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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 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.

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.

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

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 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.

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 Osteoarthritis (OA) is the most common degenerative joint disease. Currently, no satisfactory pharmacological treatment exists for OA. The potential anti-inflammatory properties of Dihydrotanshinone I (DHT) have been reported, but its effects on OA are unclear. In this study, we assess the impact of DHT on the viability of human chondrocytes in vitro. We then use a guinea pig model to investigate the effects of DHT on knee osteoarthritis progression. Twelve-week-old Dunkin Hartley guinea pigs spontaneously developing OA were intraperitoneally injected with different doses of DHT for eight weeks. Micro-CT analysis was performed on the subchondral bone in the knee, and histological assessment of the knee joint was done using stained sections, the ratio of hyaline to calcified cartilage, and Mankin scores. DHT successfully restored IL-1β-induced decreases in cell viability in human primary chondrocytes. In the guinea pig model, intraperitoneal injections of DHT ameliorated age-induced OA, effectively reduced the expression level of two cartilage metabolism-related genes (ADAMTS4 and MMP13) and decreased the inflammatory biomarker IL-6 in the serum of guinea pigs developing spontaneous osteoarthritis. These findings demonstrate DHT’s protective effects on chondrocytes and suggest that it alleviates cartilage degradation and proteoglycan loss in OA.

Abstract The skin is a vital organ in the human body, providing essential functions such as protection, sensation, and metabolism. Skin hydration is one of the crucial factors in maintaining normal skin function. Insufficient skin hydration can lead to dryness, shedding of the stratum corneum, a decrease in skin barrier function, and may cause skin inflammation. Therefore, maintaining or improving skin hydration is critical in promoting healthy skin. Currently, the commonly used method for measuring skin hydration is bioelectrical capacitance analysis, which is often affected by environmental humidity and can only provide limited information. To overcome these limitations, this study used diffuse reflectance spectroscopy (DRS) in the wavelength range of 400-1000 nm to quantify skin absorption and scattering modulation caused by changes in skin hydration states. The advantages of this technique include rapid measurements, non-invasiveness, a straightforward optical setup, and suitability for prolonged skin monitoring. We found that DRS-derived skin absorption coefficients had a correlation coefficient of 0.93 with the skin capacitance at various skin hydration states. In addition, our findings reveal that absorption and scattering coefficients may be useful in discerning skin hydration enhancement induced by applying soaked cotton pads or cosmeceutical facial masks, as well as evaluating skin sensation. This study verifies that the DRS method could be a convenient and effective tool for evaluating skin hydration related information.

Porcine Parvovirus (PPV) and porcine circovirus type 2 (PCV2) often have mixed infection in the process of clinical breeding, and PCV2 infection will cause immunosuppression in pigs, which is easy to stimulate or complicated with other infectious pathogens. Haemophilus parasuis (HPS) is a typical "opportunistic" pathogen, which often leads to mixed infection with PCV2 as a secondary pathogen. In order to establish a rapid and simultaneous detection of three pathogens of PPV, PCV2 and HPS, referring to the relevant genome sequence of GenBank, specific primers were designed according to the conserved region of VP2 gene of PPV, Cap gene of PCV2 and infB gene of HPS, and the amplified fragments were cloned into the vector to construct plasmid standard. Using standard samples with different dilutions as templates, adjusting primer concentration, annealing temperature and other conditions, a real-time fluorescence quantitative PCR method for PPV, PCV2 and HPS triple SYBR Green I was established. Three specific Tm peaks could be generated on the same melting curve without cross-reaction with other pathogens. The minimum detection limits of this method were 153 copies/μL, 128 copies/μL and 91 copies/μL, with good specificity and repeatability, which provided technical support for rapid diagnosis of these three diseases and could be used for clinical tissue material detection.

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells. Pharmacological induction of excessively asymmetric mitofission-associated cell death (MFAD) by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy. By screening a series of pan-inhibitors, we identified pracinostat, a pan-histone deacetylase (HDAC) inhibitor, as a novel MFAD inducer, that exhibited a significant anticancer effect on colorectal cancer (CRC) in vivo and in vitro. Pracinostat increased the expression of cyclin-dependent kinase 5 (CDK5) and induced its acetylation at residue lysine 33, accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1 (Drp1)-mediated mitochondrial peripheral fission. CRC cells with high level of CDK5 (CDK5-high) displayed midzone mitochondrial division that was associated with oncogenic phenotype, but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells. Mechanistically, pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor (MFF) to mitochondrial fission 1 protein (FIS1). Thus, our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells, which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Abstract Background Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood. Results In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway. Conclusions Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine. Video Abstract

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.

