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Abstract Background Evidence-based and evidence-informed interventions designed to address gaps in the HIV care continuum have the potential to improve HIV care and treatment. However, inadequate organizational readiness can derail intervention uptake, prevent the integration of interventions, and contribute to suboptimal HIV treatment outcomes. This study sought to understand organizational readiness to implement bundled interventions for Black women with HIV and inform facilitators and barriers to implementation. Methods We conducted a mixed methods readiness assessment across 12 sites participating in the Black Women First (BWF) initiative to gauge preparedness to implement bundled interventions. Readiness was assessed using the organizational readiness for implementing change (ORIC) scale, and two open-ended questions examined facilitators and barriers. Associations between participant and organizational level factors were evaluated using linear models with clustering by site at baseline, 6- and 12-months. Pre-implementation interviews were conducted with staff virtually and transcripts were managed in NVivo. Directed content analysis was used to explore implementation barriers and facilitators. Findings Sites demonstrated high levels of organizational readiness at baseline; overall organizational readiness for implementing change (ORIC) (mean 56.4, median 59, interquartile range [IQR] 5) and subscales of the ORIC change efficacy (mean 32.4, median 35, IQR 4), change commitment (mean 24, median 25, IQR 1), which is consistent with willingness and capability to implement bundled interventions for Black women with HIV. Organizational readiness remained high at 6- and 12-month follow-up periods. Staff role was significantly associated with organizational readiness (p = 0.007), change efficacy (p = 0.006), and change commitment (p = 0.020) at 6 months. Qualitative analysis indicated strategic planning and assessment (e.g., team coordination and the development of workflows to support implementation); organizational change through network weaving across silos within the organization, and communications systems that engage external partners, as well as resources available for hiring and training, supported readiness. Collaborative leadership and organizational buy-in, staff motivation, and partnerships facilitated implementation processes. Conclusions Organizations in the BWF initiative have high levels of organizational readiness reflecting willingness and capability to implement bundled interventions for Black women with HIV. Future research should examine the relationship between readiness and clinical outcomes.

A new hybrid conjugate gradient algorithm for solving the unconstrained optimization problem was presented. The algorithm could be considered as a modification of the memoryless Broyden-Fletcher-Goldfarb-Shanno (BFGS) quasi-Newton method. Based on a normalized gradient difference, we introduced a new combining conjugate gradient direction close to the direction of the memoryless BFGS quasi-Newton direction. It was shown that the search direction satisfied the sufficient descent property independent of the line search. For general nonlinear functions, the global convergence of the algorithm was proved under standard assumptions. Numerical experiments indicated a potential performance of the new algorithm, especially for solving the large-scale problems. In addition, the proposed method was used in practical application problems for image restoration and machine learning.

BackgroundWith the continuous progress and in-depth implementation of the reform of the medical and health care system, alongside the gradual enhancement of the standardized training framework for residents, such training has become a crucial avenue for cultivating high-level clinicians and improving medical quality. However, due to various constraints and limitations in their own capabilities, residents undergoing standardized training are often susceptible to job burnout during this process. Numerous factors contribute to job burnout, which is closely associated with depression and anxiety. To promote effective standardized training and develop high-quality resident personnel, it is essential to investigate the influencing factors of job burnout and implement strategies to mitigate its occurrence.ObjectiveExplore the job burnout and its influencing factors among standardized training residents of Affiliated Hospital of Yan ‘an University, and to provide favorable basis for effective prevention of job burnout.MethodsAn online questionnaire survey was conducted among all standardized training residents at the hospital from June 2020 to September 2022. The evaluation utilized a general situation questionnaire, the Job Burnout Inventory - General Survey (MBI-GS), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS).ResultsA total of 660 valid questionnaires were collected, and 315 people had positive reaction for job burnout, and the detection rate was 47.7%. Difference in gender, marital status, whether they held practicing certificates, participated in work before training, used sleep medication, age, grade, sleep state were the influencing factors of different dimensions of job burnout. 175 people were in a state of anxiety (26.5%), while 357 (54.1%) were depressed. Pearson correlation analysis showed that anxiety and depression were highly correlated with job burnout (p

Abstract Alzheimer’s disease (AD) is an age-associated neurodegenerative disease. Recently, studies have demonstrated the potential involvement of microRNA-181c-5p (miR-181c-5p) in AD. However, the mechanism through which miR-181c-5p is responsible for the onset and progression of this disease remains unclear, and our study aimed to explore this problem. Differential expression analysis of the AD dataset was performed to identify dysregulated genes. Based on hypergeometric analysis, AD differential the upstream regulation genes miR-181c-5p was found. We constructed a model where SH-SY5Y and BV2 cells were exposed to Aβ1-42 to simulate AD. Levels of tumor necrosis factor-alpha, interleukin-6, and IL-1β were determined using enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Phosphorylation levels of p-P38 and P38 were detected by Western blot. The level of apoptosis in BV2 cells under Aβ1-42 stress was exacerbated by miR-181c-5p mimic. Downregulated miR-181c-5p impaired the phagocytosis and degradation of Aβ by BV2 cells. The release of proinflammatory cytokines in BV2 cells with Aβ1-42 stress was alleviated by miR-181c-5p upregulation. Additionally, miR-181c-5p downregulation alleviated the phosphorylation of P38 in Aβ1-42-induced SH-SY5Y cells. In conclusion, miR-181c-5p improves the phagocytosis of Aβ by microglial cells in AD patients, thereby reducing neuroinflammation.

