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Abstract The run-up velocity and jumping ground reaction force directly influence gymnasts’ ability to perform more difficult manoeuvres and win competitions on vault. However, the variables influencing them among elite female gymnasts remain inadequately understood and warrant detailed investigation. This study aimed to analyse critical variables including run-up velocity and jumping ground reaction force, and to compare these factors across different vault types while further exploring the correlations among them. The study hypothesized that there are significant differences in run-up velocity and jumping ground reaction force across vaulting types, and that these differences will affect athletes’ performance. To test this hypothesis, the study analyzed data from performance tests on 16 elite Chinese female gymnasts, focusing on vaulting run-up velocity and jumping ground reaction force. Descriptive statistics were used to summarize the data, and binary logistic regression analysis was employed to investigate the relationships between the variables. The study found significant differences in interval run-up velocities between the Front handspring vaults and the Tsukahara vaults, particularly before the last 10 m (p = 0.04) and the last 5 m (p = 0.03). Specifically, the Front handspring vaults had higher velocities before the last 10 m, while the Tsukahara vaults had higher velocities within the last 5 m. Differences were also noted in the lengths of the penultimate (p = 0.03), last (p = 0.01), and hurdle steps (p = 0.04). The jumping ground reaction force showed a strong negative correlation with run-up velocity before the last 10 m (ρ = -0.469, p

Abstract Objective To evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI Ktrans map, and metabolomics. Materials and methods 24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI Ktrans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research. Results The FF ratio and Ktrans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P

Abstract Pediatric trauma plays a crucial role in pediatric mortality, with traffic injuries and falls frequently cited as leading causes of significant injuries among children. A comprehensive investigation, including geographical factors, is essential for developing effective strategies to prevent injuries and alleviate the burden of pediatric trauma. This study involved a retrospective analysis of clinical data from pediatric patients admitted to our hospital’s intensive care unit (ICU) due to trauma over a 10-year period. Comprehensive analyses were conducted to elucidate trends, demographics, injury patterns, and risk factors associated with these admissions. This retrospective study included 951 pediatric patients (mean age: 4.79 ± 3.24 years; mean weight: 18.45 ± 9.02 kg; median time to ICU admission post-injury: 10.86 ± 14.95 h). Among these patients, 422 (44.4%) underwent emergency surgery, and 466 (49%) required mechanical ventilation support, with a mean duration of 70.19 ± 146.62 h. The mean duration of ICU stay was 6.24 ± 8.01 days, and the overall mean hospitalization duration was 16.08 ± 15.56 days. The predominant cause of unintentional injury was traffic accidents (47.9%), followed by falls (42.5%) and burns/scalds (5.3%). Most incidents involved children aged 0–6 years (70.7%), with males comprising 60.0% of patients. Injury incidents predominantly occurred between 12 and 6 PM (44.5%) and on non-workdays (37.6%). The most common locations where injuries occurred were roadsides (49%) and rural areas (64.35%). Single-site injuries (58.78%) were more prevalent than multiple-site injuries (41.22%), and head injuries were the most common among single-site injuries (81.57%). At ICU admission, the mean injury severity score was 18.49 ± 8.86. Following active intervention, 871 patients (91.59%) showed improvement, while 80 (8.41%) succumbed to their injuries. Traffic injuries remain the primary cause of pediatric trauma leading to ICU admission, underscoring the importance of using appropriate child restraint systems and protective gear as fundamental preventive measures. The increased incidence of injuries among children aged

Metal hydride hydrogen storage is a hydrogen storage method based on the principle of chemical absorption. Featuring high volumetric hydrogen storage density and high safety, its potential applications in the field of hydrogen storage on ships have attracted significant attention. Against this background, there is a series of issues to be studied, such as material properties, reactor performance, thermal management systems, cost, etc. This paper categorizes metal hydride hydrogen storage technology, summarizes its working principle and research progress on its material properties, and introduces its applications on ships. Next, combined with the application environment and demands of hydrogen ships, the paper analyzes the technological and economic feasibility of the application of metal hydride hydrogen storage technology on ships. To meet the requirements of hydrogen ships for hydrogen storage capacity and release rate, research on marine metal hydride hydrogen storage systems is introduced, including hydrogen storage system performance research, hydrogen storage reactor structure, reactor structure optimization and design ideas for thermal management systems coupled with marine fuel cell and hydrogen storage systems. Finally, the research direction of marine metal hydride hydrogen storage systems is predicted and summarized.

Abstract Single-cell sequencing is frequently affected by “omission” due to limitations in sequencing throughput, yet bulk RNA-seq may contain these ostensibly “omitted” cells. Here, we introduce the single cell trajectory blending from Bulk RNA-seq (BulkTrajBlend) algorithm, a component of the OmicVerse suite that leverages a Beta-Variational AutoEncoder for data deconvolution and graph neural networks for the discovery of overlapping communities. This approach effectively interpolates and restores the continuity of “omitted” cells within single-cell RNA sequencing datasets. Furthermore, OmicVerse provides an extensive toolkit for both bulk and single cell RNA-seq analysis, offering seamless access to diverse methodologies, streamlining computational processes, fostering exquisite data visualization, and facilitating the extraction of significant biological insights to advance scientific research.

Abstract Infrared images have important applications in military, security and surveillance fields. However, limited by technical factors, the resolution of infrared images is generally low, which seriously limits the application and development of infrared images in various fields. To address the problem of difficult recovery of edge information and easy ringing effect in the super-resolution reconstruction process of infrared images, an edge-enhanced infrared image super-resolution reconstruction model TESR under transformer is proposed. The main structure of this model is transformer. First, in view of the problem of difficult recovery of edge information of infrared images, an edge detection auxiliary network is designed, which can obtain more accurate edge information from the input low-resolution images and enhance the edge details during image reconstruction; then, the CSWin Transformer is introduced to compute the self-attention of horizontal and vertical stripes in parallel, so as to increase the receptive field of the model and enable it to utilize features with higher semantic levels. The super-resolution reconstruction model proposed in this paper can extract more comprehensive image information, and at the same time, it can obtain more accurate edge information to enhance the texture details of super-resolution images, and achieve better reconstruction results.

