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Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

316L stainless steel is used in a wide variety of corrosion-prone locations. However, its low hardness and poor tribological properties limit its application under heavy wear conditions. In this study, 316L Fe-based composite coatings co-doped with TB2 hard phases and rare-earth CeO2 exhibited excellent wear and corrosion resistance. Firstly, 316L-TiB2 cermet powder and (316L-TiB2)/CeO2 composite powder with high sphericity and density were prepared by high energy ball milling (HEBM), spraying drying granulation (SD), plasma spheroidization (PS) process. Then, 316L coatings, 316L-TiB2 and (316L-TiB2)/CeO2 cermet coatings were deposited by high velocity air fuel (HVAF) spraying. Finally, the effects of TiB2 and CeO2 additions on the microstructure, wear and corrosion behavior of the coatings were investigated. The results showed that TiB2 hard particles and CeO2 were uniformly distributed in the HVAF sprayed 316L-TiB2 and (316L-TiB2)/CeO2 coatings. The wear resistance of the coating prepared by 316L Fe-based composite powder with TiB2 and CeO2 is significantly improved. The hardness of the (316L-TiB2)/CeO2 composite coating was increased from 269 Hv0.3 to 826 Hv0.3 for the pure 316L coating, while the volumetric wear rate was only 3.6 % of that of the pure 316L coating (110 × 10−5 down to 4 × 10−5 mm3/N). Electrochemical tests show that the corrosion resistance of the coating decreases with the addition of TiB2 alone, but it can be improved by doping CeO2. The 316L Fe-based coating prepared by adding TiB2 and CeO2 can significantly improve the wear resistance of the coating, while the corrosion resistance decreases only slightly.

Background: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. Objective: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. Methods: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. Results: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. Conclusion: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

In urban smart city environments, traffic hazards can lead to catastrophic outcomes, including significant property losses and severe threats to public safety. Conventional traffic monitoring systems are limited in terms of accuracy and speed, presenting significant challenges for real-time traffic surveillance. To tackle these challenges, this paper introduces the GC-YOLOv9 algorithm. Specifically, we have enhanced the YOLOv9 model by incorporating Ghost Convolution, markedly improving the model’s perceptual abilities and detection accuracy. Furthermore, this study designed an integrated smart city framework that includes layers for service applications, the Internet of Things, edge processing, and data centers. By deploying the enhanced YOLOv9 model within this framework, our method achieved mAP@0.5 scores of 77.15 and 74.95 on the BDD100K and Cityscapes datasets, respectively, surpassing existing technologies. Additionally, the potential applications of this method in public area fire safety management, forest fire monitoring, and intelligent security systems further underscore its significant value in improving the safety and efficiency of smart cities.

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

In the context of a low-carbon economy, it is crucial to integrate environmentally friendly and intelligent designs into fitness facilities to ensure sustainable economic, environmental, and energy development. However, traditional fitness facilities face challenges in effectively monitoring user movements, conserving energy, and optimizing efficiency. The need to conserve energy and reduce resource costs in a low-carbon economy calls for the development of efficient algorithms that can maintain accuracy while minimizing computation and energy consumption. This study proposes a method that combines machine learning and computer vision techniques to enhance monitoring accuracy while minimizing computation and energy consumption. The ResNet-50 model is utilized to extract image features associated with human movements, while real-time object detection and tracking are performed using the YOLOv5 model. Experimental evaluations are conducted on a dataset comprising multiple action categories, and the results demonstrate the excellent performance and model efficiency of the proposed method. Specifically, on the KU-HAR dataset, the proposed algorithm achieves a reduction of over 46.8% in inference time and more than 45.9% in FLOPs, while improving the MAPE by more than 42.8%. These advancements significantly enhance the accuracy and robustness of human motion recognition, highlighting the importance of this approach in the green transformation and intelligent design of fitness facilities.

The micaceous weathered granitic soil (WGS) is frequently encountered in civil engineering worldwide, unfortunately little information is available regarding how mica affects the physico-mechanical behaviors of WGS. This study prepares reconstituted WGS with different mica contents by removing natural mica in the WGS, and then mixes it with commercial mica powders. The geotechnical behavior as well as the microstructures of the mixtures are characterized. The addition of mica enables the physical indices of WGS to be specific combinations of coarser gradation and high permeability but high Atterberg limits. However, high mica content in WGS was found to be associated with undesirable mechanical properties, including increased compressibility, disintegration, and swelling potential, as well as poor compactability and low effective frictional angle. Microstructural analysis indicates that the influence of mica on the responses of mixtures originates from the intrinsic nature of mica as well as the particle packing being formed within WGS. Mica exists in the mixture as stacks of plates that form a spongy structure with high compressibility and swelling potential. Pores among the plates give the soil high water retention and high Atterberg limits. Large pores are also generated by soil particles with bridging packing, which enhances the permeability and water-soil interactions upon immersion. This study provides a micro-level understanding of how mica dominates the behavior of WGS and provides new insights into the effective stabilization and improvement of micaceous soils.

2D profile lines play a critical role in cost-effectively evaluating rock joint properties and shear strength. However, the interval (ΔIL) between these lines significantly impacts roughness and shear strength assessments. A detailed study of 45 joint samples using four statistical measures across 500 different ΔIL values identified a clear line interval effect with two stages: stable and fluctuation-discrete. Further statistical analysis showed a linear relationship between the error bounds of four parameters, shear strength evaluation, and their corresponding maximum ΔIL values, where the gradient k of this linear relationship was influenced by the basic friction angle and normal stress. Accounting for these factors, lower-limit linear models were employed to determine the optimal ΔIL values that met error tolerances (1%–10%) for all metrics and shear strength. The study also explored the consistent size effect on joints regardless of ΔIL changes, revealing three types of size effects based on morphological heterogeneity. Notably, larger joints required generally higher ΔIL to maintain the predefined error limits, suggesting an increased interval for large joint analyses. Consequently, this research provides a basis for determining the optimal ΔIL, improving accuracy in 2D profile line assessments of joint characteristics.

