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Abstract Osteosarcoma (OS) is the most common primary malignant tumour of the bone with high mortality. Here, we comprehensively analysed the hypoxia signalling in OS and further constructed novel hypoxia-related gene signatures for OS prediction and prognosis. This study employed Gene Set Enrichment Analysis (GSEA), Weighted correlation network analysis (WGCNA) and Least absolute shrinkage and selection operator (LASSO) analyses to identify Stanniocalcin 2 (STC2) and Transmembrane Protein 45A (TMEM45A) as the diagnostic biomarkers, which further assessed by Receiver Operating Characteristic (ROC), decision curve analysis (DCA), and calibration curves in training and test dataset. Univariate and multivariate Cox regression analyses were used to construct the prognostic model. STC2 and metastasis were devised to forge the OS risk model. The nomogram, risk score, Kaplan Meier plot, ROC, DCA, and calibration curves results certified the excellent performance of the prognostic model. The expression level of STC2 and TMEM45A was validated in external datasets and cell lines. In immune cell infiltration analysis, cancer-associated fibroblasts (CAFs) were significantly higher in the low-risk group. And the immune infiltration of CAFs was negatively associated with the expression of STC2 (P

Abstract Serious solvation effect of zinc ions has been considered as the cause of the severe side reactions (hydrogen evolution, passivation, dendrites, and etc.) of aqueous zinc metal batteries. Even though the regulation of cationic solvation structure has been widely studied, effects of the anionic solvation structures on the zinc metal were rarely examined. Herein, co-reconstruction of anionic and cationic solvation structures was realized through constructing a new multi-component electrolyte (Zn(BF4)2-glycerol-boric acid-chitosan-polyacrylamide, simplified as ZGBCP), which incorporates double crosslinking network via the esterification, protonation and polymerization reactions, thereby combining multiple advantages of ‘liquid-like’ high conductivity, ‘gel-like’ robust interface, and ‘solid-like’ high Zn2+ transfer number. Based on the ZGBCP electrolyte, the Zn anodes achieve record-low polarization and stable cycling. Furthermore, the ZGBCP electrolyte renders the AZMBs ultrawide working temperature (−50 °C ~ +100 °C) and ultralong cycle life (30000 cycles), which further validates the feasibility of the dual solvation structure strategy and provides a innovative perspective for the development of high-performance AZMBs.

MOX (mixed oxide) fuel plays a positive role in promoting sustainable development in nuclear energy. The quantitative determination of plutonium in mixed MOX fuel is also essential to nuclear security and safeguards. In this regard，neutron multiplicity measurement methods serve as crucial non-destructive testing techniques and play a vital role in quantitatively detecting plutonium in MOX fuel. In order to study the factors that influence the quantification process of plutonium，enhance measurement accuracy，and streamline the process，this study develops a comprehensive and specific simulation system for the multiplicity-based plutonium quantification method in MOX fuel. Based on the AWCC device as the basic model (simulation model with a detection efficiency of 23.89% and a die-away time of 45.42 μs)，the combination of MCNP and MATLAB software is utilized to recombine the detector capture times of fission neutrons and (α，n) neutrons obtained from MCNP software with the particle emission time series obtained by MATLAB sampling，forming a complete pulse time series. After receiving the multiplicity moments of fission neutrons in MOX fuel (vs1=2.157，vs2=3.808，vs3=5.283，vi1=2.855，vi2=6.953，vi3=13.899)，simulated pulse sequence acquisition，multiplicity analysis，and quantitative calculation are performed on four samples with different shapes and sizes. Each sample is measured for 300 s with a pre-delay time of 3 μs，a gate width of 54 μs，a long delay of 2 ms，and repeated three time’s measurements. Additionally，the simulated quantitative calculation results 240Pu are compared with the set values. The results indicate that the mass of 240Pu and the α-value obtained through simulated pulse analysis meet the requirement of less than 5% relative error compared to the actual input values. This work provides technical support for data interpretation in the quantitative measurement of plutonium in MOX fuel.

Abstract While proposing dual carbon strategy goals, research on carbon reduction in integrated energy systems (IESs) has become a focus of attention. Traditional IES carbon emission flow is mostly based on energy flow, without considering the differences in energy quality. Exergy can be used as a reasonable measure of energy quality. Combining the theory of exergy flow and carbon emission flow, a modeling and analysis method for IES carbon emission flow considering energy quality is proposed. First, exergy flow models for electric and natural gas systems, equivalent exergy flow models for heat systems, and exergy hub models are introduced. Afterward, the exergy branch losses are allocated to the nodes at both ends. A networked modeling method for the carbon emission flow of energy stations is proposed. A unified matrix calculation model for IES carbon emission flow considering energy quality is established. On this basis, an IES carbon emission flow calculation method considering energy quality is proposed. Finally, this method is applied to the test IES, and the results show that the carbon emission flow calculation results reflect the distribution of carbon emissions borne by the effective energy supplied by the source and consumed by the load in the system, taking into account both the quantity and quality of energy. The reasonable allocation of new energy is conducive to synchronously improving the energy efficiency, exergy efficiency, and cleanliness of the system.

The large amount of source and load uncertainty in new power systems poses challenges to the optimization of power supply and demand balance. The traditional optimization methods have not fully considered the uncertainty characteristics of different sources and loads. In this regard, a supply–demand balance optimization method based on ISAO-BiTCN-BiGRU-SA-IPBLS is proposed. Firstly, the ISAO algorithm is introduced into the hyperparameter optimization of BiTCN-BiGRU-SA, and the source and load interval prediction method based on LINMAP selection is proposed. Afterwards, a multi-objective optimization method for power supply and demand balance based on two-stage robust optimization is proposed. The first stage takes the daily planned output of adjustable power sources as the optimization variable, with daily operating cost, renewable energy delivery rate, and maximum loss in extreme scenarios as the optimization objectives. The second stage takes the daily operation of energy storage as the optimization variable and minimizes the maximum loss in the extreme scenario as the optimization objective. Finally, the method is applied to the county-level new power system in Hunan Province, China. The results show that the MAPE of the load and PV point prediction results in this work decreases by 13.43 % and 16.93 % after introducing the ISAO, respectively. Compared with the traditional Gaussian method, the Euclidean distance of error indicators between the load/PV interval prediction results in this work and the ideal results at an 85 % confidence interval decreases by 53.19 %/100 %. Compared with the traditional optimization method only considering economy, the work’s method improves the renewable energy delivery rate by 0.10 and 0.02 respectively, and reduces the maximum loss in extreme scenarios by 76.75 % and 3.62 % respectively on the maximum load day and maximum renewable energy output day.

Chinese bayberry residue (CBR) is a by-product of processing, which can be used as an auxiliary material during the processing of quinoa rice wine. In this study, the effects of CBR on the chemical profile, bioactive function, taste traits, and flavor of Chinese quinoa rice wine (CQRW) were investigated. The results showed that adding CBR increased the total phenolics, the total flavonoids, and antioxidant capacity. Malic acid content was the highest in Chinese rice wine (CRW), while the total content of components detected in HPLC-MS/MS was the highest in 10%CBR + CQRW. The CQRW exhibited the highest amino acid content, followed by 20%CBR + CQRW. E-tongue analysis results showed that 10%CBR + CQRW, 20%CBR + CQRW, and CQRW had the closest taste traits. Moreover, GC–MS analysis identified 72 aroma compounds in 10%CBR + CQRW sample, more than other samples. In summary, adding 10% CBR significantly improved the quality of CQRW.