Abstract Wild medicinal plants are prominent in the field of Traditional Chinese Medicine (TCM), but their availability is being impacted by human activities and ecological degradation in China. To ensure sustainable use of these resources, it is crucial to scientifically plan areas for wild plant cultivation. Thesium chinense, a known plant antibiotic, has been overharvested in recent years, resulting in a sharp reduction in its wild resources. In this study, we employed three atmospheric circulation models and four socio-economic approaches (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) to investigate the primary environmental factors influencing the distribution of T. chinense. We also examined changes in its suitable area using the Biomod2 package. Additionally, we utilized the PLUS model to project and analyze future land use changes in climate-stable regions for T. chinense. Our planning for wild tending areas of T. chinense was facilitated by the ZONATION software. Over the next century, the climate-stable regions for T. chinense in China is approximately 383.05 × 104 km2, while the natural habitat in this region will progressively decline. Under the current climate conditions, about 65.06% of the habitats in the high suitable areas of T. chinense are not affected by future land use changes in China. Through hotspot analysis, we identified 17 hotspot cities as ideal areas for the wild tending of T. chinense, including 6 core hotspot cities, 6 sub-hotspot cities, and 5 fringe hotspot cities. These findings contribute to a comprehensive research framework for the cultivation planning of T. chinense and other medicinal plants.

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin.

Diffuse large B-cell lymphoma (DLBCL) stands as the most prevalent subtype of non-Hodgkin's lymphoma and exhibits significant heterogeneity. Various forms of programmed cell death (PCD) have been established to have close associations with tumor onset and progression. To this end, this study has compiled 16 PCD-related genes. The investigation delved into genes linked with prognosis, constructing risk models through consecutive application of univariate Cox regression analysis and Lasso-Cox regression analysis. Furthermore, we employed RT-qPCR to validate the mRNA expression levels of certain diagnosis-related genes. Subsequently, the models underwent validation through KM survival curves and ROC curves, respectively. Additionally, nomogram models were formulated employing prognosis-related genes and risk scores. Lastly, disparities in immune cell infiltration abundance and the expression of immune checkpoint-associated genes between high- and low-risk groups, as classified by risk models, were explored. These findings contribute to a more comprehensive understanding of the role played by the 16 PCD-associated genes in DLBCL, shedding light on potential novel therapeutic strategies for the condition.

Traditional coordinated motion planning schemes for mobile robot manipulators are primarily designed at the velocity level, which limits their applicability to acceleration-oriented systems. To address this limitation, this paper proposes, for the first time, a kinematic model and a trajectory tracking scheme for a two-wheeled mobile robot manipulator (TWMRM) at the acceleration level. This innovation enables the TWMRM system to achieve improved precision and stability under complex dynamic conditions. Compared to velocity-level approaches, the proposed acceleration-level scheme is applicable to both acceleration-oriented and velocity-oriented mobile robot manipulators, offering a broader range of applications. To verify the proposed approach, trajectory-tracking simulations show that the TWMRM’s end-effector closely follows the desired trajectory, with position errors on the order of ${10}^{-7}$ and no divergence issue. Additionally, practical experiments confirm the feasibility of the acceleration-level kinematic model and trajectory tracking scheme for real-world applications.

AbstractContext Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear.Objective As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS.Materials and methods Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE−/− mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver.Results Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB’s treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE−/− mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE−/− mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%).Conclusions AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB.

Cold start is a critical operating scenario for the proton exchange membrane fuel cell (PEMFC), particularly in the field of transportation. Under sub-freezing temperatures, the water inside the cell will freeze and obstruct gas flow paths as well as cover catalyst reaction sites, resulting in a failed startup. This study proposes an optimization method for the -30°C cold start of PEMFC based on a data-driven surrogate model to improve cold start performance and reduce irreversible damage to the cell. A validated PEMFC cold start mechanism model is utilized as the basis for developing an extreme learning machine (ELM) based data-driven surrogate model, which is trained using data collected from the mechanism model and has higher computational efficiency compared with the original model. In addition, the NSGA-II multi-objective optimization algorithm is employed to optimize the current loading strategies and operating parameters using the surrogate model as fitness function. The objectives are to enhance the minimum voltage and reduce startup duration time. Moreover, experimental validation confirms the effectiveness of the proposed method. The test results demonstrate that a cold start from -30°C is achieved within 97 s, with the minimum voltage reaching 0.44 V. Notably, there is a reduction in startup time by 26 s and an increase in the minimum voltage by 0.06 V compared to the base case. This study establishes a foundation for researchers to adjust operating settings during cold start based on diverse applications and requirements.

Owing to the rapid advancement of genome engineering technologies, the scale of genome engineering has expanded dramatically. Genome editing has progressed from one genomic alteration at a time that could only be employed in few species, to the simultaneous generation of multiple modifications across many genomic loci in numerous species. The development and recent advances in multiplex automated genome engineering (MAGE)-associated technologies and clustered regularly interspaced short palindromic repeats and their associated protein (CRISPR-Cas)-based approaches, together with genome-scale synthesis technologies offer unprecedented opportunities for advancing genome-scale engineering in a broader range. These approaches provide new tools to generate strains with desired phenotypes, understand the complexity of biological systems, and directly evolve a genome with novel features. Here, we review the recent major advances in genome-scale engineering tools developed for Escherichia coli, focusing on their applications in identifying essential genes, genome reduction, recoding, and beyond.