Thermal barrier coatings with varied bond coat structures were deposited using high-velocity air fuel spraying. Highly hard YSZ particles are introduced into the NiCrAlY bond layer by accelerating to supersonic speeds at low temperatures to change the porous structure of the bond coat. We systematically increased the YSZ content in NiCrAlY bond coats and extensively investigated microstructure, oxidation behavior, thermal cycling life, and residual stress variation of the bond coats suing a combination of scanning electron microscopy, optical microscope, confocal Raman microprobe. Introduction of YSZ particles reduced the porosity of NiCrAlY bond coat from 2.69% to 0.45%, and altered the oxidation behavior of the bond layer. The NiCrAlY mixed YSZ composite structure induced the formation of a complex and thin thermal growth oxide layer on the bond coat during oxidation process, greatly alleviating and reducing the thermal stress generated of the coating and during the thermal cycling test. And the thermal cycling life of the NiCrAlY mixed YSZ composite structure coating is 2.8 times longer than that of the ordinary NiCrAlY coating. This finding highlights the significance of the bond coat structure in enhancing the service life of thermal barrier coatings.

Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion: The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

The field of person re-identification (re-ID) encounters challenges such as inter-person similarity and occlusion. In this paper, we introduce an occluded pedestrian re-ID method based on Multiple Fusion and Semantic feature Mining (MFSM) to mitigate the adverse effects of occlusion on feature representation. Specifically, we devise a Multi-branch Strategic Enhancement Module (SEM) to bolster the robustness of data augmentation in addressing the issues posed by data memorization more consistently. This module emulates various real-world disturbances by implementing distinct and independent augmentation strategies. Furthermore, we propose the Triplet Cross Unit (TCU) to comprehensively exploit and consolidate both regional and relational visual cues, as well as multi-level features. The TCU facilitates transformers in acquiring an early understanding of translation invariance in images by transferring local patterns such as edges, textures, and colors from the lower CNN layers to the shallower transformer layers. Simultaneously, deeper transformer features offer more abstracted semantic visual representations that complement CNN's high-level semantic features. Lastly, we introduce the Global Squeeze-Excitation Fusion (GSEF) module to address the challenge of global feature segregation across different models in final outputs. The GSEF selectively merges features based on attention mechanisms, prioritizing the comprehensive utilization of valid global features. Extensive experiments demonstrate the state-of-the-art performance of our model in handling pedestrian occlusion, thus validating the efficacy of our method.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored. Method: We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated. Results: Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence. Conclusions: This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.

Study region: Yellow River Basin (YRB) in China. Study focus: This study attempts to shed new light on regional land-atmosphere coupling and relevant impacts on basin-scale water resource management. Specifically, the objectives are to investigate the driving factors and physical mechanisms of SM changes via land-atmosphere coupling. New hydrological insights for the region: Ecological conservation and the high-quality development in the YRB stand as a pivotal national strategy. The equilibrium of water availability (PME，precipitation minus evapotranspiration) poses a significant challenge to the sustainability of the basin's ecosystem. Unfortunately, a comprehensive examination of the regional response, spatiotemporal heterogeneity, and the mechanism governing soil moisture (SM) in response to PME remains limited. An enhanced multiple linear regression method is implemented to quantify monthly sensitivity coefficients, revealing a notable correlation: reduced SM in arid regions correlates with heightened PME. This decline in SM triggers a decrease in evapotranspiration, attenuates the cooling effect of evapotranspiration, and amplifies temperature disparities. Consequently, this process results in an intensified boundary layer and tropospheric ascending motion, thereby increasing water vapor transport. This feedback loop is most pronounced during drought conditions, particularly in summer arid areas (sensitivity coefficient =-0.27). The findings underscore the intricate interplay between land and atmosphere, elucidating the discernible impact of climate change on water resources at a sub-basin scale.

Dual-comb photoacoustic spectroscopy (DC-PAS) advances spectral measurements by offering high-sensitivity and compact size in a wavelength-independent manner. Here, we present a novel cantilever-enhanced DC-PAS scheme, employing a high-sensitivity fiber-optic acoustic sensor based on an optical cantilever and a non-resonant photoacoustic cell (PAC) featuring a flat-response characteristic. The dual comb is down-converted to the audio frequency range, and the resulting multiheterodyne sound waves from the photoacoustic effect, are mapped into the response frequency region of the optical cantilever microphone. This cantilever-enhanced DC-PAS method provides advantages such as high sensitivity, compact design, and immunity to electromagnetic interference. Through 10 seconds averaging time, the proposed approach experimentally achieved a minimum detection limit of 860 ppb for acetylene. This technology presents outstanding opportunities for highly sensitive detection of trace gases in a wavelength-independent manner, all within a compact volume.

Background: Tripterygium glycosides (TG) is extracted from the roots of Tripterygium wilfordii Hook F (Lei gong teng, a traditional Chinese medicine). It is widely used in China to treat immunoglobulin A vasculitis nephritis (IgAVN), which is a common secondary glomerular disease. As there are no guidelines for the rational application of TG, we performed this study to evaluate the efficacy and safety of different doses of TG and to determine the optimal treatment for IgAVN. Methods: Ten databases were searched from their inception to April 2023 for randomised controlled trials (RCTs) using TG, TG combined with glucocorticoids (GC), or TG combined with traditional Chinese medicine (TCM) to treat IgAVN. A network meta-analysis was performed following the protocol (CRD42023401645). Results: Forty-four eligible RCTs involving 3402 patients were included. For effective rate, TG 1.5 mg/kg/d (TG1.5) + TCM was ranked as the best intervention, followed by TG 1.0 mg/kg/d (TG1.0) + TCM, TG1.5, TG1.0+GC, TG1.0, TCM, GC, and routine treatment (RT). TG1.0+TCM ranked best in reducing recurrence, followed by TG1.0+GC, GC, TG1.5, and RT. Compared with TG1.0, TG1.0+TCM and TG1.5+TCM effectively reduced liver injury events. Compared with TG1.5, TG1.5+TCM and TG1.0+TCM effectively reduced leukopenia events. No significant differences in the reduction of gastrointestinal events were observed between the interventions. Subgroup analyses explored the effects of the participants’ age. The intervention rankings of the outcomes generally remained consistent. Only a small difference was observed in gastrointestinal events. TCM was the best treatment for reducing gastrointestinal events in paediatric patients. Conclusions: The results showed a positive correlation between dose and efficacy, whereas no relationship was found between dose and adverse events. TCM can boost the efficacy and reduce adverse events when combined with TG. In conclusion, we consider TG1.5+TCM as the best treatment for IgAVN. However, further research is required to confirm these findings.

