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Abstract Background Early detection through screening dramatically improves lung cancer survival rates, including among war Veterans, who are at heightened risk. The effectiveness of low dose computed tomography scans in lung cancer screening (LCS) prompted the Veteran’s Affairs Lung Precision Oncology Program (VA LPOP) to increase screening rates. We aimed to develop an adaptive population health tool to determine adequate resource allocation for the program, with a specific focus on primary care providers, nurse navigators, and radiologists. Methods We developed a tool using C + + that uses inputs that represents the process of the VA LCS program in Ann Arbor, Michigan to calculate FTEs of human resource needs to screen a given population. Further, we performed a sensitivity analysis to understand how resource needs are impacted by changes in population, screening eligibility, and time allocated for the nurse navigators’ tasks. Results Using estimates from the VA LCS Program as demonstrative inputs, we determined that the greatest number of full-time equivalents required were for radiologists, followed by nurse navigators and then primary care providers, for a target population of 75,000. An increase in the population resulted in a linear increase of resource needs, with radiologists experiencing the greatest rate of increase, followed by nurse navigators and primary care providers. These resource requirements changed with primary care providers, nurse navigators and radiologists demonstrating the greatest increase when 1–20, 20–40 and > 40% of Veterans accepted to be screened respectively. Finally, when increasing the time allocated to check eligibility by the nurse navigator from zero to three minutes, there was a linear increase in the full-time equivalents required for the nurse navigator. Conclusion Variation of resource utilization demonstrated by our user facing tool emphasizes the importance of tailored strategies to accommodate specific population demographics and downstream work. We will continue to refine this tool by incorporating additional variability in system parameters, resource requirements following an abnormal test result, and resource distribution over time to reach steady state. While our tool is designed for a specific program in one center, it has wider applicability to other cancer screening programs.

Abstract The influence of precipitated nanophases on the mechanical properties of Fe-based amorphous nanocrystalline alloys is an urgent issue to be explored. Two amorphous nanocrystalline alloys, i.e., (Fe0.9Ni0.1)86B14 and (Fe0.7Ni0.3)86B14 containing nanophase of the body-centered cubic and face-centered cubic structures, respectively, were selected to investigate the effect of the structure and volume fraction of nanophase on their mechanical properties. The results of nanoindentation experiments and the calculation of the volume and size of the shear transition zone reveal that the two alloys show different mechanical properties. When the volume fraction of the nanophase in (Fe0.9Ni0.1)86B14 is larger than 50%, the elastic modulus is increased suddenly and the volume and size of the shear transition zone is decreased dramatically, while no dramatic change occurs in (Fe0.7Ni0.3)86B14. Moreover, it was found by using molecular dynamics simulations that the main reason for these abnormal mechanical properties is the change of cluster type in the system due to the incorporation of nanophases with different structures.

The effect of the volume fraction of nanocrystals on the macroscopic mechanical properties and microscopic atomic structure of Fe-based nanocrystalline alloys, as well as the relationship between the two, is an urgent issue to be explored. Seven nanocrystalline alloys with different volume fractions of nanocrystals were formed by annealing treatment of (Fe0·9Ni0.1)86B14 amorphous precursor. Through hardness, flat plate bending, and nanoindentation experiments, it is found that when the volume fraction of nanocrystals reaches the range of 45–55 %, there is an abrupt change in the macroscopic mechanical properties. Specifically, when the volume fraction is less than this range, the properties inherit the amorphous matrix, however, larger than this range, the properties are dominated by precipitated nanocrystalline phases. Meanwhile, based on the molecular dynamics simulation method, seven Fe90Ni10 amorphous nanocrystalline models with different volume fractions of body-centered cubic nanocrystals are established, and the deformation mechanism of models and the evolution of their microstructures during the nanoindentation process are obtained intuitively. Moreover, it is further revealed that the significant changes in the Voronoi polyhedral index, which represents the microscopic atomic structure in this range of nanocrystal volume fractions, are the main reason for the abrupt changes in the mechanical properties at the macroscopic level.

In order to solve the problem of high temperature and heat damage in the 10303 coal mining face of Jining No.2 Coal Mine, numerical analysis method was used to establish a physical model of the working face and to analyze the influence of multiple factors on the cooling system, such as the length of the wind pipe, the distance between the air outlet of the wind pipe and the temperature, and determine the temperature control parameters for different working conditions (production and shutdown), and then control the temperature of the air cooler air outlet through the automatic opening and closing of the temperature-control facilities, so that the required cooling capacity of the coal mining face is realized under different operations. The cooling capacity required by the working face is realized under different operations, and the problem of high-temperature heat damage in the working face is solved. The results show that the cooling effect of 100 m length of wind pipe and 50 m distance of wind pipe is the best. When the working face is under normal mining operation, the outlet temperature setting should be less than 16.5 ℃, and the average temperature of the working face will be reduced by 3.7 ℃; when the mining operation is stopped, the outlet temperature setting should be less than 20.5 ℃, and the average temperature of the working face will be reduced by 3.5 ℃, and the parameters of the two working conditions can achieve the temperature control target of the coal mining working face.

Abstract Objectives Homopolymer (HP) sequencing is error-prone in next-generation sequencing (NGS) assays, and may induce false insertion/deletions and substitutions. This study aimed to evaluate the performance of dichromatic and tetrachromatic fluorogenic NGS platforms when sequencing homopolymeric regions. Results A HP-containing plasmid was constructed and diluted to serial frequencies (3%, 10%, 30%, 60%) to determine the performance of an MGISEQ-2000, MGISEQ-200, and NextSeq 2000 in HP sequencing. An evident negative correlation was observed between the detected frequencies of four nucleotide HPs and the HP length. Significantly decreased rates (P

Abstract Huntington’s disease (HD) is a monogenic neurodegenerative disease, caused by the CAG trinucleotide repeat expansion in exon 1 of the Huntingtin (HTT) gene. The HTT gene encodes a large protein known to interact with many proteins. Huntingtin-associated protein 40 (HAP40) is one that shows high binding affinity with HTT and functions to maintain HTT conformation in vitro. However, the potential role of HAP40 in HD pathogenesis remains unknown. In this study, we found that the expression level of HAP40 is in parallel with HTT but inversely correlates with mutant HTT aggregates in mouse brains. Depletion of endogenous HAP40 in the striatum of HD140Q knock-in (KI) mice leads to enhanced mutant HTT aggregation and neuronal loss. Consistently, overexpression of HAP40 in the striatum of HD140Q KI mice reduced mutant HTT aggregation and ameliorated the behavioral deficits. Mechanistically, HAP40 preferentially binds to mutant HTT and promotes Lysine 48-linked ubiquitination of mutant HTT. Our results revealed that HAP40 is an important regulator of HTT protein homeostasis in vivo and hinted at HAP40 as a therapeutic target in HD treatment.

