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Abstract A novel prefabricated segmental guardrail is proposed to facilitate connections between guardrails and between guardrails and bridge decks by casting ultrahigh-performance concrete (UHPC) joints in situ. Through finite element crash simulation analysis of three types of vehicles and crash tests of real vehicles, the prefabricated segmental guardrail with a UHPC connection was systematically evaluated in terms of its energy-absorbing capacity, vehicular acceleration, post-impact trajectory of the impacting vehicle, and behaviour of the guardrail upon impact. During the evaluation process, performance comparisons of the prefabricated segmental guardrails are made with the monolithic concrete guardrails. The results indicate that the performance of the prefabricated segmental guardrail with a UHPC connection was superior to that of the conventional concrete monolithic guardrails: it exhibited a higher level of crash performance, the occupants of the impacting vehicle were better protected, and the impacting vehicle exhibited better post-collision stability. Finally, the convenience of the prefabricated segmental guardrails with UHPC connections was proven in practical engineering applications.

Abstract. Background:. There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. Methods:. In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. Results:. At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P

A novel precast segmental barrier system was proposed to facilitate the connections between barriers and between the barrier and bridge deck by casting ultra-high-performance concrete joints in situ. To assess the performance of the barrier with this connection, a full-scale pseudo-static tests were conducted. At the same time, a comparative assessment was considered the failure mode and load capacity of the precast barrier for two different bridge deck stiffnesses. The results indicated that the ultimate capacity of the precast barrier was comparable to that of a traditional cast-in-place barrier and emphasised the critical role of the deck slab stiffness in the overall load capacity. Based on the damage patterns observed in the barrier and deck slab during the pseudo-static tests, a refined trapezoidal yield-line model considering the deck slab stiffness contribution was derived to more accurately evaluate the load capacity of a precast segmental barrier. Moreover, the calibrated numerical model of the barrier system was employed to investigate the structural dynamic performance under varying scenarios, specifically examining the effects of different impact masses and velocities. Numerical results demonstrated that upon impact by a high-mass, high-velocity object, the barrier experienced a shift in damage mode from flexural–shear to more critical punching shear. This transition concentrated the dynamic load exclusively on the impacted barrier segment, which in turn markedly diminished its dynamic load capacity.

Abstract Background Pregnant women belong to the special population of drug therapy, and their physiological state, pharmacokinetics and pharmacodynamics are significantly different from the general population. Drug safety during pregnancy involves two generations, which is a hot issue widely concerned in the whole society. Global Trigger Tool (GTT) of the Institute for Healthcare Improvement (IHI) has been wildly used as a patient safety measurement strategy by several institutions and national programs, and the effectiveness had been demonstrated. But only one study reports the use of GTT in obstetric delivery until now. The aim of the study is to establish triggers detecting adverse drug events (ADEs) suitable for obstetric inpatients on the basis of the GTT, to examine the performance of the obstetric triggers in detecting ADEs experienced by obstetric units compared with the spontaneous reporting system and GTT, and to assess the utility and value of the obstetric trigger tool in identifying ADEs of obstetric inpatients. Methods Based on a literature review searched in PubMed and CNKI from January of 1997 to October of 2023, retrospective local obstetric ADEs investigations, relevant obstetric guidelines and the common adverse reactions of obstetric therapeutic drugs were involved to establish the initial obstetric triggers. According to the Delphi method, two rounds of expert questionnaire survey were conducted among 16 obstetric and neonatological physicians and pharmacists until an agreement was reached. A retrospective study was conducted to identity ADEs in 300 obstetric inpatient records at the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital from June 1 to September 30, 2018. Two trained junior pharmacists analyzed the first eligible records independently, and the included records reviewed by trained pharmacist and physician to identify ADEs. Sensitivity and specificity of the established obstetric triggers were assessed by the number of ADEs/100 patients and positive predictive value with the spontaneous reporting system (SRS) and GTT. Excel 2010 and SPSS22 were used for data analysis. Results Through two rounds of expert investigation, 39 preliminary triggers were established that comprised four modules (12 laboratory tests, 9 medications, 14 symptoms, and 4 outcomes). A total of 300 medical records were reviewed through the obstetric triggers, of which 48 cases of ADEs were detected, with an incidence of ADEs of 16%. Among the 39 obstetric triggers, 22 (56.41%) were positive and 11 of them detected ADEs. The positive predictive value (PPV) was 36.36%, and the number of ADEs/100 patients was 16.33 (95% CI, 4.19–17.81). The ADE detection rate, positive trigger rate, and PPV for the obstetric triggers were significantly augmented, confirming that the obstetric triggers were more specific and sensitive than SRS and GTT. Conclusion The obstetric triggers were proven to be sensitive and specific in the active monitoring of ADE for obstetric inpatients, which might serve as a reference for ADE detection of obstetric inpatients at medical institutions.