Loop closure detection is a crucial technique supporting localization and navigation in autonomous vehicles. Existing research focuses on feature extraction in global scenes while neglecting considerations for local dense environments. In such local scenes, there are a large number of buildings, vehicles, and traffic signs, characterized by abundant objects, dense distribution, and interlaced near and far. The current methods only employ a single strategy for constructing descriptors, which fails to provide a detailed representation of the feature distribution in dense scenes, leading to inadequate discrimination of descriptors. Therefore, this paper proposes a multi-information point cloud descriptor to address the aforementioned issues. This descriptor integrates three types of environmental features: object density, region density, and distance, enhancing the recognition capability in local dense scenes. Additionally, we incorporated wavelet transforms and invariant moments from the image domain, designing wavelet invariant moments with rotation and translation invariance. This approach resolves the issue of point cloud mismatch caused by LiDAR viewpoint variations. In the experimental part, We collected data from dense scenes and conducted targeted experiments, demonstrating that our method achieves excellent loop closure detection performance in these scenes. Finally, the method is applied to a complete SLAM system, achieving accurate mapping.

In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO2, TiO2 and SiO2 NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO2 NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO2 NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO2 NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO2 and SiO2 NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO2 NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO2 and TiO2 NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.

Background: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common bone and joint disease. There is currently a lack of effective treatment for GIONFH, and the disease progression may lead to total hip arthroplasty (THA). The exact mechanism of GIONFH pathogenesis remains unsettled, and emerging evidence indicates that the overactivation of osteoclasts plays a pivotal role in the occurrence and progression of this condition. Our previous study has shown that cycloastragenol (CAG), a triterpenoid saponin with multiple bioactivities, is a natural osteoclast inhibitor and has a protective effect on bone loss. However, its effect on GIONFH remains unclear. Methods: In this study, methylprednisolone (MPS) (20 mg/kg) was administered via gluteal muscle injection to female Sprague–Dawley (SD) rats to induce GIONFH, and different doses of CAG (5 and 15 mg/kg) were dispensed intraperitoneally for intervention. Micro-CT screening and angiography were applied to determine the shaping of necrotic lesions, the loss of trabecular bone, and the change in the local blood supply. The molecular mechanism was established by Real-time qPCR and Western blotting. Hematoxylin and eosin (H&E) staining was performed to identify empty lacunae in the femoral head. Results: CAG treatment shanked the necrotic lesion area, inhibited the trabecular bone loss, and improved the local blood supply in the femoral head. In addition, CAG medication lowered the ratio of Tnfsf11 (encoding RANKL) to Tnfrsf11b (encoding OPG) and the expression of osteoclast-specific genes, including Acp5 and Ctsk. Consistently, CAG treatment exhibited a dose-dependent weakening effect on the expression of osteoclastogenesis and bone resorption-related proteins, including TRAP, CTSK, and MMP9. CAG addition also alleviated the occurrence of empty lacunae in the subchondral region. Conclusion: Our discoveries demonstrate that CAG is a potential option for hip preservation therapy in GIONFH patients. Translational potential of this article: The protective effect of CAG on rats with GIONFH can be translated into clinical use.

The mechanical behaviors and microstructure evolutions of different aluminum materials including high-purity aluminum, 7075 aluminum alloy and selective laser melted (SLM) AlSi10Mg alloy under shock loading were investigated through plate impact experiments and microstructure characterization. The results show that the Hugoniot elastic limit stress has nothing to do with impact velocity, but is related to material type; the peak shock stress significantly increases with increasing impact velocity and is somewhat affected by material type. The microstructure variation is highly dependent on the material type. In the 7075 aluminum alloy and selectively laser melted (SLM) AlSi10Mg alloy with relatively high strengths, the microstructure, including the grain size, grain shape and misorientation angle, is slightly influenced by the impact velocity. In high-purity aluminum with low strength, the microstructure is closely related to the impact velocity. As the impact velocity increases, dislocations, elongated subgrains, equiaxed subgrains and a fraction of low angle grain boundaries (LAGBs) first increase and then decrease, accompanied by the formation of numerous ultrafine equiaxed grains with sizes in the range of 1–5 μm. The limited adiabatic temperature rise during high-velocity impact cannot affect the microstructure. High rate loading was confirmed as an effective and promising method to refine grain structure for low strength materials.

The effects of heat treatment on the intermetallic compounds (IMCs) and morphology at the interface of stainless steel 304 bonded to aluminum 6061 by electromagnetic pulse welding (EMPW) were investigated in this study. A thin discontinuous non-uniform wavy transition layer with an average thickness of 1.144 μm was formed at the interface of the as-welded joint. After heat treatment, the average grain size of the Al/SS304 interface grew from 6.85 μm to 7.42 μm. The thickness of the transition layer increased significantly, reaching an average thickness of 4.109 μm after heating at 210 °C for 4 h. In addition, the wavy interface grew gradually and became smooth with increasing heating temperature, suggesting the growth rate of the IMCs at the trough was greater than that at the adjacent crest. Then the effect of heating time on the growth of IMCs was studied. According to the characteristics of the transition layer and the diffusion law, the IMCs grew faster at the trough than at the crest of the transition layer. Differences in element concentration, crystal deformation, grain boundaries, dislocation density, and energy storage were observed at the trough and crest of the interface as a result of the different growth rates of the IMCs.

