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Abstract The Steptoean positive carbon isotope excursion (SPICE) event, one of the largest carbon cycle perturbations in the Cambrian, coincides with shallow-shelf-fauna extinction and plankton revolution (critical transition of plankton). The event is globally documented, but biogeochemical responses of these biotic evolutions in varying facies environments are not well understood. Here high-resolution paired δ18Ocarb, δ13Ccarb and δ13Corg datasets from varied paleodepth environments in the Tarim Basin, NW China reveal facies-dependent signatures of the event, with globally synchronous patterns but notable intra-basinal variability. Shallow marine facies record the end-Marjuman extinction with a distinct negative δ13Corg excursion prior to the event, while the transitional facies region marks twice positive δ13C excursions corresponding to an asynchronous plankton revolution from shallow and deep areas during the event. The varying isotope responses are interpreted in the context of primary productivity and redox conditions, with deeper basins recording more 13C enriched signals (i.e., higher δ13C) due to greater organic matter preservation under anoxic conditions, compared to the platform area. The biotic extinction, the planktonic revolution and the interaction of organisms along the shallow to deep marine depth gradient were reflected by the significant isotopic shifts recorded during the event, suggesting depth-dependent biogeochemical processes that shaped marine ecosystems.

Abstract This study investigates the impact of habitual late calorie intake on glucose metabolism in adults with overweight or obesity and diet or metformin-controlled prediabetes or type 2 diabetes independently of body weight, fat mass, energy intake or diet composition. Participants (n = 26) were classified as Later Eaters (LE) if ≥45% daily calories were consumed after 5 pm and Early Eaters (EE) if not, based on daily caloric intake assessed over 2-wk. EE and LE did not differ in anthropometrics or daily energy intake, but LE consumed more carbohydrates (p = 0.038) and fats (p = 0.039) after 5 pm. Fasting glucose, insulin, and C-peptide did not differ between groups but LE exhibited higher glucose concentrations after an oral glucose tolerance test (p = 0.001), even after adjusting for body weight, fat mass, energy intake and diet composition (p

Abstract Background Oral squamous cell carcinoma (OSCC) remains a major death cause in head and neck cancers, but the exact pathogenesis mechanisms of OSCC are largely unclear. Results Saliva derived from OSCC patients but not healthy controls (HCs) significantly promotes OSCC development and progression in rat models, and metabolomic analyses reveal saliva of OSCC patients but not HCs and OSCC tissues but not adjacent non-tumor tissues contain higher levels of kynurenic acid (KYNA). Furthermore, large amounts of Streptococcus mutans (S. mutans) colonize in OSCC tumor tissues, and such intratumoral S. mutans mediates KYNA overproductions via utilizing its protein antigen c (PAc). KYNA shifts the cellular types in the tumor microenvironment (TME) of OSCC and predominantly expedites the expansions of S100a8highS100a9high neutrophils to produce more interleukin 1β (IL-1β), which further expands neutrophils and induces CD8 + T cell exhaustion in TME and therefore promotes OSCC. Also, KYNA compromises the therapeutic effects of programmed cell death ligand 1 (PD-L1) and IL-1β blockades in oral carcinogenesis model. Moreover, KYNA-mediated immunosuppressive program and aryl hydrocarbon receptor (AHR) expression correlate with impaired anti-tumor immunity and poorer survival of OSCC patients. Conclusions Thus, aberration of oral microbiota and intratumoral colonization of specific oral bacterium such as S. mutans may increase the production of onco-metabolites, exacerbate the oral mucosal carcinogenesis, reprogram a highly immunosuppressive TME, and promote OSCC, highlighting the potential of interfering with oral microbiota and microbial metabolism for OSCC preventions and therapeutics. Video Abstract

Oxidative stress and inflammation are key drivers of osteoarthritis (OA) pathogenesis and disease progression. Herein we report the synthesis of poly(p-coumaric) nanoparticles (PCA NPs) from p-courmaic acid (p-CA), a naturally occurring phytophenolic acid, to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis (TMJOA). Compared to hyaluronic acid (HA) that is clinically given as viscosupplementation, PCA NPs exhibited long-term efficacy, superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA. Notably, TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis, while reducing inflammation, oxidative stress, matrix degradation, and chondrocyte ferroptosis. Overall, our study demonstrates a multifunctional nanoparticle, synthesized from natural p-coumaric acid, that is stable and possess potent antioxidant, anti-inflammatory properties and ferroptosis inhibition, beneficial for treatment of TMJOA.

Abstract Oral lichen planus (OLP) is a chronic inflammatory disease that is associated with an increased risk of carcinogenesis. The typical pathological features of OLP include submucosal T-cell banding, infiltration, and liquefactive degeneration of basal epithelial cells. However, the histological appearance of basal cell death cannot be explained by apoptosis of keratinocytes alone. The aim of this study was to explore a novel mechanism of epithelial cell death, pyroptosis, and its role in the development of OLP. The immunohistochemical results initially revealed pyroptosis in the epithelial cells of OLP. There was significant upregulation of pyroptosis-related inflammatory cytokines, specifically IL-1β. The expression of IL-1β is closely related to the severity of the patient’s condition. In vitro, the culture supernatant from epithelial cells and exogenous IL-1β significantly promote the proliferation and activation of T cells. This effect can be inhibited by neutralizing antibody or receptor inhibitor of IL-1β. Stimulation with exogenous IL-1β enhances both glycolysis and oxidative phosphorylation in T cells, with a more pronounced increase in glycolysis. This is due to the regulation of NAD+ availability and mitochondrial dynamics by IL-1β. IL-1β specifically stimulates the expression of optic atrophy 1 (OPA1), particularly L-OPA1, which promotes mitochondrial fusion and increases NAD+ availability. This process upregulated glycolysis in T cells. The knockdown of OPA1 reverses these changes by reducing the proliferation and activation of T cells. In this study, IL-1β promoted OPA1 transcription by activating the NF-κB pathway. The expression of OPA1 is inhibited by the inhibitor of NF-κB pathway. These results suggest that OLP keratinocytes undergo pyroptosis, which then secrete inflammatory factors that activate the NF-κB signaling pathway of T cells. This pathway regulates OPA1-mediated mitochondrial fusion and energy metabolism reprogramming in T cells, contributing to the development of OLP. These findings provide new insights into the mechanisms and therapeutic strategies for OLP.