Passenger density is a major factor influencing indoor climate conditions and the corresponding energy consumption in the transfer halls of metro transportation hubs. In this study, passenger flow in a subway transfer hall in Beijing was measured across three typical seasons. A differential equation model was established to account for the characteristics of passenger density. Based on this, a passenger density prediction model was developed and utilized for analysis. The results show that passenger density is primarily affected by operation time and the surrounding population composition, with a relatively weak correlation to outdoor weather conditions. Additionally, passenger density differs significantly between weekdays and weekends, with the weekday peak being 2.5 times higher than that on weekends. During the four peak hours on weekdays, both in the morning and evening, passenger density exceeds the design capacity, resulting in insufficient fresh air supply. However, for most of the weekday hours and for all hours on weekends, passenger density remains below the design capacity. This indicates a substantial potential for energy savings by adjusting the fresh air supply according to actual passenger density.

The energy ecological footprint measures the environmental impact of energy consumption and is an important indicator for assessing sustainable development. This study introduced the concept of embodied carbon and developed a new energy ecological footprint accounting model. The Spatial Durbin Model was used to analyze the spillover effects of various factors influencing the energy ecological footprint. The quantile regression method was applied to examine the phased impact of each influencing factor on spatio-temporal evolution of the energy ecological footprint. A nested matrix was constructed to classify the quantile response types of each influencing factor and the spatio-temporal transition types. Additionally, a governance model for regional energy ecological footprint reduction was proposed. The results showed that: First, the spatio-temporal distribution of the energy ecological footprint of China's 29 provinces was not completely random while the energy ecological footprint of each province had significant spatial correlation characteristics. Moreover, the change of energy ecological footprint affected by its neighboring provinces. Second, industrial structure, environmental regulation, and urbanization level had a critical effect on the spatio-temporal evolution of China's energy ecological footprint. Furthermore, each factor will affect the change of the energy ecological footprint in the surrounding areas through the spatial transmission mechanism of the influencing factors, and there was a significant spatio-temporal spillover effect. Third, there were driving and constraint modes of spatio-temporal transition in the process of spatial agglomeration of energy ecological footprint in each province. Quantile regression model can well explain the driving mechanism of each driving factor on the spatio-temporal transition of energy ecological footprint, and there was a strong nesting between the quantile of driving factors at different response stages and the types of spatio-temporal transition of energy ecological footprint. These findings can serve as a basis for decision-making and help formulate targeted policies, considering the “common but differentiated” approach, to reduce China's energy ecological footprint at the provincial level.

