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Abstract A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (Cmin) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid Cmin additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid Cmin, and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid Cmin had better predictive capability than that containing linezolid Cmin for predicting linezolid-induced thrombocytopenia in patients with renal impairment.

Abstract Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine; however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca2+/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

Abstract Background There has been a growing interest in characterizing factors influencing teaching decisions of science, technology, engineering, and mathematics (STEM) instructors in order to address the slow uptake of evidence-based instructional practices (EBIPs). This growing body of research has identified contextual factors (e.g., classroom layout, departmental norms) as primary influencers of STEM instructors’ decision to implement EBIPs in their courses. However, models of influences on instructional practices indicate that context is only one type of factor to consider. Other factors fall at the individual level such as instructors’ past teaching experience and their views on learning. Few studies have been able to explore in depth the role of these individual factors on the adoption of EBIPs since it is challenging to control for contextual features when studying current instructors. Moreover, most studies exploring adoption of EBIPs do not take into account the distinctive features of each EBIP and the influence these features may have on the decision to adopt the EBIP. Rather, studies typically explore barriers and drivers to the implementation of EBIPs in general. In this study, we address these gaps in the literature by conducting an in-depth exploration of individual factors and EBIPs’ features that influence nine future STEM instructors’ decisions to incorporate a selected set of EBIPs in their teaching. Results We had hypothesized that the future instructors would have different reasoning to support their decisions to adopt or not Peer Instruction and the 5E Model as the two EBIPs have distinctive features. However, our results demonstrate that instructors based their decisions on similar factors. In particular, we found that the main drivers of their decisions were (1) the compatibility of the EBIP with their past experiences as students and instructors as well as teaching values and (2) experiences provided in the pedagogical course they were enrolled in. Conclusions This study demonstrates that when considering the adoption of EBIPs, there is a need to look beyond solely contextual influences on instructor’s decisions to innovate in their courses and explore individual factors. Moreover, professional development programs should leverage their participants past experiences as students and instructors and provide an opportunity for instructors to experience new EBIPs as learners and instructors.

Soft strain sensors that can transduce stretch stimuli into electrical readouts are promising as sustainable wearable electronics. However, most strain sensors cannot achieve highly-sensitive and wide-range detection of ultralow and high strains. Inspired by bamboo structures, anti-freezing microfibers made of conductive poly(vinyl alcohol) hydrogel with poly(3,4-ethylenedioxythiphene)-poly(styrenesulfonate) are developed via continuous microfluidic spinning. The microfibers provide unique bamboo-like structures with enhanced local stress to improve both their length change and resistance change upon stretching for efficient signal conversion. The microfibers allow highly-sensitive (detection limit: 0.05% strain) and wide-range (0%–400% strain) detection of ultralow and high strains, as well as features of good stretchability (485% strain) and anti-freezing property (freezing temperature: −41.1 °C), fast response (200 ms), and good repeatability. The experimental results, together with theoretical foundation analysis and finite element analysis, prove their enhanced length and resistance changes upon stretching for efficient signal conversion. By integrating microfluidic spinning with 3D-printing technique, the textiles of the microfibers can be flexibly constructed. The microfibers and their 3D-printed textiles enable high-performance monitoring of human motions including finger bending and throat vibrating during phonation. This work provides an efficient and general strategy for developing advanced conductive hydrogel microfibers as high-performance wearable strain sensors.

BackgroundDepression poses a major threat to public health with an increasing prevalence in the United States. Mindfulness-based interventions, such as mindfulness-based cognitive therapy (MBCT), are effective methods for managing depression symptoms and may help fortify existing efforts to address the current disease burden. The in-person group format of MBCT, however, incurs barriers to care such as expenses, childcare needs, and transportation issues. Alternate delivery modalities such as MBCT delivered via the web can be investigated for their capacity to overcome these barriers and still reduce symptoms of depression with adequate feasibility and efficacy. ObjectiveThis study protocol aims to examine the feasibility and efficacy of MBCT delivered via the web for the treatment of depression. MethodsTo attain study aims, 2 phases will be implemented using a waitlist control design. A total of 128 eligible participants will be randomized into either an 8-week MBCT intervention group plus treatment as usual (MBCT + TAU; group 1) or an 8-week waitlist control group (group 2). In phase I (8 weeks), group 1 will complete the intervention and group 2 will proceed with TAU. In phase II (8 weeks), group 2 will complete the intervention and group 1 will continue with TAU until reaching an 8-week follow-up. TAU may consist of receiving psychotherapy, pharmacotherapy, or combined treatment. Data collection will be completed at baseline, 8 weeks (postintervention for group 1 and preintervention for group 2), and 16 weeks (follow-up for group 1, postintervention for group 2). The primary outcomes will include (1) current, residual, or chronic depression symptoms and (2) psychiatric distress. Secondary outcomes will include perceived stress and facets of mindfulness. The feasibility will be measured by assessing protocol adherence, retention, attendance, and engagement. Finally, the extent of mindfulness self-practice and executive functioning skills will be assessed as mediators of intervention outcomes. ResultsThis study began screening and recruitment in December 2022. Data collection from the first cohort occurred in January 2023. By November 2023, a total of 30 participants were enrolled out of 224 who received screening. Data analysis began in February 2024, with an approximate publication of results by August 2024. Institutional review board approval took place on September 11, 2019. ConclusionsThis trial will contribute to examining mindfulness-based interventions, delivered via the web, for improving current, residual, or chronic depression symptoms. It will (1) address the feasibility of MBCT delivered via the web; (2) contribute evidence regarding MBCT’s efficacy in reducing depression symptoms and psychiatric distress; and (3) assess the impact of MBCT on several important secondary outcomes. Findings from this study will develop the understanding of the causal pathways between MBCT delivered via the web and depression symptoms further, elucidating the potential for future larger-scale designs. Trial RegistrationClinicalTrials.gov NCT05347719; https://www.clinicaltrials.gov/ct2/show/NCT05347719 International Registered Report Identifier (IRRID)DERR1-10.2196/53966