Abstract Background Failure to restore missing teeth in time can easily lead to the mesial tilting of the distal abutment teeth. However, a fixed partial denture (FPD) can improve stress conduction and distribution and prevent periodontal injuries. In these more complex cases, it is necessary to consider various factors comprehensively to improve conventional treatment planning and achieve better results. Methods We selected a patient with a missing first molar and a mesial inclination of the second molar, leaving inadequate space or bone mass for implant denture restoration, necessitating an FPD for restoration. Three-dimensional finite element analysis (3D-FEA) combined with photoelastic analysis were used to explore how the inclination angle (0 ‒ 30°) and different dental restoration materials (zirconia, lithium disilicate, polymer-infiltrated ceramic network, and resin composite) affect the biomechanical behaviour of FPD‒abutments‒periodontal tissue complex. Results The stress was easily concentrated in the FPD connectors, enamel shoulder collar, periapical area, and root bifurcation. The stress on FPD and the periodontal ligament (PDL) of the second premolar increased with an increase in the elastic modulus of FPD, with an opposite trend in the abutments, the alveolar bone, and the PDL of the second molar. The stress on the FPD and alveolar bone increased with increased inclination angle of the distal abutment. The stress on two abutments and their PDL were positively correlated with the inclination angle in two stages; however, when the inclination angle > 12°, the second premolar and its PDL showed a negative correlation. Conclusions FPDs can be used for restoration within 24° of distal abutment inclination, but protecting the abutments ( 12° especially) must be taken seriously. For this purpose, an FPD material with higher strength is recommended.

Abstract A derivative is a financial asset whose future payoff is a function of underlying assets. Pricing a financial derivative involves setting up a market model, finding a martingale (“fair game”) probability measure for the model from the existing asset prices, and using that probability measure to price the derivative. When the number of underlying assets and/or the number of market outcomes in the model is large, pricing can be computationally demanding. In this work, we first formulate the pricing problem in a linear algebra setting, including the realistic setting of incomplete markets where derivatives do not have a unique price. We show that the problem can be solved with a variety of quantum techniques such as quantum linear programming and the quantum linear systems algorithm. While in previous works the martingale measure is assumed to be given, here it is extracted from market variables akin to bootstrapping, a common practice among financial institutions. We discuss the quantum zero-sum game algorithm and the quantum simplex algorithm as viable subroutines. For quantum linear systems solvers, we formalize a new market assumption milder than market completeness, which allows the potential for large speedups. Towards prototype use cases, we conduct numerical experiments motivated by the Black–Scholes–Merton model.

Abstract Background Sjögren’s Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations. Methods The study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts. Findings CTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM’s diagnostic accuracy is closer to skilled pathologists compared to beginners. Interpretation Our findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.

Abstract The second-order nonlinear Hall effect (NLHE) in non-centrosymmetric materials has recently drawn intense interest, since its inherent rectification could enable various device applications such as energy harvesting and wireless charging. However, previously reported NLHE systems normally suffer from relatively small Hall voltage outputs and/or low working temperatures. In this study, we report the observation of a pronounced NLHE in tellurium (Te) thin flakes at room temperature. Benefiting from the semiconductor nature of Te, the obtained nonlinear response can be readily enhanced through electrostatic gating, leading to a second-harmonic output at 300 K up to 2.8 mV. By utilizing such a giant NLHE, we further demonstrate the potential of Te as a wireless Hall rectifier within the radiofrequency range, which is manifested by the remarkable and tunable rectification effect also at room temperature. Extrinsic scattering is then revealed to be the dominant mechanism for the NLHE in Te, with symmetry breaking on the surface playing a key role. As a simple elemental semiconductor, Te provides an appealing platform to advance our understanding of nonlinear transport in solids and to develop NLHE-based electronic devices.

Abstract Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine–glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8+ T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Abstract Thermal comfort studies are usually employed to find subjective thermal responses [indicated by neutral temperature (NT), i.e. the temperature with no thermal stress] of residents from a region towards thermal environments. According to the recently published works in the literature, NTs are affected by many factors, such as geographical location and microenvironments. To elucidate the origins of these effects, the impact of microenvironment elements around a water surface on pedestrians’ thermal perceptions was systematically investigated in this work. The Fujiang River (FJR) in Mianyang City was taken as the sample site. The municipal meteorology station is located next to the site by around 2.5 km. By performing meteorology measurements combining questionnaires, it was found that the riverside NT (indicated by physiologically equivalent temperature, PET) of Mianyang in the summer of 2023 was 21.4 °C. The relationship between the distance from the water (DFW) and NT was quadratic linear. The same phenomenon took place by using either PET or Universal Thermal Climate Index (UTCI) indexes. Meanwhile, the meteorological contexts also affected NTs, including relative humidity (RH) and air velocity (Va). Regarding RH, the NPET increased from 15.2 °C (RH = 50%) to 26.9 °C (RH = 90%). In contrast, the NPET dropped from 23.0 to − 50.6 °C when the Va increased from 0.2 to 2.5 m/s, respectively. From our analysis, it was demonstrated that human thermal responses are significantly affected by both the microenvironmental and meteorological backgrounds around the water surface. Our work provides valuable insights for the proper use of water surfaces in urban design for adjusting thermal comfort.

Abstract Nonreciprocal quantum transport effect is mainly governed by the symmetry breaking of the material systems and is gaining extensive attention in condensed matter physics. Realizing electrical switching of the polarity of the nonreciprocal transport without external magnetic field is essential to the development of nonreciprocal quantum devices. However, electrical switching of superconducting nonreciprocity remains yet to be achieved. Here, we report the observation of field-free electrical switching of nonreciprocal Ising superconductivity in Fe3GeTe2/NbSe2 van der Waals (vdW) heterostructure. By taking advantage of this electrically switchable superconducting nonreciprocity, we demonstrate a proof-of-concept nonreciprocal quantum neuronal transistor, which allows for implementing the XOR logic gate and faithfully emulating biological functionality of a cortical neuron in the brain. Our work provides a promising pathway to realize field-free and electrically switchable nonreciprocity of quantum transport and demonstrate its potential in exploring neuromorphic quantum devices with both functionality and performance beyond the traditional devices.