MYCN activates canonical MYC targets involved in ribosome biogenesis, protein synthesis, and represses neuronal differentiation genes to drive oncogenesis in neuroblastoma (NB). How MYCN orchestrates global gene expression remains incompletely understood. Our study finds that MYCN binds promoters to up-regulate canonical MYC targets but binds to both enhancers and promoters to repress differentiation genes. MYCN binding also increases H3K4me3 and H3K27ac on canonical MYC target promoters and decreases H3K27ac on neuronal differentiation gene enhancers and promoters. WDR5 facilitates MYCN promoter binding to activate canonical MYC target genes, whereas MYCN recruits G9a to enhancers to repress neuronal differentiation genes. Targeting both MYCN's active and repressive transcriptional activities using both WDR5 and G9a inhibitors synergistically suppresses NB growth. We demonstrate that MYCN cooperates with WDR5 and G9a to orchestrate global gene transcription. The targeting of both these cofactors is a novel therapeutic strategy to indirectly target the oncogenic activity of MYCN.

Abstract The strong excitonic effects widely exist in polymer-semiconductors and the large exciton binding energy (E b) seriously limits their photocatalysis. Herein, density functional theory (DFT) calculations are conducted to assess band alignment and charge transfer feature of potential donor-acceptor (D-A) covalent organic frameworks (COFs), using 1,3,5-tris(4-aminophenyl)triazine (TAPT) or 1,3,5-tris(4-aminophenyl)benzene (TAPB) as acceptors and tereph-thaldehydes functionalized diverse groups as donors. Given the discernable D-A interaction strengths in the D-A pairs, their E b can be systematically regulated with minimum E b in TAPT-OMe. Guided by these results, the corresponding D-A COFs are synthesized, where TAPT-OMe-COF possesses the best activity in photocatalytic H2 production and the activity trend of other COFs is associated with that of calculated E b for the D-A pairs. In addition, further alkyne cycloaddition for the imine linkage in the COFs greatly improves the stability and the resulting TAPT-OMe-alkyne-COF with a substantially smaller E b exhibits ~20 times higher activity than the parent COF.

Abstract Objectives: We investigated the prospective associations between meat consumption and CVD and whether these relationships differ by dietary quality among African American (AA) adults. Design: Baseline diet was assessed with a regionally specific FFQ. Unprocessed red meat included beef and pork (120 g/serving); processed meat included sausage, luncheon meats and cured meat products (50 g/serving). Incident total CVD, CHD, stroke and heart failure were assessed annually over 9·8 years of follow-up. We characterised dietary quality using a modified Healthy Eating Index-2010 score (m-HEI), excluding meat contributions. Setting: Jackson, MS, USA. Participants: AA adults (n 3242, aged 55 y, 66 % female). Results: Mean total, unprocessed red and processed meat intakes were 5·7 ± 3·5, 2·3 ± 1·8 and 3·3 ± 2·7 servings/week, respectively. Mostly, null associations were observed between meat categories and CVD or subtypes. However, greater intake of unprocessed red meat (three servings/week) was associated with significantly elevated risk of stroke (hazard ratio = 1·43 (CI: 1·07,1·90)). With the exception of a more positive association between unprocessed meat consumption and stroke among individuals in m-HEI Tertile 2, the strength of associations between meat consumption categories and CVD outcomes did not differ by m-HEI tertile. In formal tests, m-HEI did not significantly modify meat–CVD associations. Conclusions: In this cohort of AA adults, total and processed meat were not associated with CVD outcomes, with the exception that unprocessed red meat was related to greater stroke risk. Dietary quality did not modfiy these associations. Research is needed in similar cohorts with longer follow-up and greater meat consumption to replicate these findings.

BackgroundRecently, attention has been paid to the protective properties of active ingredients in Salvia miltiorrhiza (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on in vitro and in vivo models of doxorubicin-induced cardiotoxicity (DIC).MethodsAccording to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant in vitro and in vivo studies on “the role of AISM on DIC” published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias.ResultsTwenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in Salvia miltiorrhiza were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, etc. The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool.ConclusionThis systematic review demonstrated that AISM have chemoprotective effects on DIC in vivo and in vitro models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug’s instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2–32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity.Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.

Introduction: The aim of this study was to investigate the impact of the SARS-CoV-2 pandemic on older Hispanic adults. Methods: A total of 522 participants (or their family members, if deceased) from the Boston Puerto Rican Health Study were asked whether they had been diagnosed with SARS-CoV-2, across 2 survey phases. In Phase 1 (May 2020–August 2020, N=497), participants answered survey questions related to SARS-CoV-2 exposure, diagnosis, and transmission and 5 family members reported deaths. In Phase 2, participants were again surveyed (January 2021–June 2021; n=420, and 2 family members reported deaths). SARS-CoV-2 diagnosis and/or death apparently from SARS-CoV-2 was self-reported. Results: In 2020, 5.2% reported that they had been SARS-CoV-2 positive; by June 2021, a cumulative 11.0% reported having been SARS-CoV-2 positive (including cases and deaths in the first survey). A total of 7 participants (1.3%) reportedly died of SARS-CoV-2. Language acculturation was significantly lower among participants with SARS-CoV-2 (13.7±17.9) than among those without SARS-CoV-2 (20.0±21.4; p=0.049). The mean length of return to usual health was 28±38 days (range=0–210 days; median=15 days). Depressive symptomatology was significantly lower during the pandemic (Center for Epidemiologic Studies Depression Scale score: 13.4±11.6) than in the same participants before the pandemic (17.8±11.7; p=0.001). A total of 32% (n=135) of participants reported greater communication with friends and family than in the months before the pandemic, and 41% (n=172) reported no change. Conclusions: Public health models should be personalized to communities, considering their unique structures and cultural beliefs. Social resiliency may be key for future programmatic responses to pandemics to reduce the mental health burden.