In recent years, global attention has increasingly turned towards the urgent goal of eliminating carbon emissions. Evaluating new methods may be the key to achieving environmentally responsible growth. This study examines the impact of China's public-private energy partnerships on CO2 emissions from 1990Q1 to 2022Q4, employing Dynamic Ordinary Least Squares (DOLS) and fuzzy multi-objective least squares (FMOLS) econometric regression methods. Our analysis incorporates sustainability efforts, renewable energy sources, environmentally sound finance, and technological advancements to provide a comprehensive understanding of CO2 emissions dynamics. Our findings reveal that expanding access to credit has facilitated the development of green financing, resulting in a favorable environmental impact of China's economic growth and public-private partnerships. The reduction in carbon dioxide emissions is counter balanced by the positive effects of technological progress, increased utilization of renewable energy sources, and enhanced power efficiency. We highlight the multiplying effect of these factors, underscoring the need for global public-private collaborations in the energy sector to significantly lower carbon emissions and to achieve sustainable development goals. We assert that policymakers tasked with facilitating China's transition to renewable energy sources must prioritize environmental preservation, technological advancement, and the optimal utilization of renewable resources to achieve lasting sustainability.

Summary: The gut microbiome is crucial for nutrient metabolism, immune regulation, and intestinal homeostasis with changes in its composition linked to complex diseases like inflammatory bowel disease (IBD). Although the precise host-microbial mechanisms in disease pathogenesis remain unclear, high-throughput sequencing have opened new ways to unravel the role of interspecies interactions in IBD. Systems biology—a holistic computational framework for modeling complex biological systems—is critical for leveraging multi-omics datasets to identify disease mechanisms. This review highlights the significance of multi-omics data in IBD research and provides an overview of state-of-the-art systems biology resources and computational tools for data integration. We explore gaps, challenges, and future directions in the research field aiming to uncover novel biomarkers and therapeutic targets, ultimately advancing personalized treatment strategies. While focusing on IBD, the proposed approaches are applicable for other complex diseases, like cancer, and neurodegenerative diseases, where the microbiome has also been implicated.

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID‐19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus–host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

Abstract Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota. Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity.

Abstract With the development of cloud computing, users are more inclined to outsource complex computing tasks to cloud servers with strong computing capacity, and the cloud returns the final calculation results. However, the cloud is not completely trustworthy, which may leak the data of user and even return incorrect calculations on purpose. Therefore, it is important to verify the results of computing tasks without revealing the privacy of the users. Among all the computing tasks, the polynomial calculation is widely used in information security, linear algebra, signal processing and other fields. Most existing polynomial-based verifiable computation schemes require that the input of the polynomial function must come from a single data source, which means that the data must be signed by a single user. However, the input of the polynomial may come from multiple users in the practical application. In order to solve this problem, the researchers have proposed some schemes for multi-source outsourced data, but these schemes have the common problem of low efficiency. To improve the efficiency, this paper proposes an efficient polynomial-based verifiable computation scheme on multi-source outsourced data. We optimize the polynomials using Horner’s method to increase the speed of verification, in which the addition gate and the multiplication gate can be interleaved to represent the polynomial function. In order to adapt to this structure, we design the corresponding homomorphic verification tag, so that the input of the polynomial can come from multiple data sources. We prove the correctness and rationality of the scheme, and carry out numerical analysis and evaluation research to verify the efficiency of the scheme. The experimental indicate that data contributors can sign 1000 new data in merely 2 s, while the verification of a delegated polynomial function with a power of 100 requires only 18 ms. These results confirm that the proposed scheme is better than the existing scheme.

Abstract Background Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. Results We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation “blacklist” in the BED region to reduce errors in downstream analyses. Conclusions We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

This study investigates the feasibility and challenges of transferring traffic signal control schemes from the macroscopic signal timing optimization tool Synchro to the microscopic traffic simulator SUMO, focusing on Downtown Seattle as a case study. The research assesses the process of sharing and importing traffic signal timing plans, a crucial aspect of transportation simulations, between these two platforms. We conduct a detailed analysis of the traffic signal characteristics and data formats unique to each simulator and identify elements suitable for conversion. Subsequently, a four-stage framework is developed for semi-automatic integration of traffic signal control between the two. Our results indicate a successful conversion rate of approximately 85% of signalized intersections from Synchro to SUMO. This research not only illustrates the challenges and solutions in converting signal control across different platforms but also paves the way for future studies aimed at improving the interoperability of various traffic simulation tools.

BackgroundAnemia is prevalent among patients with cardiovascular disease and is associated with adverse outcomes. However, data regarding the impact of anemia in high-risk percutaneous coronary intervention (HRPCI) are limited.ObjectivesThis study aimed to evaluate the impact of anemia in patients undergoing Impella-supported HRPCI in the PROTECT III study.MethodsPatients undergoing Impella-supported HRPCI in the multicenter PROTECT III study were assessed for anemia based on baseline hemoglobin levels according to World Health Organization criteria. Patients were stratified into three groups, namely, no anemia, mild anemia, and moderate or severe anemia. Major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 30 and 90 days, and major bleeding events were compared across groups.ResultsOf 1,071 patients with baseline hemoglobin data, 37.9% had no anemia, 43.4% had mild anemia, and 18.7% had moderate or severe anemia. Anemic patients were older and more likely to have comorbidities. Anemia was associated with higher MACCE rates at 30 days (moderate to severe, 12.3%; mild, 9.8%; no anemia, 5.4%; p = 0.02) and at 90 days (moderate to severe, 18.7%; mild, 14.6%; none, 8.3%; p = 0.004). These differences persisted after adjustment for potential confounders at 30 and 90 days, and sensitivity analysis excluding dialysis showed similar results. Major bleeding at 30 days was also higher in anemic patients (5.5% vs. 1.2%, p = 0.002).ConclusionBaseline anemia in Impella-supported HRPCI is common and independently associated with MACCE and major bleeding, emphasizing its significance as a prognostic factor. Specific management strategies to reduce anemia-associated MACCE risk after HRPCI should be examined.Clinical Trial InformationTrial Name: The Global cVAD Study (cVAD)ClinicalTrial.gov Identifier: NCT04136392URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2