Mixtures of active self-propelled and passive colloidal particles promise rich assembly and dynamic states that are beyond reach via equilibrium routes. Yet, controllable transition between different dynamic states remains rare. Here, we reveal a plethora of dynamic behaviors emerging in assemblies of chemically propelled snowman-like active colloids and passive spherical particles as the particle shape, size, and composition are tuned. For example, assembles of one or more active colloids with one passive particle exhibit distinct translating or orbiting states while those composed of one active colloid with 2 passive particles display persistent “8”-like cyclic motion or hopping between circling states around one passive particle in the plane and around the waist of 2 passive ones out of the plane, controlled by the shape of the active colloid and the size of the passive particles, respectively. These morphology-tailored dynamic transitions are in excellent agreement with state diagrams predicted by mesoscale dynamics simulations. Our work discloses new dynamic states and corresponding transition strategies, which promise new applications of active systems such as micromachines with functions that are otherwise impossible.

Diamond tools experience severe chemical wear when machining ferrous metals, which hinders their practical applications. In order to improve the wear resistance of diamond cutting tools, in the diamond-graphite strong covalent structure prepared by laser induced solid-phase diffusion, carbon nanosheets (CNS) can be obtained by electrochemical stripping of the graphite layer onto the diamond matrix, which provides a new way to improve the limitations of diamond tools in application. After 14,400 cycles of reciprocating sliding against the GCr15 ball at a normal load of 2–8 N, friction was reduced by 45.9 %–65.6 % with high durability. The oxygen content is reduced by an order of magnitude during this process, suggesting that the CNS can prevent oxidation behavior at the sliding interface. The bare diamond had a relative wear rate of 4.1–15.4 times that of the CNS. It showed competitive inhibition of mechanochemical wear. Our work provides a convenient and green method of preparing in-situ CNS covalently bonded on a diamond surface, extending the way for the prospect of carbon materials.

A risk-aware scheduling method of multienergy virtual power plant (MEVPP) is proposed to measure the uncertainty in MEVPP. First, a novel day-ahead uncertainty scenario generation method based on denoising diffusion probabilistic model is proposed, and historical data are employed to learn the error relationship between real power curves and predict power curves. The probability distribution of the prediction error which describes the day-ahead output power curve of renewable energy source is learned by parameter training. Subsequently, the effect of risk aversion on decision-making is investigated by implementing conditional value-at-risk in the optimization model, MEVPP operation mode under the carbon trading and green certificate trading mechanism is analyzed. Finally, the proposed scheme is implemented on a test MEVPP with carbon trading, and green certificate trading is addressed in detail through a numerical study. Moreover, the effects of the operator's risk-averse behavior on the MEVPP are investigated. [ABSTRACT FROM AUTHOR]

In order to investigate the structure and properties of Al2O3/polyolefin composites, spherical Al2O3 was pretreated with a silane coupling agent, and high density polyethylene (HDPE)/polypropylene (PP) composites were prepared by primary mixing and melt blending with pretreated Al2O3 as filler and high density polyethylene (HDPE)/polypropylene (PP) mixture (mass ratio 5:95) as matrix. The investigation of the influence of the mass fraction of Al2O3 on the structure and properties of the composites was studied. The results showed that the addition of Al2O3 significantly enhanced the thermal conductivity of the composites. Specifically, the thermal conductivity increased proportionally with the mass fraction of Al2O3. When the Al2O3 mass fraction reached 25%, the thermal conductivity of the composite measured 0.331 W/(m·K), which was 231% higher than that of the pure polyolefin matrix material. Moreover, the presence of Al2O3 particles with high filler content led to a noticeable reduction in gaps within the composite, thereby facilitating the construction of thermal conductivity pathways. Additionally, the incorporation of a lower content of rigid Al2O3 particles improved crystallization ability of the polymer. Notably, the addition of the spherical Al2O3 also significantly enhanced the melt flow rate of the composites, and improved its processing performance. [ABSTRACT FROM AUTHOR]

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals. [ABSTRACT FROM AUTHOR]

