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Abstract SAR-to-optical (S2O) translation is able to covert SAR into optical images, which help the interpreter to extract information efficiently. In the absence of strictly matched datasets, it is difficult for existing methods to complete training on unpaired data with a minimum amount of data. By employing the recent Schrödinger bridge-based transformation framework, a multiscale axial residual module (MARM) based on the concept of multi-scale feature fusion has been proposed in this paper. To enable efficient translation of SAR to optical images, the generator and discriminator of the model have been designed. Extensive experiments on the SEN1-2 dataset conducted, and the results show the superiority of the proposed method in terms of the generation quality. Compared with the classical CycleGAN, the proposed method can improve the FID metrics by 42.05%.

Abstract This study examines the factors influencing COVID-19 vaccination intentions among Chinese residents over the age of 60, with a focus on the mediating roles of Health Beliefs and Cues to Vaccination Action in the relationship between vaccine knowledge and vaccination intentions. We conducted a cross-sectional online survey involving 1,305 participants from Southwest China. Multiple logistic regression analysis identified potential determinants of vaccination intention, including socioeconomic characteristics, knowledge, health beliefs, and cues to vaccination action. Furthermore, mediation analysis using the causal mediation analysis method explored the mediating effects within the knowledge-to-intention pathway. Vaccination intention and its related factors: among the 1212 elderly people included in the study, 92.9% expressed willingness to receive the COVID-19 vaccine. Main factors influencing their vaccination willingness included Residency (urban vs. rural, OR = 0.47, p

Abstract Based on the local resonance theory, the vibration isolation performance of four-component periodic pile barriers consisting of a matrix, an outer pipe, an inner pipe, and a pile core was investigated using the finite element method (FEM). This configuration is contrasted with traditional three-component periodic pile barriers, which are composed of a matrix, a pipe, and a pile core. The four-component systems demonstrate significantly broader bandgaps compared to three-component systems. To validate the efficiency of the FEM, model test on pile barriers were conducted, facilitating a comparison between the FEM and experimental observations of bandgap characteristics. Additionally, the effects of the outer pipe’s density, elastic modulus, and thickness on the complete bandgap characteristics were comprehensively studied within the four-component structure. It is found that the broadest vibration isolation band gaps occur under hexagonal arrangement pattern. In square and hexagonal lattice configurations, the density, elastic modulus, and thickness of the outer pipe pile’s pile have predominantly influenced the upper bound frequency (UBF). There has been a positive correlation between the elastic modulus and the UBF, while the density and thickness have shown inverse relationships. Moreover, there exists a elastic modulus threshold, marking a transition in the displacement mode of the UBF, from the outer irreducible Brillouin zone (M or X) to the inner zone (Γ). Once the threshold is exceeded, both the vibration displacement mode and the width of bandgap remain substantially unchanged. The results obtained in the present paper are very useful for the design and application of periodic pile barriers in ambient vibration reduction.

Abstract Background Based on their place of employment, workers with agricultural hukou (WAH) are categorized into local workers with agricultural hukou (LWAH) and migrant workers with agricultural hukou (MWAH). Research shows that although LWAH often find themselves at a disadvantage in terms of labour income and access to public services, the significant growth of this group in recent years has drawn attention to their choice of workplace and the factors influencing it. Guided by the theories of self-determination and social comparison, this study aims to explore the impact of the differences between LWAH and MWAH in psychological needs and social comparisons on life satisfaction, as well as the underlying mechanisms. Methods This study utilizes data from the China Family Panel Studies (CFPS) from 2014 to 2020, employing a two-way fixed effects model to investigate the differences in life satisfaction between 1,976 LWAH and MWAH. Additionally, propensity score matching (PSM) is used to conduct regression analysis on the matched sample, providing a more accurate comparison of life satisfaction between LWAH and MWAH under similar individual characteristics. Finally, the study further examines the mediating effects of perceived social status and job satisfaction and analyses the differences in life satisfaction between LWAH and MWAH across dimensions such as generation, region, and work conditions. Results The baseline regression results indicate that LWAH have significantly higher life satisfaction compared to MWAH, and this finding is robust to various tests. Mediation analysis reveals that perceived social status plays a mediating role in the difference in life satisfaction between LWAH and MWAH, while job satisfaction does not have a significant mediating effect. Heterogeneity analysis further shows that intergenerational, regional, and work condition differences have varying impacts on the life satisfaction of two groups. Conclusions This study provides important insights into understanding the workplace choices and quality of life of Chinese workers with agricultural hukou. Finally, to effectively promote situ urbanization processes, local governments need to prioritize enhancing workers with agricultural hukou (WAH)’s autonomy, sense of competence, and social status, thereby improving their perceived social status in society and attracting more labourers to return to their hometowns for work and entrepreneurship.

Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2+ cells to exert their biological activity. Thereby, the modular delivery system shows its potential as a promising tool for scientific studies and therapeutic applications.

Abstract Objective The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, presenting a treatment challenge due to limited options. Endoplasmic reticulum (ER) stress and associated lipid metabolism disorders are main causes of NAFLD, making it important to inhibit ER stress for effective treatment. Fagopyrum dibotrys has hypolipidemic, anti-inflammatory and hepatoprotective properties, showing promise in treating NAFLD. However, its effects on ER stress in NAFLD remain unclear. This study used a high-fat diet (HFD) to establish NAFLD mouse models and supplemented with Fagopyrum dibotrys extract (FDE) to evaluate its therapeutic effect and underlying mechanisms. Results We showed that FDE supplementation reduced the severity of hepatic steatosis and lowered triglycerides (TG) and total cholesterol (TC) levels in NAFLD mice. At the molecular level, FDE supplementation reduced hepatic lipid deposition by downregulating lipogenic markers (SREBP-1c, SCD1) and upregulating fatty acid oxidase CPT1α expression. Additionally, FDE treatment inhibited the overexpression of ER stress markers (GRP78, CHOP, and P-EIF2α) in NAFLD mice livers, and blocked the activation of the PERK-EIF2α-CHOP pathway, demonstrating its role in maintaining ER homeostasis. Considering that activation of the PERK pathway could exacerbate lipid deposition, our findings suggest that FDE has a protective effect against hepatic steatosis in NAFLD mice by attenuating ER stress, and the potential mechanism is through inhibiting the PERK pathway.

The automation degree of sealing technology in coal mine is insufficient, and the automatic directional drilling rig can improve the automation degree of sealing. A colloidal slip with double friction force for automatic directional drilling machine is designed to solve the problem that the clamping device of automatic directional drilling machine is bad. Two kinds of colloidal structures are proposed to realize the difference of friction between active drill pipe jointing and unjointing, and to ensure the smooth jointing of drill pipe. Using the nonlinear finite element method, Mooney-Rivlin strain energy function was used to describe the mechanical properties of colloid, and the simulation of colloid clamping hole sealer was carried out. The working friction of colloid of different materials was obtained, and the rationality of the two structural colloids was verified. The influence of the compression amount of adhesive strip on the surface of the colloid on the stress of the hole sealer was studied. The effect of the number of adhesive strips on the colloidal surface on the axial friction force was investigated. The results show that natural rubber and polyurethane rubber are reasonable as colloidal materials, the compression of rubber strips is 0.9 mm, and the number of rubber strips is 3.

Drilling robot for rockburst prevention is a necessary equipment for achieving unmanned pressure relief in coal mines with high in-situ stress. Developing a reliable drilling trajectory measurement system while drilling is an important measure to ensure the effectiveness of drilling pressure relief. Based on analysis of basic principle of drilling trajectory measurement while drilling, a drilling trajectory measurement drill rod based on wireless electromagnetic transmission technology is developed. The spectral efficiency and anti-noise performance of different electromagnetic signal modulation methods are analyzed, and the FSK modulation and demodulation process for drill rod attitude signals are designed, so as to develop a weak signal conditioning system that amplifies before filtering. The Corresponding functional circuits are designed and tested using Multisim software, and each circuit module met the design requirements. A comparative analysis is conducted on the accuracy and execution efficiency of five trajectory calculation algorithms, and the mean angle full range method is chosen for drilling trajectory calculation. The vibration error processing method for inertial measurement unit measurement data based on wavelet filtering is studied, and the effectiveness of wavelet filtering algorithm in improving attitude angle calculation accuracy is also verified. A drilling depth measurement method based on wire displacement sensors and robot action markers is proposed, and the surface and underground experiments are conducted. The experimental results show that the designed weak signal conditioning system can achieve the reception and processing of weak signals in underground coal mines. The drilling depth measurement method based on wire displacement sensors and robot action markers can improve the fitting accuracy of the drilling trajectory.