Abstract Determination of protein–ligand binding affinity (PLA) is a key technological tool in hit discovery and lead optimization, which is critical to the drug development process. PLA can be determined directly by experimental methods, but it is time-consuming and costly. In recent years, deep learning has been widely applied to PLA prediction, the key of which lies in the comprehensive and accurate representation of proteins and ligands. In this study, we proposed a multi-modal deep learning model based on the early fusion strategy, called DeepLIP, to improve PLA prediction by integrating multi-level information, and further used it for virtual screening of extracellular signal-regulated protein kinase 2 (ERK2), an ideal target for cancer treatment. Experimental results from model evaluation showed that DeepLIP achieved superior performance compared to state-of-the-art methods on the widely used benchmark dataset. In addition, by combining previously developed machine learning models and molecular dynamics simulation, we screened three novel hits from a drug-like natural product library. These compounds not only had favorable physicochemical properties, but also bound stably to the target protein. We believe they have the potential to serve as starting molecules for the development of ERK2 inhibitors.

Although oxidative stress is closely associated with tumor invasion and metastasis, its’ exact role and mechanism in the initial stage of oral cancer remain ambiguous. Glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) participates in glutathione synthesis to resolve oxidative stress. Currently, we firstly found that ASCT2 deletion caused oxidative stress in oral mucosa and promoted oral carcinogenesis induced by 4-Nitroquinoline-1-oxide (4-NQO) using transgenic mice of ASCT2 knockout in oral epithelium. Subsequently, we identified an upregulated gene Thbs1 linked to macrophage infiltration by mRNA sequencing and immunohistochemistry. Importantly, multiplex immunohistochemistry showed M1-like tumor-associated macrophages (TAMs) were enriched in cancerous area. Mechanically, targeted ASCT2 effectively curbed glutamine uptake and caused intracellular reactive oxygen species (ROS) accumulation, which upregulated Thbs1 in oral keratinocytes and then activated p38, Akt and SAPK/JNK signaling to polarize M1-like TAMs via exosome-transferred pathway. Moreover, we demonstrated M1-like TAMs promoted malignant progression of oral squamous cell carcinoma (OSCC) both in vitro and in vivo by a DOK transformed cell line induced by 4-NQO. All these results establish that oxidative stress triggered by ASCT2 deletion promotes oral carcinogenesis through Thbs1-mediated M1 polarization, and indicate that restore redox homeostasis is a new approach to prevent malignant progression of oral potentially malignant disorders.

Abstract Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant‐derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan‐Oxidized Dextran (CMCS‐OD) hydrogel formed via dynamic chemical bonds exhibited self‐healing capabilities and pH‐responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis‐induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis‐induced bone destruction.

Sorghum (Sorghum bicolor (L.) Moench) is a world cereal crop used in China for producing Baijiu, a distilled spirit. We report a telomere-to-telomere genome assembly of the Baijiu cultivar Hongyingzi, HYZ-T2T, using ultralong reads. The 10 chromosome pairs contained 33,462 genes, of which 93% were functionally annotated. The 20 telomeres and 10 centromeric regions on the HYZ-T2T chromosomes were predicted and two consecutive large inversions on chromosome 2 were characterized. A 65-gene reconstruction of the metabolic pathway of tannins, the flavor substances in Baijiu, was performed and may advance the breeding of sorghum cultivars for Baijiu production.

Landfast sea ice (LFSI) is sensitive to local climate change, making it an important component of the cryosphere system. In this study, the LFSI around the pan-Arctic domain was simulated from 1979 to 2021 using a well-validated snow and ice thermodynamic model (HIGHTSI) under the framework of the Fast Ice Prediction System (FIPS), forced by the ERA5 reanalysis. The simulation results agree well with the in-situ observations in the Canadian Arctic, with a mean error of −0.06 ± 0.29 m for ice thickness and −0.04 ± 0.12 m for snow depth. A decrease of −2.8 ± 0.4 cm/10a in thickness and −16.2 ± 1.5 km3/a in volume for the Arctic LFSI was modeled during this period. There was significant spatial variability among the different domains, with the fastest decline found in the Vilkitsky Strait. The modeled snow depth shows large interannual and spatial variations, which was confirmed by other modeling results. The spatiotemporal variations in both air temperature and precipitation are the driving factors for the multi-decadal variations in LFSI thickness. The decreasing air temperature during the 2010s aligned with a slower thickness decrease and a slight volume increase for LFSI, which agreed with the pan-Arctic sea ice pattern.

Applying ICESat-2 and CryoSat-2 freeboards, the Arctic snow depth (ISCS) was obtained from October 2018 to April 2022. The results were assessed using Operation Ice Bridge (OIB) and Multidisciplinary Drifting Observatory for the Study of Arctic Climate (MOSAiC) in situ observations and compared with frequently used remote sensing (AMSR-E/AMSR2), climatology (modified W99 snow climatology data; MW99), and modelled (Pan-Arctic Ice Ocean Modelling and Assimilation Systems; PIOMAS) snow products. The ISCS snow depth exhibited high correlations (r = 0.67) and small mean bias (0.01 ± 0.06 m) against OIB results. We found good correlations (statistically significant) between MOSAiC and all snow depth products, except for MW99. Mean and absolute biases between ISCS and MOSAiC in situ observations were 0.01 ± 0.06 and 0.04 ± 0.04 m, respectively. The ISCS revealed clear spatial distribution from the Canadian Arctic Archipelago to open sea areas. In contrast, the PIOMAS snow depth revealed weak autumn variation, whereas the MW99 snow depth yielded distinct seasonal variability but a weak interannual change. Snow depth in October showed large differences among the various products, from which the AMSR topped the snow depth in the first-year ice region, while MW99 had the highest values for the multiyear ice zone.

IntroductionThe importance of improving older adults' mental health is increasing worldwide with the rapid development of the aging process. Green space is an important part of the urban built environment, demonstrates a deep connection with the mental health of older adults, and its internal mechanisms have been widely studied. This study analyzed the influence of urban green spaces on the mental health of older adults via three factors: relative deprivation, physical activity, and social trust.MethodsBased on the 2018 China Labor Dynamics Survey, a multi-level structural equation model was used to explore the mediating roles of relative deprivation, physical activity, social trust in urban green spaces, and the mental health of older adults.ResultsUrban green space was positively correlated with the mental health of older adults. Relative deprivation and physical activities played a mediating role between urban green space and the mental health of older adults.DiscussionAn increase in urban green spaces can help increase the number of older adults obtaining green space resources, and help them maintain good mental health. Secondly, older adults with a relatively homogeneous environment have more equal opportunities to obtain urban green space resources, which helps to reduce the comparison of older adults in access to green space resources and reduce the adverse impact of relative deprivation on their mental health. Additionally, increasing urban green spaces can encourage older adults to engage in physical activities and improve their mental health. Finally, we suggest improving the accessibility, fairness, and quality of green spaces, paying attention to the psychological needs of older adults, encouraging older adults to engage in physical activities in green spaces, and taking various measures to enhance the positive role of green space on the mental health of older adults.

