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Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD)-related mortality have increased dramatically in past decades. Our study aims to investigate the association between plain water and this prevalent metabolic disease, as water plays a crucial role in regulating metabolic processes. A total of 3,543/3,428 individuals with NAFLD/MASLD were included in this study from National Health and Nutrition Examination Survey (NHANES). Daily plain water intake was recorded, and mortality status was tracked until December 31, 2019. Multivariate Cox regression models and restricted cubic spline (RCS) regression models were used to assess the association between plain water intake and long-term all-cause as well as cause-specific mortality among participants with NAFLD/MASLD. Furthermore, we investigated the relationship between substituting other beverages with plain water intake and the risk of mortality. The multivariate Cox regression analyses revealed a significant association between higher plain water intake and lower all-cause mortality, cerebrovascular diseases mortality, and cancer mortality in both NAFLD or MASLD patients. Dose-response analyses revealed a non-linear trend between plain water intake and mortality among NAFLD/MASLD patients. Additionally, replacing sugar or artificial beverages with plain water was linked to reduced all-cause mortality, cerebrovascular diseases mortality, and cancer mortality in patients with NAFLD/MASLD. Higher plain water intake is independently linked to lower risk of all-cause, cerebrovascular diseases mortality, and cancer mortality in NAFLD/MASLD patients. Increasing plain water intake may be an effective way for these patients to reduce their risk of mortality.

Sacha Inchi (Plukenetia volubilis L) (SI) is a traditional natural medicine from tropical rainforests of Amazon region in South America. As a raw material for edible oil, it has various pharmacological effects such as antioxidant, anti-inflammatory, hypolipidemia, and blood pressure lowering, which have attracted increasing attentions of pharmacists. This has prompted researchers to explore its pharmacological effects for potential applications in certain diseases. Among these, the study of its anti-inflammatory effects has become a particularly interesting topic, especially in rheumatoid arthritis (RA). RA is a systemic autoimmune disease, and often accompanied by chronic inflammatory reactions. Despite significant progress in its treatment, there is still an urgent need to find effective anti-RA drugs in regard to safety. This review summarizes the potential therapeutic effects of SI on RA by modulating gut microbiota, targeting inflammatory cells and pathways, and mimicking biologic antibody drugs, predicting the application prospects of SI in RA, and providing references for research aimed at using SI to treat RA.

ObjectiveThis study aimed to determine the 50% effective dose (ED50) of ciprofol when combined with different doses of remifentanil for upper gastrointestinal endoscopy of school-age children and to evaluate its safety.MethodsThis study involved school-aged children who were scheduled to undergo upper gastrointestinal endoscopy under deep sedation. The children were randomly assigned to two groups: remifentanil 0.3 μg/kg (R0.3) and remifentanil 0.5 μg/kg (R0.5). Anesthesia was induced with remifentanil, followed by ciprofol. The dose of ciprofol for each patient was determined using the Dixon up-down sequential method. If the MOAA/S score was ≤1 and the child did not exhibit significant movement or coughing during the endoscopy process, sedation was considered successful. The first patient in each group received 0.5 mg/kg ciprofol. The dose of ciprofol was adjusted by 0.05 mg/kg based on the response of the previous patient. The primary outcome was the ED50 of the ciprofol-induction dose. The total ciprofol doses, onset times, awakening times, and adverse reactions were recorded.Results1) The Dixon method was used to collect crossovers data from each group, and the ED50 values of the R0.3 and R0.5 groups were calculated to be 0.390 mg/kg (95% CI 0.356–0.424 mg/kg) and 0.332 mg/kg (95% CI 0.291–0.374 mg/kg), respectively. The ED50 of ciprofol in the R0.3 group was significantly higher than that in the R0.5 group (p < 0.05). 2) The onset time and recovery time of the R0.5 group were shorter than those of the R0.3 group (p < 0.05). When the two groups were compared, the total dose of ciprofol in the R0.5 group decreased (p < 0.05). 3) Compared with the R0.3 group, the incidence of respiratory depression during induction in the R0.5 group increased (p < 0.05).ConclusionThis study explored the ED50 of ciprofol combined with different doses of remifentanil for successful sedation in upper gastrointestinal examinations in school-aged children. Compared to the use of remifentanil 0.3 μg/kg, the combination of ciprofol with remifentanil 0.5 μg/kg significantly reduced the ED50 required to prevent body movement or cough during endoscope insertion but increased the incidence of respiratory depression.

IntroductionChemotherapy-induced cardiotoxicity poses a significant challenge in the treatment of breast cancer, potentially compromising both the efficacy of cancer therapy and cardiac health of patients. This study aimed to enhance the early detection of cardiotoxic effects by integrating advanced imaging modalities and biomarker analysis, thereby facilitating timely interventions to mitigate cardiac risk.MethodsA prospective cohort design was employed, enrolling breast cancer patients scheduled for potentially cardiotoxic chemotherapy regimens. The study utilized a comprehensive diagnostic toolkit, including echocardiography with strain imaging, cardiac MRI, and serial measurements of cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides.ResultsThe analysis revealed that subtle changes in myocardial strain parameters and early biomarker elevations were predictive of subsequent declines in left ventricular function, preceding conventional echocardiographic evidence of cardiotoxicity. Logistic regression analysis highlighted the additive predictive value of integrating biomarker data with advanced imaging findings to identify patients with the highest risk of significant cardiotoxicity.DiscussionThe study concluded that an integrated diagnostic approach, combining detailed imaging assessments with sensitive biomarker analysis, offers a superior strategy for the early detection of chemotherapy-induced cardiotoxicity in breast cancer patients. This proactive diagnostic strategy empowers clinicians to tailor cancer therapy more precisely, balancing oncologic efficacy with cardiovascular safety and underscores the importance of a multidisciplinary approach in the management of patients undergoing potentially cardiotoxic chemotherapy.

The excessive deposition and cross-linking of core matrisome components typically result in abnormal remodeling of the extracellular matrix (ECM), leading to increased liver stiffness and worsening liver fibrosis. Exploring the biochemical properties of the ECM scaffold can deepen our understanding of the pathological mechanisms driving liver fibrosis and potentially facilitate the identification of therapeutic targets. While traditional sodium dodecyl sulfate (SDS)-based liver decellularization followed by proteomics can uncover the matrisome components within the ECM scaffold, it lacks the ability to reveal physicochemical characteristics like solubility. In our present study, using adult mouse liver as an example, we introduced a novel two-step workflow that combines our previously enhanced SDS (ESDS) decellularization with the conventional SDS method, enabling the identification of matrisome members with mild and/or high solubilities. Through this approach, we visualized the atlas of the mildly and highly insoluble matrisome contents in the adult mouse liver, as well as the regulatory network of highly insoluble matrisome that largely governs liver stiffness. Given the strong correlation between increased matrisome insolubility and heightened ECM stiffness, we believe that this methodology holds promise for future research focused on liver stiffness.