Abstract Background Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host’s response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. Methods A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). Results IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. Conclusion Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Abstract Heteroaromatic N‐oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic N‐oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes. Catalytic strategies rely on the functionalization of heteroaromatic N‐oxide compounds, leading to products with a relatively limited skeletal diversity. This study introduces a Cu‐catalyzed atroposelective method for synthesizing biaryl N‐oxides via de novo heteroaromatic N‐oxide ring formation. This mild and efficient approach achieves excellent stereoselectivities (up to 99:1 er), enabling the production of a wide array of N‐oxides with novel heteroaromatic scaffolds. The axially chiral N‐oxide product 3f demonstrates high stereoselectivity and recyclability as a Lewis base catalyst. Additionally, product 3e exhibits promising therapeutic efficacy against triple‐negative breast cancer, with IC50 values of 4.8 and 5.2 µm in MDA‐MB‐231 and MDA‐MB‐468 cells, respectively. This research not only advances the synthesis of challenging chiral heteroaromatic N‐oxides but also encourages further exploration of N‐oxide entities in the discovery of bioactive small molecules.

Stem cell-mediated bio-root regeneration is an alternative tooth replacement strategy; however, physiologically functional bio-root regeneration with distinctive dentin structure remains challenging. In this study, the distinct arrangements of collagen fibril bundles were identified that account for hierarchical structural differences between dentin, cementum, and alveolar bone. Thus, an “engineered pre-dentin” was fabricated, which was a dentin hierarchical structure mimicking collagen (MC) scaffold, with well-aligned hierarchical mineralized collagen fibril bundles. The results revealed that it has a stronger effect on promoting biological root regeneration in nude mice and miniature pigs with dental pulp stem cell (DPSC) and periodontal ligament stem cell (PDLSC) sheets compared to hydroxyapatite tricalcium phosphate (HA/TCP). The success rate in the MC group was also higher than that in the HA/TCP group (67% and 33%, respectively). In conclusion, the hierarchical dentin-mimicking scaffold can enhance the regeneration of bio-roots, which provides a promising strategy for tooth regeneration.

Abstract The low ion transport is a major obstacle for low‐temperature (LT) sodium‐ion batteries (SIBs). Herein, a core‐shell structure of bismuth (Bi) nanospheres coated with carbon (Bi@C) is constructed by utilizing a novel Bi‐based complex (1,4,5,8‐naphthalenetetracarboxylic dianhydride as the ligand) as the precursor, which provides an effective template to fabricate Bi‐based anodes. At −40°C, the Bi@C anode achieves a high capacity, which is equivalent to 96% of that at 25°C, benefitting from the core‐shell nanostructured engineering and Na+‐ether‐solvent cointercalation process. The special Na+‐diglyme cointercalation behavior may effectively reduce the activation energy and accelerate the Na+ diffusion kinetics, enabling the excellent low‐temperature performance of the Bi@C electrode. As expected, the fabricated Na3V2(PO4)3//Bi@C full‐cell delivers impressive rechargeability in the ether‐based electrolyte at −40°C. Density functional theory calculations and electrochemical tests also reveal the fast reaction kinetic mechanism at LT, thanks to a much lower diffusion energy barrier (167 meV) and a lower reaction activation energy (32.2 kJ mol−1) of Bi@C anode in comparison with that of bulk Bi. This work provides a rational design of Bi‐based electrodes for rechargeable SIBs under extreme conditions.

Abstract Invertebrates greatly support the growth, development, and reproduction of insectivorous birds. However, the influence of human activity (e.g., pesticide use, deforestation, and urbanization) inevitably leads to a decrease in global arthropods. The diversity and variation in invertebrate diet influence the food composition of birds, especially species living in rapidly changing environments, such as the Tibetan Plateau. However, little is known of the seasonal variation in invertebrate diet in response to environmental changes. Here, we characterized the invertebrate diet composition in pre‐ and post‐breeding black‐necked crane (Grus nigricollis) using fecal metabarcoding. We identified 38 invertebrate genera; the top three were Tipula (82.1% of relative abundance), Ceramica (3.0%), and unclassified_Hymenoptera (2.5%), with Tipula predominated the diet in both seasons. We also observed 20 and 16 unique genera in the pre‐ and post‐breeding periods, and the genera composition was distinct between seasons (R = .036, p = .024). In pre‐breeding, black‐necked cranes tended to consume more diverse foods, and individual cranes exhibited greater heterogeneity at the genus level. At the genera and species level, pre‐breeding black‐necked cranes showed a wider dietary niche than post‐breeding cranes. We observed season‐specific features, with Tipula (common crane fly) and Stethophyma (grasshoppers) being enriched in the post‐breeding period and Ceramica (moth) being more abundant in the pre‐breeding period. Three Tipula species had the greatest importance in discriminating between seasonal diets. This study demonstrated a seasonal pattern of invertebrate diet in the black‐necked crane, suggesting diet composition in response to resource and species availability. These results elaborate on the foraging ecology of highland birds and can inform the management of black‐necked crane conservation.

Background: Because adverse reactions or drug resistance are often found after current chemotherapies for metastatic colorectal cancer (mCRC), new treatments are still in demand. Shenqi Sanjie Granules (SSG), an antitumor compound preparation of traditional Chinese medicine, has been recognized for its ability in clinical practice of oncotherapy. Nevertheless, the precise effects of SSG in colorectal cancer (CRC) and underlying mechanisms through which SSG inhibits CRC remain uncertain. The current study aimed to evaluate the anti-CRC activity of the Chinese herbal compound preparation SSG and investigate the underlying mechanisms of action. Materials and methods: Initially, nine distinct cancer cell lines, including five CRC cell lines, one breast cancer cell line, two lung adenocarcinoma cell lines and one cervical cancer cell line, were used to evaluate the antitumor activity of SSG, and the mouse CRC cell line CT26 were used for further research. In vitro experiments utilizing diverse assays were conducted to assess the inhibitory effects of the SSG on CT26. Furthermore, subcutaneous syngeneic mouse model and AOM (azoxymethane)/DSS (dextran sodium sulfate) induced in-situ colitis-related mouse CRC model were used to evaluate the antitumor potential and biotoxicity of SSG in vivo. To elucidate the underlying molecular mechanisms, transcriptome sequencing and network pharmacology analysis were performed. Meanwhile, verification is carried out with quantitative real-time PCR (qRT-PCR) and flow cytometry (FCM) analysis. Results: Our in vitro inhibition study showed that SSG could effectively inhibit CRC cell line CT26 growth and metastasis, and induce cell death. Neither of apoptosis inhibitor, necroptosis inhibitor, ferroptosis inhibitor, but the combination of the three diminished SSG-induced cell death, suggesting that multiple cell death pathways were involved. Both the syngeneic CRC model and the in-situ CRC model indicated SSG inhibited CRC in vivo with few toxic side effects. Further mechanistic study suggested SSG treatment activated the ferroptosis pathway, particularly mediated by Hmox1, which was upregulated scores of times. Network pharmacology analysis indicated that the active ingredients of SSG, including Quercetin, Luteolin and Kaempferol were potential components directly upregulated Hmox1 expression. Conclusions: Collectively, our findings indicate that the administration of SSG has the potential to inhibit CRC both in vitro and in vivo. The mechanism by which this compound preparation exerts its action is, at least partly, the induction of ferroptosis through upregulating Hmox-1 by its three active ingredients Quercetin, Luteolin and Kaempferol.

