Injury/metabolism , Animals , Interferon Regulatory Factor-1/genetics , Interferon Regulatory Factor-1/metabolism , Humans , Mice , Lung/pathology , Lung/immunology , Male , Interleukin-1alpha/genetics , Interleukin-1alpha/metabolism , Necroptosis , Mice, Inbred C57BL , Pyroptosis , Disease Models, Animal , Primary Graft Dysfunction/genetics , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/immunology , Primary Graft Dysfunction/diagnosisABSTRACT
Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome characterized by immune hyperactivation. Unlike primary HLH, immune checkpoint inhibitor (ICI)-triggered HLH is not well described, and there is a lack of theranostic guidelines. Herein, we first reported the successful management of PD-1 inhibitor-associated HLH in locally advanced cervical cancer. Case presentation: We report a case of HLH in a 47-year-old patient with International Federation of Gynecology and Obstetrics (FIGO) IIIC1r cervical cancer who received toripalimab, a programmed cell death-1 receptor inhibitor, combined with chemoradiotherapy. The patient developed pyrexia, splenomegaly, leukopenia, anemia, thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, reduced NK cell activity, elevated sCD25 levels, and hemophagocytosis in a bone marrow aspirate. Our patient was successfully treated with methylprednisolone, indicating that immune-induced HLH might respond to glucocorticoids, and is still alive with a complete response of the tumor. Conclusion: Considering the possibility of HLH is needed in patients receiving ICIs to detect rare toxicities at an early stage when the patient develops uncontrollable fever, cytopenia, and splenomegaly, our multidisciplinary treatment modality contributed to the early diagnosis and successful management of HLH, avoiding progressive tissue damage and organ failure. Whether glucocorticoids are used alone or not for immune-associated HLH needs further investigation.
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To improve the transmission efficiency of Cassegrain antennas and enable the simultaneous transmission of signals with different wavelengths in the antenna system, this study introduces Fresnel lenses and conical lenses in front of the Cassegrain antenna at the transmitting end. Reflective mirrors and focusing lenses are introduced at the receiving end. A detailed description is provided of the design process for the Fresnel lens, as well as the impact of various parameters on the hollow radius when combined with the conical lens. Based on the laws of vector reflection and refraction, simulations are performed to track the propagation of light through the entire communication system and lens pairs, providing transmission efficiency plots of the antenna system under deflection and off-axis conditions. Taking into account practical factors such as lens chamfer, transmittance, Cassegrain antenna reflectance, and material dispersion, the transmission efficiency of the antenna system at 1550 nm wavelength can still reach 93.45%. The proposed method not only improves the transmission efficiency of Cassegrain antennas, but also enables the transmission of different information through the inner and outer layers of the antenna system.
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Rheumatoid arthritis (RA) is an autoimmune disease causing progressive joint damage. Early diagnosis and treatment is critical, but remains challenging due to RA complexity and heterogeneity. Machine learning (ML) techniques may enhance RA management by identifying patterns within multidimensional biomedical data to improve classification, diagnosis, and treatment predictions. In this review, we summarize the applications of ML for RA management. Emerging studies or applications have developed diagnostic and predictive models for RA that utilize a variety of data modalities, including electronic health records, imaging, and multi-omics data. High-performance supervised learning models have demonstrated an Area Under the Curve (AUC) exceeding 0.85, which is used for identifying RA patients and predicting treatment responses. Unsupervised learning has revealed potential RA subtypes. Ongoing research is integrating multimodal data with deep learning to further improve performance. However, key challenges remain regarding model overfitting, generalizability, validation in clinical settings, and interpretability. Small sample sizes and lack of diverse population testing risks overestimating model performance. Prospective studies evaluating real-world clinical utility are lacking. Enhancing model interpretability is critical for clinician acceptance. In summary, while ML shows promise for transforming RA management through earlier diagnosis and optimized treatment, larger scale multisite data, prospective clinical validation of interpretable models, and testing across diverse populations is still needed. As these gaps are addressed, ML may pave the way towards precision medicine in RA.
Subject(s)
Arthritis, Rheumatoid , Machine Learning , Precision Medicine , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/therapy , Humans , Precision Medicine/methods , Rheumatology/methods , Disease ManagementABSTRACT
BACKGROUND: Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer. METHODS AND MATERIALS: This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS. RESULTS: Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities. CONCLUSION: VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.
Subject(s)
Brachytherapy , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated , Tomography, X-Ray Computed , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/mortality , Radiotherapy, Intensity-Modulated/methods , Radiotherapy, Intensity-Modulated/adverse effects , Brachytherapy/methods , Brachytherapy/adverse effects , Retrospective Studies , Middle Aged , Adult , Aged , Radiotherapy, Image-Guided/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Aged, 80 and over , Survival RateABSTRACT
BACKGROUND: Pesticide efficacy directly affects crop yield and quality, making targeted spraying a more environmentally friendly and effective method of pesticide application. Common targeted cabbage spraying methods often involve object detection networks. However, complex natural and lighting conditions pose challenges in the accurate detection and positioning of cabbage. RESULTS: In this study, a cabbage detection algorithm based on the YOLOv8n neural network (YOLOv8-cabbage) combined with a positioning system constructed using a Realsense depth camera is proposed. Initially, four of the currently available high-performance object detection models were compared, and YOLOv8n was selected as the transfer learning model for field cabbage detection. Data augmentation and expansion methods were applied to extensively train the model, a large kernel convolution method was proposed to improve the bottleneck section, the Swin transformer module was combined with the convolutional neural network (CNN) to expand the perceptual field of feature extraction and improve edge detection effectiveness, and a nonlocal attention mechanism was added to enhance feature extraction. Ablation experiments were conducted on the same dataset under the same experimental conditions, and the improved model increased the mean average precision (mAP) from 88.8% to 93.9%. Subsequently, depth maps and colour maps were aligned pixelwise to obtain the three-dimensional coordinates of the cabbages via coordinate system conversion. The positioning error of the three-dimensional coordinate cabbage identification and positioning system was (11.2 mm, 10.225 mm, 25.3 mm), which meets the usage requirements. CONCLUSIONS: We have achieved accurate cabbage positioning. The object detection system proposed here can detect cabbage in real time in complex field environments, providing technical support for targeted spraying applications and positioning.
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Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting pyroptosis, was encapsulated by butyrate-modified liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.
Subject(s)
Colitis, Ulcerative , Epithelial Cells , Intestinal Mucosa , Pyroptosis , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Pyroptosis/drug effects , Animals , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Mice , Humans , Epithelial Cells/drug effects , Epithelial Cells/pathology , Epithelial Cells/metabolism , Liposomes/chemistry , Mice, Inbred C57BL , Drug Delivery SystemsABSTRACT
A visible-light-mediated catalyst- and additive-free method for radical ring-opening fluorosulfonylation of methylenecyclobutanols is reported. Sulfuryl chlorofluoride acts as a FSO2 radical precursor as well as an electron acceptor to form electron donor-acceptor complexes with various methylenecyclobutanol substrates. This method shows fully regioselective and (E)-stereoselective ring-opening processes, providing a variety of FSO2-functionalized γ,δ-unsaturated carbonyls in 38-77% yields. A selection of product diversifications has been studied to demonstrate the versatility of these sulfonyl fluoride products.
ABSTRACT
Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.