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.

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.

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.

The classic targeted therapy for skin malignant tumors has issues such as efficacy attenuation, drug resistance, and recurrence. Finding new treatment targets is of great significance for patients with skin malignant tumors. The Hippo signaling pathway plays an important role in tumor proliferation, invasion, drug resistance and immunity. Targeted drugs through the Hippo signaling pathway have shown good application prospects in the combination therapy of skin malignant tumors, and are considered as an effective way to solve the problems of efficacy attenuation and drug resistance in targeted therapy in the future. This article reviews the physiological processes and potential mechanisms of Hippo pathway in skin malignant tumors, and discusses its role and significance in targeted combination therapy.

Abstract Modern communication and navigation systems are increasingly relying on atomic clocks. As timing precision requirements increase, demands for lower SWaP (size, weight, and power) clocks rise. However, it has been challenging to break through the general trade-off trend between the clock stability performance and SWaP. Here we demonstrate micro mercury trapped ion clock (M2TIC) prototypes integrated with novel micro-fabricated technologies to simultaneously achieve high performance and low SWaP. The M2TIC prototypes could reach the $$10^{-14}$$ 10 - 14 -stability level in 1 day with a SWaP of 1.1 L, 1.2 kg, and under 6 W of power. This stability level is comparable to the widely used rack-mount Microchip 5071A cesium frequency standard. These standalone prototypes survived regular commercial shipping across the North American continent to a government laboratory, where their performance was independently tested. The M2TIC sets a new reference point for SWaP and performance and opens opportunities for high-performance clocks in terrestrial and space applications.

Objective To explore the expression and significance of INHBA in cutaneous squamous cell carcinoma. Methods Immunohistochemistry, RT-PCR and western blot methods were used to measure the expression levels of INHBA in 17 cases of normal skin (NS), 30 cases of actinic keratosis (AK) and 30 cases of cutaneous squamous cell carcinoma (cSCC). Results The immunohistochemical staining indicated that the positive staining of INHBA was brown-yellow particles in the cytoplasm/nucleus, with positive rates of 23.53%, 66.67% and 86.67%, respectively, in NS, AK and cSCC (χ2=27.10,P=0.001). The relative expression levels of INHBA mRNA in NS, AK and cSCC were 1.097±0.083, 1.328±0.041, 1.731±0.064, respectively (F=48.53, P

Abstract Background To evaluate the value of a deep learning-based computer-aided diagnostic system (DL-CAD) in improving the diagnostic performance of acute rib fractures in patients with chest trauma. Materials and methods CT images of 214 patients with acute blunt chest trauma were retrospectively analyzed by two interns and two attending radiologists independently firstly and then with the assistance of a DL-CAD one month later, in a blinded and randomized manner. The consensusdiagnosis of fib fracture by another two senior thoracic radiologists was regarded as reference standard. The rib fracture diagnostic sensitivity, specificity, positive predictive value, diagnostic confidence and mean reading time with and without DL-CAD were calculated and compared. Results There were 680 rib fracture lesions confirmed as reference standard among all patients. The diagnostic sensitivity and positive predictive value of interns weresignificantly improved from (68.82%, 84.50%) to (91.76%, 93.17%) with the assistance of DL-CAD, respectively. Diagnostic sensitivity and positive predictive value of attendings aided by DL-CAD (94.56%, 95.67%) or not aided (86.47%, 93.83%), respectively. In addition, when radiologists were assisted by DL-CAD, the mean reading time was significantly reduced, and diagnostic confidence was significantly enhanced. Conclusions DL-CAD improves the diagnostic performance of acute rib fracture in chest trauma patients, which increases the diagnostic confidence, sensitivity, and positive predictive value for radiologists. DL-CAD can advance the diagnostic consistency of radiologists with different experiences.