Abstract Background Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. Methods Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. Results The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063–1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008–1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. Conclusions Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.

This study aims to address the challenges associated with information exchange during the design and construction phases of prefabricated buildings. To overcome these obstacles, we developed a web-based Smart Collaboration System(SCS), which was inspired by Massively Multiplayer Onlinen Role-playing Game (MMORPG) technology. The methodology employed in this study involves a comprehensive literature review, the development of a prototype system, and the application of this system. The study’s results demonstrate that the utilization of MMORPG-based collaboration system improves efficiency in the design and construction process. And compared to conventional systems, the MMORPG-based system developed in this study exhibits a few key distinctions. Firstly, individual stakeholder roles are explicitly designated, enabling more efficient collaborative exchange of design and construction information. Secondly, the system effectively bridges the gap between project stages, such as design to production and production to construction. Lastly, the system introduces an element of enjoyment to the design, production, and construction process, which is typically absent in existing commercial software developers’ offerings. This research contributes to the advancement of collaborative design and construction methods by leveraging the MMORPG-based technology, and provides valuable insights for industry professionals and researchers seeking to improve collaboration and optimize the design and construction process.

Background Malignant melanoma, a highly aggressive skin cancer, has remarkable incidence and mortality nowadays. This study aims to explore prognostic factors associated with nonmetastatic cutaneous melanoma of the limbs and to develop nomograms for predicting overall survival (OS) and cancer-specific survival (CSS).Methods The study cohort was derived from the Surveillance, Epidemiology, and End Results database. Univariate Cox regression, Lasso regression, and multivariate Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The receiver operating characteristic (ROC) curve, time-dependent C-index, calibration curve, decision curve analysis (DCA) and Kaplan-Meier method were used to evaluate the accuracy and clinical applicability of the nomograms.Results A total of 15,606 patients were enrolled. Multivariate analysis identified several prognostic factors for OS and CSS including age, sex, histologic type, N stage, tumor thickness, depth of invasion, mitotic rate, ulceration, surgery of primary site, systemic therapy, race, and number of lymph nodes examined. A nomogram incorporating 12 independent predictors for OS was developed, with a C-index of 0.866 (95% confidence interval [CI]: 0.858–0.874) in the training cohort and 0.853 (95% CI: 0.839–0.867) in validation. For CSS, 10 independent predictors and one related factor were included, yielding a C-index of 0.913 (95% CI: 0.903–0.923) in the training cohort and 0.922 (95% CI: 0.908–0.936) in validation. The ROC curve, time-dependent C-index, calibration curve, DCA, and K-M plot demonstrated favorable discrimination, calibration, and clinical utility.Conclusion The developed nomograms provide a precise and personalized predictive tool for risk management of patients with nonmetastatic limb melanoma.

The medium and long-term supply-demand imbalance of the power system in the context of the new power system is becoming more and more prominent due to the fluctuation and intermittency brought about by the high proportion of new energy sources connected to the grid. In this regard, a multi-objective power supply-demand balance optimization method considering the spatiotemporal correlation of source and load is proposed in this work. First, the autocorrelation and inter-correlation characteristics of source and load are analyzed. On this basis, a multi-dimensional scenario set construction method considering the spatiotemporal correlation of source and load is proposed. Then, the planning capacity of each regional power source and the system operation under each scenario are taken as the optimization variables. Renewable energy electricity curtailment, equivalent annual total cost, and inter-region transmission electricity are taken as the optimization objectives. Various constraints such as power source planning and operation, power balance, inter-region power transmission, and renewable energy power curtailment rate are considered comprehensively. The optimization method for the medium and long-term power supply and demand balance is proposed. Finally, the method is applied to Hunan Province, China to guide power planning. The results show that compared with traditional multi-dimensional correlation scene construction methods, the average probability density functions error of wind turbine output, photovoltaic output, and load constructed in this work decrease by 44.08 %, 73.64 %, and 57.54 %, respectively. It takes into account the regional, temporal, temporal autocorrelation, and inter-correlation of the source and load, and has similar characteristics to historical data. Compared with traditional planning that only considers economy, the optimization plan for power supply and demand balance in this work reduces electricity curtailment and inter-region transmission by 97.04 % and 72.71 %, respectively, balancing renewable energy consumption, economy, and regional independent balancing indicators.

ABSTRACT: Fowl adenovirus serotype 4 (FAdV-4) infections result in substantial economic losses in the poultry industry. Recent findings have revealed that FAdV-4 significantly suppresses the host immune response upon infection; however, the specific viral and host factors contributing to this immunomodulatory activity remain poorly characterized. Moreover, diverse cell types exhibit differential immune responses to FAdV-4 infection. To elucidate cell-specific host responses, we performed transcriptomic analysis of FAdV-4 infected leghorn male hepatocellular (LMH) and chicken embryo fibroblast (CEF) cells. Although FAdV-4 replicated more efficiently in LMH cells, it provoked limited interferon-stimulated gene induction. In contrast, FAdV-4 infection triggered robust antiviral responses in CEF cells, including upregulation of cytosolic DNA sensing and interferon-stimulated genes. Knockdown of key cytosolic DNA sensing molecules enhanced FAdV-4 replication in LMH cells while reducing interferon-stimulated gene expression. Our findings reveal cell-specific virus-host interactions that provide insight into FAdV-4 pathogenesis while identifying factors that mediate antiviral immunity against FAdV-4.

Background: China is confronted with the significant menace posed by hemorrhagic fever with renal syndrome (HFRS). Nevertheless, the long-term spatial-temporal variations, regional prevalence patterns, and fundamental determinants' mechanisms for HFRS remain inadequately elucidated. Methods: Newly diagnosed cases of HFRS from January 2004 to December 2019 were acquired from the China Public Health Science Data repository. We used Age-period-cohort and Bayesian Spacetime Hierarchy models to identify high-risk populations and regions in mainland China. Additionally, the Geographical Detector model was employed to quantify the determinant powers of significant driver factors to the disease. Results: A total of 199,799 cases of HFRS were reported in mainland China during 2004–2019. The incidence of HFRS declined from 1.93 per 100,000 in 2004 to 0.69 per 100,000 in 2019. The incidence demonstrated an inverted U-shaped trend with advancing age, peaking in the 50–54 age group, with higher incidences observed among individuals aged 20–74 years. Hyperendemic areas were mainly concentrated in the northeastern regions of China, while some western provinces exhibited a potential upward trend. Geographical detector model identified that the spatial variations of HFRS were significantly associated with the relative humidity (Q = 0.36), forest cover (Q = 0.26), rainfall (Q = 0.18), temperature (Q = 0.16), and the surface water resources (Q = 0.14). Conclusions: This study offered comprehensive examinations of epidemic patterns, identified high-risk areas quantitatively, and analyzed factors influencing HFRS transmission in China. The findings may contribute to the necessary implementations for the effective prevention and control of HFRS.