Autophagy is a highly conserved process in eukaryotes that is used to recycle the cellular components from the cytoplasm. It plays a crucial function in responding to both biotic and abiotic stress, as well as in the growth and development of plants. Autophagy-related genes (ATG) and their functions have been identified in numerous crop species. However, their specific tasks in potatoes (Solanum tuberosum L.), are still not well understood. This work is the first to identify and characterize the potato StATG18 subfamily gene at the whole-genome level, resulting in a total of 6 potential StATG18 subfamily genes. We analyzed the phylogenetic relationships, chromosome distribution and gene replication, conserved motifs and gene structure, interspecific collinearity relationship, and cis-regulatory elements of the ATG18 subfamily members using bioinformatics approaches. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis suggested that StATG18 subfamily genes exhibit differential expression in various tissues and organs of potato plants. When exposed to heat stress, their expression pattern was observed in the root, stem, and leaf. Based on a higher expression profile, the StATG18a gene was further analyzed under heat stress in potatoes. The subcellular localization analysis of StATG18a revealed its presence in both the cytoplasm and nucleus. In addition, StATG18a altered the growth indicators, physiological characteristics, and photosynthesis of potato plants under heat stresses. In conclusion, this work offers a thorough assessment of StATG18 subfamily genes and provides essential recommendations for additional functional investigation of autophagy-associated genes in potato plants. Moreover, these results also contribute to our understanding of the potential mechanism and functional validation of the StATG18a gene’s persistent tolerance to heat stress in potato plants.

Tomato disease image recognition plays a crucial role in agricultural production. Today, while machine vision methods based on deep learning have achieved some success in disease recognition, they still face several challenges. These include issues such as imbalanced datasets, unclear disease features, small inter-class differences, and large intra-class variations. To address these challenges, this paper proposes a method for classifying and recognizing tomato leaf diseases based on machine vision. First, to enhance the disease feature details in images, a piecewise linear transformation method is used for image enhancement, and oversampling is employed to expand the dataset, compensating for the imbalanced dataset. Next, this paper introduces a convolutional block with a dual attention mechanism called DAC Block, which is used to construct a lightweight model named LDAMNet. The DAC Block innovatively uses Hybrid Channel Attention (HCA) and Coordinate Attention (CSA) to process channel information and spatial information of input images respectively, enhancing the model’s feature extraction capabilities. Additionally, this paper proposes a Robust Cross-Entropy (RCE) loss function that is robust to noisy labels, aimed at reducing the impact of noisy labels on the LDAMNet model during training. Experimental results show that this method achieves an average recognition accuracy of 98.71% on the tomato disease dataset, effectively retaining disease information in images and capturing disease areas. Furthermore, the method also demonstrates strong recognition capabilities on rice crop disease datasets, indicating good generalization performance and the ability to function effectively in disease recognition across different crops. The research findings of this paper provide new ideas and methods for the field of crop disease recognition. However, future research needs to further optimize the model’s structure and computational efficiency, and validate its application effects in more practical scenarios.

The infection of the central nervous system (CNS) with neurotropic viruses induces neuroinflammation and an immune response, which is associated with the development of neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). The activation of both innate and adaptive immune responses, involving microglia, macrophages, and T and B cells, while required for efficient viral control within the CNS, is also associated with neuropathology. Under pathological events, such as CNS viral infection, microglia/macrophage undergo a reactive response, leading to the infiltration of immune cells from the periphery into the brain, disrupting CNS homeostasis and contributing to the pathogenesis of disease. The Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelination disease (TMEV-IDD), which serves as a mouse model of MS. This murine model made significant contributions to our understanding of the pathophysiology of MS following subsequent to infection. Microglia/macrophages could be activated into two different states, classic activated state (M1 state) and alternative activated state (M2 state) during TMEV infection. M1 possesses the capacity to initiate inflammatory response and secretes pro-inflammatory cytokines, and M2-liked microglia/macrophages are anti-inflammatory characterized by the secretion of anti-inflammatory cytokines. This review aims to discuss the roles of microglia/macrophages M1/M2-liked polarization during TMEV infection, and explore the potential therapeutic effect of balancing M1/M2-liked polarization of microglia/macrophages on MS.

Nitrate (NO3−) reduction is a key process governing the nitrogen (N) dynamics of coastal wetland sediments. Although the effects of environmental factors on the NO3− reduction mechanism in coastal wetland sediments have been examined in various studies, the effects of spatial variation in potential NO3− reduction processes in coastal wetland sediments and the factors driving geographical variation in these processes have not been widely examined. Here, we conducted research on surface sediment samples from four different vegetation types at six coastal wetland sites across two regions. We characterized potential rates of NO3− reduction processes (including denitrification (DF), anammox (ANA), and dissimilatory nitrate reduction to ammonium (DNRA)) using a15N tracer method. Additionally, we assessed the abundances of functional genes, and microbial community structure using high-throughput sequencing, and metagenomic sequencing. In six wetland sites, the contribution ranges of DF, ANA, and DNRA to NO3− reduction were 38.43%–55.69%, 31.33%–45.65%, and 5.26%–17.11%, respectively, and potential NO3− reduction was mainly driven by N removal via gaseous N (DF+ANA). Significant spatial differences were observed in the structure of bacterial and fungal microbial communities, suggesting that geographical distance has a major effect on microbial community structure. Environmental factors and Functional gene abundances were significantly related to potential NO3− reduction processes, and physicochemical properties had a stronger effect on potential NO3− reduction processes than gene abundances. Factors showing significant differences across regions were the main drivers of variation in potential NO3− reduction processes. Overall, our study showed that sediment substrates and geographical environmental factors rather than the abundance of functional genes and vegetation types were the main indicators of potential NO3− reduction activities in coastal wetlands.

BackgroundCombination therapy was associated with an increased risk of drug- drug interactions (DDIs) in patients with type 2 diabetes mellitus (T2DM). The present study aimed to investigate the epidemiology of potential DDIs (pDDIs), including potential chemical drug-drug interactions (pCDIs) and potential herb-drug interactions (pHDIs), and classify the influencing factors of pDDIs in these patients.MethodsA retrospective study of the epidemiology of pDDIs among T2DM hospitalized patients older than 18 years and treated with at least two drugs during hospitalization was conducted over a 12-month period in 2019. PDDIs were identified with C (monitor therapy), D (consider therapy modification), and X (avoid combination) risk ratings. Binary logistic regression was used to analyze the risk factors of pDDIs.ResultsA total of 6796 pDDIs were identified from 737 T2DM hospitalized patients during hospitalization, with 0.87% classified as X risk rating, 13.39% as D risk rating. Additionally, 1753 pDDIs were identified after discharge, with 0.11% as X and 25.73% as D risk rating. The drug-drug association networks showed that the majority of pCDIs were associated with cardiovascular system drugs. Chlorphenamine-potassium chloride and danshen-warfarin were the most prevalent interacting pairs of pCDIs and pHDIs with X rating during hospitalization. Multivariate analysis indicated that the likelihood of developing over 4 pDDIs was significantly higher among T2DM patients who had received over 8 medications. The presence of pDDIs after discharge was strongly associated with the complications of T2DM and the number of discharge medications.ConclusionsT2DM patients were frequently exposed to pDDIs, including pCDIs and pHDIs, both during hospitalization and after discharge. Multi-drug combination was the primary risk factor for pDDIs. Strategies such as enhancing the monitoring and warning for pDDIs, increasing clinical pharmacological experience, as well as developing universally applicable clinical guidelines for pDDIs may be beneficial in reducing the incidence of potentially harmful drug-combinations.