Abstract Background Previous studies have demonstrated the association between food security and cardiometabolic diseases (CMDs), yet none have investigated trends in prevalence of CMDs by food security status in the United States (US). Methods Serial cross-sectional analysis of the US nationally representative data from National Health and Nutrition Examination Survey (1999–2018) was conducted among adults aged 20 years or older. Food security status was defined by the US Household Food Security Survey Module (full, marginal, low, and very low food security). We estimated the age-adjusted prevalence of CMDs including obesity, hypertension, diabetes, and coronary heart disease by food security status. Racial and ethnic disparities in age-adjusted prevalence of CMDs by food security status were also assessed. Results A total of 49,738 participants were included in this analysis (weighted mean age 47.3 years; 51.3% women). From 1999 to 2018, the age-adjusted prevalence of CMDs was lower in full food secure group as compared with other groups. For example, trends in hypertension decreased from 49.7% (47.5-51.8%) to 45.9% (43.8-48.0%) (P-trend = 0.002) among the full and from 54.2% (49.9-58.5%) to 49.7% (46.8-52.6%) (P-trend = 0.02) among the marginal but remained stable among the low at 49.7% (47.9-51.6%) and among the very low at 51.1% (48.9-53.3%) (P-interaction = 0.02). Prevalence of diabetes increased from 8.85% (8.15-9.60%) to 12.2% (11.1-13.5%) among the full (P-trend

At present, tomato transplanting in facility agriculture is mainly manual operation. In an attempt to resolve the problems of high labor intensity and low efficiency of manual operation, this paper designs a clip stem automatic transplanting and seedling picking device based on the yolov5 algorithm. First of all, through the study of the characteristics of tomato seedlings of different seedling ages, the age of tomato seedlings suitable for transplanting was obtained. Secondly, the improved yolov5 algorithm was used to determine the position and shape of tomato seedlings. By adding a lightweight upsampling operator (CARAFE) and an improved loss function, the feature extraction ability and detection speed of tomato seedling stems were improved. The accuracy of the improved yolov5 algorithm reached 92.6%, and mAP_0.5 reached 95.4%. Finally, the seedling verification test was carried out with tomato seedlings of about 40 days old. The test results show that the damage rate of the device is 7.2%, and the success rate is not less than 90.3%. This study can provide a reference for research into automatic transplanting machines.

Objectives To investigate the relationships among caregiver burden, family resilience, and caregiver capacity in the care of stroke survivors. We hypothesised that family resilience would mediate the relationship between caregiver burden and caregiver capacity.Design A cross-sectional study design was used.Setting The study was conducted in a tertiary care setting in Ningbo City, Zhejiang Province, China.Participants The study involved 413 stroke survivors and their primary caregivers.Outcome measures The primary caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale, Zarit Caregiver Burden Interview and Family Caregiver Task Inventor and provided their sociodemographic information. Stroke survivors were assessed for activities of daily living, and their sociodemographic information was provided. Data were analysed, controlling for sociodemographic variables and focusing on the mediating effect of family resilience.Results Caregiver burden was influenced by the activities of daily living of stroke survivors, caregiver age and caregiver health status (p

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

BackgroundCollege athletes are a group often affected by anxiety. Few interventional studies have been conducted to address the anxiety issues in this population. ObjectiveWe conducted a mobile-delivered mindfulness intervention among college athletes to study its feasibility and efficacy in lowering their anxiety level and improving their mindfulness (measured by the Five Facet Mindfulness Questionnaire [FFMQ]). MethodsIn April 2019, we recruited 290 college athletes from a public university in Shanghai, China, and 288 of them were randomized into an intervention group and a control group (closed trial), with the former (n=150) receiving a therapist-guided, smartphone-delivered mindfulness-based intervention and the latter receiving mental health promotion messages (n=138). We offered in-person instructions during the orientation session for the intervention group in a classroom, with the therapist interacting with the participants on the smartphone platform later during the intervention. We used generalized linear modeling and the intent-to-treat approach to compare the 2 groups' outcomes in dispositional anxiety, precompetition anxiety, and anxiety during competition, plus the 5 dimensions of mindfulness (measured by the FFMQ). ResultsOur intent-to-treat analysis and generalized linear modeling found no significant difference in dispositional anxiety, precompetition anxiety, or anxiety during competition. Only the “observation” facet of mindfulness measures had a notable difference between the changes experienced by the 2 groups, whereby the intervention group had a net gain of .214 yet fell short of reaching statistical significance (P=.09). Participants who specialized in group sports had a higher level of anxiety (β=.19; SE=.08), a lower level of “nonjudgemental inner experience” in FFMQ (β=–.07; SE=.03), and a lower level of “nonreactivity” (β=–.138; SE=.052) than those specializing in individual sports. ConclusionsNo significant reduction in anxiety was detected in this study. Based on the participant feedback, the time availability for mindfulness practice and session attendance for these student athletes in an elite college could have compromised the intervention’s effectiveness. Future interventions among this population could explore a more student-friendly time schedule (eg, avoid final exam time) or attempt to improve cognitive and scholastic outcomes. Trial RegistrationChinese Clinical Trial Registry ChiCTR1900024449; https://www.chictr.org.cn/showproj.html?proj=40865

Introduction: Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This study systematically analysed and summarized EV-D68 antibody studies in databases and identified the seropositivity rates of different regions, ages, and sexes. Methods: Meta-analysis was performed using STATA 16.0 software. I2 and Q tests were used to analyse the heterogeneity of the included studies. Meta-regression analysis was performed for different groups, and Egger’s linear regression analysis was used to evaluate publication bias. Results: The results of multiple studies indicated that the serological prevalence range of EV-D68 antibody was 17.78–96.69%. The results of the meta-analysis showed that the seropositivity rate of EV-D68 antibody was 76% (95% confidence interval [CI]: 67–84%), among which that of the Chinese population was 74% (95% CI: 61–86%) and that of other countries was 79% (95% CI: 65–91%). At the same time, a subgroup analysis was conducted. The seroprevalence of EV-D68 antibody was related to age but not sex or region. Conclusion: The seropositivity rate was lower in the below 5-year age group; however, it gradually increased with age. The results of this study showed that EV-D68 infection was widespread in the population, and the current clinical infection situation could not reflect the actual epidemic situation of the virus, among which children under 5 years old were vulnerable to infection, which should be given greater attention for epidemic prevention and control.