Flexible photodetector is crucial for the intelligent industrial applications. However, the optical-sensitive materials are usually grown in a high temperature and then transferred onto the flexible substrate. This paper reported a directly fabricated flexible photodetector based on TiO2-doped Graphene Nanosheets Embedded Carbon (GNEC)film. An Electron Cyclotron Resonance (ECR) system was employed to in-situ deposit TiO2-doped GNEC film on a polyimide substrate, which were subsequently sensitized with N719 dye to fabricate the TiO2@GNEC photodetector. The GNEC film contains vertically aligned Graphene Nanosheets (GNs), which exhibit high-density edge states. The edge states suppress the recombination rate of photo-generated electron-hole pairs, thereby significantly enhancing the photo-responsive performance. The photodetector demonstrates a high photo responsivity of 0.82 mA/W and a response time of 1.93 seconds. Due to the in-situ manufacturing capabilities of the ECR system, which avoids defects from secondary material transfers, the photodetector array exhibits excellent consistency and achieves clear recognition of light patterns in both flat and bent states.

Under the heterogeneous situation of heterogeneity of farmland circulation entities, transaction costs are the key factors to optimize the selection of circulation contracts, and reducing transaction costs is an important realization path to promote farmland circulation in a reasonable and orderly manner and accelerate the process of agricultural modernization. Based on the survey data of 814 farming households in Henan Province, this study explores the transaction costs on contract selection based on the differential order governance. The results show that (a) in the transfer of farmland, farmers’ choice of contracts is restricted by their degree of association with the transaction entity, which is the result of differential order governance. (b) The influence of differential order governance on the selection of transfer contracts is constrained by the governance context. Farmers tend to choose formal written contracts in the context of weak ties governance but choose verbal or informal contracts under strong relationship governance. (c) The impact of transaction costs on the selection of farmland transfer contracts is constrained by the three-stage scenarios as before, during, and after the transaction. In different transaction stages, the higher the transaction costs are, the more likely farmers are to choose a formal written contract. The findings show the importance of the rules of human relations in the society of acquaintances in saving transaction costs. The importance of the formal system and informal institutions, such as trust and reputation, and avoiding one-size-fits-all suggestions should be involved in the formulation and implementation of farmland transfer policies.

Abstract BackgroundRates of suicide have increased by over 35% since 1999. Despite concerted efforts, our ability to predict, explain, or treat suicide risk has not significantly improved over the past 50 years. ObjectiveThe aim of this study was to use large language models to understand natural language use during public web-based discussions (on Reddit) around topics related to suicidality. MethodsWe used large language model–based sentence embedding to extract the latent linguistic dimensions of user postings derived from several mental health–related subreddits, with a focus on suicidality. We then applied dimensionality reduction to these sentence embeddings, allowing them to be summarized and visualized in a lower-dimensional Euclidean space for further downstream analyses. We analyzed 2.9 million posts extracted from 30 subreddits, including r/SuicideWatch, between October 1 and December 31, 2022, and the same period in 2010. ResultsOur results showed that, in line with existing theories of suicide, posters in the suicidality community (r/SuicideWatch) predominantly wrote about feelings of disconnection, burdensomeness, hopeless, desperation, resignation, and trauma. Further, we identified distinct latent linguistic dimensions (well-being, seeking support, and severity of distress) among all mental health subreddits, and many of the resulting subreddit clusters were in line with a statistically driven diagnostic classification system—namely, the Hierarchical Taxonomy of Psychopathology (HiTOP)—by mapping onto the proposed superspectra. ConclusionsOverall, our findings provide data-driven support for several language-based theories of suicide, as well as dimensional classification systems for mental health disorders. Ultimately, this novel combination of natural language processing techniques can assist researchers in gaining deeper insights about emotions and experiences shared on the web and may aid in the validation and refutation of different mental health theories.

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.

Summary: Background: Non-optimum temperatures are associated with a considerable mortality burden. However, evidence of temperature with all-cause and cause-specific hospital admissions in tropical countries like Thailand is still limited. Methods: Daily all-cause and cause-specific hospital admissions for outpatient and inpatient visits were collected from 77 provinces in Thailand from January 2013 to August 2019. A two-stage time-series approach was applied to assess the association between non-optimum temperatures and hospital admission. We first fitted the province-specific temperature-morbidity association and then obtained the national association in the second stage using a random-effects meta-analysis regression. The attributable fraction (AF) of hospital admissions with 95% empirical confidence interval (eCI) was calculated. Findings: A total of 878,513,460 all-cause outpatient admissions and 32,616,600 all-cause inpatient admissions were included in this study. We observed a J-shaped relationship with the risk of hospital admissions increasing for both cold and hot temperatures. The overall AFs of all-cause hospital admissions due to non-optimum temperatures were 7.57% (95% eCI: 6.47%, 8.39%) for outpatient visits and 6.17% (95% eCI: 4.88%, 7.20%) for inpatient visits. Hot temperatures were responsible for most of the AFs of hospital admissions, with 6.71% (95% eCI: 5.80%, 7.41%) for outpatient visits and 4.50% (95% eCI: 3.62%, 5.19%) for inpatient visits. The burden of hospital admissions was greater in females and in children and adolescents (0–19 years). The fractions of hospital admissions attributable to non-optimum temperatures exhibited variation among disease categories and geographical areas. Interpretation: The results indicate that low and high temperature has a significant impact on hospital admissions, especially among the females, and children and adolescents (0–19 years). The current investigation could provide evidence for policymakers to develop adaptation strategies and mitigate the adverse effects of climate change on public health in Thailand and other tropical countries. Funding: National Research Council of Thailand (NRCT): E-Asia Joint Research Program: Climate change impact on natural and human systems (N33A650979).

In order to achieve low-carbon optimization in the intelligent mix ratio design of concrete materials, this work first constructs a concrete mix ratio database and performs a statistical characteristics analysis. Secondly, it employs a standard back propagation (BP) and a genetic algorithm-improved BP (GA-BP) to predict the concrete mix ratio. The NSGA-II algorithm is then used to optimize the mix ratio. Finally, the method’s accuracy is validated through experiments. The study’s results indicate that the statistical characteristics of the concrete mix ratio data show a wide distribution range and good representativeness. Compared to the standard BP, the fitting accuracies of each GA-BP set are improved by 4.9%, 0.3%, 16.7%, and 4.6%, respectively. According to the Fast Non-Dominated Sorting Genetic Algorithm II (NSGA-II) optimization for meeting C50 concrete strength requirements, the optimal concrete mix ratio is as follows: cement 331.3 kg/m3, sand 639.4 kg/m3, stone 1039 kg/m3, fly ash 56 kg/m3, water 153 kg/m3, and water-reducing agent 0.632 kg/m3. The 28-day compressive strength, material cost, and carbon emissions show relative errors of 2.1%, 0.6%, and 2.9%, respectively. Compared with commercial concrete of the same strength grade, costs and carbon emissions are reduced by 7.2% and 15.9%, respectively. The methodology used in this study not only significantly improves the accuracy of concrete design but also considers the carbon emissions involved in the concrete preparation process, reflecting the strength, economic, and environmental impacts of material design. Practitioners are encouraged to explore integrated low-carbon research that spans from material selection to structural optimization.