This paper reports on the successful synthesis of a novel alumina powder with a unique rose-like structure composed of alumina platelets, using the molten salt method. The synthesized powder was then utilized to prepare alumina ceramic with impressive mechanical properties. The influences of the synthesizing temperature of alumina powder on the microstructure and mechanical properties of alumina ceramic are investigated in details. The results indicate that the alumina ceramic prepared using the rose-like powder synthesized at 800 °C exhibits a high relative density of 99.5 %, flexural strength of 408.2 ± 18.7 MPa, and fracture toughness of 6.14 ± 0.63 MPa m1/2. The work presented in this paper will provide a useful guideline for the preparation of high-performance alumina ceramic materials in the future.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca2+ overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca2+ overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca2+ overload and apoptosis by inhibiting CHOP-mediated Ca2+ transfer between inositol 1,4,5-trisphosphate receptor (IP3R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP3R/VDAC1 signaling pathway mediates ER-mitochondrial Ca2+ transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca2+ homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.

Herpetofauna have attracted considerable global attention due to their high risk of extinction. The Mountains of Southwest China are among the 36 global biodiversity hotspots due to their high biodiversity and irreplaceability, and the Shaluli Mountains are the core area of this region. However, the diversity and conservation status of herpetofauna in the Shaluli Mountains remain unclear. In this study, we updated the species richness and composition information of herpetofauna in the Shaluli Mountains based on extensive field expeditions, published literature, and museum specimens. In addition, we identified the local hotspots and key environmental factors limiting species distribution using environmental niche models (ENMs). Furthermore, we evaluated the conservation status of the key species via the Red List Index and gap analysis. Our results revealed a total of 68 herpetofauna species, representing 30 amphibians (21 genera in nine families) and 38 reptiles (19 genera in six families). The amphibian richness showed a hump-shaped pattern along the elevational gradient, while the reptile richness showed a monotonically decreasing pattern. The dry-hot river valley was identified as a local hotspot, and the key environmental factors limiting the richness of herpetofauna species differed. Moreover, the regional Red List indices for amphibians and reptiles were 0.87 and 0.8, respectively, showing that the overall threat level of this region was low. However, there are large conservation gaps in the protection of key species. Our study indicated that new protected areas should be established and the existing protected areas should be upgraded to protect herpetofauna with a large conservation gap.

Radial composite deviation is an important index to evaluate the precision of gear transmission, and its detection method is also an important trend of gear detection in industrial development. The ability to predict radial composite deviation while obtaining geometric deviation of gears is a key challenge in advancing intelligent online inspection within gear manufacturing workshops. This study presents a virtual measurement method for determining gear radial composite deviation using point cloud data. The method involves using an optical three-dimensional scanner to capture tooth surface cloud data, determining tooth profile deviation, and applying reverse engineering technology to reconstruct the gear model, the variation curve of gear center distance is determined by simulating, allowing for the calculation of the total radial composite deviation and tooth-to-tooth radial composite deviation. In comparison to actual measurement, the virtual measurement method is generally reliable. It can effectively illustrate the overall trend of center distance variation and has good interpretability for predicting radial composite deviation results. This method reduces the dependence on the specialized gear measuring instrument and addresses the critical issue of simultaneously obtaining tooth profile deviation and radial composite deviation.

ABSTRACT: The bird beak is mainly functioned as feeding and attacking, and its shape has extremely important significance for survival and reproduction. In chickens, since beak shape could lead to some disadvantages including pecking and waste of feed, it is important to understand the inheritance of chicken beak shape. In the present study, we firstly established 4 indicators to describe the chicken beak shapes, including upper beak length (UL), lower beak length (LL), distance between upper and lower beak tips (DB) and upper beak curvature (BC). And then, we measured the 4 beak shape indicators as well as some production traits including body weight (BW), shank length (SL), egg weight (EW), eggshell strength (ES) of a layer breed, Rhode Island Red (RIR), in order to estimate genetic parameters of chicken beak shape. The heritabilities of UL and LL were 0.41 and 0.37, and the heritabilities of DB and BC were 0.22 and 0.21, indicating that beak shape was a highly or mediumly heritable. There were significant positive genetic and phenotypic correlations among UL, LL, and DB. And UL was positively correlated with body weight (BW18) and shank length (SL18) at 18 weeks of age in genetics, and DB was positively correlated with BC in terms of genetics and phenotype. We also found that layers of chicken cages played a role on beak shape, which could be attributed to the difference of lightness in different cage layers. By a genome-wide association study (GWAS) for the chicken UL, we identified 9 significant candidate genes associated with UL in RIR. For the variants with low minor allele frequencies (MAF

In the domains of low/zero carbon energy, the ship energy storage system, coupled with phase-change storage and release technology, holds significant importance. The utilization of a flat micro-heat pipe as the primary heat transfer element prompts the development of a test platform and a transient heat transfer model for the heat storage device. This is in response to existing challenges such as a single structure, poor temperature uniformity, and low thermal efficiency in current heat storage technology. The study delves into the impact of varying temperatures and flow rates of heat transfer fluids on the overall performance of heat storage devices and heat transfer efficiency. The findings highlight that the staggered double plate micro-heat pipe structure can enhance total heat storage by 11%, average heat storage power by 19%, and heat storage efficiency by 21% compared to the heat storage device with a single flat micro-heat pipe structure. It becomes evident that the heat storage device with the staggered double heat pipe structure outperforms its counterpart. Additionally, Temperature and flow velocity play pivotal roles in determining the heat transfer performance of phase change materials. As the temperature difference between the heat transfer fluid and the phase change material increases, both the phase transition rate and the equivalent Nusselt number also rise, providing a crucial foundation for examining the heat transfer characteristics of phase change materials during different stages of phase transition.