Abstract Background The major safety concern of the clinical application of wild type FGF19 (FGF19WT) emerges given that its extended treatment causes hepatocellular carcinoma. Therefore, we previously generated a safer FGF19 variant - FGF19ΔKLB, which have same effects on glycemic control and bile acid production but much less mitogenic activity. However, it remains unclear as to whether FGF19ΔKLB ameliorates intrahepatic cholestasis. Results We found that, similar to that of FGF19WT, the chronic administration of FGF19ΔKLB protects mice from cholestatic liver injury in these two models. The therapeutic benefits of FGF19ΔKLB on cholestatic liver damage are attributable, according to the following mechanistic investigation, to the reduction of BA production, liver inflammation, and fibrosis. More importantly, FGF19ΔKLB did not induce any tumorigenesis effects during its prolonged treatment. Conclusions Together, our findings raise hope that FGF19ΔKLB may represent a useful therapeutic strategy for the treatment of intrahepatic cholestasis.

Abstract Background Although increasing physical activity (PA) has been suggested to prevent and manage cognitive decline and dementia, its economic impact on healthcare systems and society is largely unknown. This study aimed to summarize evidence on the cost-effectiveness of PA interventions to prevent and manage cognitive decline and dementia. Methods Electronic databases, including PubMed/MEDLINE, Embase, and ScienceDirect, were searched from January 2000 to July 2023. The search strategy was driven by a combination of subject-heading terms related to physical activity, cognitive function, dementia, and cost-effectiveness. Selected studies were included in narrative synthesis, and extracted data were presented in narrative and tabular forms. The risk of bias in each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list. Results Five of the 11 identified studies focused on individuals with existing dementia. Six of the 11 identified studies focused on individuals with no existing dementia, including 3 on those with mild cognitive impairment (MCI), and 3 on those with no existing MCI or dementia. PA interventions focused on individuals with no existing dementia were found to be cost-effective compared to the control group. Findings were mixed for PA interventions implemented in individuals with existing dementia. Conclusions PA interventions implemented before or during the early stage of cognitive impairment may be cost-effective in reducing the burden of dementia. More research is needed to investigate the cost-effectiveness of PA interventions in managing dementia. Most existing studies used short-term outcomes in evaluating the cost-effectiveness of PA interventions in the prevention and management of dementia; future research should consider adding long-term outcomes to strengthen the study design.

Abstract Background Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)—based quantitative proteomics analysis of skeletal muscle. Methods The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. Results After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE’s ingredients. Conclusions This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE. Graphical Abstract

Investigating the seeding mechanism of precision seeders is of great significance for improving the quality of cotton sowing operations. This paper designs a rotary type-hole cotton precision mulching dibbler. The main factors influencing the entry of cotton seeds into the seed wheel holes during the seeding process are then theoretically analyzed. Following this, an accurate discrete element model of coated cotton seeds is established and combined with a discrete element method (DEM) and multi-body dynamics (MBD)-coupled simulation model of the seed drill for seed picking and planting. Simulation experiments on the seeding performance of the precision dibbler were performed to study the influence of the seed wheel structure and motion parameters on the picking and planting performance under different speeds. The optimal parameter combination for the seed wheel is obtained through optimization experiments, and a precision dibbler is manufactured for bench testing. The bench test results are consistent with the simulation test results. At the precision dibbler rotation speed of 16 r/min, the qualified index reaches a maximum value of 93.28%, the skip sowing index increases with the precision dibbler rotation speed, and the re-sowing index decreases as the speed increases. These optimization results significantly improved seeding precision and efficiency and are of great significance for the reliability and effectiveness of cotton sowing operations.

The Lengjimanda plate is situated in the middle section of the Da Hinggan mountains, in the eastern section of the Tianshan Xingmeng orogenic belt. To determine the formation age of the volcanic rocks in the Longjiang formation in this area, to explore their origin and tectonic background, and to reconstruct the geodynamic evolution of the region, this study conducted petrological, zircon U–Pb geochronological, geochemical, and isotopic analyses of the volcanic rocks in the Longjiang formation. The Longjiang formation’s volcanic rocks are primarily composed of trachyandesite, trachyte trachydacite, and andesite, which are intermediate basic volcanic rocks. They are enriched in large-ion lithophile elements, are depleted in high-field-strength elements, are significantly fractionated between light and heavy rare earth elements, and exhibit a moderate negative Eu anomaly in most samples. The results of the LA–ICP–MS zircon U–Pb dating indicate that the volcanic rocks in this group were formed in the Early Cretaceous period at 129.1 ± 0.82 Ma. The zircon εHf(t) ranges from +1.13 to +43.77, the tDM2 ranges from +655 to +1427 Ma, the initial Sr ratio (87Sr/86Sr)i ranges from 0.7030 to 0.7036, and the εNd(t) ranges from +2.1 to +6.6. Based on the geochemical compositions and isotopic characteristics of the rocks, the initial magma of the volcanic rocks in the Longjiang formation originated from the partial melting of basaltic crustal materials, with a source material inferred to be depleted mantle-derived young crustal. These rocks were formed in a superimposed post-collisional and continental arc environment, possibly associated with the Mongol-Okhotsk Ocean closure and the oblique subduction of the Pacific plate. This study addresses a research gap regarding the volcanic rocks of the Longjiang formation in this area. Its findings can be applied to exploration and prospecting in the region.