Timber–concrete composite structure is a type of efficient combination form composed of concrete floors and timber beams or floors through shear connectors, and shows good application potential in the floor system of timber buildings. The long-term performance of the timber–concrete composite structures is complex and is affected by the creep of timber and concrete, as well as the long-term slip of the shear connectors. This article presents a comprehensive overview of the research status on the long-term behavior of timber–concrete composite members and different shear connectors. For the shear connectors, the effects of loading levels, environments, and component materials on their creep coefficients are summarized. As to the timber–concrete composite members, both the experimental and numerical investigations are gathered into discussions: the connection types, component materials, loading conditions, and durations in the long-term tests are also discussed; various models for describing long-term behavior of timber, concrete, and connection systems are provided, and then a comprehensive description of the progress of numerical investigations over the last decades is made. In addition, the suggestions for future research are proposed to reach a clearer understanding of the bending mechanisms and mechanical characteristics of timber–concrete composite structures.

Abstract A novel bone-inspired fatigue-resistant hydrogel with excellent mechanical and piezoresistive properties was developed, and it exhibited great potential as a load and strain sensor for underwater robotics and daily monitoring. The hydrogel was created by using the high edge density and aspect ratio of graphene nanosheet-embedded carbon (GNEC) nanomaterials to form a three-dimensional conductive network and prevent the expansion of microcracks in the hydrogel system. Multiscale progressive enhancement of the organic hydrogels (micrometer scale) was realized with inorganic graphene nanosheets (nanometer scale). The graphene nanocrystals inside the GNEC film exhibited good electron transport properties, and the increased distances between the graphene nanocrystals inside the GNEC film caused by external forces increased the resistance, so the hydrogel was highly sensitive and suitable for connection to a loop for sensing applications. The hydrogels obtained in this work exhibited excellent mechanical properties, such as tensile properties (strain up to 1685%) and strengths (stresses up to 171 kPa), that make them suitable for use as elastic retraction devices in robotics and provide high sensitivities (150 ms) for daily human monitoring.

The quality of the habitats and ecosystem services are significantly impacted by ecological land fragmentation brought on by human activities. However, the specific driving mechanism of the ecological land comprehensive landscape fragmentation on the habitat quality is still unclear. This study took the cities of Suzhou, Wuxi, and Changzhou along the Taihu Lake basin as its research region. The spatiotemporal variations in habitat quality and their relationship with the ecological land comprehensive landscape fragmentation were explored by the land-use dynamic rate, land-use transfer matrix, comprehensive landscape fragmentation indices, the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) habitat quality model, and the Geographically and Temporally Weighted Regression (GTWR) model during the 2000–2020 period. The findings revealed that: (1) On the whole, the ecological land area rose, and the northern and eastern areas of the research region had the greatest transformations in land use/land cover (LULC). (2) Within the research region in the study period, the ecological land comprehensive landscape fragmentation index showed a fluctuating growth trend, and there were regions with large areas of high value clustered. (3) In the 2000–2020 period, the habitat quality as a whole deteriorated, with more concentrated habitat degradation seen around the woodland and construction land. (4) Numerous factors contributed to the regional and temporal changes in habitat quality and the effect of ecological land comprehensive landscape fragmentation on the quality of its habitats varied between regions. These findings could provide theoretical guidance for ecological land protection, habitat quality improvement, and ecosystem restoration in areas with similar environments.

Mycoplasma synoviae (M. synoviae) is one of the major poultry pathogens causing infectious synovitis, airsacculitis, a high incidence of shell breakage, and egg production loss. However, the pathogenesis of M. synoviae remains unclear. Adhesion of mycoplasmas to host cells is a crucial step in infection and colonization. The purpose of this study was to determine the adhesive function of a putative P80 family lipoprotein (LP78) and evaluate its application in the detection of antibodies against M. synoviae. Recombinant LP78 (rLP78) was expressed in the supernatant component of Escherichia coli and mouse anti-rLP78 serum was prepared. Bioinformatic analysis and western blotting results revealed that LP78 was conservative among M. synoviae strains. It was distributed not only in the cytoplasm but also on the membrane of M. synoviae through western blotting and indirect immunofluorescence (IFA). The adherence of M. synoviae to DF-1 cells was significantly inhibited by mouse anti-rLP78 serum (p

Key factors for assessing the high-temperature resistance of coal gangue concrete are high-temperature residual strength and thermal properties. The high-temperature residual strength, high-temperature thermal conductivity, high-temperature specific heat capacity, and high-temperature density of concrete with various coal gangue coarse aggregate replacement ratios were tested using experimental methods in this paper to study the high-temperature resistance of coal gangue concrete. Thermal density and high-temperature residual strength tests took into account influencing factors like the water-cement ratio (0.50, 0.45, 0.40), aggregate replacement ratio (0, 25 %, 50 %, 75 %, 100 %), and temperature variation (room temperature, 200 °C，300 °C，400 °C，500 °C，600 °C，700 °C，800 °C), while thermal properties tests considered the effects of various coarse aggregate replacement ratios and temperatures. The study showed that when the temperature rises, coal gangue concrete's thermal density falls, mass loss rises, residual strength declines, thermal conductivity rises, and its specific heat capacity fluctuates. At temperatures between 20 °C and 400 °C, concrete's residual strength decreases with an increase in the coal gangue coarse aggregate replacement ratio, while thermal conductivity and specific heat capacity increase. At temperatures between 500 °C and 800 °C, however, concrete's residual strength slightly improves with an increased coal gangue coarse aggregate replacement ratio, while mass loss changes more. The research finally provides the formulae for calculating the high-temperature residual strength and thermal properties of coal gangue concrete based on the test results.

Abstract GSK3640254 (GSK'254) is a novel HIV‐1 maturation inhibitor with pharmacokinetics supporting once‐daily (QD) therapy for HIV‐1 treatment. This thorough QT/corrected QT (QTc) study evaluated the effect of GSK'254 on cardiac repolarization. In this two‐part, randomized study, healthy participants received GSK'254 or placebo QD for 7 days (part 1) to determine safety and pharmacokinetics of a 500‐mg supratherapeutic dose. Four sequential treatment periods composed the main QTc study (part 2): GSK'254 100 mg, GSK'254 500 mg, placebo QD for 7 days, or placebo QD for 6 days with a 400‐mg moxifloxacin dose on Day 7 (all with a moderate‐fat meal). Concentration‐QTc analyses modeled the relationship between GSK'254 plasma concentrations and placebo‐adjusted change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF). Of 50 participants enrolled, 48 completed the study (part 1, 8/8; part 2, 40/42). Least‐squares (LS) mean change from baseline in QTcF for GSK'254 100 mg followed the placebo pattern across time points (maximum LS mean ΔΔQTcF, 1.7 ms); the upper bound of the 90% CI remained 10 ms is expected up to GSK'254 concentrations of ~3070 ng mL−1. No clinically relevant effects on cardiac parameters were seen in healthy participants with GSK'254 at the 100‐mg dose.