C-reactive protein (CRP) plays a crucial role in the diagnosis and monitoring of the non-specific acute phase response in humans. In contrast, rat CRP (rCRP) is an atypical acute-phase protein that possesses unique features, such as a possible incapacity to trigger the complement system and markedly elevated baseline plasma concentrations. To facilitate in vitro studies on these unique characteristics, obtaining high-quality pure rCRP is essential. Here we explored various strategies for rCRP purification, including direct isolation from rat plasma and recombinant expression in both prokaryotic and eukaryotic systems. Our study optimized the recombinant expression system to enhance the secretion and purification efficiency of rCRP. Compared to traditional purification methods, we present a streamlined and effective approach for the expression and purification of rCRP in the Pichia pastoris system. This refined methodology offers significant improvements in the efficiency and effectiveness of rCRP purification, thereby facilitating further structural and functional studies on rCRP.

Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic organelles responsible for energy production and cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including mitochondrial DNA (mtDNA), proteins, and intact mitochondria. Intriguingly, mitochondria are crucial mediators of EVs release, suggesting an interplay between EVs and mitochondria and their potential implications in physiology and pathology. However, in this expanding field, much remains unknown regarding the function and mechanism of crosstalk between EVs and mitochondria and the transport of mitochondrial EVs. Herein, we shed light on the physiological and pathological functions of EVs and mitochondria, potential mechanisms underlying their interactions, delivery of mitochondria-rich EVs, and their clinical applications in regenerative medicine.

Memristor crossbar arrays are expected to achieve highly energy-efficient neuromorphic computing via implementing parallel vector–matrix multiplication (VMM) in situ. The similarities between memristors and neural synapses offer opportunities for realizing hardware-based brain-inspired computing, such as spike neural networks. However, the nonlinear I–V characteristics of the memristors limit the implementation of parallel VMM on passive memristor crossbar arrays. In our work, we propose to utilize differential conductance as a synaptic weight to implement linear VMM operations on a passive memristor array in parallel. We fabricated a TiO2/HfO2 memristor crossbar array, in which differential-conductance-based synaptic weight exhibits plasticity, nonvolatility, multi-states, and tunable ON/OFF ratio. The noise-dependent accuracy performance of VMM operations based on the proposed approach was evaluated, offering an optimization guideline. Furthermore, we demonstrated a spike neural network circuit capable of processing small spiking signals through the differential-conductance-based synapses. The experimental results showcase effective space-coded and time-coded spike pattern recognition. Importantly, our work opens up new possibilities for the development of passive memristor arrays, leading to increased energy and area efficiency in brain-inspired chips.

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.

Abstract The spin Hall effect (SHE) allows efficient generation of spin polarization or spin current through charge current and plays a crucial role in the development of spintronics. While SHE typically occurs in non-magnetic materials and is time-reversal even, exploring time-reversal-odd (T-odd) SHE, which couples SHE to magnetization in ferromagnetic materials, offers a new charge-spin conversion mechanism with new functionalities. Here, we report the observation of giant T-odd SHE in Fe3GeTe2/MoTe2 van der Waals heterostructure, representing a previously unidentified interfacial magnetic spin Hall effect (interfacial-MSHE). Through rigorous symmetry analysis and theoretical calculations, we attribute the interfacial-MSHE to a symmetry-breaking induced spin current dipole at the vdW interface. Furthermore, we show that this linear effect can be used for implementing multiply-accumulate operations and binary convolutional neural networks with cascaded multi-terminal devices. Our findings uncover an interfacial T-odd charge-spin conversion mechanism with promising potential for energy-efficient in-memory computing.

Abstract Early metastasis is the primary factor in the very poor prognosis of pancreatic ductal adenocarcinoma (PDAC), with liver metastasis being the most common form of distant metastasis in PDAC. To investigate the mechanism of PDAC liver metastasis, we found that PDAC cells can promote the formation of pre-metastatic niches (PMNs) through exosomes to facilitate liver metastasis in the early stage. In our study, hepatic stellate cells (HSCs) were treated with PDAC-derived exosomes (PDAC-exo), and the activation of HSCs was detected. A novel transfer RNA-derived fragment, the tRF-GluCTC-0005 was obtained by small RNA sequencing from serum exosomes of PDAC patients. Bioinformatics analysis and RNA pull-down assays revealed the interaction between WDR1 and tRF-GluCTC-0005. A KPC transgenic mouse model and an AAV-mediated sh-WDR1 mouse model were used to detect the mechanism of liver metastasis in vivo. Finally, the dual luciferase reporter assay, protein mutation truncation assay, Co-IP assay, and flow cytometry assay were used to explore the molecular mechanism in HSCs activation and PMNs formation. We found that the tRF-GluCTC-0005 in exosomes binds to the 3’ untranslated region of the mRNA of the WDRl in HSCs and increases mRNA stability. The N-terminals of WDR1 bind to the YAP protein directly, inhibit YAP phosphorylation, and promote the expression of YAP transcription factors. The tRF-GluCTC-0005 in PDAC-exo significantly recruits myeloid-derived suppressor cells (MDSCs) in the liver, creating a PMNs immunosuppressive microenvironment and further advancing liver metastasis from PDAC. Our results suggest that the key of PDAC liver metastasis is the activation of HSCs through upregulation of WDR1 by tRF-GluCTC-0005 in exosomes, which mediates the infiltration of MDSCs to form PMNs.