ObjectiveThis study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC).MethodsIn this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions.ResultsAmong the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%).ConclusionThe combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.

Introduction: Trauma is a significant global public health concern and the leading cause of morbidity and mortality in children. This study aimed to assess the independent predictors of trauma severity as well as mortality in pediatric patients admitted to the intensive care unit (ICU). Methods: In this cross-sectional study, following the STROBE checklist, we retrospectively analyzed the clinical and baseline characteristics of pediatric patients with trauma injuries admitted to the ICU of Children’s Hospital of Zhejiang University School of Medicine, China, over a decade. Results: 951 pediatric patients with a mean age of 4.79 ± 3.24 years (60.78% Boys) were studied (mortality rate 8.41%). Significant associations were observed between ISS and place of residence (p = 0.021), location of the injury (p = 0.010), year of injury (p

This paper presents an innovative approach for achieving rapid synchronization between two memristor chaotic circuits (MCCs), both with and without noise perturbations. The proposed adaptive control strategy effectively handles the uncertainty in control gains by adhering to predesigned update law. Additionally, this protocol is non-chattering and differentiable, avoiding the use of conventional discontinuous functions such as signum and absolute value functions. This method successfully mitigates the tremors caused by discontinuous functions. We derive two sufficient criteria using finite-time Lyapunov and stochastic finite-time Lyapunov stability methods. Numerical results validate the theoretical analysis and demonstrate the influence of noise intensity on convergence speed. Furthermore, the results have an application in image encryption transmission.

Abstract Modulation of scattering in random lasers (RLs) by magnetic fields has attracted much attention due to its rich physical insights. We fabricate magnetic gain polymer optical fiber to generate RLs. From macroscopic experimental phenomena, with the increase of the magnetic field strength, the magnetic transverse photocurrent exists in disordered multiple scattering of RLs and the emission intensity of RLs decreases, which is the experimental observation of photonic Hall effect (PHE) and photonic magnetoresistance (PMR) in RLs. At the microscopic level, based on the field dependence theory of magnetic disorder in scattered nanoparticles and the replica symmetry breaking theory, the magnetic-induced transverse diffusion of photons reduces the scattering disorder, and then decreases the intensity fluctuation disorder of RLs. Our work establishes a connection between the above two effects and RLs, visualizes the influence of magnetic field on RL scattering at the microscopic level, which is crucial for the design of RLs.

Abstract Background COVID-19-associated pulmonary fibrosis remains frequent. This study aimed to investigate pulmonary redox balance in COVID-19 ARDS patients and possible relationship with pulmonary fibrosis and long-term lung abnormalities. Methods Baseline data, chest CT fibrosis scores, N-terminal peptide of alveolar collagen III (NT-PCP-III), transforming growth factor (TGF)-β1, superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were first collected and compared between SARS-CoV-2 RNA positive patients with moderate to severe ARDS (n = 65, COVID-19 ARDS) and SARS-CoV-2 RNA negative non-ARDS patients requiring mechanical ventilation (n = 63, non-ARDS). Then, correlations between fibroproliferative (NT-PCP-III and TGF-β1) and redox markers were analyzed within COVID-19 ARDS group, and comparisons between survivor and non-survivor subgroups were performed. Finally, follow-up of COVID-19 ARDS survivors was performed to analyze the relationship between pulmonary abnormalities, fibroproliferative and redox markers 3 months after discharge. Results Compared with non-ARDS group, COVID-19 ARDS group had significantly elevated chest CT fibrosis scores (p

Abstract Sulfuryl fluoride (SO2F2) is a synthetic pesticide and a potent greenhouse gas that is accumulating in the global atmosphere. Rising emissions are a concern since SO2F2 has a relatively long atmospheric lifetime and a high global warming potential. The U.S. is thought to contribute substantially to global SO2F2 emissions, but there is a paucity of information on how emissions of SO2F2 are distributed across the U.S., and there is currently no inventory of SO2F2 emissions for the U.S. or individual states. Here we provide an atmospheric measurement-based estimate of U.S. SO2F2 emissions using high-precision SO2F2 measurements from the NOAA Global Greenhouse Gas Reference Network (GGGRN) and a geostatistical inverse model. We find that California has the largest SO2F2 emissions among all U.S. states, with the highest emissions from southern coastal California (Los Angeles, Orange, and San Diego counties). Outside of California, only very small and infrequent SO2F2 emissions are detected by our analysis of GGGRN data. We find that California emits 60-85% of U.S. SO2F2 emissions, at a rate of 0.26 ( ± 0.10) Gg yr−1. We estimate that emissions of SO2F2 from California are equal to 5.5–12% of global SO2F2 emissions.

Background: Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs). Methods: Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting. Results: The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate. Conclusion: The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes. The translational potential of this article: Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.