Abstract Introduction Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. Methods A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. Results A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p

The interest in refractory materials is increasing rapidly in recent decades due to the development of hypersonic vehicles. However, the substance that has the highest melting point (Tm) keeps a secret, since precise measurements in extreme conditions are overwhelmingly difficult. In the present work, an accurate deep potential (DP) model of a Hf–Ta–C–N system was first trained, and then applied to search for the highest melting point material by molecular dynamics (MD) simulation and Bayesian global optimization (BGO). The predicted melting points agree well with the experiments and confirm that carbon site vacancies can enhance the melting point of rock-salt-structure carbides. The solid solution with N is verified as another new and more effective melting point enhancing approach for HfC, while a conventional routing of the solid solution with Ta (e.g., HfTa4C5) is not suggested to result in a maximum melting point. The highest melting point (~4236 K) is achieved with the composition of HfC0.638N0.271, which is ~80 K higher than the highest value in a Hf–C binary system. Dominating mechanism of the N addition is believed to be unstable C–N and N–N bonds in liquid phase, which reduces liquid phase entropy and renders the liquid phase less stable. The improved melting point and less gas generation during oxidation by the addition of N provide a new routing to modify thermal protection materials for the hypersonic vehicles.

Abstract We present PepQuery2, which leverages a new tandem mass spectrometry (MS/MS) data indexing approach to enable ultrafast, targeted identification of novel and known peptides in any local or publicly available MS proteomics datasets. The stand-alone version of PepQuery2 allows directly searching more than one billion indexed MS/MS spectra in the PepQueryDB or any public datasets from PRIDE, MassIVE, iProX, or jPOSTrepo, whereas the web version enables users to search datasets in PepQueryDB with a user-friendly interface. We demonstrate the utilities of PepQuery2 in a wide range of applications including detecting proteomic evidence for genomically predicted novel peptides, validating novel and known peptides identified using spectrum-centric database searching, prioritizing tumor-specific antigens, identifying missing proteins, and selecting proteotypic peptides for targeted proteomics experiments. By putting public MS proteomics data directly into the hands of scientists, PepQuery2 opens many new ways to transform these data into useful information for the broad research community.

Abstract Background Temperature variability (TV) is associated with increased mortality risks. However, the independent impacts of interday and intraday are still unknown. Methods We proposed a new method to decompose TV into interday TV and intraday TV through algebra derivation. Intraday TV was defined as the weighted average standard deviation (SD) of minimum temperature and maximum temperature on each day. Interday TV was defined as the weighted SD of daily mean temperatures during the exposure period. We then performed an illustrative analysis using data on daily mortality and temperature in France in 2019–2021. Results The novel interday and intraday TV indices were good proxies for existing indicators, inlcluding diurnal temperature range (DTR) and temperature change between neighbouring days (TCN). In the illustrative analyses, interday and intraday TVs showed differentiated mortality risks. Mortality burden related to TV was mainly explained by the intraday component, accounting for an attributable fraction (AF) of 1.81% (95% CI: 0.64%, 2.97%) of total mortality, more than twice the AF of interday TV (0.86%, 95% CI: 0.47%, 1.24%). Conclusions This study proposed a novel method for identifying and isolating the different components of temperature variability and offered a comprehensive way to investigate their health impacts.

Abstract Hepatitis-hydropericardium syndrome (HHS) induced by fowl adenovirus serotype-4 (FAdV-4) has caused large economic losses to the world poultry industry in recent years. HHS is characterized by pericardial effusion and hepatitis, manifesting as a swollen liver with focal necroses and petechial haemorrhage. However, the process of FAdV-4 entry into hepatic cells remains largely unknown. In this paper, we present a comprehensive study on the entry mechanism of FAdV-4 into leghorn male hepatocellular (LMH) cells. We first observed that FAdV-4 internalization was inhibited by chlorpromazine and clathrin heavy chain (CHC) knockdown, suggesting that FAdV-4 entry into LMH cells depended on clathrin. By using the inhibitor dynasore, we showed that dynamin was required for FAdV-4 entry. In addition, we found that FAdV-4 entry was dependent on membrane cholesterol, while neither the knockdown of caveolin nor the inhibition of a tyrosine kinase-based signalling cascade affected FAdV-4 infection. These results suggested that FAdV-4 entry required cholesterol but not caveolae. We also found that macropinocytosis played a role, and phosphatidylinositol 3-kinase (PI3K) was required for FAdV-4 internalization. However, inhibitors of endosomal acidification did not prevent FAdV-4 entry. Taken together, our findings demonstrate that FAdV-4 enters LMH cells through dynamin- and cholesterol-dependent clathrin-mediated endocytosis, accompanied by the involvement of macropinocytosis requiring PI3K. Our work potentially provides insight into the entry mechanisms of other avian adenoviruses.

Abstract Background Non-pharmaceutical interventions (NPIs) have been implemented worldwide to suppress the spread of coronavirus disease 2019 (COVID-19). However, few studies have evaluated the effect of NPIs on other infectious diseases and none has assessed the avoided disease burden associated with NPIs. We aimed to assess the effect of NPIs on the incidence of infectious diseases during the COVID-19 pandemic in 2020 and evaluate the health economic benefits related to the reduction in the incidence of infectious diseases. Methods Data on 10 notifiable infectious diseases across China during 2010–2020 were extracted from the China Information System for Disease Control and Prevention. A two-stage controlled interrupted time-series design with a quasi-Poisson regression model was used to examine the impact of NPIs on the incidence of infectious diseases. The analysis was first performed at the provincial-level administrative divisions (PLADs) level in China, then the PLAD-specific estimates were pooled using a random-effect meta-analysis. Results A total of 61,393,737 cases of 10 infectious diseases were identified. The implementation of NPIs was associated with 5.13 million (95% confidence interval [CI] 3.45‒7.42) avoided cases and USD 1.77 billion (95% CI 1.18‒2.57) avoided hospital expenditures in 2020. There were 4.52 million (95% CI 3.00‒6.63) avoided cases for children and adolescents, corresponding to 88.2% of total avoided cases. The top leading cause of avoided burden attributable to NPIs was influenza [avoided percentage (AP): 89.3%; 95% CI 84.5‒92.6]. Socioeconomic status and population density were effect modifiers. Conclusions NPIs for COVID-19 could effectively control the prevalence of infectious diseases, with patterns of risk varying by socioeconomic status. These findings have important implications for informing targeted strategies to prevent infectious diseases.

Space-based gravitational wave detection is extremely sensitive to disturbances. The Keplerian configuration cannot accurately reflect the variations in spacecraft configuration. Planetary gravitational disturbances are one of the main sources. Numerical simulation is an effective method to investigate the impact of perturbation on spacecraft orbits. This study shows that, in the context of the Taiji project, Earth’s gravity is an essential factor in the change in heliocentric formation configuration, contributing to the relative acceleration between spacecrafts in the order of O(10−6)m·s−2. Considering 00:00:00 on 27 October 2032 as the initial orbiting moment, under the influence of Earth’s gravitational perturbation, the maximum relative change in armlengths and variation rates of armlengths for Taiji is 1.6×105km, 32m·s−1, respectively, compared with the unperturbed Keplerian orbit. Additionally, by considering the gravitational perturbations of Venus and Jupiter, the armlength and relative velocity for Taiji are reduced by 16.01% and 17.45%, respectively, compared with when only considering that of Earth. The maximum amplitude of the formation motion indicator changes with the orbit entry time. Results show that the relative velocity increase between the spacecrafts is minimal when the initial orbital moment occurs in July. Moreover, the numerical simulation results are inconsistent when using different ephemerides. The differences between ephemerides DE440 and DE430 are smaller than those between DE440 and DE421.