Abstract Background Peripheral artery disease (PAD) is a common circulatory disorder associated with increased hospitalizations and significant health care-related expenditures. Among patients with PAD, insurance status is an important determinant of health care utilization, treatment of disease, and treatment outcomes. However, little is known about PAD-costs differences across different insurance providers. In this study we examined possible disparities in length of stay and total charge of inpatient hospitalizations among patients with PAD by insurance type. Methods We conducted a cross-sectional analysis of length of stay and total charge by insurance provider for all hospitalizations for individuals with PAD in South Carolina (2010–2018). Cross-classified multilevel modeling was applied to account for the non-nested hierarchical structure of the data, with county and hospital included as random effects. Analyses were adjusted for patient age, race/ethnicity, county, year of admission, admission type, all-patient refined diagnostic groups, and Charlson comorbidity index. Results Among 385,018 hospitalizations for individuals with PAD in South Carolina, the median length of stay was 4 days (IQR: 5) and the median total charge of hospitalization was $43,232 (IQR: $52,405). Length of stay and total charge varied significantly by insurance provider. Medicare patients had increased length of stay (IRR = 1.08, 95 CI%: 1.07, 1.09) and higher total charges (β: 0.012, 95% CI: 0.007, 0.178) than patients with private insurance. Medicaid patients also had increased length of stay (IRR = 1.26, 95% CI: 1.24,1.28) but had lower total charges (β: -0.022, 95% CI: -0.003. -0.015) than patients with private insurance. Conclusions Insurance status was associated with inpatient length of stay and total charges in patients with PAD. It is essential that Medicare and Medicaid individuals with PAD receive proper management and care of their PAD, particularly in the primary care settings, to prevent hospitalizations and reduce the excess burden on these patients.

Abstract A patented strain of Bacillus amyloliquefaciens C-1 in our laboratory could produce functional sodium selenite (Na2SeO3) under optimized fermentation conditions. With the strong stress resistance and abundant secondary metabolites, C-1 showed potential to be developed as selenium-enriched postbiotics. C-1 has the ability to synthesize SeNPs when incubated with 100 μg/ml Na2SeO3 for 30 h at 30 °C aerobically with 10% seeds-culture. The transformation rate from Na2SeO3 into SeNPs reached to 55.51%. After selenium enrichment, there were no significant morphology changes in C-1 cells but obvious SeNPs accumulated inside of cells, observed by scanning electron microscope and transmission electron microscope, verified by energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. SeNPs had antioxidant activity in radical scavenge of superoxide (O2 −), Hydroxyl radical (OH−) and 1,1-diphenyl-2-picryl-hydrazine (DPPH), where scavenging ability of OH− is the highest. Selenium-enriched C-1 had obvious anti-inflammatory effect in protecting integrity of Caco-2 cell membrane destroyed by S. typhimurium; it could preventing inflammatory damage in Caco-2 stressed by 200 μM H2O2 for 4 h, with significantly reduced expression of IL-8 (1.687 vs. 3.487, P = 0.01), IL-1β (1.031 vs. 5.000, P

With the continuous increase in the resolution of high-resolution remote sensing satellite images, shadows have increasingly impacted feature target recognition and classification in images, urban reconstruction, and image interpretation. Although various shadow detection methods exist for different features, undetected small shadowed areas, misclassified dark areas, and highlighted non-shadowed areas remain. Moreover, it is still difficult to distinguish waters from shadowed regions owing to their similar characteristics. To further solve these problems, we propose a novel mixed shadow detection index (MSDI) for extracting urban feature shadows, using the original information of the first principal component that contains the differences between most of the different objects in the image, as well as the difference features in the shadowed areas and water bodies. We evaluated the effectiveness and robustness of our method by conducting comparison experiments using Gaofen-1, Gaofen-2, and WorldView-3 images from different scenes, times, and acquisition locations. Through visual analysis and data analysis of our method, we found that the method achieved excellent shadow detection results, with an average total accuracy 94% for shadow detection. The proposed shadow detection algorithm could accurately recognize waters, and it could also accurately recognize easily missed small shadowed areas and easily confused non-shadowed areas.

Objective: To characterize the effects of Qingwei San (QWS) on diabetic oral ulcer (OU) mice with stomach heat pattern through metabolomic analysis. Methods: A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db (db/db) mice with dried Zingiber officinale Rosc. rhizome (Z. officinale, Gan Jiang) decoction by gavage. All model mice had blood glucose levels of ≥11.1 mM. Subsequently, OU was induced by NaOH cauterization. After 1 week of administration of QWS, non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS). Results: The non-targeted metabolomics results indicated that tryptophan metabolism, 2-oxocarboxylic acid metabolism, serotonergic synapses, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were involved in the therapeutic effects of QWS, with tryptophan metabolism playing a predominant role. Conclusion: QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern. QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.

Abstract Background and objective Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. Methods A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. Results The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. Conclusions The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.

Background: Scrophulariae Radix (SR) is a commonly used medicinal plant. Alzheimer's disease (AD) is a neurodegenerative disease for which there is no effective treatment. This study aims to initially clarify the potential mechanism of SR in the treatment of AD based on network pharmacology and molecular docking techniques. Methods: The principal components and corresponding protein targets of SR were conducted by HPLC analysis and searched on TCMSP. AD targets were searched on DrugBank, Chemogenomics, TTD, OMIM and GeneCards databases. The compound-target network was constructed by Cytoscape3.8.2. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a PPI network. We further performed GO and KEGG enrichment analysis on the targets. Meanwhile, molecular docking study and cell experiments were approved for the core target and the active compound. Results: Through multidatabase retrieval and integration, it was found that 17 components of SR could exert anti-AD effects against 40 targets. KEGG enrichment analysis indicated that Alzheimer's disease (hsa05010) was one of the most significant AD enrichment signalling pathways. Combined with the gene expression profile information in the AlzData database, 15 targets were found to be associated with tau or beta-amyloid protein (Aβ). GO analysis indicated that the primary molecular functions of SR in the treatment of AD were neurotransmitter receptor activity (GO:0007268), postsynaptic neurotransmitter receptor activity (GO:0070997), and acetylcholine receptor activity (GO:0050435). Moreover, we explored the anti-AD effects of SR extract and ursolic acid (UA) using SH-SY5Y cells. Treatment of SH-SY5Y cells with 20 μM UA significantly reduced the oxidative damage to these neuronal cells. Conclusion: This study reveals the active ingredients and potential molecular mechanism of SR in the treatment of AD, and provides a theoretical basis for further basic research and clinical application.