ABSTRACT: Plumage color is a characteristic trait of ducks that originates as a result of natural and artificial selection. As a conspicuous phenotypic feature, it is a breed characteristic. Previous studies have identified some genes associated with the formation of black and white plumage in ducks. However, studies on the genetic basis underlying the red plumage phenotype in ducks are limited. Here, genome-wide association analysis (GWAS) and selection signal detection (Fst, θπ ratio, and cross-population composite likelihood ratio [XP-CLR]) were conducted to identify candidate regions and genes underlying duck plumage color phenotype. Selection signal detection revealed 29 overlapping genes (including ENPP1 and ULK1) significantly associated with red plumage color in Ji'an Red ducks. ENSAPLG00000012679, ESRRG, and SPATA5 were identified as candidate genes associated with red plumage using GWAS. Selection signal detection revealed that 19 overlapping genes (including GMDS, PDIA6, and ODC1) significantly correlated with light brown plumage in Brown Tsaiya ducks. GWAS to narrow down the significant regions further revealed nine candidate genes (AKT1, ATP6V1C2, GMDS, LRP4, MAML3, PDIA6, PLD5, TMEM63B, and TSPAN8). Notably, in Brown Tsaiya ducks, GMDS, ODC1, and PDIA6 exhibit significantly differentiated allele frequencies among other feather-colored ducks, while in Ji'an Red ducks, ENSAPLG00000012679 has different allele frequency distributions compared with that in other feather-colored ducks. This study offers new insights into the variation and selection of the red plumage phenotype using GWAS and selective signals.

ABSTRACT: As a Chinese local chicken breed, Hongshan chickens have 2 kinds of tail feather phenotypes, normal and taillessness. Our previous studies showed that taillessness was a sex-linked dominant trait. Abnormal development of the tail vertebrae could be explained this phenomenon in some chicken breeds. However, the number of caudal vertebrae in rumpless Hongshan chickens was normal, so rumplessness in Hongshan chicken was not related to the development of the caudal vertebrae. Afterwards, we found that rumplessness in Hongshan was due to abnormal development of tail feather rather than abnormal development of caudal vertebrae. In order to understand the genetic foundation of the rumplessness of Hongshan chickens, we compared and reanalyzed 2 sets of data in normal and rumpless Hongshan chickens from our previous studies. By joint analysis of genome-wide selection signature analysis and genome-wide association approach, we found that 1 overlapping gene (EDIL3) and 16 peak genes (ENSGALG00000051843, ENSGALG00000053498, ENSGALG00000054800, KIF27, PTPRD, ENSGALG00000047579, ENSGALG00000041052, ARHGEF28, CAMK4, SERINC5, ENSGALG00000050776, ERCC8, MCC, ADAMTS19, ENSGALG00000053322, CHRNA8) located on the Z chromosome was associated with the rumpless trait. The results of this study furtherly revealed the molecular mechanism of the rumpless trait in Hongshan chickens, and identified the candidate genes associated with this trait. Our results will help to improve the shape of chicken tail feathers and to rise individual economic value in some specific market in China.

ABSTRACT: The age of first egg (AFE) in chicken can affect early and even life-time egg production performance to some extent, and therefore is an important economic trait that affects production efficiency. To better understand the genetic patterns of AFE and other production traits including body weight at first egg (BWA), first egg weight (FEW), and total egg number from AFE to 58 wk of age (total-EN), we recorded the production performance of 2 widely used layer breeds, white leghorn (WL) and Rhode Island Red (RIR) and estimated genetic parameters based on pedigree and production data. The results showed that the heritability of AFE in both breeds ranged from 0.4 to 0.6, and AFE showed strong positive genetic and phenotypic correlations to BWA as well as FEW, while showing strong negative genetic and phenotypic correlations with total-EN. Furtherly, by genome-wide association analysis study (GWAS), we identified 12 and 26 significant SNPs to be related to AFE in the 2-layer breeds, respectively. A total of 18 genes were identified that could affect AFE based on the significant SNP annotations obtained, but there were no gene overlapped in the 2 breeds indicating the genetic foundation of AFE could differ from breed to breed. Our results provided a deeper understanding of genetic patterns and molecular basement of AFE in different breeds and could help in the selection of egg production traits.

Summary: Muscle stem cells (MuSCs) contribute to a robust muscle regeneration process after injury, which is highly orchestrated by the sequential expression of multiple key transcription factors. However, it remains unclear how key transcription factors and cofactors such as the Mediator complex cooperate to regulate myogenesis. Here, we show that the Mediator Med23 is critically important for MuSC-mediated muscle regeneration. Med23 is increasingly expressed in activated/proliferating MuSCs on isolated myofibers or in response to muscle injury. Med23 deficiency reduced MuSC proliferation and enhanced its precocious differentiation, ultimately compromising muscle regeneration. Integrative analysis revealed that Med23 oppositely impacts Ternary complex factor (TCF)-targeted MuSC proliferation genes and myocardin-related transcription factor (MRTF)-targeted myogenic differentiation genes. Consistently, Med23 deficiency decreases the ETS-like transcription factor 1 (Elk1)/serum response factor (SRF) binding at proliferation gene promoters but promotes MRTF-A/SRF binding at myogenic gene promoters. Overall, our study reveals the important transcriptional control mechanism of Med23 in balancing MuSC proliferation and differentiation in muscle regeneration.

Sea red rice bran, a new salinity-tolerant sea rice by-product, contains high levels of ceramides (Cers), which are necessary to tap into their bioactivity for improving the health effects of the organism. This study aimed to investigate the effect of Cers on the improving the oxidative stress and lifespan of C. elegans, and the relationship of the interaction through the p38/MAPK signaling pathway and under the regulation of intestinal flora. The results showed that Cers treatment effectively reversed the oxidative damage caused by paraquat and hydrogen peroxide in C. elegans and reduced overexpression of ROS and accumulation of mitochondrial membrane damage. In addition, Cers intake successfully activated all gene targets of p38/MAPK signaling pathway, significantly promoted the migration of SKN-1 to the nucleus, and increased the abundance of probiotic bacteria such as Ruminoccus, AKKermansia, and Lactobacillus in the intestinal flora and effectively mitigated the adverse effects of oxidative stress. Therefore, these results indicate that Cers could be effectively in ameliorating the level of oxidative stress in the body, thereby increasing longevity and health indicators. Providing a theoretical basis for the prevention of aging-related chronic diseases and health care, and enhancing the high-value comprehensive utilization of sea red rice by-products.