The copolyester poly(butylene glycol adipate-co-terephthalate/diphenylsilanediol adipate-co-terephthalate) (PBDAT) was synthesized by the melt polycondensation method using terephthalic acid, adipic acid, 1,4-butanediol, and diphenylsilylene glycol as the raw materials. The molecular chain structure, thermal properties, thermal stability, mechanical properties, and degradation behaviors of the copolyesters were investigated. The results showed that the prepared PBDAT copolyesters exhibited good thermal stability and mechanical properties. With the increase in diphenylsilanediol (DPSD) content, the thermal stability of PBDAT and the melting temperature both increased. The tensile strength and elastic modulus of PBDAT also exhibited an increasing tend. When the DPSD content was 12.5% (PBDAT-12.5), the tensile strength, the elastic modulus, and elongation at break were 30.56 MPa, 238 MPa, and 219%, respectively. With the increase in diphenylsilanediol content, the hydrophilicity of PBDAT decreased, but PBDAT still shows good degradability and the thermal degradation T5% temperature was 355 °C. The thermal degradation of PBDAT was also improved.

MAX phases have great research value and application prospects, but it is challenging to synthesize the MAX phases containing Cd and Sb for the time being. In this paper, we confirmed the existence of the 312 MAX phases of Zr3CdC2 and Zr3SbC2, both from theoretical calculations and experimental synthesis. The Zr3AC2 (A = Cd, Sb) phase was predicted by the first-principles calculations, and the two MAX phases were confirmed to meet the requests of thermal, thermodynamic, and mechanical stabilities using formation energy, phonon dispersion, and the Born–Huang criteria. Their theoretical mechanical properties were also systematically investigated. It was found that the elastic moduli of Zr3CdC2 and Zr3SbC2 were 162.8 GPa and 164.3 GPa, respectively. Then, differences in the mechanical properties of Zr3AC2 (A = Cd, In, Sn, and Sb) were explained using bond layouts and charge transfers. The low theoretical Vickers hardness of the Zr3CdC2 (5.4 GPa) and Zr3SbC2 (4.3 GPa) phases exhibited excellent machinability. Subsequently, through spark plasma sintering, composites containing Zr3CdC2 and Zr3SbC2 phases were successfully synthesized at the temperatures of 850 °C and 1300 °C, respectively. The optimal molar ratio of Zr:Cd/Sb:C was determined as 3:1.5:1.5. SEM and the EDS results analysis confirmed the typical layered microstructure of Zr3CdC2 and Zr3SbC2 grains.

Abstract Lysine demethylase KDM7A removes histone modifications H3K9me1/2 and H3K27me1/2. KDM7A plays critical roles in gene expression and contribute to biological processes including tumorigenesis, metabolism, and embryonic development. However, the functions of KDM7A in mammalian nervous system are still poorly explored. In this study, functional roles of KDM7A are comprehensively investigated in neuronal cells by applying CUT&Tag‐seq, RNA‐seq and mice models. Knockdown of Kdm7a in N2A cells result in the alteration of histone modifications near transcription start sites (TSSs) and the expression changes of a large number of genes. In particular, the expression of immediate early genes (IEGs), a series of genes maintaining the function of the nervous system and associating with neurological disorders, are significantly decreased upon Kdm7a knockdown. Furthermore, in vivo knockdown of Kdm7a in dentate gyrus (DG) neuron of mice hippocampus, via Adeno‐associated virus (AAV)‐based stereotaxic microinjection, led to a significant decrease of the expression of c‐Fos, a marker of neuron activity. Behavior assays in mice further revealed that Kdm7a knockdown in hippocampus repress neuron activity, which leading to impairment of emotion and memory. Collectively, the study reveals that KDM7A affects neuron functions by regulating IEGs, which may provide new clues for understanding epigenetic mechanisms in neurological disorders.

Abstract Maxillofacial hard tissue defects caused by trauma or infection often affect craniofacial function. Taking the natural hard tissue structure as a template, constructing an engineered tissue repair module is an important scheme to realize the functional regeneration and repair of maxillofacial hard tissue. Here, inspired by the biomineralization process, we constructed a composite mineral matrix hydrogel PAA-CMC-TDM containing amorphous calcium phosphates (ACPs), polyacrylic acid (PAA), carboxymethyl chitosan (CMC) and dentin matrix (TDM). The dynamic network composed of Ca 2+ ·COO − coordination and ACPs made the hydrogel loaded with TDM, and exhibited self-repairing ability and injectability. The mechanical properties of PAA-CMC-TDM can be regulated, but the functional activity of TDM remains unaffected. Cytological studies and animal models of hard tissue defects show that the hydrogel can promote the odontogenesis or osteogenic differentiation of mesenchymal stem cells, adapt to irregular hard tissue defects, and promote in situ regeneration of defective tooth and bone tissues. In summary, this paper shows that the injectable TDM hydrogel based on biomimetic mineralization theory can induce hard tissue formation and promote dentin/bone regeneration.

Background: Hypertension affects over 1 billion people globally and is the top risk factor of cardiovascular morbidity and mortality. Wuweijiangyasan (WWJYS), as an empirical prescription, has stable depressurization effects. This study investigated the chemical composition and pharmacodynamic effects of WWJYS in regulating the blood pressure (BP), emotion, and blood lipid of spontaneous hypertensive rats, and further explored the depressurization mechanism of WWJYS. Materials and Methods: This study used network pharmacology to identify the origins and predict targets of WWJYS, and artificial intelligence-based molecular docking is used to further predict targets and mechanisms. The chemical constituents of WWJYS were analyzed and identified by ultra high-performance liquid chromatography–mass spectrometry (MS)/MS. Results: In the WWJYS group, the systolic BP level significantly was decreased, and the HR was stable. The irritability became stable after the 5-week treatment compared with the model group (P < 0.05). Rats' rotation tolerance time increased after 2-weeks stabilization. Compared with the model group, angiotensin-converting enzyme 2 protein and mRNA of the WWJYS group increased significantly (P < 0.05). Network pharmacology collected 64 compounds and identified 22 potential targets of WWJYS for antihypertensive activity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that WWJYS might regulate smooth muscle cells, affect inflammatory response and improve endothelial function through multiple pathways. The molecular docking study further supported that the target proteins have good combinations with the main active components of WWJYS. Conclusions: The data indicated that WWJYS had significant depressurization, analgesic, and sedative, as well as lipid-lowering effects, and the depressurization mechanism of WWJYS may function in multiple signal pathways, especially in improving blood vessel function and intervening inflammation.

Abstract Background In the context of climate change, it has been well observed that short-term temperature variability (TV) could increase the overall and cause-specific mortality and morbidity. However, the association between long-term TV and a broader spectrum of diseases is not yet well understood, especially in the elderly. Methods Our study used data from the fourth Urban and Rural Elderly Population (UREP) study. Long-term TV was calculated from the standard deviation (SD) of daily minimum and maximum temperatures within the study periods (2010–2014, 2011–2014, 2012–2014, 2013–2014, and 2014). Ten self-reported diseases and conditions were collected by questionnaire, including cataract, hypertension, diabetes, cardio-cerebrovascular diseases, stomach diseases, arthritis, chronic lung disease, asthma, cancer, and reproductive diseases. The province-stratified logistic regression model was used to quantify the association between long-term TV and the prevalence of each disease. Results A total of 184,047 participants were included in our study. In general, there were significant associations between TV and the prevalence of most diseases at the national level. Cardio-cerebrovascular disease (OR: 1.16, 95% CI: 1.13, 1.20) generated the highest estimates, followed by stomach diseases (OR: 1.15, 95% CI: 1.10, 1.19), asthma (OR: 1.14, 95% CI: 1.06, 1.22), chronic lung diseases (OR: 1.08, 95% CI: 1.03, 1.13), arthritis (OR: 1.08, 95% CI: 1.05, 1.11), and cataract (OR: 1.06, 95% CI: 1.02, 1.10). Moreover, the associations varied by geographical regions and across subgroups stratified by sex, household income, physical activity, and education. Conclusions Our study showed that long-term exposure to TV was associated with the prevalence of main diseases in the elderly. More attention should be paid to the elderly and targeted strategies should be implemented, such as an early warning system.