ObjectivesDepression is largely preventable, and strategies that can effectively suppress its development are imperative. We aimed to examine whether physical activity and sedentary behavior were associated with depression and explore the possible mediatory role of complete blood count in this association.MethodsIn this cross-sectional study, data were integrated from the National Health and Nutrition Examination Study (2007–2018). Depression was defined using the Patient Health Questionnaire-9. The risk for depression, expressed as odds ratio (OR) and 95% confidence interval (CI), was quantified by survey-weighted logistic regression analyses.ResultsA total of 31,204 respondents were analyzed. Significance was identified for all, except walking or bicycling per week, types of physical activity, and sedentary behavior. Per 1 standard deviation (SD) increment in metabolic equivalent of task (MET) of weekly vigorous recreational physical activity was associated with 31.3% decreased depression risk (adjusted OR: 0.687, 95% CI: 0.5663–0.840). Per 1 SD increment in sitting time can increase depression risk by 22.4% (adjusted OR: 1.224, 95% CI: 1.131–1.325). In subsidiary analyses, the association with depression was reinforced in respondents aged ≤65 years and those overweight or obese. Mediation analyses revealed significant effects for red blood cell (RBC) on total MET (19.4%) and moderate work-related physical activity (MWPA) (22.0%), and for red cell distribution wide (RCDW) on vigorous work-related physical activity (17.7%), moderate work-related physical activity (13.1%), total MET (11.2%), and sitting time (16.4%) (p

The disparity between human and machine perception of spatial information presents a challenge for machines to accurately sense their surroundings and improve target detection performance. Cross-modal data fusion emerges as a potential solution to enhance the perceptual capabilities of systems. This article introduces a novel spatial perception method that integrates dual-modality feature fusion and coupled attention mechanisms to validate the improvement in detection performance through cross-modal information fusion. The proposed approach incorporates cross-modal feature extraction through a multi-scale feature extraction structure employing a dual-flow architecture. Additionally, a transformer is integrated for feature fusion, while the information perception of the detection system is optimized through the utilization of a linear combination of loss functions. Experimental results demonstrate the superiority of our algorithm over single-modality target detection using visible images, exhibiting an average accuracy improvement of 30.4%. Furthermore, our algorithm outperforms single-modality infrared image detection by 3.0% and comparative multimodal target detection algorithms by 3.5%. These results validate the effectiveness of our proposed algorithm in fusing dual-band features, significantly enhancing target detection accuracy. The adaptability and robustness of our approach are showcased through these results.

BackgroundVitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG).MethodsBSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test.ResultsIn this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1–24 h). What’s more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG.ConclusionThe study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease that affects the body. Periploca forrestii was a miao ethnic drug in China that was used to treat arthritis for hundreds of years. But, the therapeutic mechanism is so far unknown. Therefore, the chemical component and effect of Periploca forrestii on arthritis in rats were studied using HPLC-QTOF MS, micro-CT, and other experiments in this paper.MethodMale Sprague-Dawley rats were used to assess the in vivo activity. HPLC QTOF-MS was used to analyze the chemical profile of the P. forrestii (PF). Bovine type II collagen and Complete Freund’s Adjuvant were used to stimulate and construct the collagen-induced arthritis (CIA) model. Three dosages of PF (100 mg/kg, 200 mg/kg, 400 mg/kg) were used to evaluate in vivo activity. Methotrexate was used as the positive drug. H/E staining and micro-CT methods were used to monitor the pathological changes of CIA rats. ELISA method was used to assess the serum level of immune- and inflammation-related cytokines. Immunohistochemical experiments were used to test the gene expression in JAK and Nf-κB pathways.Results42 compounds were identified from PF. PF administration lowered the increased spleen index compared with that of control and MTX groups, and partially restored body weight, reduced paw swelling, and arthritis score compared with the model group. Macroscopic assessment indicated inflamed paw with significant swelling in the model group, while the extent of inflammation and swelling was attenuated by both MTX and PF. H/E staining experiments demonstrated that pathological changes of synovial cells and infiltration of inflammatory cells were observed in the model group. In contrast, the MTX and PF treatment partially reversed these pathological changes. Micro-CT examination showed severe injuries and scars caused by inflammation for the model group, and in the high-dosage group (400 mg/kg) the inflammation-caused injuries and scars were dramatically ameliorated. Mechanism study showed that PF restored Nf-κB phosphorylation and JAK2 expression compared with the model group.ConclusionP. forrestii possesses a potent effect on CIA rats. Nf-κB and JAK2 pathways are involved in its protective effect on CIA.

BackgroundsAs a conserved signaling pathway, mitogen-activated protein kinase (MAPK) cascade regulates cellular signaling in response to abiotic stress. High temperature may contribute to a significant decrease in economic yield. However, research into the expression patterns of StMAPKK family genes under high temperature is limited and lacks experimental validation regarding their role in supporting potato plant growth.MethodsTo trigger heat stress responses, potato plants were grown at 35°C. qRT-PCR was conducted to analyze the expression pattern of StMAPKK family genes in potato plants. Plant with StMAPKK5 loss-of-function and gain-of-function were developed. Potato growth and morphological features were assessed through measures of plant height, dry weight, and fresh weight. The antioxidant ability of StMAPKK5 was indicated by antioxidant enzyme activity and H2O2 content. Cell membrane integrity and permeability were suggested by relative electrical conductivity (REC), and contents of MDA and proline. Photosynthetic capacity was next determined. Further, mRNA expression of heat stress-responsive genes and antioxidant enzyme genes was examined.ResultsIn reaction to heat stress, the expression profiles of StMAPKK family genes were changed. The StMAPKK5 protein is located to the nucleus, cytoplasm and cytomembrane, playing a role in controlling the height and weight of potato plants under heat stress conditions. StMAPKK5 over-expression promoted photosynthesis and maintained cell membrane integrity, while inhibited transpiration and stomatal conductance under heat stress. Overexpression of StMAPKK5 triggered biochemical defenses in potato plant against heat stress, modulating the levels of H2O2, MDA and proline, as well as the antioxidant activities of CAT, SOD and POD. Overexpression of StMAPKK5 elicited genetic responses in potato plants to heat stress, affecting heat stress-responsive genes and genes encoding antioxidant enzymes.ConclusionStMAPKK5 can improve the resilience of potato plants to heat stress-induced damage, offering a promising approach for engineering potatoes with enhanced adaptability to challenging heat stress conditions.

Euchlorocystis marina, a new marine species of the genus Euchlorocystis discovered in 2022, has the potential to improve the water quality in mariculture ponds. However, the effects of salinity on the growth, physiology, and biochemical composition of these algae are not well understood. In this study, changes in physiological and biochemical indices such as cell density, photosynthetic pigment, polysaccharide, and lipid content of E. marina under different salinity treatments were analyzed. The results showed that the highest cell density was observed at a salinity of 15‰. The lowest photosynthetic pigment content was observed at a salinity of 60‰, and the highest polysaccharide and lipid content was observed at a salinity of 60‰. These results indicated that lower salinity was more conducive to E. marina reproduction and growth. E. marina can accumulate polysaccharides and lipids in high salinity environments. This study provides new information for understanding the salinity adaptation strategies of E. marina and has practical significance for its development and utilization.