Improving the accuracy of the six-axis force sensor Six-axis force sensors (hereafter collectively referred to as 6a-sensors) is a systematic problem, which mainly involves the optimization and improvement of three aspects: the design of the elastic body of the 6a-sensors, the acquisition and processing of the weak signal, and the decoupling of the inter-dimensional data of the force and torque of each dimension. To attain high stiffness, sensitivity, and minimal coupling, a design scheme of cross beam elastomer based on titanium alloy material is proposed. In order to realize the acquisition and processing of multi-channel weak differential signals with high gain, high linearity and precision, a high-speed programmable weak signal processing circuit design scheme is proposed. To efficiently address the interdependence issue among signal dimensions in the 6a-sensors. This paper innovatively proposes a BP-PSO decoupling algorithm using Particle Swarm Approach (PSO) to optimise the optimiser of BP neural network. To validate the algorithm’s effectiveness, comparative experiments are conducted with the 6a-sensors. designed and studied in this paper by sampling and self-designed calibration system. The sensitivity of the 6a-sensor designed in this paper reaches 4mV/V. In terms of accuracy, there is an improvement of about 1%. In terms of crosstalk, there is an improvement of about 0.2%. providing a new and improved idea for the six-dimensional force decoupling algorithm. In order to further verify the practicability of the algorithm, a flexible surface grinding robot based on six-axis force is developed based on Siasun robot platform. The grinding strength control is accurate, and the running trajectory is uniform and smooth, which can effectively meet the practical application requirements of flexible and intelligent control.

The present study employs regulatory focus theory (Higgins, 1997) to investigate the effects of L2 speakers’ chronic regulatory focus on their L2 pragmatic versus grammatical awareness. It involved the participation of 121 Chinese students, who are English language learners, at a university in the United States. Haws et al.’s (2010) questionnaire was used to examine the participants’ regulatory dispositions, and a judgment task was adapted from Bardovi-Harlig and Dörnyei (1998) to assess participants’ awareness of grammatical and pragmatic errors, as well as the severity of each type of error. Multiple regression results largely confirmed the predictions. Prevention regulatory focus, concerned with obligations, responsibilities, and negative outcomes, predicted L2 speakers’ recognition of grammatical errors and their severity. Conversely, promotion focus, which emphasizes growth, accomplishments, and positive outcomes, positively predicted L2 speakers’ perceptions of pragmatic error severity. These findings contribute to the understanding of how differences in chronic motivational orientations can lead to different L2 use patterns and characteristics.

Abstract Background Yarrowia lipolytica, one of the most charming chassis cells in synthetic biology, is unable to use xylose and cellodextrins. Results Herein, we present work to tackle for the first time the engineering of Y. lipolytica to produce lipids from cellodextrins and xylose by employing rational and combinatorial strategies. This includes constructing a cellodextrin-phosphorolytic Y. lipolytica by overexpressing Neurospora crassa cellodextrin transporter, Clostridium thermocellum cellobiose/cellodextrin phosphorylase and Saccharomyces cerevisiae phosphoglucomutase. The effect of glucose repression on xylose consumption was relieved by installing a xylose uptake facilitator combined with enhanced PPP pathway and increased cytoplasmic NADPH supply. Further enhancing lipid production and interrupting its consumption conferred the obese phenotype to the engineered yeast. The strain is able to co-ferment glucose, xylose and cellodextrins efficiently, achieving a similar μmax of 0.19 h−1, a qs of 0.34 g-s/g-DCW/h and a YX/S of 0.54 DCW-g/g-s on these substrates, and an accumulation of up to 40% of lipids on the sugar mixture and on wheat straw hydrolysate. Conclusions Therefore, engineering Y. lipolytica capable of assimilating xylose and cellodextrins is a vital step towards a simultaneous saccharification and fermentation (SSF) process of LC biomass, allowing improved substrate conversion rate and reduced production cost due to low demand of external glucosidase.

It was necessary to research an efficient treatment process suitable for township domestic wastewater. In this paper, the performance of the cyclic activated sludge system (CASS) system for simultaneous carbon (C), nitrogen (N) and phosphorus (P) removal was investigated by changing the operation cycle of the CASS reactor. Four operating conditions were set up, T1, T2, T3 and T4, with cycle times of 6, 8, 12 and 8 h (with carbon source), respectively. The results showed that the CASS system had good simultaneous removal of C, N and P. The highest removal rates of COD, TN, NH4+ -N and TP were 87.69, 72.99, 98.60 and 98.38%, respectively, at a cycle time of 8 h. The TN removal rate could be increased to 82.51% after the addition of carbon source. Microbial community analysis showed that Proteobacteria, Bacteroidetes and Candidatus Saccharibacteria were the main phylum-level bacteria. Their presence facilitated the effectiveness of the CASS process for nitrogen removal and phosphorus removal. Functional analysis of genes revealed that the abundance values of genes associated with C, N and P metabolism were higher when the treatment was effective.

Designing g-C3N4-based nanostructured photocatalysts is crucial to boosting their application in advancing clean energy and sustainable environmental solutions. In this study, cyano groups and amorphous carbon self-modified P-doped g-C3N4 (PCNx) photocatalysts were designed and prepared by one-pot calcination. Melamine phosphate was employed as a multifunctional precursor to simultaneously achieve P-doping and amorphous carbon/cyano group self-modification in the g-C3N4 photocatalyst. The molar ratio of urea to melamine phosphate regulates the content of amorphous carbon and cyano groups, which further enhances the conductivity of g-C3N4. Due to the high conductivity of amorphous carbon and cyano groups, the charge transfer process was further accelerated. As a result, the optimized P-doping and amorphous carbon/cyano-group in PCN2 photocatalyst led to an excellent H2 production rate of 157.86 µmol·g−1·h−1 under visible light, which is approximately 2.4 times and 3 times higher than those of CN and PCN. The work developed an alternative strategy for the construction of highly efficient g-C3N4-based photocatalysts.