Objective China faces the challenge of an ageing population with disabilities. Community healthcare centres (CHCs) serve as frontline community healthcare providers for older adults with and without disabilities. Despite their significance, there is a lack of literature examining the utilisation of CHC services among older adults. This study aims to examine and compare the utilisation and satisfaction of CHC healthcare services among older adults with and without disabilities.Setting Data from the 2019 Community Health Diagnosis Questionnaire, which interviewed 259 older adults residing in the Luohu district of Shenzhen, were used in the current study.Primary outcome measures Participants self-reported outcomes including use of CHCs, use of home health services from CHCs and satisfaction with CHCs. Five different disability types and an integrated disability variable were assessed as independent variables. Linear probability models were used to determine the relationship between disability types and outcome variables.Results Among 259 older adults aged 60 years and older, 70.66% self-identified as having a disability. No statistically significant associations were found between the use of CHCs, the use of home health services from CHCs and satisfaction with CHCs, and disability status. However, older adults with mobility and cognitive disabilities were more likely to receive home health services from CHCs.Conclusion Community health promotion policies should be implemented to improve access to health services for older adults with and without disabilities. In addition, CHCs should implement effective health management plans to ensure the health needs of older adults with disabilities.

Abstract Background Research on mental health disparities by race-ethnicity in the United States (US) during COVID-19 is limited and has generated mixed results. Few studies have included Asian Americans as a whole or by subgroups in the analysis. Methods Data came from the 2020 Health, Ethnicity, and Pandemic Study, based on a nationally representative sample of 2,709 community-dwelling adults in the US with minorities oversampled. The outcome was psychological distress. The exposure variable was race-ethnicity, including four major racial-ethnic groups and several Asian ethnic subgroups in the US. The mediators included experienced discrimination and perceived racial bias toward one’s racial-ethnic group. Weighted linear regressions and mediation analyses were performed. Results Among the four major racial-ethnic groups, Hispanics (22%) had the highest prevalence of severe distress, followed by Asians (18%) and Blacks (16%), with Whites (14%) having the lowest prevalence. Hispanics’ poorer mental health was largely due to their socioeconomic disadvantages. Within Asians, Southeast Asians (29%), Koreans (27%), and South Asians (22%) exhibited the highest prevalence of severe distress. Their worse mental health was mainly mediated by experienced discrimination and perceived racial bias. Conclusions Purposefully tackling racial prejudice and discrimination is necessary to alleviate the disproportionate psychological distress burden in racial-ethnic minority groups.

Abstract Purpose The purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved. Methods Thirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose

Broccoli is a rich source of diverse bioactive compounds, but how their contents are influenced by different growing seasons and variations in broccoli head sizes remains elusive. To address this question, we quantified sixteen known bioactive compounds and seven minerals in broccoli with varying head sizes obtained in two different growing seasons. Our results suggest that the contents of vitamin C, total phenols, carotenoids, and glucoraphanin were significantly higher in samples from the summer–autumn season, showing increases of 157.46%, 34.74%, 51.80%, and 17.78%, respectively, compared with those from the winter–spring season. Moreover, chlorogenic acid is a phenolic compound with relatively high contents among the six detected, while beta-sitosterol is the sterol with relatively high contents. Further, principal component analysis was conducted to rank the comprehensive scores of the profiles of phenolic compounds, phytosterols, and minerals, demonstrating that the broccoli samples grown during the summer–autumn season achieved the highest composite scores. Our results indicate that broccoli heads from the summer–autumn season are richer in a combination of bioactive compounds and minerals than those from the winter–spring season based on the composite score. This study extends our understanding of the nutrition profiles in broccoli and also lays the foundation for breeding broccoli varieties with improved nutrition quality.

As a strong interference source for the all-time optical imaging surveillance of maritime targets, sea surface glare is difficult to mitigate accurately because of its time-varying characteristics due to lighting conditions and seawater fluctuations. In this paper, we propose an adaptive suppression approach to sea surface glare, which establishes a geographic polarization suppression model based on real-time information regarding geographic positioning and the orientation information of the floating platform, and also combines dynamic polarization control and pixel normalization to achieve adaptive suppression of sea surface glare. Experimental results show that this approach can mitigate the influence of rapidly changing glare effectively, and the SSIM indexes between the images without glare and those with glare suppression of the same scenes exceed 0.8, which is suitable for all-time glare suppression on the sea surface under natural lighting conditions.

Investigating the mathematical and geometric principles embedded in ancient classic architecture is a significant tradition in the history of architectural development. Drawing inspiration from the modular design and creative ideology based on the geometric proportions of squareness and roundness in ancient Chinese architecture, we propose a new mode of squareness and roundness composition based on scale proportion specifically for the design of multi-story buildings. Taking Yingxian Wooden Pagoda as the case study, we not only re-evaluate the modular system and proportional rules followed in the design of the entire pagoda, but also reveal the technical approaches and geometric rules for effectively controlling the form of multi-story buildings. In particular, the mode of squareness and roundness composition based on scale proportion, utilizing a modular grid combined with squareness and roundness drawings as decision-making tools, can control the scale and proportion of buildings across different design dimensions and organically coordinate the design of multi-story buildings’ plans and elevations. Thus, it can achieve an effective balance of multi-story architectural forms. This study has potential applications in the creation of traditional multi-story buildings and heritage restoration projects, and offers valuable insights for future research on ancient multi-story buildings.

Automatic detection of building edge information from high-resolution remote sensing images can more accurately obtain building distribution information, which is of great significance for urban land planning, urban building planning and population estimation. The satellite image will be affected by atmospheric interference and noise, we preprocess the image to eliminate the atmospheric interference such as atmospheric correction and radiometric calibration, and utilize a new total variation and wavelet adaptive thresholding hybrid filter proposed in this paper to achieve the filtering of noise while retaining the image edge detail information. The traditional detection operator is prone to the problems of scattered edge points, discontinuity or misjudgment of too many edge points in the detection results due to the limitations of directions, template sizes. Therefore, this paper proposes a new 16-direction $5\times 5$ size Sobel operator to replace the previous Sobel operator with only horizontal and vertical directions, using these 16 directions to calculate the gradient of each pixel points. And each direction template is extracted to each direction contour image for weighted fusion. Thus, the edge information of different angles can be extracted, and the all-round information edge extraction of the image can be realized. By comparing the experimental visual effect and the evaluation criteria of the data results, the SNR, PSNR, AUC, and FOM values of the improved algorithm are much higher than other algorithms, with the advantage of higher image detection edge positioning accuracy, more complete contour lines and stronger anti-interference ability.