BackgroundCurrently, the bipolar radiofrequency ablation forceps manufactured by AtriCure are the main instrument for surgical ablation in patients with rheumatic heart disease (RHD) concomitant with atrial fibrillation (AF). The bipolar radiofrequency ablation forceps by Med-Zenith has a greater advantage in price compared with AtriCure. However, few studies have been reported on the comparison of their clinical efficacy. The aim of this study is to compare the short-term clinical efficacy of the two ablation forceps for RHD concomitant with AF.MethodsClinical data of 167 patients with RHD concomitant with AF admitted to the Department of Cardiac Major Vascular Surgery, Affiliated Hospital of North Sichuan Medical College, were retrospectively analyzed, and the restoration efficacy of sinus rhythm (SR) and cardiac function after surgery were compared with two ablation forceps.ResultsThe end-systolic diameter of the right atrium and the end-systolic diameter of the left atrium in the patients of both groups at each postoperative time point decreased compared with that of the preoperative period (P 0.05). At 12 months postoperatively, the SR maintenance rate in using the ablation forceps by Med-Zenith (73.3%) was lower than that for AtriCure (86.4%) and the cumulative recurrence rate of AF in using the Med-Zenith ablation forceps was greater than that for AtriCure.ConclusionsThe two bipolar radiofrequency ablation forceps compared in the study are safe and effective in treating patients of RHD concomitant with AF, and the ablation forceps by AtriCure may be more effective in restoring SR in the short term.

BackgroundStrengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China.MethodsA community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled.ResultsThe results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p

This study addresses the challenge of simulating fluid flow around flexible net panels, which are critical components in aquaculture systems. Traditional grid-based Eulerian methods struggle with the complex deformations and interactions of such panels. To fill this gap, a numerical approach leveraging the Smoothed Particle Hydrodynamics (SPH) method is introduced. The proposed approach employs a knot-spring model to represent the flexible net panels. The nets are idealized as a structure of physical net-knots linked by virtual elastic springs. The SPH method is used to simulate the fluid flow, capturing the movement of the knots and the resulting deformation of the nets. The model's parameters and numerical schemes are detailed, along with the implementation process. The accuracy of the model is validated through comparisons with existing experimental and simulation data. The results indicate that the SPH-based approach accurately simulates the flow past flexible net panels, providing a detailed velocity distribution and deformation analysis. The study's findings demonstrate the potential of the SPH method for aquaculture engineering applications. The proposed approach offers a promising alternative to traditional methods, particularly in scenarios involving significant net deformation or interaction with other objects. The implications for the design and operation of aquaculture facilities are discussed, along with suggestions for future research directions.

IntroductionPlant height (PH) and ear height (EH) are key plant architectural traits in maize, which will affect the photosynthetic efficiency, high plant density tolerance, suitability for mechanical harvestingMethodsQTL mapping were conducted for PH and EH using a recombinant inbred line (RIL) population and two corresponding immortalized backcross (IB) populations obtained from crosses between the RIL population and the two parental lines.ResultsA total of 17 and 15 QTL were detected in the RIL and IB populations, respectively. Two QTL, qPH1-1 (qEH1-1) and qPH1-2 (qEH1-4) in the RIL, were simultaneously identified for PH and EH. Combing reported genome-wide association and cloned PH-related genes, co-expression network analyses were constructed, then five candidate genes with high confidence in major QTL were identified including Zm00001d011117 and Zm00001d011108, whose homologs have been confirmed to play a role in determining PH in maize and soybean.DiscussionQTL mapping used a immortalized backcross population is a new strategy. These identified genes in this study can provide new insights for improving the plant architecture in maize.

Background:Most preschool children are distressed during anesthesia induction. While current pharmacological methods are useful, there is a need for further optimization to an “ideal” standard. Remimazolam is an ultra-short-acting benzodiazepine, and intranasal remimazolam for pre-induction sedation may be promising.Methods:This study included 32 preschool children who underwent short and minor surgery between October 2022 and January 2023. After pretreatment with lidocaine, remimazolam was administered to both nostrils using a mucosal atomizer device. The University of Michigan Sedation Score (UMSS) was assessed for sedation 6, 9, 12, 15, and 20 min after intranasal atomization. We used Dixon’s up-and-down method, and probit and isotonic regressions to determine the 50% effective dose (ED50) and 95% effective dose (ED95) of intranasal remimazolam for pre-induction sedation. Results: Twenty-nine pediatric patients were included in the final analysis. The ED50 and ED95 of intranasal remimazolam for successful pre-induction sedation, when processed via probit analysis, were 0.65 (95% confidence interval [CI], 0.59–0.71) and 0.78 mg/kg (95% CI, 0.72–1.07), respectively. In contrast, when processed by isotonic regression, they were 0.65 (95% CI: 0.58–0.72 mg/kg) and 0.78 mg/kg (95% CI: 0.69–1.08 mg/kg), respectively. At 6 min after intranasal remimazolam treatment, 81.2% (13/16) of “positive” participants were successfully sedated with a UMSS ≧ 1. All the “positive” participants were successfully sedated within 9 min.Conclusion:Intranasal remimazolam is feasible for preschool children with a short onset time. For successful pre-induction sedation, the ED50 and ED95 of intranasal remimazolam were 0.65 and 0.78 mg/kg, respectively.

ObjectiveTo summarize the experience with intraluminal esophageal stretching elongation (ILESE) in the successful treatment of long-gap esophageal atresia (LGEA) at a single center.MethodsClinical data of 68 neonates who underwent LGEA between February 2015 and January 2022 were retrospectively analyzed. Four patients died of multiple associated severe malformations and did not undergo ILESE. Esophageal anastomosis was successfully performed in 60 cases (93.75%) and failed in 4 cases (6.25%) treated with ILESE. The ILESE techniques, esophageal reconstruction, results, postoperative complications, and follow-up treatment were analyzed.ResultsThe beginning time of performing ILESE preoperation was 53.4 ± 39.4 days after birth, and the age of esophageal reconstruction was 122.2 ± 70.3 days after birth in 60 cases. The gap length of proximal and distal esophageal segments which were evaluated the first time at admission was 4.8 ± 1.3 vertebral bodies, whereas the gap before anastomosis was −0.46 ± 0.90 vertebral bodies. Among the patients with esophageal primary-anastomosis, 55 received thoracoscopic surgery, and 5 underwent thoracotomy in the early stage. Of the 60 children with ILESE, 58 underwent end-to-end esophagostomy, of which 17 cases were combined with circular esophagotomy (livaditis), and 2 cases of esophageal lengthening were combined with the reversal of the ligulate loop of the proximal esophagus (flap). Overall, 59 cases were cured (98.3%), and 1 patient died of respiratory failure postoperatively. All patients were followed up for 7–96 months. Postoperative anastomotic leakage occurred in 16 patients (27.6%), all of whom were successfully treated conservatively. Anastomotic stenosis occurred in 49 cases (83.1%), all of which were successfully managed by non-surgical treatment, including 12.7 ± 9.3 times of esophageal balloon dilatation and 2 cases of stent dilatation. Gastroesophageal reflux occurred in 44 patients (74.6%), including associated or acquired esophageal hiatal hernia in 22 patients, and Nissen fundoplication was performed in 17 patients.ConclusionsILESE is an effective method for prolonging the proximal and distal esophagus of the LGEA to reconstruct esophageal continuity using its esophageal tissue, with an efficacy rate of 93.75%. Postoperative anastomotic stricture and gastroesophageal reflux are common and require long-term, standardized follow-up and treatment.