Digital information on sea ice extent, thickness, volume, and distribution is crucial for understanding Earth's climate system. The Snow and Ice Mass Balance Apparatus (SIMBA) is used to determine snow and ice temperatures in Arctic, Antarctic, ice-covered seas, and boreal lakes. Snow depth and ice thickness are derived from SIMBA temperature regimes (SIMBA_ET and SIMBA_HT). In warm conditions, SIMBA_ET temperature-based ice thickness may have errors due to the isothermal vertical profile. SIMBA_HT provides a visible ice-bottom interface for manual quantification. We propose an unmanned approach, combining neural networks, wavelet analysis, and Kalman filtering (NWK), to mathematically establish NWK and retrieve ice bottoms from various SIMBA_HT datasets. In the Arctic, NWK-derived total thickness showed a bias range of −5.64 cm to 4.01 cm and a correlation coefficient of 95%−99%. For Baltic Sea ice, values ranged from 1.31 cm to 2.41 cm (88%−98% correlation), and for boreal lake ice, −0.7 cm to 2.6 cm (75%−83% correlation). During ice growth, thermal equilibrium, and melting, the bias varied from −3.93 cm to 2.37 cm, −1.92 cm to 0.04 cm, and −4.90 cm to 3.96 cm, with correlation coefficients of 76%−99%. These results demonstrate NWK's robustness in retrieving ice bottom evolution in different water environments.

Because of its unique geographical properties, the Yaoquanshan area of Wudalianchi City, Heilongjiang Province, contains rich mineral water resources. We have carried out much research on the mineral water in the Yaoquanshan area of Wudalianchi City, which has also been supplemented by of previous studies. In this paper, through a controlled audio geoelectromagnetic method, geological drilling, groundwater level monitoring and water quality analysis, the structure, regional geology, hydrogeology and water geochemistry, as well as the characteristics of the distribution of metasilicate mineral water and natural soda water, the formation mechanism and the recharge, runoff and excretion of groundwater in the study area, are discussed. The results can provide a theoretical basis for the exploitation and utilization of mineral water resources in the southern region of the Wudalianchi Pharmaceutical Spring Mountain.

Abstract The topological Hall effect (THE) presents hump signals in the Hall resistance versus magnetic field hysteresis loop, showing promise for future spintronics due to its robust chiral magnetic textures. Here, it is shown that solid‐state protonic gating can control possible topological magnetic structures in CoGd thin films. Injecting H+ leads to sizable hump signals in the film. Magneto‐optical Kerr microscopy shows that induced hump signals in transporting measurements do not scale with magnetization, supporting topological magnetism. Successive hydrogen ion extraction completely erases the effect. Thus, topological magnetism manipulations are reversible, nonvolatile, and effective. Ab inito calculations and effective chiral spin models demonstrate that hydrogen injection remarkably enhances the Dzyaloshinskii–Moriya interaction over fourfold, stabilizing chiral structures contributing to the large THE. These findings reveal the vital role of hydrogen ions in topological magnetism and suggest that amorphous ferrimagnetic CoGd thin films are outstanding platforms for realizing controllable topological spintronics at room temperature.

Abstract Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN+ CAFs) was correlated with poor survival in oral squamous cell carcinoma (OSCC). PDPN+ CAFs promoted the progression of OSCC by transferring exosomal lncRNA FTX to OSCC cells. Mechanically, FTX bound to flap endonuclease-1 (FEN1), forming an RNA‒protein complex. FTX enhanced promoter demethylation of FEN1 by recruiting ten-eleven translocation-2 (TET2). In addition, FTX/FEN1 axis promoted OSCC cells motility by inhibiting ferroptosis. In xenograft experiments, RSL-3, a ferroptosis-inducing agent, suppressed the tumorigenesis potential of FEN1-overexpressed OSCC cells. Furthermore, Acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to participate in the motility promotion induced by FEN1 overexpression. FEN1 could bind to promoter region of ACSL4 and then inhibit ferroptosis in OSCC cells. Our study reveals that PDPN+ CAFs promote the invasiveness of OSCC cells by inhibiting ferroptosis through FTX/FEN1/ACSL4 signaling cascade. PDPN+ CAFs may serve as a novel potential therapeutic target for OSCC.

Trackless rubber-tyerd vehicles are the core equipment for auxiliary transportation in inclined-shaft coal mines, and the rationality of their routes plays the direct impact on operation safety and energy consumption. Rich studies have been done on scheduling rubber-tyerd vehicles driven by diesel oil, however, less works are for electric trackless rubber-tyred vehicles. Furthermore, energy consumption of vehicles gives no consideration on the impact of complex roadway and traffic rules on driving, especially the limited cruising ability of electric trackless rubber-tyred vehichles (TRVs). To address this issue, an energy consumption model of an electric trackless rubber-tyred vehicle is formulated, in which the effects from total mass, speed profiles, slope of roadways, and energy management mode are all considered. Following that, a low-carbon routing model of electric trackless rubber-tyred vehicles is built to minimize the total energy consumption under the constraint of vehicle avoidance, allowable load, and endurance power. As a problem-solver, an improved artificial bee colony algorithm is put forward. More especially, an adaptive neighborhood search is designed to guide employed bees to select appropriate operator in a specific space. In order to assign onlookers to some promising food sources reasonably, their selection probability is adaptively adjusted. For a stagnant food source, a knowledge-driven initialization is developed to generate a feasible substitute. The experimental results on four real-world instances indicate that improved artificial bee colony algorithm (IABC) outperforms other comparative algorithms and the special designs in its three phases effectively avoid premature convergence and speed up convergence.

Abstract Background A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. Methods A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. Results Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. Conclusion PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.

The surface energy budget is crucial for Arctic sea ice mass balance calculation and climate systems, among which turbulent heat fluxes significantly affect the air–sea exchanges of heat and moisture in the atmospheric boundary layer. Satellite observations (e.g. CERES and APP-X) and atmospheric reanalyses (e.g., ERA5) are often used to represent components of the energy budget at regional and pan-Arctic scales. However, the uncertainties of the satellite-based turbulent heat fluxes are largely unknown, and cross-comparisons with reanalysis data and in-situ observations are limited. In this study, satellite-based turbulent heat fluxes were assessed against in-situ observations from the N-ICE2015 drifting ice station (north of Svalbard, January–June 2015) and ERA5 reanalysis. The turbulent heat fluxes were calculated by two approaches using the satellite-based ice surface temperature and radiative fluxes, surface atmospheric parameters from ERA5, and snow/sea ice thickness from the pan-Arctic Ice Ocean Modeling and Assimilation System (PIOMAS). We found that the bulk-aerodynamic formula based results could better capture the variations of turbulent heat fluxes, while the maximum entropy production based estimates are comparable with ERA5 in terms of root-mean-square error (RMSE). CERES-based estimates outperform the APP-X-based ones but ERA5 performs the best in all seasons (RMSE of 18 and 7 W m−2 for sensible and latent heat flux, respectively). The air–ice temperature/humidity differences and the surface radiation budget were found the primary driving factors in the bulk-formula method and maximum entropy production (MEP) method, respectively. Furthermore, errors in the surface and near-surface temperature and humidity explain almost 50% of the uncertainties in the estimates based on the bulk-formula, whereas errors in the net radiative fluxes explain more than 50% of the uncertainties in the MEP-based results.