PurposeTo evaluate organ at risk (OAR) auto-segmentation in the head and neck region of computed tomography images using two different commercially available deep-learning-based auto-segmentation (DLAS) tools in a single institutional clinical applications.MethodsTwenty-two OARs were manually contoured by clinicians according to published guidelines on planning computed tomography (pCT) images for 40 clinical head and neck cancer (HNC) cases. Automatic contours were generated for each patient using two deep-learning-based auto-segmentation models—Manteia AccuContour and MIM ProtégéAI. The accuracy and integrity of autocontours (ACs) were then compared to expert contours (ECs) using the Sørensen-Dice similarity coefficient (DSC) and Mean Distance (MD) metrics.ResultsACs were generated for 22 OARs using AccuContour and 17 OARs using ProtégéAI with average contour generation time of 1 min/patient and 5 min/patient respectively. EC and AC agreement was highest for the mandible (DSC 0.90 ± 0.16) and (DSC 0.91 ± 0.03), and lowest for the chiasm (DSC 0.28 ± 0.14) and (DSC 0.30 ± 0.14) for AccuContour and ProtégéAI respectively. Using AccuContour, the average MD was

Objective and rationale: Hospital-acquired falls are common and serious adverse events in medical institutions, with high incidence and injury rates. Studying the occurrence patterns of hospital-acquired falls is important for preventing falls in hospitalized patients. However, the effect of meteorological factors on hospital-acquired falls has not been elucidated. Therefore, this study explored the impact of meteorological parameters on hospital-acquired falls in Chongqing, China, and provided new ideas for the clinical prevention of falls in patients. Methods: Correlation analysis and distributed lag nonlinear models were employed to analyze the relationship between 3890 cases of hospital-acquired falls and meteorological data in 13 hospitals in 11 districts and counties in Chongqing from January 2013 to April 2023. Results: The number of hospital-acquired falls demonstrated a nonlinear correlation with the daily average relative humidity and negatively correlated with sunshine duration; however, temperature, air pressure, and wind speed were not correlated. Compared to the reference humidity (87 %), the immediate effects of daily average relative humidity (65–68 % and 90–97 %) increased the risk of hospital-acquired falls on the same day (relative risk [RR]:1.027–1.243). When the daily average relative humidity was 95–97 %, lags of 0–1 d and 8–12 d had greater effects on falls (RR:1.073–1.243). The daily average relative humidities of 62–74 % and 91–97 % were statistically significant at cumulative relative risk (CRR)of 4, 7, 10, and 14 d with a cumulative lag (CRR: 1.111–4.277). On sex and age stratification, the lag and cumulative effects of relative humidity more significantly impacted falls in women and patients aged ≥65 years. Conclusion: Daily average relative humidity had a nonlinear correlation and lag effect on hospital-acquired falls; therefore, medical institutions should pay attention to the effect of relative humidity on hospital-acquired falls in patients, especially old and female patients.

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1’s tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

To assess the energy saving and emission reduction effects of recycling technology, the quantitative analysis of energy consumption and carbon emission of recycled asphalt pavement is conducted of asphalt mixture production, transportation, paving and compaction. Firstly, the calculation model for energy consumption and carbon emissions of recycled asphalt pavement is established during the construction stage. In addition, the energy consumption and carbon emission of four recycling technologies, including the HCPR, HIR, CCPR and CIR, were compared. Finally, the FCE method is used to evaluate the actual effect of energy saving and emission reduction from the perspectives of the ecological benefit and the economic benefit. The research results indicate the most serious stage of energy consumption is the new material production stage, and the most serious stage of carbon emission is the asphalt mixture production stage of recycled asphalt pavement. Taking the HCPR technology as an example are calculated in detail. The energy consumption of the HCPR technology in the four stages of the construction stage was 17.59 MJ, 344.45 MJ, 228.51 MJ and 25.85 MJ, respectively, and the emissions in the four stages of the construction stage were 1307.89 g, 5971.28 g, 19,251.24 g and 1949.82 g, respectively. For different recycling technologies in the construction stage, the energy-saving ratios of HCPR, HIR and CCPR are 13.62%, 9.61% and 19.24% respectively when compared with the typical scheme, which have a certain energy-saving effect. However, the energy consumption of CIR reduced by 43.63%, which the energy saving effect is most significant. Moreover, the emission reduction ratios of HCPR, HIR and CCPR are 2.3%, 9.23% and 1.01% respectively when compared with the typical scheme, the emission of CIR reduced by 30.76%, so the emission reduction effect of CIR is most significant. Furthermore, the comprehensive evaluation score of the CIR technology with the most significant energy saving and emission reduction effect is 0.8021 in terms of ' ecological benefits ' and 0.8074 in terms of ' economic benefits '. In summary, it is recommended to adopt CIR technology in the engineering project, which can achieve the most significant energy-saving and emission reduction effects.

Abstract Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride‐based alloys are still the best for near‐room‐temperature applications. In this work, a ≈38% enhancement of the average ZT (300−473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2−yTe3‐based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6‐based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high‐density dislocations in the same region can effectively scatter the phonons, decoupling the electron‐phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single‐leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate‐matrix interface microstructure in improving the performance of materials for relatively low‐temperature applications.

Abstract Background The Internet Plus Nursing Service (IPNS) is being instigated in all provincial-level regions throughout China, in which registered nurses (with more than five years of experience from qualified medical institutions) will provide services to those in their communities or homes after receiving online applications. The growing shortage of human resources in nursing is a critical issue for this project, so effective policies for recruiting and retaining nurses are critical. Objective This study aims to pinpoint the significant job characteristics that play a crucial role in shaping the job decisions of sharing nurses in the IPNS program, and to estimate the strength of job attributes. Methods A discrete choice experiment (DCE) was used to assess job attributes influencing sharing nurses’ preferences. A qualitative design, including in-depth interview and focus interview methods, was conducted to determine the inclusion of attributes. The final included six attributes were: work modes, duration per visit, income per visit, personal safety, medical risk prevention, and refresher training. This study was conducted at 13 hospitals in Guangdong Province, China, from April to June 2022, and a total of 220 registered sharing nurses participated in the survey. The multinomial logit model explored attributes and relative valued utility. Preference heterogeneity is explored via latent class analysis (LCA) models. Results A total of 220 participants answered the questionnaire. Income was the most influential characteristic of a sharing nursing position, followed by personal safety management, duration per visit, medical risk prevention, and refresher training, and nurses’ preferences differed among different types of classes. Conclusions Sharing nurses place most value on income and personal safety with career-related decisions, which indicates an urgent need to develop complete security for personal safety. This study can be helpful to decision-makers in the Chinese government.

In the current research field of digital image encryption technology, there are some key challenges, including insufficient key space, the weak sensitivity of key parameters, and low complexity of the encryption process. To address these issues, this study proposes a double image encryption framework to enhance the security of image encryption algorithms. In the first encryption, this study proposes an improved generative adversarial network incorporating unsupervised learning properties, adaptive layer instance normalization, multi-level attention enhanced residual network structure, and feature distribution fidelity module. This study also proposes a comprehensive loss function for the network, which consists of an encryption loss function, a decryption loss function, an image space smoothness improvement loss function, a generator veracity enhancement loss function, and an identity loss function. In the second encryption, this study proposes a six-dimensional hyperchaotic system possessing four positive Lyapunov exponents for the first scrambling operation, and combines the Fibonacci Q-matrix and classical shuffling algorithms for the diffusion and second scrambling operations. By combining deep learning techniques with chaotic systems, the key space and the quality of the encrypted images are effectively improved, as well as the ability of resistance to the burst attack, salt-and-pepper noise attack and cropping attack. This study provides new perspectives and technical routes for solving the challenges faced in digital image encryption.