The accuracy of aerial work platform weighing is essential for safety. However, in practice, the same weight placed at different locations on the platform can yield varying readings, which is a phenomenon known as eccentric load. Measurement errors caused by eccentric loads can lead to missed detections and false alarms in the vehicle safety system, seriously affecting the safety of aerial work. To overcome the influence of eccentric load, the current engineering practice relies on multiple measurements at multiple points and averaging the results to eliminate the eccentric load, which greatly increases the work intensity of workers. To address the aforementioned issues, this paper proposes a three-dimensional force/torque shear force compensation scheme based on bending torque and torsional torque for pressure. The goal is to ensure that the sensor on the aerial work vehicle platform can accurately measure the anti-eccentric load under single-point measurement conditions. A three-box structure anti-eccentric load-weighing sensor for the aerial work platform was designed. Its structure has the advantages of high mechanical strength and no radial effect, ensuring the safety of aerial work, improvement of measurement sensitivity, and enabling of real-time and accurate acquisition of force/torque in three directions. In order to further improve the measurement accuracy of 3D force/torque compensation, a particle swarm optimization algorithm was adopted to optimize the 3D force/torque shear force compensation, thereby improving the safety of engineering operations. Through the verification of a self-made testing platform, the anti-eccentric load sensor designed in this study can ensure that the measurement error of objects at any position on the platform is less than 1.5%, effectively improving the safety of high-altitude platform engineering operations.

Abstract N6-methyladenosine(m6A), is the most abundant post-transcriptional modification of mRNA in biology. When the first nucleotide after the m7G cap is adenosine, it is methylated at the N6 position to form N6,2-O-dimethyladenosine (m6Am). m6Am is a reversible modification located at the first transcribed nucleotide, which is present in about 30% of cellular mRNAs, thus m6Am can have a significant impact on gene expression in the transcriptome. Phosphorylated CTD interaction factor 1(PCIF1), the unique and specific methyltransferase of m6Am, has been shown to affect mRNA stability, transcription, and translation. Several studies have shown that PCIF1 is clearly associated with tumor, viral, and endocrine diseases. Moreover, PCIF1 may be related to the tumor microenvironment, immune cell typing, and programmed cell death protein 1(PD-1) drug resistance. Here, we summarize the mechanism of PCIF1 involvement in mRNA modifications, and outline m6Am modifications and diseases in which PCIF1 is involved. We also summarized the role of PCIF1 in immune and immune checkpoint blockade(ICB) treatment, and predicted the possibility of PCIF1 as a biomarker and therapeutic target.

The reciprocating plate column is a kind of column with the plates driven by a geared motor, and it has advantages in regard to efficiency compared to traditional columns in the extraction process, however, it comes with an increase in energy consumption. A new type of reciprocating plate column driven by electro-permanent magnet technology (EPM) is proposed in this paper to obtain a better performance with lower energy consumption. The feasibility and performance of the proposed column is studied by numerical simulation and experiments with a kerosene–water system. The electro-permanent magnet chuck could provide a maximum amplitude of 12 mm in this study. Kerosene was used as the dispersed phase, and deionized water was used as the continuous phase, in a laboratory-scale 35 mm diameter reciprocating plate column driven by EPM. Hydrodynamic performance experiments were carried out with different flowrates of both phases and reciprocating frequencies. The experimental results show that the electro-permanent magnet chuck, which serves as the driving device of the reciprocating plate column, plays the role of adding energy and increasing the droplet breakage. In addition, the energy consumption of the reciprocating plate column with traditional geared motor and electro-permanent magnet chuck is calculated respectively. Compared with the traditional geared motor, the energy saving of the electro-permanent magnet chuck is as high as 98.55%.

Abstract Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in regulating immune system and skeletal homeostasis. However, the impact of CNS injury on hematopoiesis commitment was overlooked. Here, we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing; chemical sympathectomy blocks TBI-induced fracture healing. TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells (HSCs) and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days, which favor fracture healing. Knockout of β3- or β2-adrenergic receptor (AR) eliminate TBI-mediated anti-inflammation macrophage expansion and TBI-accelerated fracture healing. RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells. Importantly, flow cytometry confirmed that deletion of β2-AR inhibits M2 polarization of macrophages at 7th day and 14th day; and TBI-induced HSCs proliferation was impaired in β3-AR knockout mice. Moreover, β3- and β2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process. Thus, we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow. These results implicate that the adrenergic signals could serve as potential targets for fracture management.

Abstract Background Observational studies have reported an inverse association of type 2 diabetes (T2D) with thoracic aortic aneurysm (TAA). However, the causality of the association has not been established yet. The present study aims to clarify the causal relationship between T2D and TAA via a Mendelian randomization (MR) approach. Methods Causality of associations were assessed using a two-sample MR framework. Genome-wide association study (GWAS) summary statistics were obtained for T2D, glycated hemoglobin (HbA1c), fasting glucose (FG) and fasting insulin (FI) as exposures, and TAA, ascending aortic diameter (AAoD) and descending aortic diameter (DAoD) as outcomes. Four different methods (inverse variance weighted [IVW], weight median, MR-Egger and MR-PRESSO) were used to calculate causal estimates. Heterogeneity and horizontal pleiotropy were assessed using Cochran Q test and MR-Egger regression intercept, respectively. Results Genetically predicted T2D was inversely associated with the risk of TAA (OR: 0.931, 95% CI 0.870 to 0.997, p = 0.040, IVW method) and AAoD (Beta: -0.065, 95%CI −0.099 to − 0.031, p = 1.7e−04, IVW method), but not with DAoD (p > 0.05). Genetically predicted FG level was inversely associated with AAoD (Beta: −0.273, 95% CI −0.396 to –0.150, p = 1.41e−05, IVW method) and DAoD (Beta: −0.166, 95% CI −0.281 to −0.051, p = 0.005, IVW method), but not with TAA (p > 0.05). The effect of genetically predicted HbA1c and FI on TAA, AAoD and DAoD did not reach statistical significance (p > 0.05). Conclusions Genetic predisposition to T2D decreases the risk of TAA. Genetically predicted T2D is inversely associated with AAoD, but not with DAoD. Genetically predicted FG level was inversely associated with AAoD and DAoD.