Abstract Photovoltaic development has played a crucial role in mitigating the energy crisis and addressing global climate change. However, it has also had significant impacts on the ecological environment. To ensure the sustainable growth of the photovoltaic industry, it is essential to establish an indicator system to assess the ecological and environmental effects of photovoltaic development. This study utilizes the Driving-Pressure–Status–Impact-Response (DPSIR) framework to create an indicator system for evaluating the ecological and environmental effects of desert photovoltaic development. The study evaluates the ecological and environmental effects at the on-site (WPS), transitional zone (TPS), and off-site (OPS) areas of the Qinghai Gonghe Photovoltaic Park in China. The entropy weight method was utilized to calculate indicator weights, while the evaluation model and indicators were transformed uniformly to obtain standardized scores for ecological and environmental effects. and conducting a thorough analysis of the distribution characteristics and factors influencing the evaluation indicators’ scores. Overall, the large-scale development of desert photovoltaics in Gonghe County has had a positive impact on the ecological environment. The WPS had better ecological and environmental conditions than did the TPS and OPS, and the ecological and environmental evaluation levels of the WPS were categorized as “general” (0.439), while the ecological and environmental effect evaluation levels of the TPS (0.286) and OPS (0.28) were both “poor”, indicating significant room for improvement. Moreover, all indicators in the scheme layer, which are used to evaluate ecological and environmental quality, yielded higher scores for the WPS than for the TPS and OPS, demonstrating that photovoltaic development has a positive effect on desert area ecology and the environment.

Abstract Exploration of efficient molecular water oxidation catalysts for long-term application remains a key challenge for the conversion of renewable energy sources into fuels. Cuboidal {Co4O4} complexes keep attracting interest as molecular water oxidation catalysts as they combine features of both heterogeneous and homogeneous catalysis with bio-inspired motifs. However, the application of many cluster-based catalysts for the oxygen evolution reaction still requires new stabilization strategies. Drawing inspiration from the stabilizing effects of natural polymers, we introduce a conductive polymer-hybrid approach to covalently immobilize {Co4O4} cubane oxo clusters as oxygen evolution catalysts. Polypyrrole is applied as an efficient p-type conducting polymer that promotes hole transfer during the oxygen evolution reaction, resulting in higher turnover frequency compared to the pristine {Co4O4} oxo cluster and heterogeneous Co-oxide benchmarks. The asymmetric coordination of {Co4O4} not only mitigates catalyst decomposition pathways, but also increases the catalytic efficiency by exposing a directed cofacial dihydroxide motif during catalysis.

Yanyuan County is located on the southeastern edge of the Qinghai-Tibet Plateau, with strong regional tectonic activities. Under the internal and external dynamics actions, landslide disasters are extremely developed in the country, which has caused huge casualties and economic losses. It is necessary to carry out landslide susceptibility assessment and then control the regional landslide disasters scientifically. Based on the 1∶50000 geological disaster survey in Yanyuan County, this study selected 13 landslide susceptibility evaluation factors, including elevation, slope, slope direction, terrain curvature, distance from fault, stratigraphic lithology, distance from water body, average annual rainfall, topographic wetness index, stream power index, normalized difference vegetation index, distance from road, and land use type. Based on 27596 grid points of landslide disaster data, combining the traditional Frequency Ratio (FR) model with the advantages of quantitative analysis and data quantification and the emerging Deep Neural Network (DNN) model with the powerful nonlinear learning and fitting ability, The FR-DNN coupling model was constructed to evaluate landslide susceptibility. The study area is divided into five levels: extremely high susceptibility area, high susceptibility area, medium susceptibility area, low susceptibility area, and extremely low susceptibility area, with an area percentage of 11.90%, 18.38%, 18.34%, 9.13%, and 42.25%, respectively. The accuracy was verified by the AUC value of the ROC curve. The AUC values of the FR model and the FR-DNN coupling model are 0.754 and 0.859, respectively. The prediction accuracy of the FR-DNN coupling model is improved by 10.5% compared with that of the FR model, indicating that the FR-DNN coupling model has better prediction ability and is more suitable for landslide susceptibility evaluation in the study area.