In tackling the intricate challenge of selecting best cities for sports events, our innovative approach, the stepwise weight assessment ratio analysis (SWARA)-alternative ranking order method accounting for two-step normalization (AROMAN) method, merges the SWARA and the AROMAN under the intuitionistic fuzzy based framework. Noteworthy for its integration of linear and vector normalization techniques, the AROMAN method ensures precise data structures, enhancing the reliability of subsequent calculations. A critical facet of our methodology is its practical application, exemplified in a comprehensive case study evaluating and ranking five alternative cities for hosting sports events. Criteria such as accessibility, facilities, community engagement, weather conditions, economic viability, safety, cultural fit, and environmental impact are considered. The effectiveness of the IF-SWARA-AROMAN method in addressing the intricacies of city selection is illustrated in this practical situation, which furnishes decision-makers with a reliable instrument to make well-informed decisions in the administration of sporting events. The methodology not only recognises the intricate intricacies of the selection process but also enhances the development of comprehensive and influential sports experiences, thereby harmonising effortlessly with the ever-changing realm of sports management.

Abstract Background Hospital Examination Reservation System (HERS) was designed for reducing appointment examination waiting time and enhancing patients’ medical satisfaction in China, but implementing HERS would encounter many difficulties. This study would investigate the factors that influence patients’ utilization of HERS through UTAUT2, and provide valuable insights for hospital managements to drive the effective implementation of HERS. It is helpful for improving patients’ medical satisfaction. Methods We conducted a survey through the Sojump platform, targeting patients were who have already used HERS. We collected questionnaire information related to factors behavior intention, performance expectancy, and effort expectancy. Subsequently, we employed a structural equation model to analyze the factors influencing patients’ utilization of HERS. Results A total of 394 valid questionnaires were collected. Habit was the main direct positive factor influencing the behavioral intention of HERS (β = 0.593; 95%CI: 0.072, 1.944; P = 0.002), followed by patient innovation (β = 0.269; 95%CI: 0.002, 0.443; P

Abstract Background The Chinese government has invested significant resources to build many rural healthcare stations. However, in the face of convenient medical paths and accessible medical resources, the utilization rate of health services for older adults in rural areas is surprisingly low. This study explored why health-seeking behavior among older adults in rural China was not active. Methods Data were collected through participatory rural appraisal (PRA) with 108 participants in 12 villages in southern China. Daily schedule and social and resource mapping were employed to outline the range of activities and the routine of the older adults, as well as in-depth interviews to understand the logic of their healthcare choices. Data collected were analyzed by content analysis. Results Three themes were generated: (1) perceptions of health status (being healthy or sick): the rural older adults used the ability to handle routine chores as a measure of health status; (2) prioritization of solving symptoms over curing diseases: the older adults preferred the informal self-medication to cope with diseases, as long as there were no symptoms and no pain; (3) ‘unpredictable’ troubles: they tended to favor the ‘optimal’ solution of keeping their lives in order rather than the best medical treatment options. Conclusion This study showed that the medical practices of the rural elderly were profoundly influenced by their perceptions of health and their life experiences. In the face of diseases, they tended to keep their lives in order, preferring self-treatment practices that address symptoms or selectively following medical advice rather than medical and science-based clinical solutions. In the future, the construction of rural health care should focus on changing the ‘inaccessibility’ of healthcare resources at the subjective level of the rural elderly and develop culturally adaptable health education.

As one of the biggest ports, the aquatic ecology of Shanghai Port has a significant impact on the health of surrounding residents and aquatic animals. Therefore, this study explored the composition and distribution of bacteria, pathogens, and ARGs at Shanghai Ports by high-throughput sequencing. The results showed that the bacterial community was dominated by the Proteobacteria at the phylum level. With the refinement of classification level, the main composition of bacteria in different samples shows significant differences. In contrast, there was no significant difference in the composition and distribution of pathogens among the samples. It indicates that pathogens and ARGs have steady community composition at Shanghai Port. Pseudomonas aeruginosa and Salmonella enterica could be regarded as candidate indicator pathogens. macB, tetA (58), and evgS were the main ARGs, and they showed a close relationship with Mycobacterium tuberculosis, Magnaporthe oryzae, Streptococcus pneumonia, Xanthomonas oryzae, and Vibrio cholerae in different sites and layers. This may lead to the transfer of ARGs between different pathogens, resulting in more threatening pathogens. The results showed that the pathogens and ARGs present posed a risk of transmission and were potentially harmful to residents in the environment. They can spread to any other ports in the world through the transmission of ballast water, posing a threat to humans and local ecology. In order to keep human health, it is necessary to pay more attention to the water environment of ports and increase the monitoring. Furthermore, it is essential to strengthen the supervision of external source pollution input due to the special features of the port.

DCT is a beyond-birthday-bound (BBB) deterministic authenticated encryption (DAE) mode proposed by Forler et al. in ACISP 2016, ensuring integrity by redundancy. The instantiation of DCT employs the BRW polynomial, which is more efficient than the usual polynomial in GCM by reducing half of the multiplication operations. However, we show that DCT suffers from a small stretch problem similar to GCM. When the stretch length τ is small, choosing a special m-block message, we can reduce the number of queries required by a successful forgery to O(2τ/m). We emphasize that this attack efficiently balances space and time complexity but does not contradict the security bounds of DCT. Finally, we propose an improved scheme named Robust DCT (RDCT) with a minor change to DCT, which improves the security when τ is small and makes it resist the above attack.