MN1 C-terminal truncation (MCTT) syndrome was first reported in 2020 and only 28 patients have been recorded to date. Since MCTT syndrome is a newly defined and rare syndrome with many clinical features, the present study reviewed the manifestations and management of oral and dental anomalies. Gene variants of MCTT syndrome and their positive phenotypes were summarised. The phenotypes of variants in two exons differed from each other mainly in the craniomaxillofacial region, including brain MRI abnormalities and palatal morphology. Pathogenic mechanisms, especially in craniofacial and oral anomalies, were discussed. Appropriate treatments in the stomatology and respiratory departments could improve the symptoms of MCTT syndrome. The different sites of MN1 gene variants may influence the clinical symptoms and there may be racial differences in MCTT syndrome. We recommend oral and pulmonary evaluations for the multidisciplinary treatment of MCTT syndrome. [ABSTRACT FROM AUTHOR]

Alzheimer’s Disease (AD) is a multifaceted neurodegenerative disease predominantly defined by the extracellular accumulation of amyloid-β (Aβ) peptide. In light of this, in the past decade, several clinical approaches have been used aiming at developing peptides for therapeutic use in AD. The use of cationic arginine-rich peptides (CARPs) in targeting protein aggregations has been on the rise. Also, the process of peptide development employing computational approaches has attracted a lot of attention recently. Using a structure database containing pentapeptides made from 20 L-α amino acids, we employed molecular docking to sort pentapeptides that can bind to Aβ42, then performed molecular dynamics (MD) analyses, including analysis of the binding stability, interaction energy, and binding free energy to screen ligands. Transmission electron microscopy (TEM), circular dichroism (CD), thioflavin T (ThT) fluorescence detection of Aβ42 polymerization, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the flow cytometry of reactive oxygen species (ROS) were carried out to evaluate the influence of pentapeptides on the aggregation and cell toxicity of Aβ42. Two pentapeptides (TRRRR and ARRGR) were found to have strong effects on inhibiting the aggregation of Aβ42 and reducing the toxicity of Aβ42 secreted by SH-SY5Y cells, including cell death, reactive oxygen species (ROS) production, and apoptosis.

Several mobile telecommunication companies (MTCs), such as AT&T, Verizon, and China Mobile, are investing in content services to drive continued growth as the telecom industry has become saturated. In this study, we investigate the competition between two MTCs, one of which (MTC 1) provides both data and content services, while the other (MTC 2) provides only data services. We propose a two-stage game-theoretic model to analyze the two MTCs' optimal pricing strategies for data service and content service as well as the investment strategy for the content service. Our analysis reveals that a higher value of value-added service offered by MTC 1 will incentivize it to raise its subscription fee for the content service and induce both MTCs to reduce the prices of their data services, which results in an increased demand for the content service and a decreased demand for MTC 2's data service. As MTC 1 invests further in the quality of the content service, it would benefit from increasing the subscription fee for the content service, and the two MTCs should increase the subscription fee for the data service. However, compared to the decisions in the scenario where MTC 1 does not provide content service, the provision of this service by MTC 1 leads to a lower subscription fee for the two MTCs' data services, an increase in the demand for MTC 1's data service, and a decrease in the demand for MTC 2's data service. These findings reveal that regularly monitoring market competition, as well as adjusting pricing strategies based on market scenarios and the value of services, can enhance competitiveness and long-term profitability for MTCs.

【Objective】The symbol decomposition technique aims to decompose Optical Orthogonal Frequency Division Multiplexing (O-OFDM) symbols into multiple symbols with a small Peak to Average Power Ratio (PAPR) to mitigate the non-linear effects of Light Emitting Diodes (LEDs). However, O-OFDM generates more decomposed symbols with a higher PAPR, thereby reducing the information rate and degrading the Bit Error Rate (BER) performance.【Methods】The proposed design of Precoding O-OFDM Adaptive Symbol Decomposition with Serial Transmission (PCO-OFDM-ASDST) system uses precoding scheme to reduce the PAPR of O-OFDM symbols. The proposed method can reduce the average number of symbol decompositions for adaptive symbol decomposition. The theoretical Signal-to-Noise Ratio (SNR) expressions are derived for multipath channels, and the performance of PAPR, BER, and information rate is analyzed using Monte Carlo BER simulations.【Results】The results demonstrate that under 4 Quadrature Amplitude Modulation (QAM) modulation in Asymmetrically Clipped Optical Orthogonal Frequency Division Multiplexing (ACO-OFDM) systems, the symbol power required for PCO-OFDM-ASDST is 7 dB less than that of Adaptive Symbol Decomposition with Serial Transmission (ASDST) when the BER is 10-4. Moreover, under 64QAM, the information rate can be increased by 10 Mbit/s when the symbol power is 20 dBm.【Conclusion】The results indicate that the PCO-OFDM-ASDST outperforms ASDST systems in terms of BER and information transmission rate.