Abstract The neural crest lineage regulatory transcription factors (TFs) form a core regulatory circuitry (CRC) in neuroblastoma (NB) to specify a noradrenergic tumor phenotype. Oncogenic subversion of CRC TFs is well documented, but the role of loss of tumor suppressors plays remains unclear. Zinc-finger TF CASZ1 is a chromosome 1p36 (chr1p36) tumor suppressor. Single-cell RNA sequencing data analyses indicate that CASZ1 is highly expressed in developing chromaffin cells coincident with an expression of NB CRC TFs. In NB tumor cells, the CASZ1 tumor suppressor is silenced while CRC components are highly expressed. We find the NB CRC component HAND2 directly represses CASZ1 expression. ChIP-seq and transcriptomic analyses reveal that restoration of CASZ1 upregulates noradrenergic neuronal genes and represses expression of CRC components by remodeling enhancer activity. Our study identifies that the restored CASZ1 forms a negative feedback regulatory circuit with the established NB CRC to induce noradrenergic neuronal differentiation of NB.

Human activities and climate change have significantly impacted the quantity and sustainable utilization of medicinal plants. Gentiana manshurica Kitagawa, a high-quality original species of Gentianae Radix et Rhizoma, has significant medicinal value. However, wild resources have experienced a sharp decline due to human excavation, habitat destruction, and other factors. Consequently, it has been classified as an Endangered (EN) species on the IUCN Red List and is considered a third-level national key-protected medicinal material in China. The effects of climate change on G. manshurica are not yet known in the context of the severe negative impacts of climate change on most species. In this study, an optimized MaxEnt model was used to predict the current and future potential distribution of G. manshurica. In addition, land use data in 1980, 2000, and 2020 were used to calculate habitat quality by InVEST model and landscape fragmentation by the Fragstats model. Finally, using the above-calculated results, the priority protection areas and wild tending areas of G. manshurica were planned in ZONATION software. The results show that the suitable area is mainly distributed in the central part of the Songnen Plain. Bio15, bio03, bio01, and clay content are the environmental variables affecting the distribution. In general, the future potential distribution is expected to show an increasing trend. However, the species is expected to become threatened as carbon emission scenarios and years increase gradually. At worst, the high suitability area is expected to disappear completely under SSP585-2090s. Combined with the t-test, this could be due to pressure from bio01. The migration trends of climate niche centroid are inconsistent and do not all move to higher latitudes under different carbon emission scenarios. Over the past 40 years, habitat quality in the current potential distribution has declined yearly, and natural habitat has gradually fragmented. Existing reserves protect only 9.52% of G. manshurica’s priority conservation area. To avoid extinction risk and increase the practicality of the results, we clarified the hotspot counties of priority protection area gaps and wild tending areas. These results can provide an essential reference and decision basis for effectively protecting G. manshurica under climate change.

Tilia amurensis is a national class II endangered plant in China. It plays an essential role in maintaining the stability of regional forest communities. Moreover, it is an essential economic tree species in Northeast Asia. In recent years, the impact of rapid climate change on the distribution and adaptability of plant populations has received increasing attention. However, there is still a knowledge gap in our understanding of the future distribution changes of this important species. In this study, we used the ensemble species distribution model to simulate the distribution of T. amurensis in China under different climate scenarios. In addition, we used Fragstats and Zonation software based on the result of the ensemble species distribution model and combining the multi-year land use data. Using this method, we can clarify the landscape pattern changes and priority protection areas of T. amurensis. The results showed that the suitable area of T. amurensis in China was mainly located in the northeast region. The area of forest habitat suitable for T. amurensis has gradually decreased, and the fragmentation degree has progressively increased over the past 40 years. Under the background of future climate change, the suitable area of T. amurensis could move progressively to high latitude and high altitude, and the total area could show an upward trend. However, the area of the high suitable area could decrease sharply with the increase of year and carbon emissions. Six environmental factors: altitude (Alt), precipitation in the warmest quarter (Bio18), mean temperature of the driest quarter (Bio09), min temperature of the coldest month (Bio06), temperature seasonality (Bio04), and isothermality (Bio03), play a crucial role in the spatial distribution of T. amurensis. The counties in Northeast China are the most suitable areas for protecting T. amurensis action, located in the southern Xiaoxing'an Mountains and northern Changbai Mountains counties. In addition, among the existing protected areas, Fenglin National Nature Reserve has the highest area of mandatory reserves. It is expected to become a preferred location for T. amurensis conservation actions. Our results can provide a helpful reference for the effective protection and sustainable utilization of T. amurensis under climate change.