BackgroundPatients with severe neurological conditions are at high risk during withdrawal and extubation, so it is important to establish a model that can quantitatively predict the risk of this procedure.MethodsBy analyzing the data of patients with traumatic brain injury and tracheal intubation in the ICU of the affiliated hospital of Hangzhou Normal University, a total of 200 patients were included, of which 140 were in the modeling group and 60 were in the validation group. Through binary logistic regression analysis, 8 independent risk factors closely related to the success of extubation were screened out, including age ≥ 65 years old, APACHE II score ≥ 15 points, combined chronic pulmonary disease, GCS score

Abiotic/biotic stresses pose a major threat to agriculture and food security by impacting plant growth, productivity and quality. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long non-coding RNAs (lncRNAs) with sizes larger than 200 nucleotides in length, provides an important new perspective on the centrality of RNA in gene regulation. In plants, lncRNAs are widespread and fulfill multiple biological functions in stress response. In this paper, the research advances on the biological function of lncRNA in plant stress response were summarized, like as Natural Antisense Transcripts (NATs), Competing Endogenous RNAs (ceRNAs) and Chromatin Modification etc. And in plants, lncRNAs act as a key regulatory hub of several phytohormone pathways, integrating abscisic acid (ABA), jasmonate (JA), salicylic acid (SA) and redox signaling in response to many abiotic/biotic stresses. Moreover, conserved sequence motifs and structural motifs enriched within stress-responsive lncRNAs may also be responsible for the stress-responsive functions of lncRNAs, it will provide a new focus and strategy for lncRNA research. Taken together, we highlight the unique role of lncRNAs in integrating plant response to adverse environmental conditions with different aspects of plant growth and development. We envisage that an improved understanding of the mechanisms by which lncRNAs regulate plant stress response may further promote the development of unconventional approaches for breeding stress-resistant crops.

BackgroundTo investigate the pathogenic characteristics and risk factors of pediatric severe community-acquired pneumonia (CAP).MethodsWe retrospectively analyzed the clinical data of hospitalized children with severe CAP from April 2014 to June 2019 in China. Data of age, sex and pathogenic results were collected: bacterial and fungal cultures, respiratory viruses from sputum or bronchoalveolar lavage fluid (BALF), serum Mycoplasma pneumoniae (MP)-IgM and Chlamydia Pneumoniae-IgM, and BALF or blood (1-3)-β-D-glucan/galactomannan test.ResultsA total of 679 children with severe CAP were included in the analysis. The number of cases infected with MP was higher in males than in females. There were significant differences between the ≤1-year and >1-year groups in terms of pathogen. The top three bacteria cultured were Haemophilus influenzae (57/679, 8.4%), Streptococcus pneumoniae (50/679, 7.4%), and Pseudomonas aeruginosa (25/679, 3.7%). The top three viruses detected were adenovirus (AdV, 124/679, 18.3%), respiratory syncytial virus (24/679, 3.5%), and parainfluenza virus (21/679, 3.1%). AdV and MP were the leading pathogens, detected in 18.3% and 32.6% cases, respectively. MP infection increased the risk of AdV infection (OR 3.77, p

Anal adenocarcinoma combined with perianal Paget’s disease (PPD) involving the vulva is rare, and there is no established standard treatment. We present the case of a 69-year-old woman with symptoms of intermittent hematochezia and perianal discomfort for 7 months. Upon examination, we discovered a plaque-like hard mass on the right posterior wall of the anal canal, which extended to encompass the anus and dentate line. The lesion skin also extended forward from the gluteal groove, involving the bilateral labial area. Colonoscopy revealed an extensive protruding lesion on the dentate line, which was confirmed as anal adenocarcinoma (mrT4N0M0). The presence of Paget’s cells in perianal and vulvar skins led to the diagnosis of PPD. The strategy of neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery was then made after multi-disciplinary discuss. The scope and extent of perianal and vulvar disease were significantly diminished after nCRT. The patient underwent laparoscopic abdominoperineal resection and vulvar lesion resection, confirming the diagnosis of anal adenocarcinoma (ypT2N0). No evidence of tumor cells was found in perianal and vulvar skin, indicating a complete response. The patient is regularly monitored without recurrence or metastasis.

Myxococcus xanthus and Escherichia coli represent a well-studied microbial predator-prey pair frequently examined in laboratory settings. While significant progress has been made in comprehending the mechanisms governing M. xanthus predation, various aspects of the response and defensive mechanisms of E. coli as prey remain elusive. In this study, the E. coli MG1655 large-scale chromosome deletion library was screened, and a mutant designated as ME5012 was identified to possess significantly reduced susceptibility to predation by M. xanthus. Within the deleted region of ME5012 encompassing seven genes, the significance of dusB and fis genes in driving the observed phenotype became apparent. Specifically, the deletion of fis resulted in a notable reduction in flagellum production in E. coli, contributing to a certain level of resistance against predation by M. xanthus. Meanwhile, the removal of dusB in E. coli led to diminished inducibility of myxovirescin A production by M. xanthus, accompanied by a slight decrease in susceptibility to myxovirescin A. These findings shed light on the molecular mechanisms underlying the complex interaction between M. xanthus and E. coli in a predatory context.

BackgroundCurrent guidelines lack a standardized management for patients with family history of thyroid carcinoma (fTC),particularly benign thyroid neoplasm (fBTN). Our objective was to investigate the influence of various family histories on the selection of surgical approaches and disease-free survival (DFS).MethodsA cohort study was conducted involving 2261 patients diagnosed with differentiated thyroid carcinoma including those with fTC (n=224), fBTN (n=122), and individuals without a family history of thyroid carcinoma (nfTC; n=1915). Clinicopathological characteristics were collected. DFS was estimated using Kaplan-Meier analysis and factors affecting DFS were identified using Cox proportional hazard model.ResultsCompared to nfTC, small tumor size, clinically lymph node-positive, extrathyroidal extension, vascular invasion, Hashimoto’s disease and nodular goiter were more common in fTC and fBTN groups. They had lower T stage and a lower rate of good response to TSH suppression therapy but received more radioiodine therapy. It is worth noting that fTC is associated with male, bilateral and multifocal tumors, as well as central lymph node metastasis and distant metastasis. Both fTC (aHR = 2.45, 95% CI=1.11-5.38; P = 0.03) and fBTN (aHR = 3.43, 95% CI=1.27-9.29; P = 0.02) were independent predictors of DFS in patients who underwent lobectomy, but not total thyroidectomy. For 1-4 cm thyroid carcinomas with clinically node-negative, fTC was identified as an independent predictor, whereas fBTN was not.ConclusionOur findings indicate that a family history, particularly of malignancy, is associated with a more aggressive disease. Family history does not affect the prognosis of patients who undergo total thyroidectomy, but it may increase the risk of postoperative malignant events in those who have a lobectomy. Additionally, it may be necessary to monitor individuals with a family history of benign thyroid neoplasms.