Abstract The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Shenzhen Innovation Light source Facility (SILF) is a 3.0 GeV fourth generation diffraction limited synchrotron light source currently under construction in Shenzhen. The SILF storage ring is proposed to use two 500 MHz single cell superconducting radio frequency (SRF) cavities to provide 2.4 MV RF voltage. In this study, we examined the geometric structure of mature CESR superconducting cavities and adopted a beam-pipe-type extraction scheme for high-order modes (HOM). One of the objectives of SRF cavity design and optimization in this study is to reduce Ep/Eacc and Bp/Eacc as much as possible to reduce power loss and ensure stable operation of the cavity. To reduce the risk of beam instability and thermal breakdown, the HOM and Multipacting (MP) are simulated. Moreover, the mechanical properties of the cavity are analyzed, including frequency sensitivity from pressure of liquid helium (LHe), stress, tuning, Lorentz force detuning (LFD), the microphone effect, and buckling. By comprehensive design and optimization of 500 MHz single-cell SRF cavities, a superconducting cavity for SILF storage ring was developed. This paper will detailed present the design and simulation.

Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein–protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death.

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.

This paper explores all student related data using educational data mining techniques to draw conclusions about their performance and behavior. The main idea and theoretical basis of Random Forest is described, the importance of each feature is calculated using Random Forest based Important Feature Selection Algorithm, and each feature is ranked and the best feature is selected as the effective feature for constructing the performance prediction model. By Light GBM is to further improve the GBDT algorithm and XGBoost algorithm to construct the Light GBM grade prediction model in order to improve the training speed and the prediction ability of the model. In order to verify the feasibility of the constructed model, the application of sustainable education in Chinese language education is tested from various aspects such as model testing as well as learning behavior. The results show that the accuracy of the Ligth GBM grade prediction model increases from 0.68 to 0.918 when the course progress is raised from 10 to 100, i.e., the accuracy of the Ligth GBM grade prediction model in predicting students’ grades gradually increases as the course progresses, so that it can effectively analyze the application of sustainable education in Chinese education.

Tumor microenvironment (TME)‐responsive nanozymes‐based catalytic therapy shows great potential in combating malignant tumor. However, their biological application still suffers from deficient catalytic activity. Herein, the MoOx‐Rh metallene nanozyme demonstrates highly efficient multiple enzymatic catalytic activities, where MoOx species atomically dispersed on Rh metallene surface. The resulting structures enable MoOx‐Rh metallene with maximally exposed active oxide‐metallene interface and more atoms sites around interface can be well finely regulated. Results of experiment and density functional theory (DFT) simulations support the notion that atomic interface structure facilitates multiple enzyme‐like reactions. As a TME‐responsive nanozyme, MoOx‐Rh metallene exhibits remarkable therapeutic effect of tumor due to intrinsic near‐infrared photothermal effect and laser‐enhanced multiple enzymatic catalytic activities. This study illustrates the great promise of atomic interface engineering strategy in tumor catalytic therapy. [ABSTRACT FROM AUTHOR]

Abstract Background The prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension. Methods 132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity. Results The feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively. Conclusions Radiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD.