Summary: Single-cell sequencing is a powerful technology to understand the heterogeneity of clinical biospecimens. Here, we present a protocol for obtaining single-cell suspension from neurofibromatosis type 1-associated nerve sheath tumors for transcriptomic profiling on the 10x platform. We describe steps for clinical sample collection, generation of single-cell suspension, and cell capture and sequencing. We then detail methods for integrative analysis, developmental Schwann cell trajectory building using bioinformatic tools, and comparative analysis. This protocol can be adapted for single-cell sequencing using mouse nerve tumors.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ObjectivePhellodendron amurense, a special species in Northeast Asia, is the source of the wild medicinal Phellodendri Amurensis Cortex, the second-level key protection in China. Because of its dual value of medicine and timber, it has been cut in large quantities, resulting in a sharp decline in wild resources. It has been listed as a national first-class rare tree species. Here, we aim to plan protection area and wild tending area for Chinese P. amurense in the context of climate change.MethodIn this study, based on the Biomod2 model, the main environmental factors affecting the distribution and the potentially suitable areas of the current and future were investigated. Furthermore, the correlation between the main environmental factors and the chemical components was determined by full subset regression. Habitat quality and landscape pattern change were determined by InVEST and Fragstats software based on the land use data in 1980, 2000, and 2020. Then, Zonation software was used to plan the priority protection and wild tending areas.ResultsThe results showed that in the future, the potential habitat of P. amurense will gradually move to the high latitude and high altitude areas in the northwest direction, and the high suitability area will decrease sharply. Since 1980, the habitat quality of P. amurense habitat has gradually deteriorated, and the fragmentation has gradually intensified. In the future, the central part of the Greater Khingan Mountains and the forest area of the Lesser Khingan Mountains will be the long-term stable sanctuary. Fengcheng City and Tonghua County are the most suitable for the wild tending areas.ConclusionThe existing nature reserve only contains 6.01% of the priority protection area, so we propose to expand the area to cover a larger proportion of the sanctuary and implement management and restoration plans to increase the suitability and connectivity. These results can support the protection action and provide a reference and scientific basis for further research, rational development, and utilization of P. amurense.

The phenomenon of blocking pipe would appear for a trailing suction hopper dredger (TSHD) rake arm pipe in the construction process. Thus, based on the theory of particle flow mechanics, a transient three-dimensional two-phase hydrodynamic and sediment mixture model was established in this paper. Besides, different particle sizes of sediment concentration and velocity in the piping in the rake arm of the law were analyzed to solve the problem of blocking pipe and the prevention of dredging to provide theoretical support. Then, a model predictive controller was designed to regulate the mudflow in the pipeline by controlling the mud pump speed and compared with the proportional-integral (PI) controller. According to the results, the particle size of sediment affects concentration distribution in the pipeline under the same construction conditions for the TSHD. Besides, the larger the particle size of the sediment, the more significant the difference in the sediment concentration distribution in the pipeline. Similarly, the flow velocity is another influencing factor behind the change in concentration distribution in the pipeline, the increase in the flow velocity will improve the uniformity of concentration distribution in the pipeline, and the critical velocity will maintain the concentration distribution within a reasonable range. In terms of transportation control, the designed predictive model controller is capable of reducing overshoot and shorten the time required for adjustment. To sum up, the research result not only provides a valuable reference for the theoretical analysis and a controller design of the pipeline transportation system in the TSHD but also verifies the feasibility of the computational fluid dynamics model used in the study of pipeline transportation mechanisms. HIGHLIGHTS A transient three-dimensional two-phase hydrodynamic and sediment mixture model was established.; Different particle sizes of sediment concentration and velocity in the piping in the rake arm of the law were analyzed to solve the problem of blocking the pipe and prevention of dredging.; A model predictive controller was designed to regulate the mudflow in the pipeline by controlling the mud pump speed.;

CoicisSemen is an important food product and traditional Chinese medicine (TCM) derived from the dried and mature seeds of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf. An increasing number of studies have investigated its use, either alone or in combination with other botanical drugs, to treat female reproductive system malignancies, and its pharmacological effects have been confirmed clinically. This review aims to provide an overview of Coicis Semen’s historical role in treating female reproductive system malignancies based on TCM theory, to summarize clinical trials results, and to analyze information pertaining to the main phytochemical components, pharmacokinetics, related anti-cancer pharmacological effects, and toxicology of Coicis Semen. Information on Coicis Semen was collected from internationally accepted scientific databases. Seventy-four clinical trials were identified that used Coicis Semen in combination with other Chinese medicine to treat female reproductive system malignancies, most of which demonstrated good anti-tumor efficacy and few adverse reactions. To date, more than 80 individual compounds have been isolated from this botanical drug. In terms of anti-tumor effects, Coix seed oil has been studied the most. Pharmacokinetic data suggest that the active ingredients in Coicis Semen are widely distributed after administration, and Coicis Semen and its active compounds play a beneficial role in treating female reproductive system malignancies. Mechanistically, the anti-cancer effects may be related to inhibition of tumor cell proliferation and promotion of apoptosis, inhibition of tumor angiogenesis, suppression of the chronic inflammatory microenvironment of tumors, modulation of immune function, and regulation of the female reproductive system. Most acute toxicity and genotoxicity studies have shown that Coicis Semen is non-toxic. However, the existing studies have many limitations, and the future research direction should emphasize 1) the relationship between drug concentration and pharmacological action as well as toxicity; 2) the structural modification or the synthesis of analogues led by the active ingredients of Coicis Semen to enhance pharmacological activities and bioavailability; 3) accurately revealing the anti-cancer pharmacological effects of Coicis Semen and its compounds through multi-omics technology. We hope that this review can determine future directions and inform novel drug development for treating female reproductive malignancies.