BackgroundCancer as a global public health problem, imposes a heavy disease burden. With the rapid development of oral anti-neoplastic drugs, there has been a paradigm shift in the treatment of cancer from intravenous to oral administration.ObjectiveThis study was conducted to investigate the trends and prescribing patterns of oral anti-neoplastic drugs in an academic tertiary hospital in China.MethodsA single-center and retrospective analysis was performed based on the prescriptions of outpatients treated with oral anti-neoplastic drugs from 2017 to 2022. Yearly prescriptions and expenditure were calculated according to their pharmacological classes, and trends were further analyzed. Defined daily doses (DDDs) and defined daily cost (DDC) of oral targeted anti-neoplastic drugs were also determined.ResultsBoth the number of prescriptions and expenditure of oral anti-neoplastic drugs increased progressively. There was a significant upward trend in the number and proportion of prescriptions for the older adult group, male group, and patients with gynecologic/genitourinary and respiratory cancer. Hormonal therapy agents accounted for the highest proportion of prescriptions, and letrozole was initially the most frequently prescribed drug. The number of DDDs of total oral targeted anti-neoplastic drugs showed a continuously ascending trend, primarily driven by the usage of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and BCR-ABL TKIs.ConclusionThe prescriptions and expenditure of oral anti-neoplastic drugs, and the number of DDDs of oral targeted anti-neoplastic drugs all showed a progressively ascending trend. Further studies are needed to evaluate the long-term health and financial outcomes, and the factors influencing these prescribing patterns.

PurposeBone metastasis of unknown origin is a rare and challenging situation, which is infrequently reported. Therefore, the current study was performed to analyze the clinicopathologic features and risk factors of survival among patients with bone metastasis of unknown origin.Patients and methodsWe retrospectively analyzed the clinical data for patients with bone metastasis of unknown origin between 2010 and 2016 based on the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were first analyzed by applying univariable Cox regression analysis. Then, we performed multivariable analysis to confirm independent survival predictors.ResultsIn total, we identified 1224 patients with bone metastasis of unknown origin for survival analysis, of which 704 males (57.5%) and 520 females (42.5%). Patients with bone metastasis of unknown origin had a 1-year OS rate of 14.50% and CSS rate of 15.90%, respectively. Race, brain metastasis, liver metastasis, radiotherapy, and chemotherapy were significant risk factors of OS on both univariable and multivariable analyses (p

IntroductionThe hepatobiliary-specific phase can help in early detection of changes in lesion tissue density, internal structure, and microcirculatory perfusion at the microscopic level and has important clinical value in hepatocellular carcinoma (HCC). Therefore, this study aimed to construct a preoperative nomogram for predicting the positive expression of glypican-3 (GPC3) based on gadoxetic acid-enhanced (Gd-EOB-DTPA) MRI hepatobiliary phase (HBP) radiomics, imaging and clinical feature.MethodsWe retrospectively included 137 patients with HCC who underwent Gd-EOB-DTPA-enhanced MRI and subsequent liver resection or puncture biopsy at our hospital from January 2017 to December 2021 as training cohort. Subsequently collected from January 2022 to June 2023 as a validation cohort of 49 patients, Radiomic features were extracted from the entire tumor region during the HBP using 3D Slicer software and screened using a t-test and least absolute shrinkage selection operator algorithm (LASSO). Then, these features were used to construct a radiomics score (Radscore) for each patient, which was combined with clinical factors and imaging features of the HBP to construct a logistic regression model and subsequent nomogram model. The clinicoradiologic, radiomics and nomogram models performance was assessed by the area under the curve (AUC), calibration, and decision curve analysis (DCA). In the validation cohort,the nomogram performance was assessed by the area under the curve (AUC).ResultsIn the training cohort, a total of 1688 radiomics features were extracted from each patient. Next, radiomics with ICCs400ng/mL, and non-smooth tumor margin (AUC=0.888, sensitivity 77.7%, specificity 91.2%) was superior to the radiomics (AUC=0.822, sensitivity 81.6%, specificity 70.6%) and clinicoradiologic (AUC=0.746, sensitivity 76.7%, specificity 64.7%) models, with good consistency in calibration curves. DCA also showed that the nomogram had the highest net clinical benefit for predicting GPC3 expression.In the validation cohort, the ROC curve results showed predicted GPC3-positive expression nomogram model AUC, sensitivity, and specificity of 0.800, 58.5%, and 100.0%, respectively.ConclusionHBP radiomics features are closely associated with GPC3-positive expression, and combined clinicoradiologic factors and radiomics features nomogram may provide an effective way to non-invasively and individually screen patients with GPC3-positive HCC.

Alzheimer’s disease (AD) emerges as a perturbing neurodegenerative malady, with a profound comprehension of its underlying pathogenic mechanisms continuing to evade our intellectual grasp. Within the intricate tapestry of human health and affliction, the enteric microbial consortium, ensconced within the milieu of the human gastrointestinal tract, assumes a role of cardinal significance. Recent epochs have borne witness to investigations that posit marked divergences in the composition of the gut microbiota between individuals grappling with AD and those favored by robust health. The composite vicissitudes in the configuration of the enteric microbial assembly are posited to choreograph a participatory role in the inception and progression of AD, facilitated by the intricate conduit acknowledged as the gut-brain axis. Notwithstanding, the precise nature of this interlaced relationship remains enshrouded within the recesses of obscurity, poised for an exhaustive revelation. This review embarks upon the endeavor to focalize meticulously upon the mechanistic sway exerted by the enteric microbiota upon AD, plunging profoundly into the execution of interventions that govern the milieu of enteric microorganisms. In doing so, it bestows relevance upon the therapeutic stratagems that form the bedrock of AD’s management, all whilst casting a prospective gaze into the horizon of medical advancements.

Ubiquitination is a specific protein degradation and reversible post-translational modification process that can be reversed by deubiquitinase (DUBs). DUBs can hydrolyze and release ubiquitin in the substrate protein so that the substrate can avoid degradation or change its activity, and it has an impact on plant growth and development, cell cycle, abiotic stress response, and other biological processes. Transcript sequences of potato varieties “DM1-3”, “Atlantic” and “Cooperation-88” downloaded from Potato Genome Resources were used for genome-wide identification of the DUB gene family using Hidden Markov Models and verified in the NCBI CD-Search tool. The characteristics of DUB genes from different potato varieties were analyzed including subcellular localization, gene structural motifs, phylogenetic tree, and sequence homology. Polyethylene glycol 6000 (PEG6000) induced drought stress transcriptome analysis was performed on the “Atlantic”, and differentially expressed genes were screened, with emphasis on the characterization of deubiquitinase. DUB genes have a complex gene structure, often with a large number of exons and alternative splicing. Their promoters contain abundant abiotic stress-responsive elements, such as 425 MYC, 325 ABRE, and 320 MYB. There are also a large number of orthologous genes in the DUBs of the three potato varieties, and these genes are often clustered in similar regions on the genome. We performed transcriptome sequencing of the potato under PEG-induced drought stress and analyzed it for the first time using the Atlantic as a reference genome. We identified a total of 6067 down-regulated differentially expressed genes (DEGs) and 4950 up-regulated DEGs under PEG-induced drought stress. We screened the expression of DUBs and observed that 120 DUBs were up-regulated where most of them functioned in the nucleus, and the interacting proteins of DUBs were also localized in the nucleus. We have comprehensively identified and analyzed potato DUBs, and the accurately aligned transcriptome data which will further deepen the understanding of DUBs involved in the regulation of osmotic stress.