The objective of this study was to optimize the ultra-high pressure extraction (UPE) process of anthocyanins extracted from blueberry pomace and to investigate the antioxidant activity of the anthocyanin extracts. In the present study, the extraction process of anthocyanins was optimized by single factor experiments and Box-Behnken response surface methodology, using blueberry pomace as raw extraction material. The DPPH free radical scavenging rate, hydroxyl radical scavenging rate, and FRAP iron ion reducing ability of the extracts were determined to evaluate the in vitro antioxidant activity of blueberry pomace anthocyanins, with vitamin C (VC) used as a positive control. The components of anthocyanins extracted from blueberry pomace were analyzed by high performance liquid chromatography (HPLC). The optimum conditions of the anthocyanins extraction from blueberry pomac were as follows: extraction pressure at 400 MPa, extraction time for 9 min, 60% ethanol concentration, solid-liquidratio at 1:20 g/mL. Under these conditions, the extraction yield of blueberry pomace anthocyanins was 5.93±0.06 mg/g. Compared to conventional solvent extraction (CSE) and ultrasonic-assisted extraction (USE), ultra-high pressure-assisted extraction (UPE) had the better extraction effect, with the extraction yield of blueberry pomace anthocyanins increased 25.11% and 10.02%, respectively. Blueberry pomace anthocyanins had strong DPPH free radical scavenging effect, which was comparable to the same concentration of VC (P>0.05). However, the hydroxyl radical scavenging activity and the FRAP iron ion reducing ability of blueberry pomace anthocyanins were significantly lower than those of VC at the same concentration (P

Memory augmented neural network for lifelong on-device learning is bottlenecked by limited bandwidth in conventional hardware. Here, the authors demonstrate its efficient in-memristor realization with a close-software accuracy, supported by hashing and similarity search in crossbars.

Abstract Peste des petits ruminants (PPR) is an acute and highly contagious disease and has long been a significant threat to small ruminant productivity worldwide. However, the molecular mechanism underlying host-PPRV interactions remains unclear and the long noncoding RNAs (lncRNAs) regulation of PPR virus (PPRV) infection has rarely been reported so far. Here, we first demonstrated that PPRV infection can induce an obvious innate immune response in caprine endometrial epithelial cells (EECs) at 48 h post-infection (hpi) with an MOI of 3. Subsequently, we determined that PPRV infection is associated with 191 significantly differentially expressed (SDE) lncRNAs, namely, 137 upregulated and 54 downregulated lncRNAs, in caprine EECs compared with mock control cells at 48 hpi by using deep sequencing technology. Importantly, bioinformatics preliminarily analyses revealed that these DE lncRNAs were closely related to the immune response. Furthermore, we identified a system of lncRNAs related to the immune response and focused on the role of lncRNA 10636385 (IRF1-AS) in regulating the innate immune response. Interestingly, we found that IRF1-AS was a potent positive regulator of IFN-β and ISG production, which can significantly inhibit PPRV replication in host cells. In addition, our data revealed that IRF1-AS was positively correlated with its potential target gene, IRF1, which enhanced the activation of IRF3 and the expression of ISGs and interacted with IRF3. This study suggests that IRF1-AS could be a new host factor target for developing antiviral therapies against PPRV infection.

To analyze the robustness and reliability of field area network (FAN) in the power distribution network, a quantifiable network resilience characterization and evaluation model was proposed.The elasticity indicator was defined from network connectivity, robustness and redundancy, and the total network elasticity was calculated by the weighted sum.The resilience performance of FAN was evaluated by simulating random failures and malicious attacks.A single node failure was simulated and tested to evaluate the difference in network resilience a affected by different node failures and find the weak points of resilience in the network.The elastic characterization and evaluation model was extended to general network topologies, and simulation experiments were carried out using BA scale-free network and ER random network.The experimental results demonstrate the universality of the model.

To improve the removal efficiency of antibiotics in moving bed biofilm reactor, suspended biochar block was prepared by the one-pot process and was used as carriers to construct a reaction device to study the treatment effect of antibiotic wastewater. The characteristics of the hanging biofilm in wastewater were investigated. And the mechanism of biochar as a biological carrier has been studied. The results showed that in the 45-day experiment, the maximum number of biofilms for suspended biochar carriers was twice 3.4 times that of the high-density polyethylene carriers. When 10 mg/L tetracycline was added to the reactor, the removal efficiency of the tetracycline removal rate was 71.85% and the chemical oxygen demand (COD), total nitrogen (TN), and NH4+-N removal efficiency reached to 89.95, 61.91 and 85.47% respectively. Suspension biochar carriers can reduce fluctuations in redox potentials, thereby improving the cellular efficiency of microorganisms. Meanwhile, it inhibits the production of soluble microbial products and extracellular polymers, reduces toxic effects, and enhances the adhesion between microorganisms and carriers. The microbial communities of the two carriers were investigated by high-throughput sequencing techniques. Suspended biochar significantly increased the relative abundance of Hydrogenophaga and Comamonas, and improved the ability of nitrification and denitrification. Comamonas could be responsible for tetracycline degradation. HIGHLIGHTS Suspended biochar block was prepared by a one-pot process using peanut shells, floating beads and waste electrode graphite as raw materials.; The removal efficiency of the tetracycline and the biological characteristics of biofilms were investigated.; The adsorption and aggregation of microorganism action were investigated using the biochar as carriers in a moving bed biofilm reactor tank.;

Abstract Background Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods. Methods T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin–eosin staining, and Masson’s trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes. Results We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency. Conclusions HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED.

Abstract We report the safety and pharmacokinetic properties of the HIV‐1 maturation inhibitor GSK3739937 (GSK'937) in healthy participants. This was a phase I, first‐in‐human, double‐blind, randomized, placebo‐controlled, single‐ (part 1) and multiple‐ (part 2) dose escalation study with an additional open‐label relative bioavailability and food effect study (part 3). Participants received oral ascending single doses (10–800 mg) in part 1, up to 18 once‐daily 25‐ to 100‐mg or 3 once‐weekly 500‐mg doses in part 2, and single 100‐mg doses as powder‐in‐bottle or tablet (in fed and fasted states) formulations in part 3. Primary and secondary objectives were safety and pharmacokinetic assessments, respectively. Ninety‐one participants were enrolled; 38 reported 81 total adverse events (AEs). All AEs in participants receiving GSK'937 were grade 1 or 2 and resolved during the study. Most drug‐related AEs were gastrointestinal (14/17, 82%). The terminal phase half‐life of GSK'937 was ~3 days for all doses following single and repeat dosing. Geometric mean maximum concentration and total drug exposures exhibited dose‐proportional increases during part 1. Accumulation in exposure following repeat dosing was 6‐ to 7‐fold with daily dosing and ~1.7‐fold after weekly treatment, as expected due to the long half‐life. Bioavailability of GSK'937 after a meal was 1.35‐ to 1.40‐fold greater as a tablet versus powder‐in‐bottle and >2‐fold higher in fed versus fasted states when provided as a tablet. No unexpected or dose‐limiting safety events occurred. Pharmacokinetic parameters of long half‐life and accumulation of exposure following repeat dosing suggest the potential for weekly oral dosing. ClinicalTrials.gov identifier: NCT04493684.