Background The education of general practice has developed rapidly in recent years in China, but there is still a lack of comprehensive survey for undergraduate general practice education. Objective To understand the current situation and development trend of undergraduate general practice teaching in China. Methods A questionnaire survey was conducted to investigate the offices of academic affairs of all colleges and universities offering clinical medicine programs in China (n=189) in December 2019, the questionnaires included teaching institutions, faculty and curriculum construction of general practice, which were collected in June 2020. The colleges and universities were categorized into four types for analysis, including comprehensive universities, single-subject colleges (medical colleges or pharmaceutical colleges) , Chinese medicine (TCM) colleges and independent colleges to compare differences in the teaching of undergraduate general practice at different types of colleges and universities. Results A total of 175 valid questionnaires were returned, with a response rate of 92.6%. In 2019, 85.7% (150/175) of colleges and universities had undergraduate general practice teaching institutions, and the total number of general practice faculty members in colleges and universities nationwide reached 3 371, with 59.8% (2 016/3 371) of them working in the department of general practice in affiliated hospitals. Among the 175 colleges and universities that participated in the survey, 142 (81.1%) offered elective or compulsory courses in general practice, 68 (38.9%) offered graduation practice in general practice in community health centers, and 22 (12.6%) offered graduation practice in general practice in general hospitals. Among the four types of colleges and universities, the proportion of general practice departments set up in general hospitals and affiliated hospitals of single-subject colleges was over 90.0%, the proportion of TCM colleges was 70.0% (7/10) , and the proportion of independent colleges was only 63.3% (19/30) ; the proportion of independent colleges offering elective or compulsory courses in general practice was 60.0% (18/30) , while the proportions of other three types of colleges and universities offering elective or compulsory courses were ≥80.0%. The proportion of single-subject colleges carrying out graduation practice in general practice in community health centers was the highest (61.2%, 30/49) , followed by comprehensive universities (36.0%, 31/86) , and the proportions of independent colleges and TCM colleges were≤20.0%; the proportion of comprehensive universities and single-subject colleges carrying out graduation practice in general practice in general hospital was over 10.0%, while the proportion of independent colleges was 6.7% (2/30) . Conclusion The development of undergraduate general practice education has been relatively rapid in recent years, but there are still many problems, such as general practice undergraduate education is not widely carried out and developed unevenly, non-community faculty members lack practice experience in primary care, teaching and evaluation methods are simple. There is still a need to further improve the universality and balance of development in the future, and to strengthen teacher training, and enrich teaching methods and evaluation tools.

Abstract Purpose To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. Methods A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). Results Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. Conclusions Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. Critical relevance statement Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. Key points • Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. • The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. • The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation. Graphical Abstract

Particulate matter (PM) significantly contributes to the global health crisis of respiratory diseases. It is known to induce and exacerbate conditions such as asthma and respiratory infections. Long exposure to PM can increase the risk of combined allergic rhinitis and asthma syndrome (CARAS). Although therapeutic drugs can be used to improve symptoms of respiratory diseases caused by PM, their usage is often accompanied by side effects. Therefore, many studies are being conducted to discover functional food materials that can more effectively treat respiratory diseases while minimizing the side effects of these therapeutic drugs. This study was conducted to investigate the efficacy of Hydrangea serrata extract (HSE) in airway inflammation in a mouse model of CARAS exacerbated by PM. In the CARAS mouse model worsened by PM, the airway inflammation improvement effect of HSE was evaluated by analyzing allergic nasal symptoms, changes in inflammatory cells, OVA-specific immunoglobulin (Ig) levels, cytokines, mast cell activation, and histopathological findings of both nasal mucosa and lung tissue. HSE effectively reduced OVA-specific IgE and IgG1 and inhibited the production of T helper type 2 (Th2)-related cytokines such as IL-4 and IL-5. Importantly, HSE reduced IL-33 and ST2 expression and inhibited the activation of the NF-κB signaling pathway. In addition, HSE inhibited airway hypersensitivity, mucus production, and inflammatory cell infiltration. These results suggest that HSE may inhibit airway inflammation in CARAS/PM mice by regulating the IL-33/ST2/NF-κB signaling pathway, opening avenues for considering HSE as a potential material for treating allergic airway inflammation diseases in the future.

Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Abstract Background Allergic rhinitis (AR) is the most prevalent form of atopic disease. Undaria pinnatifida has potent antioxidative, antidiabetic, and anti‐inflammatory properties. Aims We investigated the immunomodulatory effect of Undaria pinnatifida extract (UPE) on allergic inflammation in an AR mouse model. Materials & Methods Mice were sensitized and intranasally challenged with ovalbumin (OVA), and the Th1/Th2 and Th17/Treg‐related cytokines and histopathology were exanimated after UPE treatments. Enzyme‐linked immunosorbent assay was performed using serum samples and NALF to detect OVA‐specific immunoglobulins and inflammatory cytokines. Mitogen‐activated protein kinases (MAPKs) were measured by western blotting analysis, and an in vitro study measured mast cell activation induced by compound 48/80. Results After UPE treatment, nasal and lung allergy symptoms, nasal mucosal swelling, and goblet cell hyperplasia were ameliorated. Oral UPE regulated the balance of Th1/Th2 and Th17/Treg cell differentiation in AR mice in a dose‐dependent manner. In addition, UPE attenuated the migration of eosinophils and mast cells to the nasal mucosa by suppressing nuclear factor kappa B (NF‐κB)/MAPKs. The levels of anti‐OVA IgE and IgG1 were also decreased. Discussion UPE inhibited inflammation by regulating the NF‐κB/MAPKs signaling pathway and supressing the activation of critical immune cells such as eosinophils and mast cells. Conclusion UPE may have therapeutic potential for AR.

To address the current issues of complex structures and low accuracies in citrus pest identification models, a lightweight pest identification model was proposed. First, a parameterized linear rectification function was introduced to avoid neuronal death. Second, the model’s attention to pest characteristics was improved by incorporating an improved mixed attention mechanism. Subsequently, the network structure of the original model was adjusted to reduce architectural complexity. Finally, by employing transfer learning, an SCHNet model was developed. The experimental results indicated that the proposed model achieved an accuracy rate of 94.48% with a compact size of 3.84 MB. Compared to the original ShuffleNet V2 network, the SCHNet model showed a 3.12% accuracy improvement while reducing the model size by 22.7%. The SCHNet model exhibited an excellent classification performance for citrus pest identification, enabling the accurate identification of citrus pests.

Chaenomeles sinensis has traditionally been used as an herbal medicine due to its characteristics that protect against inflammation, hypertension, and mutagenesis. However, the effect of Chaenomeles sinensis extract (CSE) on allergic rhinitis (AR) and its underlying mechanisms have yet to be thoroughly investigated. The current study explored the likely effect of CSE on AR in an ovalbumin (OVA)-induced AR mouse model. To this end, OVA-specific immunoglobulins, nasal symptoms, cytokine production, the infiltration of inflammatory cells, and nasal histopathology were assessed to determine the role of CSE against AR. The supplementation of CSE was found to suppress OVA-specific IgE, while OVA-specific IgG2a was increased in the serum. Further, CSE ameliorated the production of T helper type 2 (Th2) cytokines whereas it increased Th1 cytokine levels in nasal lavage fluid. Moreover, the CSE treatment group exhibited significant inhibition of IL-33/ST2 signaling. Subsequently, CES reversed the OVA-induced enhancement of epithelial permeability and upregulated E-cadherin, thus indicating that CES plays a protective role on epithelial barrier integrity. Altogether, the oral administration of CSE effectively controlled allergic response by restricting the buildup of inflammatory cells, enhancing nasal and lung histopathological traits, and regulating cytokines associated with inflammation. Collectively, the results show that the supplementation of CSE at different doses effectively regulated AR, thus suggesting the therapeutic efficiency of CSE in suppressing airway diseases.