In heat exchangers, solar collectors, and geophysical transport, the temperature difference is significant, so the linear form of the density-temperature approximation (the Boussinesq approximation) is inadequate to describe actual density variations. Thus, the current study took into account the effect of nonlinear buoyancy on the thermal performance of a homogeneous nanofluid with hybrid nanoparticles in a free convective inclined energy system. In addition, response surface methodology with central composite design (RSM-CCD) is implemented to build a quadratic model based on three factors and levels (Ha, α, ϕ). To perform thermal evaluation, the experimental correlations are utilized with dimensionless controlling parameters such as Rayleigh number (Ra = 103 to 106), Hartmann number (Ha = 0 to 50), nanoparticle volume fraction (ϕ = 0 to 0.02) and angle of inclination (α = 0 to π) using Galerkin finite element method (GFEM) with a refined mesh (degree of freedoms (DOFs) = 208977, domain elements = 25636 and boundary elements = 858) for grid independent results. According to RSM-CCD, the Hartmann number has a significant impact on the thermal behavior of energy system. Also, the maximum average Nusselt number (Nur = 5.4938) is achieved with the optimal combination of key parameters i.e., Ha=36.707, α=0.5236 and ϕ=0.001.

Within the classical convection–diffusion approximation, we show that the angular distribution of cosmic rays (CRs) in a highly turbulent flow may exhibit significant small-scale anisotropies. The CR intensity angular power spectrum C _ℓ is then a direct reflection of interstellar turbulence, from which one expects C _ℓ ∝ ℓ ^− ^γ ^−1 for ℓ ≫ 1, where γ is the power-law turbulence spectral index. Observations by IceCube and HAWC at TeV energies can be explained approximately with the Kolmogorov law γ = 5/3 with a convection velocity dispersion of 20 km s ^−1 on the scale of 10 pc.

Biodiversity underpins grassland ecological functions and productive capacities. By studying the mechanisms for the maintenance of species diversity in animal communities, we can provide important theoretical guidance for the optimization of grazing management and biodiversity protection. The typical grassland of Xilingol in Inner Mongolia, China, was used as the experimental area, and a grazing intensity experiment was set up. This consisted of four gradient levels that were grazed by sheep, which were available for continuous monitoring, namely control standard sheep unit·day·hectare-1·year-1 (CK, 0 SSU·d·hm-2y-1), light grazing (LG, 170 SSU·d·hm-2·y-1), moderate grazing (MG, 340 SSU·d·hm-2·y-1), and high grazing (HG, 510 SSU·d·hm-2·y-1). Nine consecutive years of multi-indicator monitoring of vegetation was carried out from 2014–2022, using monitoring data coupled with time series and inter-annual climatic (relative moisture index, RMI) fluctuations. This was done to analyze the impacts of disturbances, such as grazing use and climatic fluctuations, on the diversity of species and above-ground productivity of the community, thereby exploring the relationship between diversity and productivity, and provide possible explanations for the emergence of a range of ecological responses. The statistical analysis methods used were One-way Analysis of Variance (ANOVA), general linear regression and mixed-effects models. The main conclusions of this study are as follows: (1) The grassland in the experimental area under CK had the highest diversity and productivity and the ecosystem was better able to buffer the negative impacts of climatic drought. Furthermore, the effect of climate on productivity and diversity weakened as the intensity of grazing increased. (2) LG to MG had a constant diversity. (3) Grazing utilization changed the relationship between community species diversity and aboveground productivity by releasing spatial community resources, altering the structure of plant communities, weakening competitive exclusion, and strengthening complementary effects. However, under all of the conditions there is a brief stage in the time series when diversity is stimulated to increase, and the higher the grazing intensity, the earlier this occurs.

PurposeTOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been shown an essential role in tumorigenesis by accelerating the DNA replication of tumor cells.MethodsRT-qPCR was used to detect the mRNA expression of TICRR in LUAD tumors and adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the critical role of TICRR expression in survival prognosis and clinicopathology characters in LUAD. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR expression with immune cell infiltration, RNA epigenetic modification, DNA damage repair (DDR) pathway, and cell metabolism of LUAD was further explored to verify significant conclusions.ResultsTICRR was significantly upregulated in most cancer types, including LUAD, lung squamous cell carcinoma (LUSC), and others. Cox regression analysis indicated the overexpression of TICRR was associated with poor survival in several cancers. In LUAD, TICRR expression was positively correlated with tumor stage and was increased in smoking, male, and high tumor mutational burden (TMB) patients. Enrichment analysis revealed that TICRR could influence tumor proliferation and prognosis via activating pathways involving cell cycle, DNA repair, DNA replication, cysteine metabolism, oxidative phosphorylation, and ubiquitin-mediated proteolysis pathways. Interestingly, high TICRR expression correlated with DDR pathway signature (34 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Silencing the TICRR gene affects cysteine metabolism and modifies cancer-related pathways, with decreased cell cycle and increased B/T cell receptor signaling. Our TICRR risk model accurately predicts LUAD patient prognosis, validated across GEO datasets, and is integrated with clinical characteristics via a nomogram, facilitating personalized treatment strategies and enhancing patient management.ConclusionsTaken together, TICRR has emerged as a promising prognostic biomarker in lung adenocarcinoma (LUAD), with implications in immune activation, cell cycle regulation, RNA modification, and tumor energy metabolism. These findings suggest that TICRR could serve as a viable therapeutic target and a reliable prognostic indicator for LUAD.

Summary: Our previous work has established a knockin (KI) pig model of Huntington’s disease (HD) that can replicate the typical pathological features of HD, including selective striatal neuronal loss, reactive gliosis, and axonal degeneration. However, HD KI mice exhibit milder neuropathological phenotypes and lack overt neurodegeneration. By performing RNA sequencing to compare the gene expression profiles between HD KI pigs and mice, we find that genes related to interleukin-17 (IL-17) signaling are upregulated in the HD pig brains compared to the mouse brains. Delivery of IL-17 into the brain striatum of HD KI mice causes greater reactive gliosis and synaptic deficiency compared to HD KI mice that received PBS. These findings suggest that the upregulation of genes related to IL-17 signaling in HD pig brains contributes to severe glial pathology in HD and identify this as a potential therapeutic target for treating HD.

Abstract Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.