Abstract Background Unreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective. Methods The study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother–child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes. Discussion The findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers. Trial registration The study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021).

Abstract Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin’s effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction.

Cloud detection is of great significance for optical remote sensing images. Most existing cloud detection approaches often rely on many thresholds among multiple bands with a wide spectrum range, and normally just can be applied to specific satellite data. Cloud detection is difficult in some sensor data with limited number of available spectral bands. To tackle this challenge, we propose a cloud detection method based on random forest (RFCD) only with the most common RGB and NIR bands. The RFCD normalizes different sensor data by calculating the top-of-atmosphere (TOA) reflectance and combines stable spectral and texture features extracted from the most common bands, which improves accuracy, reduces reliance on multi-band information, and improves the extendibility of the method. Moreover, the RFCD effectively avoids the complicated threshold setting and reduces subjective factors. Few parameters and strong generalization ability of RF further improve the extendibility of RFCD and provide the application possibility in a variety of data. Experimental results show the total validity obtained by 107 Landsat-8 images is 93.46%. The accuracy of the RFCD is higher than the Function of mask method and similar to the SegNet deep learning method, while the RFCD need fewer training samples and hyperparameters which makes it easier to be used. The extended experimental results show RFCD also gets good detection results in Sentinel-2 and GaoFen-1 images. The new RFCD is an accurate cloud detection method with strong extendibility and stability, also avoiding the complicated threshold setting.

The COVID-19 pandemic has resulted in more than 600 million confirmed cases worldwide since December 2021. Cardiovascular disease (CVD) is both a risk factor for COVID-19 mortality and a complication that many COVID-19 patients develop. This study uses Twitter data to identify the spatiotemporal patterns and correlation of related tweets with daily COVID-19 cases and deaths at the national, regional, and state levels. We collected tweets mentioning both COVID-19 and CVD-related words from February to July 2020 (Eastern Time) and geocoded the tweets to the state level using GIScience techniques. We further proposed and validated that the Twitter user registration state can be a feasible proxy of geotags. We applied geographical and temporal analysis to investigate where and when people talked about COVID-19 and CVD. Our results indicated that the trend of COVID-19 and CVD-related tweets is correlated to the trend of COVID-19, especially the daily deaths. These social media messages revealed widespread recognition of CVD’s important role in the COVID-19 pandemic, even before the medical community started to develop consensus and theory supports about CVD aspects of COVID-19. The second wave of the pandemic caused another rise in the related tweets but not as much as the first one, as tweet frequency increased from February to April, decreased till June, and bounced back in July. At the regional level, four regions (Northeast, Midwest, North, and West) had the same trend of related tweets compared to the country as a whole. However, only the Northeast region had a high correlation (0.8–0.9) between the tweet count, new cases, and new deaths. For the second wave of confirmed new cases, the major contributing regions, South and West, did not ripple as many related tweets as the first wave. Our understanding is that the early news attracted more attention and discussion all over the U.S. in the first wave, even though some regions were not impacted as much as the Northeast at that time. The study can be expanded to more geographic and temporal scales, and with more physical and socioeconomic variables, with better data acquisition in the future.

Background/purpose: Glide path management (GPM) is a consequential clinical step that serves to influence predictably successful root canal therapy. However, the effect of GPM on the shaping ability of single-file system remains controversial. This study compared the performance of rotary single-file One Curve (OC) and reciprocating single-file Reciproc Blue (RCB) in combination with/without different glide path techniques: no glide path preparation (NG), PathFile (PF), ProGlider (PG) and WaveOne Gold Glider (WOGG), respectively. Materials and methods: 80 simulated curved canals (n = 10 canals/per group) were instrumented to an apical size of 0.25 mm using OC and RCB in combination with/without different glide path techniques, respectively. The amount of resin removal, canal transportation, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis of the data was performed by using Kruskal–Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: Post–glide path analysis found that WOGG and PG produced less canal transportation and curvature straightening than PF (P

Abstract Background A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices. Methods This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC). Results Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P

Ferulic acid (FA) is a natural polyphenol, a derivative of cinnamic acid, widely found in Angelica, Chuanxiong and other fruits, vegetables and traditional Chinese medicine. FA contains methoxy, 4-hydroxy and carboxylic acid functional groups that bind covalently to neighbouring adjacent unsaturated Cationic C and play a key role in many diseases related to oxidative stress. Numerous studies have shown that ferulic acid protects liver cells and inhibits liver injury, liver fibrosis, hepatotoxicity and hepatocyte apoptosis caused by various factors. FA has protective effects on liver injury induced by acetaminophen, methotrexate, antituberculosis drugs, diosbulbin B and tripterygium wilfordii, mainly through the signal pathways related to TLR4/NF-κB and Keap1/Nrf2. FA also has protective effects on carbon tetrachloride, concanavalin A and septic liver injury. FA pretreatment can protect hepatocytes from radiation damage, protects the liver from damage caused by fluoride, cadmium and aflatoxin b1. At the same time, FA can inhibit liver fibrosis, inhibit liver steatosis and reduce lipid toxicity, improve insulin resistance in the liver and exert the effect of anti-liver cancer. In addition, signalling pathways such as Akt/FoxO1, AMPK, PPAR γ, Smad2/3 and Caspase-3 have been shown to be vital molecular targets for FA involvement in improving various liver diseases. Recent advances in the pharmacological effects of ferulic acid and its derivatives on liver diseases were reviewed. The results will provide guidance for the clinical application of ferulic acid and its derivatives in the treatment of liver diseases.