PURPOSETo investigate the value of clinical characteristics and radiological features for predicting spread through air spaces (STAS) in patients with clinical stage IA non-small cell lung cancer (NSCLC).METHODSA total of 336 patients with NSCLC from our hospital were randomly divided into two groups, i.e., the training cohort (n = 236) and the internal validation cohort (n = 100) (7:3 ratio). Furthermore, 69 patients from two other hospitals were collected as the external validation cohort. Eight clinical patient characteristics were recorded, and 20 tumor radiological features were quantitatively measured and qualitatively analyzed. In the training cohort, the differences in clinical characteristics and radiological features were compared using univariate and multivariate analysis. A nomogram was created, and the predictive efficacy of the model was evaluated in the validation cohorts. The receiver operating characteristic curve and area under the curve (AUC) value were used to evaluate the discriminative ability of the model. In addition, the Hosmer–Lemeshow test and calibration curve were used to evaluate the goodness-of-fit of the model, and the decision curve was used to analyze the model’s clinical application value.RESULTSThe best predictors included gender, the carcinoembryonic antigen (CEA), consolidation-to-tumor ratio (CTR), density type, and distal ribbon sign. Among these, the tumor density type [odds ratio (OR): 6.738] and distal ribbon sign (OR: 5.141) were independent risk factors for predicting the STAS status. Moreover, three different STAS prediction models were constructed, i.e., a clinical, radiological, and combined model. The clinical model comprised gender and the CEA, the radiological model included the CTR, density type, and distal ribbon sign, and the combined model comprised the above two models. A DeLong test results revealed that the combined model was superior to the clinical model in all three cohorts and superior to the radiological model in the external validation cohort; the cohort AUC values were 0.874, 0.822, and 0.810, respectively. The results also showed that the combined model had the highest diagnostic efficacy among the models. The Hosmer–Lemeshow test showed that the combined model showed a good fit in all three cohorts, and the calibration curve showed that the predicted probability value of the combined model was in good agreement with the actual STAS status. Finally, the decision curve showed that the combined model had a better clinical application value than the clinical and radiological models.CONCLUSIONThe nomogram created in this study, based on clinical characteristics and radiological features, has a high diagnostic efficiency for predicting the STAS status in patients with clinical stage IA NSCLC and may support the creation of personalized treatment strategies before surgery.

The Three Gorges Reservoir area presents a complex geological environment, where the deterioration of rock masses in the riparian zone of karst bank slopes is expedited by the fluctuating reservoir water levels of the reservoir, thereby hastening the evolution of the bank slopes towards instability. This study focuses on the Huangyanwo dangerous rock mass in the Three Gorges Reservoir area. A comprehensive filed investigation was conducted to scrutinize the deterioration phenomenon of rock masses within the water–level fluctuation zone, and a numerical analysis was performed to assess the long–term stability of the dangerous rock mass. The findings reveal the presence of a vertical karst zone and a bottom seepage zone in the Huangyanwo dangerous rock mass. The bottom seepage zone is situated within the water–level–fluctuation zone, characterized by areas of weakness and rock mass deterioration. Considering the influence of reservoir water levels and rainfall events, the stability coefficient of karst water pressure on the bank slope is calculated to be 1.69, indicating that the dangerous rock mass remains stable. Nevertheless, due to the progressive deterioration of rock mass parameters within the weak area at the bottom, the stability coefficient experiences an annual decline of approximately 0.01. It is predicted that the Huangyanwo dangerous rock mass will transition to an unstable state after approximately 57 cycles of periodic water level variations, and the instability failure will occur after 62 cycles. The failure mode of the dangerous rock mass involves a compound failure mechanism of toppling and sliding subsequent to the connection of the weak zone at the bottom, aligning closely with the qualitative understanding grained from field investigations. The research results hold significant instructive implications for the early warning and prevention strategies concerning analogous geological disasters in reservoir areas.

In this paper, combining B-spline function and Tikhonov regularization, we propose an online identification approach for reconstructing a smooth function and its derivative from scattered data with heteroscedasticity. Our methodology offers the unique advantage of enabling real-time updates based on new input data, eliminating the reliance on historical information. First, to address the challenge of heteroscedasticity and computation cost, we employ weight coefficients along with a judiciously chosen set of knots for interpolation. Second, a reasonable approach is provided to select weight coefficients and the regularization parameter in objective functional. Finally, We substantiate the efficacy of our approach through a numerical example and demonstrate its applicability in solving inverse problems. It is worth mentioning that the algorithm not only ensures the calculation efficiency, but also trades the data accuracy through the data volume.

Abstract Background It has been reported that metformin use may reduce the risk of thyroid cancer, but existing studies have generated inconsistent results. The purpose of this study was to investigate such association between metformin use and the risk of thyroid cancer. Methods Studies of metformin use for the risk of thyroid cancer were searched in Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Database, Wanfang Data, and Chinese Scientific Journals Database (VIP) from the establishment date to December 2022. Newcastle–Ottawa scale is adopted for assessing the methodological quality of included studies, and the inter-study heterogeneity was assessed by using the I-squared statistic. Combined odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated through either fixed-effects or random-effects model according to the heterogeneity. Besides, subgroup analyses, sensitivity analyses and test for publication bias were conducted. Results Five studies involving 1,713,528 participants were enrolled in the qualitative and quantitative synthesis. The result of the meta-analyses showed that metformin use was associated with a statistically significant lower risk of thyroid cancer (pooled OR = 0.68, 95% CI = 0.50–0.91, P = 0.011). Moreover, in the subgroup analysis, we found that the use of metformin may also aid in the prevention of thyroid cancer in Eastern population (pooled OR = 0.55, 95% CI = 0.35–0.88, P = 0.012) rather than Western population (pooled OR = 0.89, 95% CI = 0.52–1.54, P = 0.685). Sensitivity analysis suggested the results of this meta-analyses were relatively stable. No publication bias was detected. Conclusion Metformin use is beneficial for reducing the risk of thyroid cancer. For further investigation, more well-designed studies are still needed to elucidate the association between metformin use and the risk of thyroid cancer.

Abstract To eliminate unnecessary background information, such as soft tissues in original CT images and the adverse impact of the similarity of adjacent spines on lumbar image segmentation and surgical path planning, a two‐stage approach for localising lumbar segments is proposed. First, based on the multi‐scale feature fusion technology, a non‐linear regression method is used to achieve accurate localisation of the overall spatial region of the lumbar spine, effectively eliminating useless background information, such as soft tissues. In the second stage, we directly realised the precise positioning of each segment in the lumbar spine space region based on the non‐linear regression method, thus effectively eliminating the interference caused by the adjacent spine. The 3D Intersection over Union (3D_IOU) is used as the main evaluation indicator for the positioning accuracy. On an open dataset, 3D_IOU values of 0.8339 ± 0.0990 and 0.8559 ± 0.0332 in the first and second stages, respectively is achieved. In addition, the average time required for the proposed method in the two stages is 0.3274 and 0.2105 s respectively. Therefore, the proposed method performs very well in terms of both precision and speed and can effectively improve the accuracy of lumbar image segmentation and the effect of surgical path planning.