Abstract Objective Sarcopenia has been recognized as a third category of complications in people with diabetes. However, few studies focus on the reduction of skeletal muscle mass in young people with diabetes. The aim of this study was to investigate risk factors of pre-sarcopenia in young patients with diabetes and establish a practical tool to diagnose pre-sarcopenia in those people. Methods Patients (n = 1246) enrolled from the National Health and Nutrition Examination Survey (NHANES) cycle year of 2011 to 2018 were randomly divided into the training set and validation set. The all-subsets regression analysis was used to select the risk factors of pre-sarcopenia. A nomogram model for the prediction of pre-sarcopenia in the diabetic population was established based on the risk factors. The model was evaluated by the area under the receiver operating characteristic curve for discrimination, calibration curves for calibration, and decision curve analysis curves for clinical utility. Results In this study, gender, height, and waist circumference were elected as predictive factors for pre-sarcopenia. The nomogram model presented excellent discrimination in training and validation sets with areas under the curve of 0.907 and 0.912, respectively. The calibration curve illustrated excellent calibration, and the decision curve analysis showed a wide range of good clinical utility. Conclusions This study develops a novel nomogram that integrates gender, height, and waist circumference and can be used to easily predict pre-sarcopenia in diabetics. The novel screen tool is accurate, specific, and low-cost, highlighting its potential value in clinical application.

With significant improvement in High Temperature Superconductors (HTS), several projects are adopting HTS technology for fusion power systems. Compact HTS tokamaks offer potential advantages including lower plant costs, enhanced plasma control, and ultimately lower cost of electricity. However, as compact reactors have a reduced radial build to accommodate shielding, HTS degradation due to radiation damage or heating is a significant and potentially design limiting issue. Shielding must mitigate threats to the superconducting coils: neutron cascade damage, heat deposition and potentially organic insulator damage due x-rays. Unfortunately, there are currently no hi-performance shielding materials to enable the potential performance enhancement offered by HTS. In this work, we present a manufacturing method to fabricate a new class of composite shields that are high performance, high operating temperature, and simultaneously neutron absorbing and neutron moderating. The composite design consists of an entrained metal-hydride phase within a radiation stable MgO ceramic host matrix. We discuss the fabrication, characterization, and thermophysical performance data for a series of down-selected composite materials inspired by future fusion core designs and their operational performance metrics. To our knowledge these materials represent the first ceramic composite shield materials containing significant metal hydrides.

Accurate aircraft turnaround time prediction is an important way to coordinate the operation time of airport ground service and improve the efficiency of airport operation. In this paper, by analyzing the aircraft turnaround operation process, a description model based on Time Transition Petri Net is proposed. The model describes the flight turnaround operation process and the logical relationship of the operation. According to the model, a dynamic prediction method of turnaround time based on Bayesian theorem is designed. According to the actual landing time of the flight, the aircraft turnaround time is predicted. The specific method is to obtain the prior probability distribution and joint distribution law of each operation link according to the flight history data, and use Shapiro-Wilke to test the prior probability distribution of each link. Based on the analysis and comparison between the actual turnaround data of a large airport in China and the forecast data proposed in this paper, the root-mean-square error 3.75 minutes and the mean absolute error 3.40 minutes can be calculated. This paper contributes to the improvement of flight punctuality rate and airport clearance level.

BackgroundThe relationship between the patterns of physical activity (PA) and frailty, including its various subdomains, remains poorly understood. Therefore, this study aims to investigate the correlations between the patterns of physical activity and frailty and its various subdomains in community-dwelling older women.MethodsA cross-sectional study investigated the association between physical activity and frailty in 1,099 women aged between 60 to 70 years. Triaxial accelerometers were used to measure bouted PA (a minimum duration of 10 min) and sporadic PA (a duration of

Cognitive decline has been linked to periodontitis through an undetermined pathophysiological mechanism. This study aimed to explore the mechanism underlying periodontitis-related cognitive decline and identify therapeutic strategies for this condition. Using single-nucleus RNA sequencing we found that changes in astrocyte number, gene expression, and cell‒cell communication were associated with cognitive decline in mice with periodontitis. In addition, activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was observed to decrease the phagocytic capability of macrophages and reprogram macrophages to a more proinflammatory state in the gingiva, thus aggravating periodontitis. To further investigate this finding, lipid-based nanoparticles carrying NLRP3 siRNA (NPsiNLRP3) were used to inhibit overactivation of the NLRP3 inflammasome in gingival macrophages, restoring the oral microbiome and reducing periodontal inflammation. Furthermore, gingival injection of NPsiNLRP3 reduced the number of Serpina3nhigh astrocytes in the hippocampus and prevented cognitive decline. This study provides a functional basis for the mechanism by which the destruction of periodontal tissues can worsen cognitive decline and identifies nanoparticle-mediated restoration of gingival macrophage function as a novel treatment for periodontitis-related cognitive decline.

AbstractBackground This study aimed to evaluate the diagnostic value of a non-invasive methylation gene test in clinical colorectal tumour screening.Method The quantitative methylation-specific PCR technique was used to detect faecal methylated syndecan-2 (mSDC2) in patients who received the screening of colorectal cancer (CRC).To evaluate the positive predictive value (PPV) of mSDC2 in patients with colorectal cancer, advanced adenoma (AA), and colorectal tumor (CRN) in risk factor stratification.Results The PPV of CRC, CRC + AA and CRN in male patients were 28.03%, 43.55% and 56.24%, respectively, which were higher than female patients. The positive detection rate of mSDC2 and the PPV of CRC gradually increased with age; The PPV in patients aged over 80 years was up to 78.05%, which was more significant than in younger patients with CRC. The PPV of CRC, AA and CRN were 37.10%, 11.80% and 63.37%, respectively. mSDC2 has a high detection rate of 85–100% in AA with intramucosal carcinoma alone or in combination with severe atypical hyperplasia or villous adenoma.Conclusion The mSDC2 test has a higher PPV in patients with colorectal cancer and colorectal adenoma (AD), especially in high-risk groups over 50 years of age, and may help in the early diagnosis of colorectal tumours in the future.