Objective: To observe the relationship between the different stages of type 2 diabetes mellitus (T2DM) and the intestinal flora and verify its underlying mechanism. Methods: T2DM rats were generated by high-fat diet (HFD) combined with intraperitoneal streptozotocin (STZ) injection. The rats were divided into four groups: the control group (fed with normal feed for 1 month), the HFD group (fed with HFD for 1 month), the T2DM group (HFD combined with STZ and blood glucose ≥11.1 mM), and the unformed T2DM model (Un-mod) group (HFD combined with STZ and blood glucose

Abstract. Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a group of highly heterogeneous multi-system diseases, which is closely related to metabolic dysfunction and is one of the most important public health problems in the world. Studies have shown that paracrine fibroblast growth factors (FGFs) play an important role in the occurrence and development of MAFLD by regulating glucose and lipid metabolism, inflammation, and fibrosis. This article reviews the latest progress in understanding of the distribution, function, and metabolic regulation of paracrine FGFs, which paves the way for future FGF-based therapies targeting MAFLD.

The Saima alkaline rock-hosted niobium–tantalum deposit (hereafter referred to as the Saima Deposit) is situated in the Liaodong Peninsula, which constitutes the eastern segment of the northern margin of the North China Craton. The rock types of the Saima Deposit include phonolite, nepheline syenite, and aegirine nepheline syenite, which hosts niobium–tantalum ore bodies. In this study, the primary niobium-bearing minerals identified include loparite, betafite, and fersmite. The Saima pluton is characterized as a potassium-rich, low-sodium, and peraluminous alkaline pluton. Trace element characteristics reveal that the metallization-associated syenite is enriched in large-ion lithophile elements (LILEs) such as K and Rb but is relatively depleted in high-field strength elements (HFSEs). As indicated by the rare earth element (REE) profile, the Saima pluton exhibits a high total REE content (∑REE), dominance of light REEs (LREEs), and scarcity of heavy REEs (HREEs). The Sr-Nd-Pd isotopic data suggest that aegirine nepheline syenite and nepheline syenite share consistent isotopic signatures, indicating a common origin. The Saima alkaline pluton displays elevated ISr values ranging from 0.70712 to 0.70832 coupled with low εNd(t) values between −12.84 and −11.86 and two-stage model ages (tDM2) from 1967 to 2047 Ma. These findings indicate that the metallogenic materials for the Saima Deposit derive from both an enriched mantle source and some crustal components. The lithium (Li) isotopic fractionation observed during the genesis of the Saima pluton could be attributed to the differential diffusion rates of 6Li and 7Li under non-equilibrium fluid–rock interactions.

Pulmonary drug delivery via microspheres has gained growing interest as a noninvasive method for therapy. However, drug delivery through the lungs via inhalation faces great challenges due to the natural defense mechanisms of the respiratory tract, such as the removal or deactivation of drugs. This study aims to develop a natural polymer-based microsphere system with a diameter of around 3 μm for encapsulating pulmonary drugs and facilitating their delivery to the deep lungs. Pectin was chosen as the foundational material due to its biocompatibility and degradability in physiological environments. Electrospray was used to produce the pectin-based hydrogel microspheres, and Design-Expert software was used to optimize the production process for microsphere size and uniformity. The optimized conditions were determined to be as follows: pectin/PEO ratio of 3:1, voltage of 14.4 kV, distance of 18.2 cm, and flow rate of 0.95 mL/h. The stability and responsiveness of the pectin-based hydrogel microspheres can be altered through coatings such as gelatin. Furthermore, the potential of the microspheres for pulmonary drug delivery (i.e., their responsiveness to the deep lung environment) was investigated. Successfully coated microspheres with 0.75% gelatin in 0.3 M mannitol exhibited improved stability while retaining high responsiveness in the simulated lung fluid (Gamble’s solution). A gelatin-coated pectin-based microsphere system was developed, which could potentially be used for targeted drug delivery to reach the deep lungs and rapid release of the drug.

Background/purpose: Calcium hydroxide [Ca(OH)2], a wildly used intracanal medicament, should be completely removed from the root canal before obturation to avoid negative effects on the treatment. This study evaluated the effectiveness of conventional needle irrigation (CNI), passive ultrasonic activation (PUI), photon-induced photoacoustic streaming (PIPS), XP-endo Finisher (XP) and EDDY for the removal of Ca(OH)2 from S-shaped root canal. Materials and methods: Eighty-four S-shaped root canals in resin blocks were prepared using Protaper Gold up to size #25/0.08 and filled with Ca(OH)2. Five groups were established according to the removal techniques (n = 16): CNI, PUI, PIPS, XP and EDDY group. The positive and negative control group (n = 2) were also established. Sodium hypochlorite 3% was used as the irrigant. Digital radiographs were used to measure the remaining Ca(OH)2. Statistical analysis of the data was performed by using the Kruskal–Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: All the tested techniques completely removed Ca(OH)2 from the straight portion and coronal curve of the S-shaped root canal in 100% of cases. Regarding the apical curve, PUI, EDDY, PIPS and XP removed significantly more Ca(OH)2 than CNI (P 0.05). The complete clearance of Ca(OH)2 from the apical curve was observed in 75%, 62.5%, 56.3%, 43.8% and 0% of cases of PUI, EDDY, PIPS, XP and CNI group, respectively. Conclusion: Irrigant activation enhanced Ca(OH)2 removal from the apical region of the S-shaped root canal. CNI was significantly less effective than all activation techniques.

Background/purpose: Gold metal technology improves flexibility and the resistance to cyclic fatigue of the endodontic mechanical files. This study compared the performance of ProTaper Gold (PTG) multiple file system and WaveOne Gold (WOG) single file system in simulated S-shaped root canals, which represents one of the most challenging root canal morphology. Materials and methods: Forty S-shaped canals (n = 20 canals/per group) in resin blocks were instrumented to an apical size of 0.25 mm using PTG and WOG Primary, respectively. The total amount of resin removal, canal transportation, centering ratio, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis was performed by using Mann–Whitney U-test (α = .05). Results: None of the files fractured during the instrumentation. The WOG group removed significantly less amount of resin at 0, 3, 6, 7 and 9 mm from the apex (P .05). Conclusion: The WOG Primary file has a less aggressive dentin cutting and more centered apical preparation. The PTG system is more advantageous in shaping the coronal curvature of S-shaped canal.