Cyclic glycine-proline (cGP), a prevalent marine cyclic dipeptide, possesses a distinct pyrrolidine-2,5-dione scaffold, which contributes to the chemical diversity and broad bioactivities of cGP. The diverse sources from marine-related, endogenous biological, and synthetic pathways and the in vitro and in vivo activities of cGP are reviewed. The potential applications for cGP are also explored. In particular, the pivotal roles of cGP in regulating insulin-like growth factor-1 homeostasis, enhancing neuroprotective effects, and improving neurotrophic function in central nervous system diseases are described. The potential roles of this endogenous cyclic peptide in drug development and healthcare initiatives are also highlighted. This review underscores the significance of cGP as a fundamental building block in drug discovery with exceptional drug-like properties and safety. By elucidating the considerable value of cGP, this review aims to reignite interest in cGP-related research within marine medicinal chemistry and synthetic biology.

Abstract Background The gefitinib resistance mechanism in non-small cell lung cancer (NSCLC) remains unclear, albeit exosomal circular RNA (circRNA) is known to possibly play a vital role in it. Methods We employed high-throughput sequencing techniques to detect the expressions of exosomal circRNA both in gefitinib-resistant and gefitinib-sensitive cells in this study. The circKIF20B expression was determined in serum exosomes and tissues of patients by qRT-PCR. The structure, stability, and intracellular localization of circKIF20B were verified by Sanger sequencing, Ribonuclease R (RNase R)/actinomycin D (ACTD) treatments, and Fluorescence in situ hybridization (FISH). The functions of circKIF20B were investigated by 5-Ethynyl-20-deoxyuridine (EdU), flow cytometry, Cell Counting Kit-8 (CCK-8), oxygen consumption rate (OCR), and xenograft model. Co-culture experiments were performed to explore the potential ability of exosomal circKIF20B in treating gefitinib resistance. The downstream targets of circKIF20B were determined by luciferase assay, RNA pulldown, and RNA immunoprecipitation (RIP). Results We found that circKIF20B was poorly expressed in the serum exosomes of gefitinib-resistant patients (n = 24) and the tumor tissues of patients with NSCLC (n = 85). CircKIF20B was negatively correlated with tumor size and tumor stage. Decreasing circKIF20B was found to promote gefitinib resistance by accelerating the cell cycle, inhibiting apoptosis, and enhancing mitochondrial oxidative phosphorylation (OXPHOS), whereas increasing circKIF20B was found to restore gefitinib sensitivity. Mechanistically, circKIF20B is bound to miR-615-3p for regulating the MEF2A and then altering the cell cycle, apoptosis, and mitochondrial OXPHOS. Overexpressing circKIF20B parental cells can restore sensitivity to gefitinib in the recipient cells by upregulating the exosomal circKIF20B expression. Conclusions This study revealed a novel mechanism of circKIF20B/miR-615-3p/MEF2A signaling axis involving progression of gefitinib resistance in NSCLC. Exosomal circKIF20B is expected to be an easily accessible and alternative liquid biopsy candidate and potential therapeutic target in gefitinib-resistant NSCLC. Graphical Abstract The schematic diagram of mechanism in this study. Exosomal circKIF20B inhibits gefitinib resistance and cell proliferation by arresting the cell cycle, promoting apoptosis, and reducing OXPHOS via circKIF20B/miR-615-3p/MEF2A axis in NSCLC.

Abstract Small molecule direct BAK activators can potentially be used for the development of anti-cancer drugs or as tools to study BAK activation. The thrombopoietin receptor agonist eltrombopag (Eltro) inhibits BAX activation and BAX-mediated apoptosis. Here we report that, in contrast to its function as a BAX inhibitor, Eltro directly binds BAK but induces its activation in vitro. Moreover, Eltro induces or sensitizes BAK-dependent cell death in mouse embryonic fibroblasts (MEFs) and Jurkat cells. Chemical shift perturbation analysis by NMR indicates that Eltro binds to the BAK α4/α6/α7 groove to initiate BAK activation. Further molecular docking by HADDOCK suggests that several BAK residues, including R156, F157, and H164, play an important role in the interaction with Eltro. The introduction of an R156E mutation in the BAK α4/α6/α7 groove not only decreases Eltro binding and Eltro-induced BAK activation in vitro but also diminishes Eltro-induced apoptosis. Thus, our data suggest that Eltro directly induces BAK activation and BAK-dependent apoptosis, providing a starting point for the future development of more potent and selective direct BAK activators.

The traditional calculation of roller contact load and contact deformation includes a number of calculation, which is prone to system collapse. In this research, three equivalent mathematical models are established by using the equivalent substitution method, the deformation of rollers is solved by using the Newton iterative principle, and then the contact deformation and contact load of different rollers under the three mathematical models are obtained. According to the number arrangement from small to large, the change range of contact deformation and contact load of any roller at different times is obtained. Compared with the traditional calculation method, the program generated in this study is fast, not prone to system collapse, and the calculation results meet the numerical value of the traditional method.

Objectives Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies. Methods During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3–V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform. Results The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05). Conclusions The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

High-cadence, multiwavelength observations have continuously revealed the diversity of tidal disruption events (TDEs), thus greatly advancing our knowledge and understanding of TDEs. In this work, we conducted an intensive optical-UV and X-ray follow-up campaign of TDE AT 2023lli and found a remarkable month-long bump in its UV/optical light curve nearly 2 months prior to maximum brightness. The bump represents the longest separation time from the main peak among known TDEs to date. The main UV/optical outburst declines as t ^−4.10 , making it one of the fastest-decaying optically selected TDEs. Furthermore, we detected sporadic X-ray emission 30 days after the UV/optical peak, accompanied by a reduction in the period of inactivity. It is proposed that the UV/optical bump could be caused by the self-intersection of the stream debris, whereas the primary peak is generated by the reprocessed emission of the accretion process. In addition, our results suggest that episodic X-ray radiation during the initial phase of decline may be due to the patched obscurer surrounding the accretion disk, a phenomenon associated with the inhomogeneous reprocessing process. The double TDE scenario, in which two stars are disrupted in sequence, is also a possible explanation for producing the observed early bump and main peak. We anticipate that the multicolor light curves of TDEs, especially in the very early stages, and the underlying physics can be better understood in the near future with the assistance of dedicated surveys such as the deep high-cadence survey of the 2.5 m Wide Field Survey Telescope.