BackgroundNasopharyngeal carcinoma (NPC) is prevalent in Southern China. The expression profile and functions of kinesin family member 18B (KIF18B) remain unclear in NPC.MethodsBulk and single-cell transcriptome data for NPC were downloaded. KIF18B expression differences in NPC and normal tissues and its prognostic value were validated by immunohistochemistry and Cox model. We performed multi-faceted functional enrichment analysis on KIF18B. Immune infiltration was analyzed comprehensively by the CIBERSORT, EPIC, and quanTIseq algorithms and the BisqueRNA package and confirmed by immunofluorescence assay. The intercellular communication were investigated by the CellChat package. We explored the dynamics of KIF18B expression by pseudotime trajectory. M6A modification analysis rely on SRAMP platform. The treatment response were evaluated by Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore and IC50 value.ResultsKIF18B overexpression in NPC led to unfavorable prognosis, and significantly associated with advanced T, N, and stage classifications. Functional analysis demonstrated that KIF18B was involved in immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification and therapeutic responses. The deconvolution algorithm indicated that activated regulatory T cells (Tregs) had the strongest positive correlation with KIF18B among immune cells (R = 0.631). Validated by immunofluorescence assay, the high KIF18B expression group displayed a notable rise in Tregs infiltration, accompanied by a substantial decrease in the infiltration of CD8+ T cells and macrophages. In the intercellular communication network, malignant cells with high KIF18B expression implicated in more interactions, and activated and recruited Tregs by modulating cytokines, chemokines, and immune checkpoints. KIF18B was upregulated in more advanced malignant cells and influenced EMT by regulating ITGA6, VIM, and ZEB1/2. KIF18B expression was positively related to m6A “writer” and “reader” genes, and negatively related to “eraser” genes. The KIF18B high expression group exhibited a higher TIDE score and elevated IC50 values for the commonly used chemotherapy drugs, gemcitabine, oxaliplatin, and 5-fluorouracil.ConclusionKIF18B is a significant prognostic marker in NPC, and may modulate immune evasion and EMT. M6A modification may account for the aberrant overexpression of KIF18B in NPC. Furthermore, KIF18B may predict response to immunotherapy and chemotherapy.

BackgroundPulmonary sclerosing pneumocytoma (PSP) is a rare lung tumor that is mostly isolated and commonly reported among middle-aged East Asian women. Recently, Immunohistochemistry (IHC) analysis has suggested that PSP is of primitive epithelial origin, most likely derived from type II alveolar air cells. Patients with PSP are generally asymptomatic and usually detected for other unrelated reasons during routine imaging. Several studies have already investigated the computed tomography (CT) features of PSP and their correlation with pathology. Magnetic resonance imaging (MRI) is a radiation-free imaging technique with important diagnostic value for specific pulmonary nodules. However, very few case reports or studies focus on the MRI findings of PSP.Case reportWe reported a case of an asymptomatic 56-year-old female with a solitary, well-defined soft-tissue mass in the lower lobe of the left lung. The mass showed iso-to-high signal intensity (SI) than muscle on T1-weighted image (T1WI) and T2-weighted image (T2WI) and a much higher SI on fat-suppressed T2WI, diffusion-weighted image, and apparent diffusion coefficient image. Contrast-enhanced fat-suppressed T1WI revealed noticeable inhomogeneous progressive enhancement throughout the mass. The mass revealed early enhancement without a significant peak, followed by a plateau pattern on dynamic contrast-enhanced MRI images. The patient underwent left basal segmentectomy via thoracoscopic surgery. Histopathology and IHC results of the surgical specimen confirmed that it was a PSP. We concluded that the MRI findings of PSP might adequately reflect the different components within the tumor and aid clinicians in preoperative diagnosis and assessment. To the best of our knowledge, this is the most comprehensive case report on the MRI findings of PSP.ConclusionThe MRI findings of PSP correspond to its histopathological features. Here, we present a case of PSP with the most comprehensive MRI findings, emphasizing the importance of multiple-sequence MRI in diagnosing PSP.

BackgroundMyeloperoxidase (MPO), released by activated neutrophils, is significantly increased in atrial fibrillation (AF). MPO may play a role in the progression of atrial fibrillation and further involved in AF recurrence after catheter ablation. We compared plasma MPO levels in paroxysmal and persistent AF and explored their role in AF recurrence after catheter ablation.MethodsPlasma MPO levels were measured in consecutive patients with paroxysmal AF (n = 225) and persistent AF (n = 106). Samples of patients were collected from the femoral vein during catheter ablation and all patients included were followed up after catheter ablation.ResultsPlasma MPO levels increased from paroxysmal AF to persistent AF patients (56.31 [40.33–73.51] vs. 64.11 [48.65–81.11] ng/ml, p

BackgroundDysregulated inflammation is associated with many skeletal diseases and disorders, such as osteolysis, non-union of fractures, osteonecrosis, osteoarthritis and orthopaedic infections. We previously showed that continuous infusion of lipopolysaccharide (LPS) contaminated polyethylene particles (cPE) caused prolonged inflammation and impaired bone formation. However, the metabolic and bioenergetic processes associated with inflammation of bone are unknown. Mitochondria are highly dynamic organelles that modulate cell metabolism and orchestrate the inflammatory responses that involve both resident and recruited cells. Glycolytic reprogramming, the shift from oxidative phosphorylation (OXPHOS) to glycolysis causes inappropriate cell activation and function, resulting in dysfunctional cellular metabolism. We hypothesized that impaired immunoregulation and bone regeneration from inflammatory states are associated with glycolytic reprogramming and mitochondrial dysfunction in macrophages (Mφ) and mesenchymal stromal cells (MSCs).MethodsWe used the Seahorse XF96 analyzer and real-time qPCR to study the bioenergetics of Mφ and MSCs exposed to cPE. To understand the oxygen consumption rate (OCR), we used Seahorse XF Cell Mito Stress Test Kit with Seahorse XF96 analyzer. Similarly, Seahorse XF Glycolytic Rate Assay Kit was used to detect the extracellular acidification rate (ECAR) and Seahorse XF Real-Time ATP Rate Assay kit was used to detect the real-time ATP production rates from OXPHOS and glycolysis. Real-time qPCR was performed to analyze the gene expression of key enzymes in glycolysis and mitochondrial biogenesis. We further detected the gene expression of proinflammatory cytokines in Mφ and genes related to cell differentiation in MSC during the challenge of cPE.ResultsOur results demonstrated that the oxidative phosphorylation of Mφ exposed to cPE was significantly decreased when compared with the control group. We found reduced basal, maximal and ATP-production coupled respiration rates, and decreased proton leak in Mφ during challenge with cPE. Meanwhile, Mφ showed increased basal glycolysis and proton efflux rates (PER) when exposed to cPE. The percentage (%) of PER from glycolysis was higher in Mφ exposed to cPE, indicating that the contribution of the glycolytic pathway to total extracellular acidification was elevated during the challenge of cPE. In line with the results of OCR and ECAR, we found Mφ during cPE challenge showed higher glycolytic ATP (glycoATP) production rates and lower mitochondrial ATP (mitoATP) production rates which is mainly from OXPHOS. Interestingly, MSCs showed enhanced glycolysis during challenge with cPE, but no significant changes in oxygen consumption rates (OCR). In accordance, seahorse assay of real-time ATP revealed glycoATP rates were elevated while mitoATP rates showed no significant differences in MSC during challenge with cPE. Furthermore, Mφ and MSCs exposed to cPE showed upregulated gene expression levels of glycolytic regulators and Mφ exposed to cPE expressed higher levels of pro-inflammatory cytokines.ConclusionThis study demonstrated the dysfunctional bioenergetic activity of bone marrow-derived Mφ and MSCs exposed to cPE, which could impair the immunoregulatory properties of cells in the bone niche. The underlying molecular defect related to disordered mitochondrial function could represent a potential therapeutic target during the resolution of inflammation.