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson’s disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

China is not considered as an endemic area of Rickettsia conorii, so there is no routine clinical way to diagnose this infection. This study aims to determine whether 2 febrile patients who had a tick bite in East China were indeed infected with R. conorii. The citrate synthase gene (gltA) was amplified with universal rickettsial primers by real-time fluorescent PCR from the patients’ blood samples. Nested PCR was used to amplify the outer membrane protein A gene (ompA) for positive specimens. PCR products were further identified and analyzed through nucleic acid sequencing. Positive amplification of the gltA and ompA genes was found in both patients. The nucleotide sequences (303 bp) of the ompA gene of the 2 patients had high homology (99%) with the R. conorii Indian tick typhus strain in GenBank. A more than 4-fold increase in IgG against R. conorii provided supportive evidence of SFG Rickettsia infection. And the rapid recovery after doxycycline treatment also supported a rickettsial cause for the disease. Physicians in East China should be aware of human infections with R. conorii. PCR-based diagnostic methods offer a rapid and precise way to diagnose rickettsiosis, improving patient identification and management.

The asperity wear of rock joints significantly affects their shear behaviour. This study discusses the wear damage of the asperities on the joint surface, highlighting the roughness degradation characteristics during the shear process. The direct shear experiment of artificial specimens containing rock joints was conducted under different normal stresses based on three-dimensional scanning technology. These experimental results showed the contribution of joint wear to roughness degeneration, such as the height, zone, and volume of asperity degeneration. The wear coefficient of the rock joint was obtained based on the volume wear of asperities in the laboratory experiment. The functional relationship between the friction coefficient and wear coefficient is subsequently determined. To quantitatively analyse the wear damage of a joint surface, a calculation method for determining the wear depth of the rock joint after shearing was proposed based on wear theory. The relationship between the ultimate dilation and wear depth was analysed. A coefficient m, which can describe the damage degree of the joint surface, and a prediction method of joint surface roughness after shearing are established. Good agreement between analytical predictions and measured values demonstrates the capability of the developed model. Lastly, the sensitivity factors on the wear depth are explored.

Purpose: Predictors of ‘imminent’ risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals. Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes. Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32–26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25–3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32–3.34). Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration.

As data privacy issues become more and more sensitive, increasing numbers of websites usually encrypt traffic when transmitting it. This method can largely protect privacy, but it also brings a huge challenge. Aiming at the problem that encrypted traffic classification makes it difficult to obtain a global optimal solution, this paper proposes an encrypted traffic identification model called the ET-BERT and 1D-CNN fusion network (BCFNet), based on multi-scale feature fusion. This method combines feature learning with classification tasks, unified into an end-to-end model. The local features of encrypted traffic extracted based on the improved Inception one-dimensional convolutional neural network structure are fused with the global features extracted by the ET-BERT model. The one-dimensional convolutional neural network is more suitable for the encrypted traffic of a one-dimensional sequence than the commonly used two-dimensional convolutional neural network. The proposed model can learn the nonlinear relationship between the input data and the expected label and obtain the global optimal solution with a greater probability. This paper verifies the ISCX VPN-nonVPN dataset and compares the results of the BCFNet model with the other five baseline models on accuracy, precision, recall, and F1 indicators. The experimental results demonstrate that the BCFNet model has a greater overall effect than the other five models. Its accuracy can reach 98.88%.

Compared to commercial magnesium (Mg) alloys, recently the low-alloyed Mg alloys have attracted extensive research interest for their advantages in formability, corrosion resistance, and low cost. However, their strain hardening behavior is yet fully understood. In this work, the strain hardening of an extruded lean Mg-Al-Ca-Mn alloy is qualitatively and quantitatively analyzed. As compared to the dislocation-dominated deformation along the extrusion direction (ED), the hardening along the transverse direction (TD) is significantly improved due to the activation of twinning. We quantified the specific contributions of twinning and dislocations to the net hardening effect through cyclic stress relaxation and calculations. Interestingly, the dominant hardening mechanism is always related to dislocations, even though the twin volume faction reaches ∼40 %. This work furthers our understanding of the deformation behavior of lean Mg alloys and indicates that the strain hardening of Mg alloys can be improved if the twin morphology is properly controlled.

CRISPR/Cas systems have become integral parts of nucleic acid detection apparatus and biosensors. Various CRISPR/Cas systems such as CRISPR/Cas9, CRISPR/Cas12, CRISPR/Cas13, CRISPR/Cas14 and CRISPR/Cas3 utilize different mechanisms to detect or differentiate biological activities and nucleotide sequences. Usually, CRISPR/Cas-based nucleic acid detection systems are combined with polymerase chain reaction, loop-mediated isothermal amplification, recombinase polymerase amplification and transcriptional technologies for effective diagnostics. Premised on these, many CRISPR/Cas-based nucleic acid biosensors have been developed to detect nucleic acids of viral and bacterial pathogens in clinical samples, as well as other applications in life sciences including biosecurity, food safety and environmental assessment. Additionally, CRISPR/Cas-based nucleic acid detection systems have showed better specificity compared with other molecular diagnostic methods. In this review, we give an overview of various CRISPR/Cas-based nucleic acid detection methods and highlight some advances in their development and components. We also discourse some operational challenges as well as advantages and disadvantages of various systems. Finally, important considerations are offered for the improvement of CRISPR/Cas-based nucleic acid testing.

Cardiac dysfunction frequently emerges in the initial stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model. Concurrently, these mice underwent a low-intensity exercise regimen to investigate its potential role in cardiac function during cachexia. Our findings indicate that exercise training can help prevent metastatic melanoma-induced muscle loss without significant alterations to body and fat weight. Moreover, exercise improved the melanoma-induced decline in left ventricular ejection fraction and fractional shortening, while also mitigating the increase in high-sensitive cardiac troponin T levels caused by metastatic melanoma in mice. Transcriptome analysis revealed that exercise significantly reversed the transcriptional alterations in the heart induced by melanoma, which were primarily enriched in pathways related to heart contraction. These results suggest that exercise can improve systolic heart function and directly influence the transcriptome of the heart during metastatic melanoma-induced cachexia.