Abstract Immune checkpoint blockade (ICB) is a promising treatment strategy for colorectal cancer (CRC) patients. However, most CRC patients do not response well to ICB therapy. Increasing evidence indicates that ferroptosis plays a critical role in immunotherapy. ICB efficacy may be enhanced by inducing tumor ferroptosis. Cytochrome P450 1B1 (CYP1B1) is a metabolic enzyme that participates in arachidonic acid metabolism. However, the role of CYP1B1 in ferroptosis remains unclear. In this study, we demonstrated that CYP1B1 derived 20-HETE activated the protein kinase C pathway to increase FBXO10 expression, which in turn promoted the ubiquitination and degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4), ultimately inducing tumor cells resistance to ferroptosis. Furthermore, inhibiting CYP1B1 sensitized tumor cells to anti-PD-1 antibody in a mouce model. In addition, CYP1B1 expression was negatively correlated with ACSL4 expression, and high expression indicates poor prognosis in CRC. Taken together, our work identified CYP1B1 as a potential biomarker for enhancing anti-PD-1 therapy in CRC.

Lung aging triggers the onset of various chronic lung diseases, with alveolar repair being a key focus for alleviating pulmonary conditions. The regeneration of epithelial structures, particularly the differentiation from type II alveolar epithelial (AT2) cells to type I alveolar epithelial (AT1) cells, serves as a prominent indicator of alveolar repair. Nonetheless, the precise role of aging in impeding alveolar regeneration and its underlying mechanism remain to be fully elucidated. Our study employed histological methods to examine lung aging effects on structural integrity and pathology. Lung aging led to alveolar collapse, disrupted epithelial structures, and inflammation. Additionally, a relative quantification analysis revealed age-related decline in AT1 and AT2 cells, along with reduced proliferation and differentiation capacities of AT2 cells. To elucidate the mechanisms underlying AT2 cell functional decline, we employed transcriptomic techniques and revealed a correlation between inflammatory factors and genes regulating proliferation and differentiation. Furthermore, a D-galactose-induced senescence model in A549 cells corroborated our omics experiments and confirmed inflammation-induced cell cycle arrest and a >30% reduction in proliferation/differentiation. Physiological aging-induced chronic inflammation impairs AT2 cell functions, hindering tissue repair and promoting lung disease progression. This study offers novel insights into chronic inflammation’s impact on stem cell-mediated alveolar regeneration.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Abstract Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium‐based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel‐associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease‐free survival in CRC patients. Gain‐ and loss‐of‐function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial‐mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte‐conditional Tcaf2‐knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro‐metastatic effects of TPCs from the perspective of cold‐sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.

Abstract Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

The synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted considerable attention in the field of cancer therapy because of its excellent anti-tumor effect. This work provides a novel pH/NIR responsive therapeutic nanoplatform, IrO2@ZIF-8/BSA-FA (Ce6), producing a synergistic effect of PTT-PDT in the treatment of osteosarcoma. Iridium dioxide nanoparticles (IrO2 NPs) with exceptional catalase-like activity and PTT effects were synthesized by a hydrolysis method and decorated with zeolitic imidazolate framework-8 (ZIF-8) shell layer to promote the physical absorption of Chlorin e6 (Ce6), and further functionalized with bovine serum albumin-folate acid (BSA-FA) for targeting tumor cells. The IrO2@ZIF-8/BSA-FA nanocomposite indicated an outstanding photothermal heating conversion efficiency of 62.1% upon laser irradiation. In addition, the Ce6 loading endows nanoplatform with the capability to induce cell apoptosis under 660 nm near-infrared (NIR) laser irradiation through a reactive oxygen species (ROS)-mediated mechanism. It was further testified that IrO2@ZIF-8/BSA-FA can function as a catalase and convert the endogenous hydrogen peroxide (H2O2) into oxygen (O2) to improve the local oxygen pressure under the acidic tumor microenvironment (TME), which could subsequently amplified PDT-mediated ROS cell-killing performance via relieving hypoxia microenvironment of tumor. Both in vitro and in vivo experimental results indicated that the nanomaterials were good biocompatibility, and could remarkably achieve tumor-specific and enhanced combination therapy outcomes as compared with the corresponding PTT or PDT monotherapy. Taken together, this work holds great potential to design an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

The proposed Ni–M/sepiolite (SEP) catalysts (M=Ce, Pr, and La) were developed to improve syngas production in biomass pyrolysis. A homogeneous precipitation method was used to synthesize these catalysts. These catalysts were characterized using X-ray fluorescence, X-ray diffraction, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and the Brunauer–Emmett–Teller method. A series of experiments were conducted to investigate the effects of catalyst types and M loading on gas composition and content in gas production. Simultaneously, the catalyst’s stability was tested. The experiments showed that the synthesized Ni–La/SEP catalyst with 12 wt% La and 20 wt% Ni loading had a high catalytic activity of improving gas quality compared with Ni–Pr/SEP, Ni–Ce/SEP, and Ni/SEP, giving a high hydrogen yield (41.18 vol.%) and CO yield (32.23 vol.%).

Abstract Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and has resulted in a protracted pandemic. Infections caused by new coronavirus strains, primarily Delta and Omicron and currently highly prevalent globally. In response to the epidemic, countries, and cities implemented isolation and quarantine guidance, such as limiting social contact, which have affected the lifestyles and quality of life of the population. Parental feeding behaviors may vary as a result of factors such as prolonged home isolation of parents and children, lack of supplies during isolation, and stress. This study was designed to assess the available evidence and its implications for parental feeding practices in the context of COVID-19. We screened and reviewed research published in five electronic databases between 2020 and 2022, and eight studies met the selection criteria. Parents were observed to use a variety of feeding practices, including high levels of coercive control and reduction of rules and limits according to Vaughn’s food parenting constructs. The findings suggest that parental feeding practices are changing as a result of the pandemic and that more research is needed to further explore how to provide supportive feeding guidance to parents during emergencies in order to jointly promote child health.

Food safety is closely related to human health. However, the regulation and testing processes for food safety are intricate and resource-intensive. Therefore, it is necessary to address food safety risks using a combination of deep learning, the Internet of Things, smartphones, quick response codes, smart packaging, and other smart technologies. Intelligent designs that combine digital systems and advanced functionalities with biosensors hold great promise for revolutionizing current food safety practices. This review introduces the concept of Food Safety 4.0, and discusses the impact of intelligent biosensors, which offer attractive smarter solutions, including real-time monitoring, predictive analytics, enhanced traceability, and consumer empowerment, helping improve risk management and ensure the highest standards of food safety.