New psychoactive substances (NPS) have become a global health and social problem. Their structures are variable and can be easily modified to produce new compounds. Traditional analytical techniques mostly rely on standard substances and mass spectrometry databases. The increased structural diversity of NPS makes the mass spectrometry databases be unable to comprehensively cover the mass spectra of all possible NPS, which in turn makes it difficult to perform structural identification of completely unknown compounds. Advances in machine learning have emerged as a potential solution to this dilemma. In this study, the k-nearestneighbor (KNN), support vector machine (SVM), random forests (RF) and artificial neural network (ANN) algorithms were constructed based on a dataset of mass spectra of 871 compounds. The four algorithmic models for identifying new psychoactive substances were used for structural classification prediction. The training and test sets were divided according to the ratio of 7:3, and the fit method was invoked on the training set to construct the model and train the parameters of the model, and the generalization ability of the model was evaluated on the test set. A grid search with 5-fold cross-validation was used to optimize the hyperparameters of the models. The performance of the four classification prediction models was evaluated by using the confusion matrix, accuracy, precision, recall and f-scores for each of the four models for characterizing 261 samples from the test set. Overall, the RF prediction model has the best classification prediction for the seven NPS as well as negative samples, with an overall accuracy of 89.27%, which is higher than the other three classification prediction models. The overall accuracies of the KNN, SVM, and ANN models are 79.31%, 83.14%, and 83.52%, respectively. In addition, the RF prediction model also has high accuracy for the NPS prediction of specific classes, and the accuracies for synthetic cathinones, fentanyl, synthetic cannabinoids, and benzodiazepines are 100%, 93%, 95%, and 100%, respectively, which can warrant good prediction for the structural classes of unknown compounds. In conclusion, this study develops a strategy for rapid analysis of new psychoactive substances using machine learning algorithms based on mass spectral datasets, realizing the classification prediction of structural classes of unknown compounds, thus providing a basis for the structural identification of unknown psychoactive compounds.

Abstract Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (

Abstract Hyperuricemia is associated with an increased risk of gout, hypertension, diabetes, and cardiovascular diseases. Most mammals maintain normal serum uric acid (SUA) via urate oxidase (Uox), an enzyme that metabolizes poorly-soluble UA to highly-soluble allantoin. In contrast, Uox became a pseudogene in humans and apes over the long course of evolution. Here we demonstrate an atavistic strategy for treating hyperuricemia based on endogenous expression of Uox in hepatocytes mediated by mRNA (mUox) loaded with an ionizable lipid nanoparticle termed iLAND. mUox@iLAND allows effective transfection and protein expression in vitro. A single dose of mUox@iLAND lowers SUA levels for several weeks in two female murine models, including a novel long-lasting model, which is also confirmed by metabolomics analysis. Together with the excellent safety profiles observed in vivo, the proposed mRNA agent demonstrates substantial potential for hyperuricemia therapy and the prevention of associated conditions.

Abstract Wireless sensing of the wave propagation direction from radio sources lays the foundation for communication, radar, navigation, etc. However, the existing signal processing paradigm for the direction of arrival estimation requires the radio frequency electronic circuit to demodulate and sample the multichannel baseband signals followed by a complicated computing process, which places the fundamental limit on its sensing speed and energy efficiency. Here, we propose the super-resolution diffractive neural networks (S-DNN) to process electromagnetic (EM) waves directly for the DOA estimation at the speed of light. The multilayer meta-structures of S-DNN generate super-oscillatory angular responses in local angular regions that can perform the all-optical DOA estimation with angular resolutions beyond the diffraction limit. The spatial-temporal multiplexing of passive and reconfigurable S-DNNs is utilized to achieve high-resolution DOA estimation over a wide field of view. The S-DNN is validated for the DOA estimation of multiple radio sources over 5 GHz frequency bandwidth with estimation latency over two to four orders of magnitude lower than the state-of-the-art commercial devices in principle. The results achieve the angular resolution over an order of magnitude, experimentally demonstrated with four times, higher than diffraction-limited resolution. We also apply S-DNN’s edge computing capability, assisted by reconfigurable intelligent surfaces, for extremely low-latency integrated sensing and communication with low power consumption. Our work is a significant step towards utilizing photonic computing processors to facilitate various wireless sensing and communication tasks with advantages in both computing paradigms and performance over electronic computing.