This study proposes a hybrid approach for accurately predicting water demand by integrating socio-economic variables, such as population and GDP (per capita), with climatic variables, including temperature and precipitation. The prediction model utilizes an Extreme Learning Machine (ELM), effectively capturing the dynamic relationships between the input variables and water demand. The Improved Ant Nesting Algorithm is employed to fine-tune the weights and biases to optimize the network's performance. To evaluate the predictive accuracy of the model, a comprehensive dataset consisting of socio-economic and climatic factors is utilized for training and testing purposes. Performance metrics, namely Root Mean Square Error (RMSE) and Correlation Coefficients (R2), are employed as evaluation criteria. The results demonstrate that the hybrid approach achieves accurate water supply predictions, showcasing its potential to contribute significantly to effective water resource management and decision-making processes. Based on the results, IANA-ELM is considered the best model due to its high R2 values. Specifically, in the training data, the R2 values are 0.693 for population, 0.624 for GDP per capita, 0.607 for temperature, and 0.708 for rainfall. Similarly, in the test data, the R2 values are 0.672 for population, 0.608 for GDP per capita, 0.592 for temperature, and 0.708 for rainfall. This integrated approach provides a robust tool for policymakers, water utility companies, and researchers in the field of water managements, enabling them to make informed decisions based on accurate predictions of water demand.

Inadequate information sharing and difficult information diffusion are the main factors that cause upstream and downstream enterprises to default on supply chain finance. Blockchain technology, which exploits distributed storage and a consensus mechanism, can provide effective solutions to overcome these problems such as information sharing. When blockchain technology is adopted by the enterprises that comprise the supply chain finance business, this technology shows a diffusion trend. As a result, the decision pertaining to the application of novel technologies is affected. Therefore, to investigate the diffusion mechanism pertaining to the blockchain technology that is applied in supply chain finance, the study exploited the idea of a class of SEIR infectious disease models, and built a blockchain model that considers the supply chain financial system. Besides, the study verifies the stability of the model by constructing a Lyapunov function. The results indicate that the basic reproduction number determines the proliferation of the blockchain technology. When the basic reproduction number is less than 1, the proliferation of the blockchain technology that is applied in supply chain finance system would terminate. By contrast, when the basic reproduction number is greater than 1, during the average infection period, the number of non-adopting enterprises that accept the blockchain technology becomes greater than 1, which can maintain a continuous impact on supply chain finance system. Over time, the number of enterprises that accept blockchain technology tends to be stable. Through numerical simulations that consider the influencing parameters pertaining to the basic regeneration number, which has important effect on blockchain technology diffusion, we enlarge the diffusion efficiency and increase the transfer rate of potential on-chain enterprises or decrease the default exit rate. As a result, we facilitate the diffusion of blockchain technology in the system.

Objective: This study trains a U-shaped fully convolutional neural network (U-Net) model based on peripheral contour measures to achieve rapid, accurate, automated identification and segmentation of periprostatic adipose tissue (PPAT). Methods: Currently, no studies are using deep learning methods to discriminate and segment periprostatic adipose tissue. This paper proposes a novel and modified, U-shaped convolutional neural network contour control points on a small number of datasets of MRI T2W images of PPAT combined with its gradient images as a feature learning method to reduce feature ambiguity caused by the differences in PPAT contours of different patients. This paper adopts a supervised learning method on the labeled dataset, combining the probability and spatial distribution of control points, and proposes a weighted loss function to optimize the neural network's convergence speed and detection performance. Based on high-precision detection of control points, this paper uses a convex curve fitting to obtain the final PPAT contour. The imaging segmentation results were compared with those of a fully convolutional network (FCN), U-Net, and semantic segmentation convolutional network (SegNet) on three evaluation metrics: Dice similarity coefficient (DSC), Hausdorff distance (HD), and intersection over union ratio (IoU). Results: Cropped images with a 270 × 270-pixel matrix had DSC, HD, and IoU values of 70.1%, 27 mm, and 56.1%, respectively; downscaled images with a 256 × 256-pixel matrix had 68.7%, 26.7 mm, and 54.1%. A U-Net network based on peripheral contour characteristics predicted the complete periprostatic adipose tissue contours on T2W images at different levels. FCN, U-Net, and SegNet could not completely predict them. Conclusion: This U-Net convolutional neural network based on peripheral contour features can identify and segment periprostatic adipose tissue quite well. Cropped images with a 270 × 270-pixel matrix are more appropriate for use with the U-Net convolutional neural network based on contour features; reducing the resolution of the original image will lower the accuracy of the U-Net convolutional neural network. FCN and SegNet are not appropriate for identifying PPAT on T2 sequence MR images. Our method can automatically segment PPAT rapidly and accurately, laying a foundation for PPAT image analysis.

The thermal error caused during the high-speed operation of a high-speed motorized spindle has a significant impact on machine tool precision. In this paper, we firstly built, constructed an experimental platform for variable voltage preloaded motorized spindle, used the natural deceleration experimental method to ascertain the spindle's thermal displacement and temperature information when bearing preload is 1400 N, 1450 N, 1550 N and 1700 N, and combined with the thermoelasticity theoretical analysis, the thermal displacement of affected by the heat generation of motor and bearing was separated, and a new artificial bee colony algorithm-optimized BP neural network-based thermal error prediction model has been presented. The thermal displacements of the spindles are separated and a BP neural network optimization of a novel thermal error prediction model based on Improved Artificial Bee Colony Algorithm (IABC-BP) is proposed for transformer preloaded spindles. Combined with the experimental data of bearing preload of 1400 N, the thermal displacements of the spindle at preloads of 1450 N, 1550 N and 1700 N are predicted, and the evaluation indexes obtained from the simulation of the BP, ABC-BP, and IABC-BP models are compared. absolute error (MAE) and root-mean-square error (RMSE), higher goodness-of-fit (R2), and 20.37 % lower mean absolute error and 26.83 % lower root-mean-square error compared with the traditional thermal error prediction model. The IABC-BP prediction model proposed in this paper provides a more accurate compensation method for transformer preloaded spindles.