Abstract Background Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms. Methods The main components of QWS aqueous extract were analyzed by LC–MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin–eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B2 (TXB2), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting. Results A total of 183 compounds in QWS were identified by LC–MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB2 and the ratio of TXB2/6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IκΒα and NF-κB p65 were decreased. Conclusion QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.

The selective C—C bond activation is a frontier research topic and of great significance in the field of chemistry, especially for biosciences. Due to the existence of many C—C bonds with similar activities in compounds, it is difficult to selectively activate one of the C—C bonds. In this paper, the newly synthesized peptide derivatives composed of unnatural amino acids were used as a subject to demonstrate how radical-mediated selective C—C bond activation and isomer differentiation work. TEMPO radical initiator was employed to introduce o-methylbenzoyl (Bz) radical into the peptide derivatives, and successfully prepared ［Bz-M+H］•+ radical ions in the gas phase. Through tandem mass spectrometry experiments, it had been found that ［Bz-M+H］•+ showed higher reactivity than the protonated peptide molecule ［M+H］+, giving a more diversified gas-phase dissociation reactions. The main fragmentation of ［M+H］+ was the cleavage of amide bond to give rise to ［y1+2H］+ (m/z 160.134 0, RA 100%), a1+ (m/z 86.097 2, RA 74%), and ［(M+H)-HCOOEt］+ (m/z 199.181 5, RA 52%). In contrast, the fragment ions of ［Bz-M+H］•+ included ［Bz•-a1］+ (m/z 202.97), ［Bz•-b1］+ (m/z 231.03), ［Bz•-c1+H］+ (m/z 133.95) and ［(Bz-M+H)-HCOOEt］+ (m/z 316.18, RA 100%). N-terminal fragments of ［Bz-M+H］•+ were observed with the radical part •CH2C6H4CO still attached to the fragmentation. To distinguish these ions from the normal fragments, the prefix Bz• was introduced, such as, ［Bz•-a1］+. More interestingly, ［(Bz-M+H)-HCOOEt］+ was the base peak of ［Bz-M+H］•+, which was produced by breaking the Cα—C adjacent to the ester group of peptide derivative. In contrast, the relative abundance of ［(M+H)-HCOOEt］+ from ［M+H］+ was only 50%. The formation mechanism of ［(M+H)-HCOOEt］+ had been experimentally confirmed to be completed by the two-step reaction of losing EtOH and CO successively. For isomers B1 and B2, their CID spectra of ［Bz-M+H］•+ had high similarity, but the abundance of fragment ion ［Bz•-a1］+ was obviously different (m/z 203, RA 40% for B1, RA 60% for B2). The fragment ions ［Bz•-a1］+ and ［(Bz-M+H)-HCOOEt］+ of ［Bz-M+H］•+ can be used as sensitive probes for isomer discrimination and selective C—C bond cleavage. The research provides new strategy to distinguish peptide isomers and to cleavage selective C—C bond with radical participation in mass spectrometer.

OBJECTIVES During the coronavirus disease 2019 (COVID-19) pandemic, a growing prevalence of racial and ethnic discrimination occurred when many Americans struggled to maintain healthy lifestyles. This study investigated the associations of racial and ethnic discrimination with changes in exercise and screen time during the pandemic in the United States. METHODS We included 2,613 adults who self-identified as non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, or Hispanic from the Health, Ethnicity, and Pandemic study, a cross-sectional survey conducted among a nationally representative sample of United States adults between October and November 2020. We assessed self-reported racial and ethnic discrimination by measuring COVID-19-related racial and ethnic bias and examined its associations with changes in exercise and screen time using multivariable logistic regression models. We analyzed data between September 2021 and March 2022. RESULTS COVID-19-related racial and ethnic bias was associated with decreased exercise time among non-Hispanic Asian (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.13 to 1.89) and Hispanic people (OR, 1.91; 95% CI, 1.32 to 2.77), and with increased screen time among non-Hispanic Black people (OR, 1.94; 95% CI, 1.33 to 2.85), adjusting for age, sex, education, marital status, annual household income, insurance, and employment status. CONCLUSIONS Racial and ethnic discrimination may have adversely influenced exercise and screen time changes among racial and ethnic minorities during the COVID-19 pandemic in the United States. Further studies are needed to investigate the mechanisms through which racial and ethnic discrimination can impact lifestyles and to develop potential strategies to address racial and ethnic discrimination as a barrier to healthy lifestyles.

Although free-space optical communication (FSOC) is a promising means of high data rate satellite-to-ground communication, beam distortion caused by atmospheric optical turbulence remains a major challenge for its engineering applications. Accurate prediction of atmospheric optical turbulence to optimize communication plans and equipment parameters, such as adaptive optics (AO), is an effective means to address this problem. In this research, a hybrid multi-step prediction model for atmospheric optical turbulence, EMD-Seq2Seq-LSTM, is proposed by combining empirical mode decomposition (EMD), sequence-to-sequence (Seq2Seq), and long short-term memory (LSTM) network. First, using empirical mode decomposition to decompose the non-linear and non-stationary atmospheric optical turbulence dataset into a set of stationary components for which internal feature information can be easily extracted significantly reduces the training difficulty and improves the forecast accuracy of the model. Second, sequence-to-sequence is combined with LSTM networks to build a prediction model that can eliminate time delay and make full use of long-term information and then use the model to predict each component separately. Finally, the prediction results of each component are combined to obtain the final atmospheric turbulence forecasting results. To validate the performance of the proposed method, three comparative models, including WRF, LSTM, and sequence-to-sequence-LSTM, are demonstrated in this study. The forecasting results reveal that the proposed model outperforms all other models both qualitatively and quantitatively and thus can be a powerful method for atmospheric optical turbulence forecasting.