Recent evidence highlights multifaceted biological needs to recapitulate the bone microenvironment for bone regeneration. Neurotization has great potential for realizing multi-system modulations in bone tissue engineering (BTE). However, a neural strategy involving all the key bone repair steps temporally has not yet been reported. In this study, we reported the neural tissue engineering hydrogel-encapsulated Schwann cell-derived exosomes (SC Exo). This sustained-release SC Exo system prominently enhanced bone regeneration by promoting innervation, immunoregulation, vascularization, and osteogenesis in vivo. Moreover, the in vitro results further confirmed that this system significantly induced M2 polarization of macrophages, tube formation of HUVECs, and BMSCs osteogenic differentiation. Furthermore, BMSCs osteogenesis was promoted by upregulating the TGF-β1/SMAD2/3 signaling pathway. In summary, a novel cell-free and easily prepared SC Exo neural engineering was successfully developed to promote bone regeneration by orchestrating the entire bone healing microenvironment, which may provide a new strategy for tissue engineering and clinical treatment of bone defects.

Abstract Mitochondria are essential organelles in balancing oxidative stress and cell death during cancer cell proliferation. Rapid tumor growth induces tremendous stress on mitochondria. The mammalian tumor necrosis factor-α-induced protein 8-likes (TIPEs) family plays critical roles in balancing cancer cell death and survival. Yet, the roles of TIPEs in HNSCC tumorigenesis and mitochondria stress maintenance is unclear. Based on an integrative analysis of public HNSCC datasets, we identified that the downregulation of TIPE3 via its promoter hypermethylation modification is the major event of TIPEs alterations during HNSCC tumorigenesis. Low expression levels of TIPE3 were correlated with high malignancy and poor clinical outcomes of HNSCC patients. Restoring TIPE3 represses HNSCC proliferation, migration, and invasion in vitro and in vivo, while silencing TIPE3 acted on an opposite way. Mechanistically, TIPE3 band to the PGAM5 and electron transport chain (ETC) complex. Restoring TIPE3 promoted PGAM5 recruiting BAX and dephosphorylating p-DRP1(Ser637), which triggered mitochondrial outer membrane permeabilization and fragmentation. Ultimately, TIPE3 induced ETC damage and oxygen consumption rate decrease, ROS accumulation, mitochondrial membrane potential depolarization, and cell apoptosis. Collectively, our work reveals that TIPE3 plays critical role in maintaining mitochondrial stress and cancer cell progression in HNSCC, which might be a potential therapeutic target for HNSCC patients.

Abstract Background Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. It has been shown in various cancer studies that stanniocalcin-1 (STC1) is secreted by CAFs, however, its function in HCC is still not clear. Methods The serum concentration and intracellular expression level of STC1 were quantified by ELISA and western blotting, respectively. The role of CAF-derived STC1 in HCC stemness was investigated by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and in an orthotopic liver xenograft model in vivo. An HCC tissue microarray containing 72 samples was used to evaluate the expression of STC1 and Notch1 in HCC tissues. Coimmunoprecipitation (CoIP) and dual-luciferase reporter assays were performed to further explore the underlying mechanisms. ELISAs were used to measure the serum concentration of STC1 in HCC patients. Results We demonstrated that CAFs were the main source of STC1 in HCC and that CAF-derived STC1 promoted HCC stemness through activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with Notch1 expression and poor prognosis. The co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC cells. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than in patients with early liver cancer. Conclusions CAF-derived STC1 promoted HCC stemness via the Notch1 signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could constitute an effective therapeutic target for HCC patients.

Abstract Background This study explored the specialty preferences of China-educated international medical students (IMSs), who are mainly from low- and middle-income countries (LMICs) and constitute a potential medical workforce both for their home countries and foreign countries, and the influence of migration intentions on their specialty preferences. Methods A cross-sectional, questionnaire-based survey was conducted at 5 universities in China. The questionnaire link was distributed electronically among the IMSs at the 5 universities via emails. The questionnaire enquired IMSs’ demographic information, migration intentions and their specialty preferences. The Chi-square test was applied to determine the influence of the respondent’s gender, intention to practise in the home country and intention to practise in a high-income country on their specialty choices. The Chi-square test was also applied to determine the influence of the respondent’s gender, year of study and country of origin on their preferences for generalist-orientated or non-generalist orientated specialties. Results Altogether, 452 IMSs returned their responses, yielding a response rate of 64.1%. Approximately half of the IMSs planned to not return to their home country. The most selected specialty was general surgery and the least selected specialty was physical medicine and rehabilitation. No significant differences were evident in most specialty preferences between those who intended to return home and those who intended to stay abroad. Among the IMSs having intentions of returning to their home country, male students tended to choose a generalist-orientated specialty, while female students tended to choose a non-generalist-orientated specialty. Conclusion China-educated IMSs could play important roles in the primary care services as well as other shortage specialties both for their home countries or foreign countries. Therefore, it is recommended that governments in these countries plan migration and recruitment policies that cater for these studying-abroad medical students from LMICs, especially in this challenging time during the COVID-19 pandemic.

Flight delay identification is an important way to coordinate the operation time of airport ground service providers and improve the efficiency of airport operations. By analyzing the flight turnaround operation process, considering the randomness and synchronization of the turnaround process, and using Colored Petri Nets and Python (4.0.1), we explore the correlation between various links in the flight turnaround process and the take-off delay at the next station. This paper is committed to improving the service performance of airports and airlines, dynamically predicting flight delays, and providing guidance for avoiding excessive time in the actual operation of bad combinations. The results show that there are six kinds of bad combinations in the departure slip-out link, which is the most likely to affect the transit time. The maximum lifting degree in the bad combination is 2.043, and the maximum average delay time in the bad combination is 22.5 min. When the combination of passenger boarding and departure slip-out time is too long, it has a great positive correlation with delay. When the other links are in a state of being able to pass the station on time, the departure time and baggage loading and unloading are the two links that most affect the flight delay value.

This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (β = −2.3, SE = 1.0, p = 0.03) in D-GLYC, while a later last EO predicted a higher GV (β = 1.5, SE = 0.6, p = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (β = 0.9, SE = 0.4, p = 0.02) and GV (β = 0.4, SE = 0.2, p = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.