Abstract Background Atelectasis is the primary cause of hypoxemia during general anesthesia. This study aimed to evaluate the impact of the combination of recruitment maneuvers (RM) and positive end-expiratory pressure (PEEP) on the incidence of atelectasis in adult women undergoing gynecologic laparoscopic surgery using pulmonary ultrasound. Methods In this study, 42 patients with healthy lungs undergoing laparoscopic gynecologic surgery were randomly divided into the recruitment maneuver group (RM group; 6 cm H2O PEEP and RM) or the control group (C group; 6 cm H2O PEEP and no RM), 21 patients in each group. Volume-controlled ventilation was used in all selected patients, with a tidal volume of 6–8 mL·kg−1 of ideal body weight. When atelectasis was detected, patients in the RM group received ultrasound-guided RM, while those in the C group received no intervention. The incidence and severity of atelectasis were determined using lung ultrasound scores. Results A total of 41 patients were investigated. The incidence of atelectasis was lower in the RM group (40%) than in the C group (80%) 15 min after arrival in the post-anesthesia care unit (PACU). Meanwhile, lung ultrasound scores (LUSs) were lower in the RM group compared to the C group. In addition, the differences in the LUS between the two groups were mainly due to the differences in lung ultrasound scores in the posterior regions. However, this difference did not persist after 24 h of surgery. Conclusions In conclusion, the combination of RM and PEEP could reduce the incidence of atelectasis in patients with healthy lungs 15 min after arrival at the PACU; however, it disappeared within 24 h after surgery. Trial registration (Prospectively registered): ChiCTR2000033529 . Registered on 4/6/2020.

To prepare an ophthalmic solution with a cell-permeable TAT peptide (TAT-N24) as the main cell-permeable peptide inhibitor of p55PIK signaling and observe its therapeutic effect on suture-induced corneal neovascularization (CNV) in rats. Sprague-Dawley rats were used to establish a corneal suture (CS) model of CNV. The vehicle and 0.9% TAT-N24 ophthalmic solution was topically administered. CNV induction was assessed on the basis of the clinical performance of each group. Hematoxylin-eosin staining was used to observe pathological changes, and immunohistochemical staining and confocal immunofluorescence were used to determine the localization of factors associated with corneal tissue. The mRNA expression levels of hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF-A), nuclear transcription factor κB (NF-κB p65), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin (IL)-6 were determined using real-time quantitative polymerase chain reaction. Western blotting was performed to detect the protein expression levels of HIF-1α and NF-κB p65. TAT-N24 slowed CNV production and reduced the expression of HIF-1α and inflammatory factors in CS models. The mRNA levels of HIF-1α, VEGF-A, NF-kB, TNF-α, IL-1β, and IL-6 significantly decreased. Moreover, the protein levels of HIF-1α and NF-κB p65 were significantly decreased. TAT-N24 can treat CNV and ocular inflammation by inhibiting the HIF-1α/NF-κB signaling pathway in CS. In the early treatment of corneal foreign body trauma, topical application of TAT-N24 can not only reduce the inflammatory response but also inhibit corneal neovascularization.

BackgroundTrochanteric fractures usually require surgical treatment. The currently used classification system, such as AO classification, cannot cover all variant types, and is poor in reliability, causing confusion in surgical decision making. This study describes a simple, well-covered, re-liable, accurate, and clinically useful classification.MethodsWe retrospectively reviewed the records of 907 patients with trochanteric fractures treated by us from 1,999 to 2019 and proposed a new classification according to radiographs. Then, 50 records randomly selected in proportion were examined by 10 observers (5 experienced and 5 inexperienced) independently according to AO and the new classification. After a 2-week interval, repeat evaluation was completed. The Kappa coefficient was used to investigate the intra-observer reliability, inter-observer reliability and the agreement between the observers and the “reference standard”.ResultsThe new classification system includes 12 types composed of 3 medial groups and 4 lateral groups. According to the medial buttress, the fractures are divided into group I (intact lesser trochanter, adequate but-tress), group II (incomplete lesser trochanter, effective cortical buttress after reduction) and group III (huge defect of the medial cortex). According to the penetration region of the lateral fracture line, the fractures are divided into group A (intact lateral cortex), group B (incomplete lateral cortex), group C (subtrochanteric fractures) and group D (multiple lateral fracture lines). All of the included cases can be classified according to the new classification, of which 34 (3.75%) cases are unclassifiable by the AO classification. Intra-observer: The experienced achieved substantial agreement using both AO [k = 0.61 (95% confidence interval 0.46–0.76)] and new classification [k = 0.65 (0.55–0.76)]. The inexperienced reached moderate agreement using both AO [k = 0.48 (0.33–0.62)] and new classification [k = 0.60 (0.50–0.71)]. Inter-observer: The overall reliabilities for AO [k = 0.51 (0.49–0.53)] and for new classification [k = 0.57 (0.55–0.58)] were both moderate. The agreement between the experienced and the reference standard according to AO [k = 0.61 (0.49–0.74)] and new classification [k = 0.63 (0.54–0.72)] were both substantial. The agreement between the inexperienced and the reference standard according to AO [k = 0.48 (0.45–0.50)] and the new classification [k = 0.48 (0.41–0.54)] were both moderate.ConclusionCompared with AO classification, our new classification is better in coverage, reliability and accuracy, and has the feasibility of clinical verification and promotion.

Introduction: Mitochondria-targeted low-temperature photothermal therapy (LPTT) is a promising strategy that could maximize anticancer effects and overcome tumor thermal resistance. However, the successful synthesis of mitochondria-targeted nanodrug delivery system for LPTT still faces diverse challenges, such as laborious preparations processes, low drug-loading, and significant systemic toxicity from the carriers.Methods: In this study, we used the tumor-targeting folic acid (FA) and mitochondria-targeting berberine (BBR) derivatives (BD) co-modified polyethylene glycol (PEG)-decorated graphene oxide (GO) to synthesize a novel mitochondria-targeting nanocomposite (GO-PEG-FA/BD), which can effectively accumulate in mitochondria of the osteosarcoma (OS) cells and achieve enhanced mitochondria-targeted LPTT effects with minimal cell toxicity. The mitochondria-targeted LPTT effects were validated both in vitro and vivo.Results:In vitro experiments, the nanocomposites (GO-PEG-FA/BD) could eliminate membrane potential (ΔΨm), deprive the ATP of cancer cells, and increase the levels of reactive oxygen species (ROS), which ultimately induce oxidative stress damage. Furthermore, in vivo results showed that the enhanced mitochondria-targeted LPTT could exert an excellent anti-cancer effect with minimal toxicity.Discussion: Taken together, this study provides a practicable strategy to develop an ingenious nanoplatform for cancer synergetic therapy via mitochondria-targeted LPTT, which hold enormous potential for future clinical translation.