Background: Coronavirus disease (COVID)-19 can lead to chronic lung damage and respiratory issues, potentially increasing surgical difficulty and risk for patients with non-small-cell lung cancer (NSCLC). However, the impacts of a COVID-19 history on early outcomes in NSCLC patients remain controversial. Objectives: To evaluate the effect of COVID-19 history on early outcomes in NSCLC patients and identify high-risk groups undergoing radical resection based on the largest Chinese multi-center real-world data to date. Design: Multi-center retrospective cohort study. Methods: NSCLC patients with (POCVD group) or without (NCVD group) a history of COVID-19 who underwent radical surgery at six institutions from January 2022 to January 2024 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM) was utilized to minimize patient selection bias. Results: Out of 7932 cases included, PSM resulted in 3021 cases per group. The two groups were comparable regarding the proportion of male patients (52.0% vs 51.6%) and those aged ⩾70 years (13.3% vs 13.8%). Although the two groups had comparable incidences of complications with Clavien-Dindo grades ⩾II (13.0% vs 14.4%, p = 0.117), the POCVD group had longer surgical durations (120.87 ± 40.23 min vs 110.74 ± 38.76 min, mean difference (95% confidence interval (CI) = 10.13 (8.138–12.122)) and higher rates of respiratory complications than the NCVD group. Subgroup logistic regression analysis indicated that patients aged ⩾70 years (odds ratio (OR) (95% CI) = 1.322 (1.022–1.876)) and those with a smoking history (OR (95% CI) = 1.235 (1.008–1.543)) had an increased risk of developing complications with Clavien-Dindo grades ⩾II. Further analysis confirmed that these high-risk patients experienced extended surgical durations, longer chest tube drainage, and prolonged postoperative hospital stay, along with increased postoperative respiratory complications following COVID-19. Conclusion: Generally, radical resection is safe for NSCLC patients with a COVID-19 history. However, these patients experienced prolonged surgical durations and a higher incidence of postoperative respiratory complications compared to those without a COVID-19 history. In addition, individuals aged ⩾70 years or with a smoking history faced elevated surgical risks following COVID-19.

BackgroundAirway mucus hypersecretion (AMH) can occur in children with acute respiratory diseases, but its underlying mechanisms and relationship with the lower respiratory tract microbiota (LRTM) are not yet fully understood. This study investigates the characteristics of LRTM in children with Mycoplasma pneumoniae pneumonia (MPP) and its impact on AMH.MethodsWe collected bronchoalveolar lavage fluid and related clinical indicators from 202 children with MPP. 16S rRNA gene amplicon sequencing was used for detection and identification. Microbial diversity and characteristic genera were compared, and their abundance was analyzed for correlations with clinical factors.ResultsAs the disease course (days from onset to bronchoscopy, grouped into T1, T2, T3) extended, α-diversity of the LRTM gradually increased, particularly in the T3 hypersecretion group. Moreover, significant differences were observed in the incidence of AMH, co-infection rates, peripheral white blood cell (WBC) count, and C-reactive protein levels. In AMH, Mycoplasmoides and Veillonella abundance and peripheral neutrophils were risk factors for increased secretions. In addition, in the T3 co-infection group, Streptococcus and Prevotella increased, replacing Stenotrophomonas as the dominant genus, possibly due to β-lactam antibiotic use. Prevotella abundance was strongly correlated with WBC.ConclusionThe composition and structure of LRTM in children with MPP played a crucial role in AMH and disease progression.