Summary: CD1d-restricted invariant NKT (iNKT) cells play a critical role in tumor immunity. However, the scarcity and limited persistence restricts their development and clinical application. Here, we demonstrated that iNKT cells could be efficiently expanded using modified cytokines combination from peripheral blood mononuclear cells. Introduction of IL-21 significantly increased the frequency of CD62L-positive memory-like iNKT cells. iNKT cells armoring with B7H3-targeting second generation CAR and IL-21 showed potent tumor cell killing activity. Moreover, co-expression of IL-21 promoted the activation of Stat3 signaling and reduced the expression of exhaustion markers in CAR-iNKT cells in vitro. Most importantly, IL-21-arming significantly prolonged B7H3 CAR-iNKT cell proliferation and survival in vivo, thus improving their therapeutic efficacy in mouse renal cancer xerograph models without observed cytokine-related adverse events. In summary, these results suggest that B7H3 CAR-iNKT armored with IL-21 is a promising therapeutic strategy for cancer treatment.

The search for the chiral magnetic effect (CME) in heavy-ion collisions has been impeded by the significant background arising from the anisotropic particle emission pattern, particularly elliptic flow. To alleviate this background, the event shape selection (ESS) technique categorizes collision events according to their shapes and projects the CME observables to a class of events with minimal flow. In this study, we explore two event shape variables to classify events and two elliptic flow variables to regulate the background. Each type of variable can be calculated from either single particles or particle pairs, resulting in four combinations of event shape and elliptic flow variables. By employing a toy model and the realistic event generator, event-by-event anomalous-viscous fluid dynamics (EBE-AVFD), we discover that the elliptic flow of resonances exhibits correlations with both the background and the potential CME signal, making the resonance flow unsuitable for background control. Through the EBE-AVFD simulations of Au+Au collisions at sNN=200 GeV with various input scenarios, we ascertain that the optimal ESS strategy for background control entails utilizing the single-particle elliptic flow in conjunction with the event shape variable based on particle pairs.

Background: For locally advanced rectal cancer (LARC), accurate response evaluation is necessary to select complete responders after neoadjuvant therapy (NAT) for a watch-and-wait (W&W) strategy. Algorithms based on deep learning have shown great value in medical image analyses. Here we used deep learning algorithms of endoscopic images for the assessment of NAT response in LARC. Method: 214 LARC patients were retrospectively included in the study. After NAT, these patients underwent total mesorectal excision (TME) surgery. Among them, 51 (23.8%) of the patients achieved a pathological complete response (pCR). 160 patients from Shanghai Changzheng Hospital were regarded as primary dataset, and the other 54 patients from Zhejiang Cancer Hospital were regarded as validation dataset. ResNet-18 and DenseNet-121 were applied to train the models based on endoscopic images after NAT. Deep learning models were valid in the validation dataset and compared to manual method. Results: The performances were comparable in AUC between deep learning models and manual method. For mean metrics, sensitivity (0.750 vs. 0.417) and AUC (0.716 vs. 0.601) in ResNet-18 deep learning model were higher than those in the manual method. The deep learning models were able to identify the endoscopic features associated with NAT response by the heatmaps. A diagnostic flow diagram which integrated the deep learning model to assist the clinicians in making decisions for W&W strategy was constructed. Conclusions: We created deep learning models using endoscopic features for assessment of NAT in LARC. The deep learning models achieved modest accuracies and performed comparably to manual method.

Objectives: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal dynamics of the SFTSV-specific neutralizing antibody (NAb) and the related factors in patients with SFTS. Methods: A prospective cohort study of patients with laboratory-confirmed SFTS were conducted. Antiglomerulonephritis-immunoglobulin G (anti-Gn-IgG) and NAb titers were examined in serially collected serum samples, and their dynamic features were analyzed. Results: NAb was initially detected at 15 days after symptom onset in surviving patients with SFTS, with positive rates of 37.21% (16/43), whereas neither anti-Gn-IgG antibody nor NAb was detected in patients with fatal SFTS during their hospitalization. The NAb levels reached the peak at 2 months after symptom onset, and then gradually declined, with a rapid downward trend from 6 months to 4 years and a relatively slow downward trend from 5 to 10 years. There was a positive correlation between NAb and anti-Gn-IgG titers in surviving patients with SFTS (r = 0.699, P

Graphene has recently gained significant interest as a promising lubricant and additive for metal matrix composites. In this work, the microstructure and tribological properties of Mg-based composites were systematically investigated by introducing nano-ZnO modified graphene. It was found that graphene can be uniformly distributed in Mg matrix. In addition, MgO, the interfacial reaction product with nanoscale structure, can enhance the interfacial bonding strength of the composite. Compared to pure Mg matrix, the composite shown significant improvements in hardness and wear resistance. Finally, the mechanism of the wear resistance of the composite was discussed. This work provides technical support and theoretical guidance for the preparation and design of metal matrix composite with high wear resistance.

Faced-centred cubic nanoparticles-strengthened FeCoNiAlTi system high-entropy alloy (HEA) has demonstrated unique mechanical performance advantages with recently developed HEA alloy compositions. One of the key factors determining the performance of an alloy is the efficient manipulation of precipitation. However, the traditional aging method used to achieve this can be problematic. It is time-consuming and difficult to accurately control the distribution of the precipitated phase, which restricts the development of new, high-performance structural materials. Consequently, researchers have been exploring alternative methods to more precisely and effectively manipulate precipitation in alloys. Here, we have utilized both high-efficiency additive manufacturing processes and a short-term aging process to produce (FeCoNi)85·84Al7·07Ti7.09 high-entropy alloys that exhibit outstanding mechanical properties with an ultimate tensile strength of 1625 MPa, yield strength of 1214 MPa and an elongation to failure of 11.6%. Our findings reveal the formation of L12 and L21 nanoparticles phases after aging treatment, and their contents gradually decrease with increasing aging treatment temperature. And, we introduce two strengthening mechanisms of dislocation strengthening and precipitation strengthening into the alloys, and realized the coexistence of high-density dislocations and precipitated phases, thereby exhibiting excellent comprehensive mechanical properties. This approach represents a promising new direction in the development of high-performance alloys, offering a more efficient and effective means of producing materials with improved properties.