The stage of cancer is a discrete ordinal response that indicates the aggressiveness of disease and is often used by physicians to determine the type and intensity of treatment to be administered. For example, the FIGO stage in cervical cancer is based on the size and depth of the tumor as well as the level of spread. It may be of clinical relevance to identify molecular features from high-throughput genomic assays that are associated with the stage of cervical cancer to elucidate pathways related to tumor aggressiveness, identify improved molecular features that may be useful for staging, and identify therapeutic targets. High-throughput RNA-Seq data and corresponding clinical data (including stage) for cervical cancer patients have been made available through The Cancer Genome Atlas Project (TCGA). We recently described penalized Bayesian ordinal response models that can be used for variable selection for over-parameterized datasets, such as the TCGA-CESC dataset. Herein, we describe our ordinalbayes R package, available from the Comprehensive R Archive Network (CRAN), which enhances the runjags R package by enabling users to easily fit cumulative logit models when the outcome is ordinal and the number of predictors exceeds the sample size, P>N, such as for TCGA and other high-throughput genomic data. We demonstrate the use of this package by applying it to the TCGA cervical cancer dataset. Our ordinalbayes package can be used to fit models to high-dimensional datasets, and it effectively performs variable selection.

The cloud storage service provides the storage and access function for massive data, reducing the management cost for large amounts of data. The data integrity verification scheme in cloud storage can be employed to help users confirm the integrity of outsourced data. Although public data integrity verification schemes allow users to outsource data integrity verification to third-party auditor (TPA), there are still many problems with centralized TPA in terms of security and efficiency. In recent years, researchers have tried to apply blockchain technology to solve the centralization problem of traditional methods, but these schemes do not pay attention to the problem of efficiency degradation caused by the use of blockchain technology. This paper proposes an efficient data integrity verification scheme for multi-cloud storage services by using blockchain technology. The overall verification can verify the integrity of multiple CSPs, which solves the problems of low computational efficiency. Local verification can trace the source to the specific damaged CSP, which is more secure and reliable. In addition, this paper puts the data verification process directly in the blockchain for public execution and provides data integrity verification services without the assistance of any third-party audit platform, avoiding the security problems caused by untrusted TPA. Theoretical analysis and experiments verify the safety and effectiveness of the scheme.

ObjectivesTo analyze the evolution of research on children and adolescents mental health issues during COVID-19 pandemic and discuss research hotspots and cutting-edge developments.MethodsThe literature obtained from the web of science core collection as of June 28, 2022, was analyzed using Citespace, VOSviewer bibliometric visualization mapping software.ResultsA total of 6,039 relevant papers were found, of which 5,594 were included in the study. The number of literatures is growing since 2020; and the country, institution, and journal publications were analyzed. The co-citation analysis shows that there are more research articles among the highly cited articles and a lack of systematic reviews that use critical thinking for review. In the cluster analysis, mental health and life change were the most representative. The timeline view of the keywords shows that Online learning (#0), Public health (#1), and Mental health (#2) are the three largest clusters and shows the change over time.ConclusionThis study helped analyze the mental health of children and adolescents during the COVID-19 pandemic and identified hot trends and shortcomings, which are important references for the theoretical basis of future research and decision making and technical guidance for systematic reviews.

Abstract Background Acute myeloid leukemia (AML) is a heterogeneous cancer of the blood, though specific recurring cytogenetic abnormalities in AML are strongly associated with attaining complete response after induction chemotherapy, remission duration, and survival. Therefore recurring cytogenetic abnormalities have been used to segregate patients into favorable, intermediate, and adverse prognostic risk groups. However, it is unclear how expression of genes is associated with these prognostic risk groups. We postulate that expression of genes monotonically associated with these prognostic risk groups may yield important insights into leukemogenesis. Therefore, in this paper we propose penalized Bayesian ordinal response models to predict prognostic risk group using gene expression data. We consider a double exponential prior, a spike-and-slab normal prior, a spike-and-slab double exponential prior, and a regression-based approach with variable inclusion indicators for modeling our high-dimensional ordinal response, prognostic risk group, and identify genes through hypothesis tests using Bayes factor. Results Gene expression was ascertained using Affymetrix HG-U133Plus2.0 GeneChips for 97 favorable, 259 intermediate, and 97 adverse risk AML patients. When applying our penalized Bayesian ordinal response models, genes identified for model inclusion were consistent among the four different models. Additionally, the genes included in the models were biologically plausible, as most have been previously associated with either AML or other types of cancer. Conclusion These findings demonstrate that our proposed penalized Bayesian ordinal response models are useful for performing variable selection for high-dimensional genomic data and have the potential to identify genes relevantly associated with an ordinal phenotype.

Abstract Background Although lower temperature (

Abstract Background Several studies have demonstrated a relationship between the posterior tibial slope (PTS) and meniscal tears in adults. However, little is known about the association between the PTS of the adolescents and medial meniscal tears (MMT). The purpose of this study was to evaluate the association between the PTS and MMT in adolescents, and to determine the optimal cut-off values of PTS for discriminating between the MMT and the control groups. Methods Between January 2018 and January 2020, a retrospective case-control study was performed. In this study, isolated MMT adolescent patients with no ligamentous injuries were matched by age and sex to a control group of radiologically normal images. The PTS was defined as the angle between the perpendicular line to proximal tibial cortex (PTC) and the tangent line along the tibial plateau. Then, both the medial posterior tibial slope (MPTS) and lateral posterior tibial slope (LPTS) were measured by plain radiographs on the lateral views. In addition, the optimal cut-off values of PTS were determined by the receiver operating characteristic (ROC) curve analysis. Results A total of seventy-two patients who met the inclusion criteria were enrolled in the final analysis (36 patients with isolated MMT, 36 controls). The MPTS was greater in the knees with isolated MMT (10.7° ± 2.1°) than that of the control group (8.8° ± 1.7°), showing significant difference (P0.05). In the ROC curve analysis, the calculated cutoff value of the MPTS discriminating between the groups was 10.3°, with a sensitivity of 73.3% and specificity of 78.9%. Conclusions This study demonstrated that steep MPTS is associated with MMT, and MPTS≥10.3° was identified to be a risk factor for MMT in adolescents.