Two-dimensional semiconductors simultaneously having suitable electronic properties and high carrier motilities are highly required in next-generation photoelectronic devices. Herein, we propose a new single-layer semiconductor, CdIn2S4, and investigate its photoelectronic properties utilizing first-principles calculations. Interestingly, we find that single-layer CdIn2S4 holds a quasi-direct moderate bandgap of 1.73 eV. Its valence band maximum and conduction band minimum are located at different atomic regions, which hinders the recombination of generated electrons and holes. Hence, single-layer CdIn2S4 has a suitable electronic structure for optoelectronics. The suitable electronic property also exists under the biaxial strains of −4%, −2%, 2 %, and 4 %, while the electron mobility ranges from ∼3000 to ∼11,000 cm2·V−1·s−1, revealing its potential application in high-speed electronics. In addition, its strong visible absorption and much-reduced exciton binding energy render abundant photogenerated electrons and holes. Summarily, the suitable electronic property, ultrahigh carrier mobility, and abundant visible absorption demonstrate that single-layer CdIn2S4 is a hopeful candidate for high-speed optoelectronics.

The sustainable development of low-carbon buildings has aroused widespread concern in the whole society. This study aims to propose a three-step carbon reduction strategy based on innovative design, intelligent construction and secondary utilization, and provide a new solution for carbon reduction in the construction industry. Based on the life cycle assessment method, the system boundary and calculation model of carbon emission and carbon compensation in each stage of building life cycle are redefined, and the carbon reduction effect of the mixed three-step strategy is quantitatively analyzed through the case carbon emission data, which proves the scientific feasibility of the carbon reduction strategy in this paper. The research shows that it has a good carbon reduction effect whether it is adopting structural optimization aided design in the architectural design stage, upgrading the traditional construction technology with 3D printing intelligent construction technology, or effectively disposing of the construction waste for recycling.

ABSTRACTThe MCL1 inhibitors are undergoing clinical testing for multiple leukemia. However, because that MCL1 inhibition has on-target hematopoietic, hepatic and cardiac toxicities, there is substantial interest in finding agents can sensitize leukemia cells to the MCL1 inhibitors. Here we describe that the AKT inhibitors MK-2206 and Gsk690693 sensitize multiple leukemia cells to the MCL1 inhibitor S63845. Further experiments demonstrate that MK-2206 and Gsk690693 sensitize S63845 through the mitochondrial apoptosis pathway. Moreover, MK-2206 downregulates the anti-apoptotic protein BCLXL and induces the BH3-only pro-apoptotic protein BAD dephosphorylation and mitochondrial translocation. Knockdown of BAD significantly inhibits MK-2206-induced sensitization to S63845. Thus, our results suggest that MK-2206 sensitizes multiple leukemia cells to S63845-induced apoptosis, with the mechanisms involving BAD dephosphorylation and BCLXL downregulation.

The growth of the Internet of Things makes it possible to share information on risky vehicles openly and freely. How to create dynamic knowledge graphs of continually changing risky vehicles has emerged as a crucial technology for identifying risky vehicles, as well as a research hotspot in both artificial intelligence and field knowledge graphs. The node information of the risky vehicle knowledge graph is not rich, and the graph structure plays a major role in its dynamic changes. The paper presents a fusion algorithm based on relational graph convolutional network (R-GCN) and Long Short-Term Memory (LSTM) to build the dynamic knowledge graph of risky vehicles and conducts a comparative experiment on the link prediction task. The results showed that the fusion algorithm based on R-GCN and LSTM had better performance than the other methods such as GCN, DynGEM, ROLAND, and RE-GCN, with the MAP value of 0.2746 and the MRR value of 0.1075. To further verify the proposed algorithm, classification experiments are carried out on the risky vehicle dataset. Accuracy, precision, recall, and F-values were used as heat-tolerance evaluation indexes in classification experiments, the values were 0.667, 0.034, 0.422, and 0.52 respectively.

Background: 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) is a polyphenol ellagic compound with a variety of pharmacological effects and has an inhibitory effect on lots of cancers. Objective: To explore the antitumor effects and mechanism of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose on human hepatocellular carcinoma HepG2 cells. Design: A network pharmacology method was first used to predict the possible inhibition of hepatocellular carcinoma growth by 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) through the p53 signaling pathway. Next, the Cell Counting Kit (CCK-8) assay was performed to evaluate changes in the survival rate of human hepatocellular carcinoma HepG2 cells treated with different concentrations of the drug; flow cytometry was used to detect changes in cell cycle, apoptosis, mitochondrial membrane potential (MMP) and intracellular Ca2+ concentration; real-time fluorescence quantification and immunoblotting showed that the expression of P53 genes and proteins associated with the p53 signaling pathway was significantly increased by β-PGG treatment. Reasult: It was found that β-PGG significantly inhibited survival of HepG2 cells, promoted apoptosis, decreased MMP and intracellular Ca2+ concentration, upregulated P53 gene and protein expression, increased CASP3 expression, and induced apoptosis in HepG2 cells. Conclusion: This study has shown that network pharmacology can accurately predict the target of β-PGG’s anti-hepatocellular carcinoma action. Moreover, it was evident that β-PGG can induce apoptosis in HepG2 cells by activating the p53 signaling pathway to achieve its anti-hepatocellular carcinoma effect in vitro.

Synchrosqueezed transform (SST) is a time–frequency analysis method that can improve energy aggregation and reconstruct signals, which has been applied in the fields of medical treatment, fault diagnosis, and seismic wave processing. However, when dealing with time-varying signals, SST suffers from poor time–frequency resolution and is unable to deal with long signals. In order to accurately extract the characteristic frequency of variable speed rolling bearing faults, this paper proposes a synchrosqueezed transform method based on fast kurtogram and demodulation and piecewise aggregate approximation (PAA). The method firstly filters and demodulates the original signal using fast kurtogram and Hilbert transform to reduce the influence of background noise and improve the time–frequency resolution. Then, it compresses the signal by using piecewise aggregate approximation, so that the SST can deal with long signals and, thus, extract the fault characteristic frequency. The experimental data verification results indicate that the method can effectively identify the fault characteristic frequency of variable-speed rolling bearings.