Abstract Background Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe 99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts. Methods The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated 99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software. Results The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated 99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group. Conclusion The liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

BackgroundAs a malignant digestive system tumor, pancreatic cancer has unique metabolic characteristics. In recent years, the study of pancreatic cancer metabolism is in full swing, which provides a new direction for the treatment of pancreatic cancer patients. However, there is no systematic report of pancreatic cancer metabolism. In this paper, bibliometrics and visualization methods were used to analyze the number of publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism articles, to summarize the research trends and predict research hotspots.MethodsWe searched, screened and downloaded articles on pancreatic cancer metabolism through the Web of Science Core Collection (WoSCC). Using CiteSpace, VOSviewer and Bibliometrix Package to analyze publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism to identify research trends and predict research hotspots.ResultsAccording to the inclusion and exclusion criteria, a total of 5,255 articles were retrieved during the period 1943-2022. The number of publications on pancreatic cancer metabolism is increasing year by year. The United States (n=1602, 30.49%), China (n=1074, 20.44%), and Italy (n=313, 5.96%) are the three countries with the largest number of publications and citations, and there is close cooperation between countries. LI J (n=55) is the most prolific author. FUDAN UNIV (n=348) is the most published institution. CANCERS (n=118), PLOS ONE (n=93), and CANCER RESEARCH (n=80) are the most popular journals in this field. “Nutriment-deficient environment”, “cancer chemoprevention” and “targeting cancer stem cell” are the main areas of focus. “immunotherapy”, “ferroptosis” and “targeted therapy” are hot keywords in recent years. Taking pancreatic cancer metabolism as an entry point to study the role of traditional Chinese medicine (TCM) mainly focuses on curcumin and resveratrol, lack of broader and deeper research on TCM.ConclusionsThe number of publications on pancreatic cancer metabolism has generally increased, and scholars have generally paid more attention to this field. “immunotherapy”, “ferroptosis” and “targeted therapy” are the current research hotspots. The in-depth study of pancreatic cancer metabolism will provide new ideas for the treatment of pancreatic cancer.

Saposhnikovia divaricata is an important economic medicinal plant in eastern Asia. It is the National Grade III Key Protected Wild Medicinal Plants in China. However, little is known about the effects of projected climate change on its adaptability and future distribution. In this study, we simulated the suitable area of S. divaricata under current (1970–2000) and four climate change scenarios (i.e., SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5) in 2050s (2041–2060), 2070s (2061–2080) and 2090s (2081–2100) using maximum entropy model (MaxEnt). The results demonstrated that temperature seasonality (Bio04), precipitation seasonality (Bio15), elevation (Ele), and isothermally (Bio03) were the most important environmental variables determining the distribution of S. divaricata. Under the current climate situation, the suitable areas were mainly located in Northeast China and North China, with a total area of 134.87 × 104km2. The grassland is the largest land use type in the suitable area of S. divaricata. The priority planting region of S. divaricata are located in the southwest of Heilongjiang and the northwest of Jilin Province. The wild tending region is located in the middle east of Inner Mongolia. Under the future climate scenarios, the suitable areas of S. divaricata showed increasing trends. SSP5-8.5 scenario would have the highest area growth, with 43.09 %, 61.15 %, and 62.11 % increase in the three periods (2050s, 2070s, and 2090s). In addition, the high latitude migration of the geometric center of the total suitable area is predicted. Our results could provide a reference for the conservation and sustainable development and utilization of this species in the future.

To define alterations early in tumor formation, we studied nerve tumors in neurofibromatosis 1 (NF1), a tumor predisposition syndrome. Affected individuals develop neurofibromas, benign tumors driven by NF1 loss in Schwann cells (SCs). By comparing normal nerve cells to plexiform neurofibroma (PN) cells using single-cell and bulk RNA sequencing, we identified changes in 5 SC populations, including a de novo SC progenitor–like (SCP-like) population. Long after Nf1 loss, SC populations developed PN-specific expression of Dcn, Postn, and Cd74, with sustained expression of the injury response gene Postn and showed dramatic expansion of immune and stromal cell populations; in corresponding human PNs, the immune and stromal cells comprised 90% of cells. Comparisons between injury-related and tumor monocytes/macrophages support early monocyte recruitment and aberrant macrophage differentiation. Cross-species analysis verified each SC population and unique conserved patterns of predicted cell-cell communication in each SC population. This analysis identified PROS1-AXL, FGF-FGFR, and MIF-CD74 and its effector pathway NF-κB as deregulated in NF1 SC populations, including SCP-like cells predicted to influence other types of SCs, stromal cells, and/or immune cells in mouse and human. These findings highlight remarkable changes in multiple types of SCs and identify therapeutic targets for PN.

Abstract Exosomes have been associated with chemoresistance in various cancers, but such a role in ovarian cancer is not yet clear. Here, using in vitro cell-based and in vivo mouse model experiments, we show that downregulation of O-GlcNAcylation, a key post-translational protein modification, promotes exosome secretion. This increases exosome-mediated efflux of cisplatin from cancer cells resulting in chemoresistance. Mechanistically, our data indicate that downregulation of O-GlcNAclation transferase (OGT) reduces O-GlcNAclation of SNAP-23. Notably, O-GlcNAcylation of SNAP-23 is vital for regulating exosome release in ovarian cancer cells. Reduced O-GlcNAclation of SNAP-23 subsequently promotes the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of SNAP-23, VAMP8, and Stx4 proteins. This enhances exosome release causing chemoresistance by increasing the efflux of intracellular cisplatin.

Abstract Although the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg–Nd–Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(d,l-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.