Soil erosion is a significant global environmental issue and a crucial aspect of global change. Exploring the interactive effect of ecological land agglomeration and habitat quality on soil erosion can effectively guide the positive intervention of ecological restoration activities. The study calculated the comprehensive ecological land agglomeration with Fragstats 4.2 and the habitat quality with InVEST 3.7.0 for the years 2000, 2010, and 2020 within the Jinsha River Basin in Yunnan, China. In addition, the RUSLE model was utilized to calculate soil erosion in the study area. The Geographic and Temporally Weighted Regression (GTWR) model was employed to obtain the regression coefficients and their spatial and temporal variations. The findings of this study revealed the following: (1) During the study period, there was an overall 29.06% reduction in the soil erosion modulus with an annual rate of 1.70% reduction on average, accompanied by an increase in both the comprehensive ecological land agglomeration and habitat quality. Soil erosion was more severe in the eastern regions than in the western ones and the other two indicators were higher in the northeast and southwest. (2) The GTWR results demonstrate that comprehensive ecological land agglomeration and habitat quality were negatively correlated with soil erosion, with results of −0.1383 and 0.0021, respectively. However, in northwest regions, there was a significant positive correlation between habitat quality and soil erosion. (3) The interaction term between comprehensive ecological land agglomeration and habitat quality was significantly negatively correlated with soil erosion with a result of −0.0299, and the interaction coefficients have regional variations. This study offers valuable guidance for land-use development and soil and water conservation in the Jinsha River Basin.

Floods have been the most common type of disaster and are expected to increase in frequency and intensity due to climate change. Although there is growing evidence on the impacts of floods on human health, none has so far investigated the association between flooding exposure and biological aging acceleration. We collected data from 364 841 participants from the UK Biobank project. Flooding data before baseline were retrieved from the Dartmouth Flood Observatory and linked to each participant. Cumulative flooding exposure within six years before the baseline was calculated. We calculated the two biological aging measures at baseline: PhenoAge and Klemera-Doubal method biological age (KDM-BA) and assessed their associations with flooding exposure using mixed-effects linear regression models. We observed that participants exposed to higher levels of floods were more likely to have accelerated biological aging. The risks associated with flooding exposure could last for several years, with the highest cumulative effect observed over 0–4 years. In the fully adjusted model, per interquartile increase in cumulative flood exposure was associated with an increase of 0.24 years (95% CI: 0.14, 0.34) in PhenoAge acceleration and 0.14 years (95% CI: 0.07, 0.21) in KDM-BA acceleration over lag 0–4 years. The associations were consistent regardless of lifestyles, demographics, and socio-economic status. Our findings suggest that exposure to floods may lead to accelerated biological aging. Our work provides the basis for further understanding of the flood-related health impacts and suggests that public health policies and adaptation measures should be initiated in the short-, medium- and even long-term after flooding.

This paper presents a cost-effective, quantitative, point-of-care solution for urinalysis screening, specifically targeting nitrite, protein, creatinine, and pH in urine samples. Detecting nitrite is crucial for the early identification of urinary tract infections (UTIs), while regularly measuring urinary protein-to-creatinine (UPC) ratios aids in managing kidney health. To address these needs, we developed a portable, transmission-based colorimeter using readily available components, controllable via a smartphone application through Bluetooth. Multiple colorimetric detection strategies for each analyte were identified and tested for sensitivity, specificity, and stability in a salt buffer, artificial urine, and human urine. The colorimeter successfully detected all analytes within their clinically relevant ranges: nitrite (6.25–200 µM), protein (2–1024 mg/dL), creatinine (2–1024 mg/dL), and pH (5.0–8.0). The introduction of quantitative protein and creatinine detection, and a calculated urinary protein-to-creatinine (UPC) ratio at the point-of-care, represents a significant advancement, allowing patients with proteinuria to monitor their condition without frequent lab visits. Furthermore, the colorimeter provides versatile data storage options, facilitating local storage on mobile devices or in the cloud. The paper further details the setup of the colorimeter’s secure connection to a cloud-based environment, and the visualization of time-series analyte measurements in a web-based dashboard.

Global warming has been changing the planet’s climate pattern, leading to increasing frequency, intensity and duration of extreme weather events and natural disasters. These climate-changing events affect various health outcomes adversely through complicated pathways. This paper reviews the main signs of climate change so far, e.g., suboptimal ambient temperature, sea-level rise and other conditions, and depicts the interactive pathways between different climate-changing events such as suboptimal temperature, wildfires, and floods with a broad range of health outcomes. Meanwhile, the modifying effect of socioeconomic, demographic and environmental factors on the pathways is summarised, such that the youth, elderly, females, poor and those living in coastal regions are particularly susceptible to climate change. Although Earth as a whole is expected to suffer from climate change, this review article discusses some potential benefits for certain regions, e.g., a more liveable environment and sufficient food supply. Finally, we summarise certain mitigation and adaptation strategies against climate change and how these strategies may benefit human health in other ways. This review article provides a comprehensive and concise introduction of the pathways between climate change and human health and possible solutions, which may map directions for future research.

Background: Wildfire imposes a high mortality burden on Brazil. However, there is a limited assessment of the health economic losses attributable to wildfire-related fine particulate matter (PM2.5). Methods: We collected daily time-series data on all-cause, cardiovascular, and respiratory mortality from 510 immediate regions in Brazil during 2000–2016. The chemical transport model GEOS-Chem driven with Global Fire Emissions Database (GFED), in combination with ground monitored data and machine learning was used to estimate wildfire-related PM2.5 data at a resolution of 0.25° × 0.25°. A time-series design was applied in each immediate region to assess the association between economic losses due to mortality and wildfire-related PM2.5 and the estimates were pooled at the national level using a random-effect meta-analysis. We used a meta-regression model to explore the modification effect of GDP and its sectors (agriculture, industry, and service) on economic losses. Results: During 2000–2016, a total of US$81.08 billion economic losses (US$5.07 billion per year) due to mortality were attributable to wildfire-related PM2.5 in Brazil, accounting for 0.68% of economic losses and equivalent to approximately 0.14% of Brazil’s GDP. The attributable fraction (AF) of economic losses due to wildfire-related PM2.5 was positively associated with the proportion of GDP from agriculture, while negatively associated with the proportion of GDP from service. Conclusion: Substantial economic losses due to mortality were associated with wildfires, which could be influenced by the agriculture and services share of GDP per capita. Our estimates of the economic losses of mortality could be used to determine optimal levels of investment and resources to mitigate the adverse health impacts of wildfires.