BackgroundThe management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated.MethodsDTC patients’ data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score–matched was performed to make 1:1 case-control matching.Results105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC.ConclusionRAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.

BackgroundFew studies have explored the use of machine learning models to predict the recurrence of atrial fibrillation (AF) in patients who have undergone cryoballoon ablation (CBA). We aimed to explore the risk factors for the recurrence of AF after CBA in order to construct a nomogram that could predict this risk.MethodsData of 498 patients who had undergone CBA at Ruijin Hospital, Shanghai Jiaotong University School of Medicine, were retrospectively collected. Factors such as clinical characteristics and biophysical parameters during the CBA procedure were collected for the selection of variables. Scores for all the biophysical factors—such as time to pulmonary vein isolation (TTI) and balloon temperature—were calculated to enable construction of the model, which was then calibrated and compared with the risk scores.ResultsA 36-month follow-up showed that 177 (35.5%) of the 489 patients experienced AF recurrence. The left atrial volume, TTI, nadir cryoballoon temperature, and number of unsuccessful freezes were related to the recurrence of AF (P

Porphyromonas gingivalis (P. gingivalis) is the most common species that causes peri-implantitis. It forms an irreversible dense biofilm and causes inflammation. A novel 3D-printed porous TC4-6Cu alloy was fabricated using selective laser melting (SLM) technology for the dental implant, which is anticipated to inhibit biofilm formation. We attempted to investigate the antibacterial ability and antibacterial mechanism of the 3D-printed porous TC4-6Cu alloy against P. gingivalis. This work used scanning electron microscopy (SEM) and laser confocal microscopy (CLSM) to detect the antimicrobial ability of the alloy against sessile P. gingivalis. The results indicated that the 3D-printed porous TC4-6Cu alloy could cause bacterial fragmentation and deformation. Plate antimicrobial counting experiments showed that the antibacterial rates of the alloy against adherent bacteria and planktonic bacteria after 24 h were 98.05% and 73.92%, respectively. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cu2+ were tested to appraise the antibacterial property of the alloy against planktonic P. gingivalis. The relationship between the antibacterial mechanism of the alloy with oxidative stress was evaluated through ROS fluorescence intensity and protein leakage concentration. The results revealed that the alloy significantly eliminated adherent bacteria and inhibited biofilm formation. Moreover, 3D-printed porous TC4-6Cu alloy demonstrated significant bactericidal ability by inducing the production of reactive oxygen species (ROS), which could result in protein leakage from the bacterial cell membrane. This research may open a new perspective on the development and biomedical applications for dental implantation.

Secreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or BM-40, is a matricellular protein which regulates cell adhesion, extracellular matrix production, growth factor activity, and cell cycle. Although SPARC does not perform a structural function, it, however, modulates interactions between cells and the surrounding extracellular matrix due to its anti-proliferative and anti-adhesion properties. The overexpression of SPARC at sites, including injury, regeneration, obesity, cancer, and inflammation, reveals its application as a prospective target and therapeutic indicator in the treatment and assessment of disease. This article comprehensively summarizes the mechanism of SPARC overexpression in inflammation and tumors as well as the latest research progress of functional nanomaterials in the therapy of rheumatoid arthritis and tumors by manipulating SPARC as a new target. This article provides ideas for using functional nanomaterials to treat inflammatory diseases through the SPARC target. The purpose of this article is to provide a reference for ongoing disease research based on SPARC-targeted therapy.

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling.Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored.Methods: Ultra-performance liquid chromatography–tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models.Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue.Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.

Novel minimally invasive strategies are needed to obtain robust bone healing in complex fractures and bone defects in the elderly population. Local cell therapy is one potential option for future treatment. Mesenchymal stromal cells (MSCs) are not only involved in osteogenesis but also help direct the recruitment of macrophages during bone regeneration via MSC-macrophage crosstalk. The C-C motif chemokine ligand 2 (CCL2) is an inflammatory chemokine that is associated with the migration of macrophages and MSCs during inflammation. This study investigated the use of CCL2 as a therapeutic target for local cell therapy. MSCs and macrophages were isolated from 10 to 12 week-old BALB/c male mice. Genetically modified CCL2 over-expressing MSCs were produced using murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture. Cell migration assays were also performed. MSCs transfected with murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector showed higher levels of CCL2 secretion compared to unaltered MSCs (p < 0.05). Genetic manipulation did not affect cell proliferation. CCL2 did not affect the osteogenic ability of MSCs alone. However, acute (1 day) but not sustained (7 days) stimulation with CCL2 increased the alizarin red-positive area when MSCs were co-cultured with macrophages (p < 0.001). Both recombinant CCL2 (p < 0.05) and CCL2 released from MSCs (p < 0.05) facilitated macrophage migration. We demonstrated that acute CCL2 stimulation promoted subsequent osteogenesis in co-culture of MSCs and macrophages. Acute CCL2 stimulation potentially facilitates osteogenesis during the acute inflammatory phase of bone healing by directing local macrophage migration, fostering macrophage-MSC crosstalk, and subsequently, by activating or licensing of MSCs by macrophage pro-inflammatory cytokines. The combination of CCL2, MSCs, and macrophages could be a potential strategy for local cell therapy in compromised bone healing.

Users of mobile phone applications (apps) often have to wait for the pages of apps to load, a process that substantially affects user experience. Based on the Attentional Gate Model and Emotional Contagion Theory, this paper explores the effects of the urgency expressed by a spokes-character’s movement in the loading page of a social app the app type on users’ switching intention through two studies. In Study 1 (N = 173), the results demonstrated that for a hedonic-orientated app, a high-urgency (vs. low-urgency) spokes-character resulted in a lower switching intention, whereas the opposite occurred for a utilitarian-orientated app. We adopted a similar methodology in Study 2 (N = 182) and the results showed that perceived waiting time mediated the interaction effect demonstrated in Study 1. Specifically, for the hedonic-orientated (vs. utilitarian-orientated) social app, the high-urgency (vs. low-urgency) spokes-character made participants estimate a shorter perceived waiting time, which induces a lower user switching intention. This paper contributes to the literature on emotion, spokes-characters, and human–computer interaction, which extends an enhanced understanding of users’ perception during loading process and informs the design of spokes-characters for the loading pages of apps.

The extracellular matrix (ECM) is assembled by hundreds of proteins orchestrating tissue patterning and surrounding cell fates via the mechanical–biochemical feedback loop. Aberrant ECM protein production or assembly usually creates pathological niches eliciting lesions that mainly involve fibrogenesis and carcinogenesis. Yet, our current knowledge about the pathophysiological ECM compositions and alterations in healthy or diseased tissues is limited since the methodology for precise insoluble matrisome coverage in the ECM is a “bottleneck.” Our current study proposes an enhanced sodium dodecyl sulfonate (E-SDS) workflow for thorough tissue decellularization and an intact pipeline for the accurate identification and quantification of highly insoluble ECM matrisome proteins. We tested this pipeline in nine mouse organs and highlighted the full landscape of insoluble matrisome proteins in the decellularized ECM (dECM) scaffolds. Typical experimental validations and mass spectrometry (MS) analysis confirmed very little contamination of cellular debris remaining in the dECM scaffolds. Our current study will provide a low-cost, simple, reliable, and effective pipeline for tissue insoluble matrisome analysis in the quest to comprehend ECM discovery proteomic studies.