Remote sensing technology is widely used for the dynamic monitoring of Enteromorpha prolifera (EP) blooms due to its high temporal resolution and large scale monitoring. Recently, deep learning(DL) methods have been applied to EP analysis due to their excellent feature representation. However, EP information extraction methods based on DL from low-spatial-resolution satellite images are still immature. The main problems with such methods include the insufficiency of spectral and spatial feature learning in low-resolution satellite images, as well as the sample imbalance that DL-based neural networks face in EP information extraction. To solve the above problems, a neural network-based EP extraction method considering sample balance is proposed in this article and named EP rough-then-accurate extraction network. The method consists of two components: EP rough extraction, a strategy that attends to sample balance, and EP accurate extraction, a deep neural network based on one-dimensional convolutional neural network and bidirectional long short-term memory (Bi-LSTM), which fully considers the learned spectral information of each pixel and interpixel contextual dependencies. Geostationary Ocean Color Imager images with 500-m resolution were applied as the LR images in the experiments. The experimental results show that the proposed method has the capability to enhance adaptability in areas with different EP densities (achieving stable and excellent performance) and exhibits at least a 10% gain in F1-score and at least a 6% gain in IoU in extracting EP coverage information over other representative and traditional EP extraction methods in the Yellow Sea region.

Embryonal rhabdomyosarcoma (ERMS) is a childhood cancer with impaired myogenic differentiation despite the presence of myogenic transcription factors. Here, the authors show that CASZ1 directly regulates these myogenic factors and the loss of CASZ1 is due to RAS-MEK signaling in ERMS.

We address the determination of the time resolution for the 100 μm 4H-SiC PIN detectors fabricated by Nanjing University (NJU). The time response to β particles from a 90Sr source is investigated for the detection of the minimum ionizing particles (MIPs). We study the influence of different reverse voltages, which correspond to different carrier velocities and device sizes, and how this correlates with the detector capacitance. We determine a time resolution (94 ± 1) ps for a 100 μm 4H-SiC PIN detector. A fast simulation software, termed RASER (RAdiation SEmiconductoR), is developed and validated by comparing the waveform obtained from simulated and measured data. The simulated time resolution is (73 ± 1) ps after considering the intrinsic leading contributions of the detector to time resolution.

As an individual plant participating in the power market, the virtual power plant (VPP) is regarded as the ultimate configuration of the energy Internet, and effective dispatching is a challenge. This paper proposes a multi-agent optimal bidding strategy based on a self-adaptive global optimal harmony search algorithm (SGHSA) to solve the problem of multi-operator participation in virtual power station scheduling. The method takes multiple agents to simulate the bidding process in the VPPs and distributes the profits for the operators based on the market mechanism to optimize the distributed energy resources (DERs). Case studies are provided and show that the proposed method realizes the optimal distribution of power generation and demand level, which improves the comprehensive advantage of the VPP in electricity market transactions.

This article firstly structures a detailed combustion reaction mechanism including methane N-butanol nitrogen oxide. According to two-stroke low-speed diesel engine’s parameter with the characteristics of engine firing, homogeneous charge compression ignition is selected as simulation model. At the same the output power and the excess air coefficient is 1.5, by means of the simulation calculation and analysis of reaction path and reaction mechanism, when N-butanol and methane are mixed in different proportions, the exhaust temperature in the reactor reduces with the increase of methane proportion in reactants. At the same time NO mole fraction increases with the proportion of CH4 in the mixed fuel decreases, but the NO2 mole fraction will increase with the proportion of CH4 in the mixed fuel increases.

Abstract Ethanol is an oxygen‐containing renewable clean fuel. The use of ethanol in engines can reduce greenhouse emissions and pollutant emissions of NOx and soot. However, ethanol has limited solubility in diesel fuel. Polyoxymethylene dimethyl ethers (PODE) can improve the miscibility and cetane number of ethanol‐diesel blend. To evaluate the solubilizing ability of PODE on the mixture of ethanol and diesel, the phase behavior of the ternary system (PODE, anhydrous ethanol, and diesel) was investigated at different ambient temperatures. Additionally, the blend can easily absorb water from ambient humidity because of the additional ethanol, which may cause phase separation. Thus, the effect of water addition on the phase behavior of the system was studied. In the current study, the blend of ethanol (100%, 98%, 95% purity) and diesel fuel was used as a solute with different diesel blending ratios. Then, PODE was gradually added into blend until phase boundaries of ternary system appeared. Results show that the ability of PODE in the blend is greatly affected by ambient temperature, particularly above 10°C. The addition of water greatly destroys the phase stability of the ternary system and increases demand for PODE due to the hydrophobicity of diesel.

One of the most common malignancies affecting adults with Neurofibromatosis type 1 (NF1) is the malignant peripheral nerve sheath tumor (MPNST), an aggressive and often fatal sarcoma that commonly arises from benign plexiform neurofibromas. Despite advances in our understanding of MPNST pathobiology, there are few effective therapeutic options, and no investigational agents have proven successful in clinical trials. To further understand the genomic heterogeneity of MPNST, and to generate a preclinical platform that encompasses this heterogeneity, we developed a collection of NF1-MPNST patient-derived xenografts (PDX). These PDX were compared with the primary tumors from which they were derived using copy number analysis, whole exome sequencing, and RNA sequencing. We identified chromosome 8 gain as a recurrent genomic event in MPNST and validated its occurrence by FISH in the PDX and parental tumors, in a validation cohort, and by single-cell sequencing in the PDX. Finally, we show that chromosome 8 gain is associated with inferior overall survival in soft-tissue sarcomas. These data suggest that chromosome 8 gain is a critical event in MPNST pathogenesis and may account for the aggressive nature and poor outcomes in this sarcoma subtype.