Microchannel heat dissipation systems are widely used in micro-electro mechanical systems owing to their high thermal conductivity and small size. Laser processing has the advantages of high efficiency and no tool contact, and is one of the best ways to process ceramic materials. However, the roughness of the machined surface will significantly affect the heat dissipation performance of the microchannel. In order to study the influence of roughness element characteristics on the heat dissipation efficiency of the micro-channel radiator, the surface roughness was simulated with typical shape, and the influence of different roughness element shape, height and spacing on the pressure field, velocity field and temperature field of the micro-channel radiator was analysed. The results indicate that the semi-circular roughness element has the highest heat transfer efficiency and that the overall flow is stable. With an increase in the height of the roughness element and a reduction in the spacing, the heat transfer efficiency and inlet/outlet pressure drop increased. When the height of the roughness element is 17.2 μm, the heat transfer ability was significantly improved and the pressure drop ratio is reduced by >20% compared with that for a height of 19.5 μm. When the distance between roughness elements is 33.5 μm, the maximum temperature of the heat dissipation system was only 331.85 K. Compared with other models, the temperature of the optimized model is reduced by 14.44K, and the heat transfer efficiency is the highest. The results of heat dissipation experiments show that compared with dry burning temperature, the optimized model can reduce the temperature of the micro-channel heat dissipation system by more than 73 K.

Construction 3D printing (C3DP) has emerged as an important force in automation and sustainable transformation of the construction industry. Despite the implementation of numerous incentive policies, its development and application remain at a relatively slow pace in developing countries. This research employs the Q methodology to explore the perspectives of China's stakeholders on the innovation policies for the development and application of C3DP. The study reviews the development of C3DP in China and identifies statements related to C3DP promotion policy and development. Based on data from C3DP industrial experts, the results reveal four distinct policy perspectives: conservative exploration, aggressive progression, intensive investigation, and tentative stimulation. A consensus exists that provides direction for policymaking though the divergences among stakeholders highlight the complexity of implementing policy mixes. This study has theoretical and practical significance in supporting policy mixes for C3DP development and adoption in fast-growing areas.

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.

Nitric oxide (NO) is synthesized in all kingdoms of life, where it plays a role in the regulation of various physiological and developmental processes. In terms of endogenous NO biology, fungi have been less well researched than mammals, plants, and bacteria. In this review, we summarize and discuss the studies to date on intracellular NO biosynthesis and function in fungi. Two mechanisms for NO biosynthesis, NO synthase (NOS)-mediated arginine oxidation and nitrate- and nitrite-reductase-mediated nitrite reduction, are the most frequently reported. Furthermore, we summarize the multifaceted functions of NO in fungi as well as its role as a signaling molecule in fungal growth regulation, development, abiotic stress, virulence regulation, and metabolism. Finally, we present potential directions for future research on fungal NO biology.

BackgroundElderly patients frequently experience a high incidence of adverse drug events (ADEs) due to the coexistence of multiple diseases, the combination of various medications, poor medication compliance, and other factors. Global Trigger Tool (GTT) is a new method for identifying ADEs, introducing the concept of a trigger, that is, clues including abnormal laboratory values, reversal drugs, and clinical symptoms that may suggest ADEs, and specifically locating information related to ADEs in the medical record to identify ADEs. The aim of this study was to establish a GTT-based trigger tool for adverse medication events in elderly patients and to investigate the risk variables associated with such events.MethodsThe triggers were identified by reviewing the frequency of ADEs in elderly patients in Sichuan, China, retrieving relevant literature, and consulting experts. A retrospective analysis was carried out to identify adverse medication occurrences among 480 elderly inpatients in Sichuan People’s Hospital.ResultsA total of 56 ADEs were detected in 51 patients (10.62%), 13.04 per 1,000 patient days, and 11.67 per 100 admissions. The overall positive predictive value (PPV) of the triggers was 23.84, and 94.64% of ADEs caused temporary injury. Gastrointestinal system injury (27.87%) and metabolic and nutritional disorders (24.53%) were the primary organ-systems affected by ADEs. The majority of ADEs were caused by drugs used to treat cardiovascular diseases. 71.43% of ADE occurred within 2 days of administration and the risk factor analysis of ADE revealed that the number of medicines had a significant correlation.ConclusionThis study demonstrated GTT’s value as a tool for ADEs detection in elderly inpatients in China. It enhances the level of medication management and comprehensively reflects the situation of ADE of the elderly.