The dynamic evolution behavior of submerged water jet cavitation clouds was studied by combining experiments and simulation. The formation, development, shedding, and collapsing process of a void cloud was analyzed by high-speed camera technology, and the influence of jet pressure was studied. Cavitation water jet erosion experiments were carried out on AL6061 specimens with standard cylindrical nozzles, and the correlation between cavitation cloud evolution and material erosion was studied by surface analysis. The results showed that the evolution of a cavitation cloud has obvious periodicity, that one period is about 0.8 ms, and its action region can be divided according to the attenuation rate of the jet velocity of the nozzle axis. The attenuation rate of the jet velocity at the nozzle axis in the central jet action zone is less than or equal to 82.5%, in the mixed action zone greater than 82.5% and less than 96%, and in the cavitation action zone greater than or equal to 96%. The erosion damage characteristics in different regions of the mixed action zone are significantly different.

Bridge cable wires suffer from alternating stress and environmental erosion, leading to premature failure prior to its design life. This paper investigates the fatigue and mechanical behaviors of corroded bridge cable wires with a zinc–aluminum (Zn-Al) alloy coating. Based on the salt spray corrosion test and microstructure analysis, the anti-corrosion resistance and corrosion appearance characteristics of the Zn-Al alloy coating and galvanized coating were investigated. The Zn-Al alloy coating was superior in resistance to corrosion fatigue for the improvement in toughness and the generation of anti-corrosion Zn-Al and Fe-Zn-Al phases. Equations of the accelerated corrosion depth of the steel wires had been regressed to roughly estimate the corrosion life of the Zn-Al alloy coating, which can reach 29.1 years with a thickness of 70 μm. The fatigue and mechanical properties of the bare wires after the salt spray test were further studied based on tensile tests and fatigue tests. The fatigue properties of the bridge cable wire would decrease with the corrosion degree due to the deterioration and embrittlement of materials, where ductility characterized by the elongation rate was the most affected. Fracture surfaces of the wires were captured and analyzed based on a method for recognizing graphical contours. Insufficient fatigue life may occur in the steel wires after corrosion and increase with the degree of corrosion. The pit depth logarithmically weakened the fatigue life of steel wires for the weakening of fatigue toughness and the bearing area. The flat fracture was more common with a single fatigue source, while multiple fatigue sources led to step-like fractures for the generation of multiple dispersed crack propagation regions. Corrosion fatigue was more sensitive to the existence of fatigue sources than the reduction. Multiple initiation sources significantly reduced the fatigue life due to the cracking facilitation of the joint effect of multiple pits. The electrochemical reactions of corrosion can lead to material embrittlement and a reducing effect on the fracture toughness of the steel wires.

China is experiencing unprecedented urbanization and aging. Previous studies mostly ignored the internal mechanism of the effect of urban green space on the mental health of older adults. Consequently, the relationship between social participation in urban green spaces and mental health remains uncertain. Therefore, this study explored the impact of urban green spaces, social participation, and other factors on the mental health of older adults and investigated the mechanisms of these effects. This study used linear regression models and conducted a moderating effect analysis using data from the 2018 China Labor Dynamics Survey, comprising 3501 older adults in 146 cities in China. Furthermore, we analyzed differences between solitary and non-solitary older adults. The results indicated that urban green space, road density, physical health, history of hospitalization, subjective well-being, and economic satisfaction significantly affected mental health. Social participation played a significant positive moderating role in the connection between green spaces and mental health among older adults. For solitary older adults, social participation weakened the positive impact of green spaces on mental health; for non-solitary older adults, social participation enhanced the positive impact of green spaces on mental health. These findings could contribute to the future construction of aging-friendly cities in China and help optimize urban construction and strategies for building healthy environments.

Shading-induced soybean stem lodging is a prevalent concern in the maize (Zea mays L.)-soybean (Glycine max L. Merr.) strip intercropping system, leading to a substantial decline in yield. Nevertheless, the associations between soybean growth, stem lodging, and yield formation in this scenario remain unclear. To investigate this, the logistic and beta growth models were utilized to analyze the growth process of soybean organs (stems, leaves, branches, and pods) and the accumulation of carbohydrates (lignin, cellulose, and sucrose) at three planting densities (8.5, 10, and 12.5 plants m−2) in both strip intercropping and skip strip monoculture systems. The results indicate that shading stress caused by maize in the intercropping system reduced lignin and cellulose accumulation in soybean stems, thus decelerating soybean organ growth compared to monoculture. Furthermore, intercropped soybean at higher planting density (PD3) exhibited a 28% reduction in the maximum dry matter growth rate (cm) and a 11% decrease in the time taken to reach the maximum dry matter growth rate (te) compared to the lower planting density (PD1). Additionally, a 29% decrease in the maximum accumulation rate (cmax) of sucrose, lignin, and cellulose was observed, along with a 13% decrease in the continuous accumulation time (tc) of these carbohydrates in intercropped soybean at PD3. Interspecific and intraspecific shading stress led to a preferential allocation of assimilates into soybean stems, enhancing plant height during the initial stage, while at later stages, a greater proportion of sucrose was allocated to leaves. Consequently, this hindered the conversion of sucrose into lignin and cellulose within the stems, ultimately resulting in a reduction in the lodging resistance index (LRI). Overall, this study provides valuable insights into the effects of shading stress on soybean growth and yield. It also emphasizes how optimizing planting density in intercropping systems can effectively alleviate shading stress and enhance crop productivity.

Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and inflammatory profiles. Methods and Results Seventy‐eight participants (56 women [12 postmenopausal]; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m2) with habitual sleep duration 7 to 9 h/night (adequate sleep [AS]) underwent two 6‐week conditions in a randomized crossover design: AS versus SR (AS–1.5 h/night). Total cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP [C‐reactive protein], interleukin 6, and tumor necrosis factor‐α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high‐density lipoprotein cholesterol compared with AS (β=1.2±0.5 mg/dL; P=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (P‐interaction=0.04), LDL‐C (P‐interaction=0.03), and interleukin 6 (P‐interaction=0.07). Total cholesterol and LDL‐C decreased in SR versus AS in premenopausal women (total cholesterol: β=−4.2±1.9 mg/dL; P=0.03; LDL‐C: β=−6.3±2.0 mg/dL; P=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor‐α during SR tended to relate to lower LDL‐C in premenopausal women (interleukin 6: β=−5.3±2.6 mg/dL; P=0.051; tumor necrosis factor‐α: β=−32.8±14.2 mg/dL; P=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL‐C in premenopausal women, resembling the “lipid paradox” in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.