BackgroundPuerto Rican adults have higher odds of peripheral artery disease (PAD) compared with Mexican Americans. Limited studies have examined relationships between clinical risk assessment scores and ABI measures in this population.MethodsUsing 2004-2015 data from the Boston Puerto Rican Health Study (BPRHS) (n = 370-583), cross-sectional, 5-y change, and patterns of change in Framingham Risk Score (FRS) and allostatic load (AL) with ankle brachial index (ABI) at 5-y follow-up were assessed among Puerto Rican adults (45-75 y). FRS and AL were calculated at baseline, 2-y and 5-y follow-up. Multivariable linear regression models were used to examine cross-sectional and 5-y changes in FRS and AL with ABI at 5-y. Latent growth mixture modeling identified trajectories of FRS and AL over 5-y, and multivariable linear regression models were used to test associations between trajectory groups at 5-y.ResultsGreater FRS at 5-y and increases in FRS from baseline were associated with lower ABI at 5-y (β = -0.149, P = 0.010; β = -0.171, P = 0.038, respectively). AL was not associated with ABI in cross-sectional or change analyses. Participants in low-ascending (vs. no change) FRS trajectory, and participants in moderate-ascending (vs. low-ascending) AL trajectory, had lower 5-y ABI (β = -0.025, P = 0.044; β = -0.016, P = 0.023, respectively).ConclusionsFRS was a better overall predictor of ABI, compared with AL. Puerto Rican adults, an understudied population with higher FRS over 5 years, may benefit from intensive risk factor modification to reduce risk of PAD. Additional research examining relationships between FRS and AL and development of PAD is warranted.

Abstract Background Liver is the crucial organ as a hub for metabolic reactions. p16(INK4a) is a well-established cyclin-dependent kinase (CDK) inhibitor that plays important role in the molecular pathways of senescence, which lead to irreversible cell cycle arrest with secretion of proinflammatory cytokines and mitochondrial dysfunction. This study tested the hypothesis that cellular senescence regulated by p16(INK4a) is associated with high-fat diet in adult male rats. Methods Sprague Dawley rats were fed a high-fat (HF) diet or a control (C) diet for 9 weeks after weaning. At 12 weeks of age, liver samples of male rats were collected to investigate the key genes and liver physiological status. Results Both mRNA and protein expression level of cellular senescence marker, p16(INK4a), was increased significantly in HF group when compared to C group. A decrease of tri-methylated histone H3 lysine 27 (H3K27Me3) in the coding region of p16(INK4a) was observed. On the other hand, mRNA and protein expression of another inhibitor of cyclin-dependent kinase, p21(Cip1), was decreased significantly in HF group; however, no significant chromatin modification was found in this gene. Histological analysis demonstrated hepatic steatosis in HF group as well as severe fat accumulation. Conclusions Our study demonstrated that HF diet regulated cellular senescence marker p16(INK4a) through chromatin modifications, which may promote hepatic fat accumulation and steatosis.

To meet the high radiation challenge for detectors in future high-energy physics, a novel 3D 4H-SiC detector was investigated. Three-dimensional 4H-SiC detectors could potentially operate in a harsh radiation and room-temperature environment because of its high thermal conductivity and high atomic displacement threshold energy. Its 3D structure, which decouples the thickness and the distance between electrodes, further improves the timing performance and the radiation hardness of the detector. We developed a simulation software—RASER (RAdiation SEmiconductoR)—to simulate the time resolution of planar and 3D 4H-SiC detectors with different parameters and structures, and the reliability of the software was verified by comparing the simulated and measured time-resolution results of the same detector. The rough time resolution of the 3D 4H-SiC detector was estimated, and the simulation parameters could be used as guideline to 3D 4H-SiC detector design and optimization.

Abstract Background Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. Methods Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1–F3 generations were fed only the control diet. Results Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p

Background. Sugar-sweetened beverage (SSB) consumption is highly associated with obesity, but the metabolic mechanism underlying this correlation is not understood. Objective. Our objective was to examine metabolomic links between SSB intake and obesity to understand metabolic mechanisms. Design. We examined the association of plasma metabolomic profiles with SSB intake and obesity risk in 781 participants, aged 45–75 y, in the Boston Puerto Rican Health Study (BPRHS) using generalized linear models, controlling for potential confounding factors. Based on identified metabolites, we conducted pathway enrichment analysis to identify potential metabolic pathways that link SSB intake and obesity risk. Variants in genes encoding enzymes known to function in identified metabolic pathways were examined for their interactions with SSB intake on obesity. Results. SSB intake was correlated with BMI (β = 0.607, P=0.045). Among 526 measured metabolites, 86 showed a significant correlation with SSB intake and 148 with BMI (P≤0.05); 28 were correlated with both SSB intake and BMI (P≤0.05). Pathway enrichment analysis identified the phosphatidylcholine and lysophospholipid pathways as linking SSB intake to obesity, after correction for multiple testing. Furthermore, 8 of 10 genes functioning in these two pathways showed strong interaction with SSB intake on BMI. Our results further identified participants who may exhibit an increased risk of obesity when consuming SSB. Conclusions. We identified two key metabolic pathways that link SSB intake to obesity, revealing the potential of phosphatidylcholine and lysophospholipid to modulate how SSB intake can increase obesity risk. The interaction between genetic variants related to these pathways and SSB intake on obesity further supports the mechanism.