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

Objective Most dengue cases are managed in an outpatient setting, where patients are advised to return to the clinic daily for monitoring. Some patients can develop severe dengue at home and fail to recognise the deterioration. An application called DengueAid was designed as a self-monitoring tool for patients to reduce delay in seeking timely treatment. This study aimed to assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of the DengueAid application. Methods Dengue patients were recruited from a public health clinic in Malaysia and randomised to either use the DengueAid application plus standard care for dengue or receive only the standard care. The outcomes evaluated were the (1) feasibility of recruitment, data collection and follow-up procedures; (2) preliminary clinical outcome measures; and (3) acceptability of DengueAid. Qualitative interviews were conducted for participants in the intervention arm to assess the acceptability of DengueAid. Results Thirty-seven patients were recruited with 97% ( n = 36) retention rates. The recruitment rate was low (63% refusal rate, n = 62/99) with difficulty in data collection and follow-up due to the variable interval of care for dengue in an outpatient setting. DengueAid application was acceptable to the participants, but preliminary clinical outcomes and qualitative data suggested limited utility of the application. Unwell conditions of patients and limited access to healthcare are important factors impacting the application's utility. Conclusion The feasibility trial uncovered issues with recruitment, data collection and follow-up processes. Further research and modification to the application are needed to improve its utility and usability.

Electroencephalography (EEG) analysis extracts critical information from brain signals, enabling brain disease diagnosis and providing fundamental support for brain–computer interfaces. However, performing an artificial intelligence analysis of EEG signals with high energy efficiency poses significant challenges for electronic processors on edge computing devices, especially with large neural network models. Herein, we propose an EEG opto-processor based on diffractive photonic computing units (DPUs) to process extracranial and intracranial EEG signals effectively and to detect epileptic seizures. The signals of the EEG channels within a second-time window are optically encoded as inputs to the constructed diffractive neural networks for classification, which monitors the brain state to identify symptoms of an epileptic seizure. We developed both free-space and integrated DPUs as edge computing systems and demonstrated their applications for real-time epileptic seizure detection using benchmark datasets, that is, the Children’s Hospital Boston (CHB)–Massachusetts Institute of Technology (MIT) extracranial and Epilepsy-iEEG-Multicenter intracranial EEG datasets, with excellent computing performance results. Along with the channel selection mechanism, both numerical evaluations and experimental results validated the sufficiently high classification accuracies of the proposed opto-processors for supervising clinical diagnosis. Our study opens a new research direction for utilizing photonic computing techniques to process large-scale EEG signals and promote broader applications.

Abstract The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Abstract Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.

Abstract A novel non-volatile photonic-electronic memory, 3D integrating an Al-doped HfO2 ferroelectric thin film onto a silicon photonic platform using fully compatible electronic and photonic fabrication processes, enables electrically/optically programmable, non-destructively readable, and multi-level storage functions.

PRPF6, located on chromosome 20, is required for the formation of the spliceosome. Mutations in the PRPF6 gene can lead to retinitis pigmentosa (RP), a common inherited retinal disease characterized by progressive degeneration of retinal pigment epithelium and photoreceptors. Here, we generated an induced pluripotent stem cell (iPSC) line carrying the PRPF6 c.2699 G > A mutation using CRISPR/Cas9 technology, which will provide a valuable resource for RP pathogenesis and treatment research.

Objective: To investigate the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea (FHA).Methods: A retrospective cohort study was conducted to summarize the clinical and endocrine characteristics of 58 patients with FHA at initial diagnosis and to follow up the recovery of ovulation and spontaneous menstruation in the patients to investigate these biochemical indicators and their effects on recovery outcomes.Results: Among patients with FHA, 13.8% (8/58) and 15.5% (9/58) had above moderately severe depressive and severe anxiety symptoms respectively, and 25.9% (15/58) were at high risk for eating disorders. 34.5% (20/58) were included assessed as having recovered. The non-recovered group had higher scores on the Patient Health Questionnaire (PHQ-9) (p = .022) and higher scores on the Eating Attitude Test-26 (EAT-26) (p = .03) as well as bulimia and food preoccupation (p = .041). Follicle diameter >5 mm at initial diagnosis was an independent factor influencing recovery of reproductive axis function (odds ratio = 7.532; 95% confidence interval, 1.321–42.930; p = .023).Conculsions: Mood disorders and a certain risk of eating disorders were present in FHA.These, together with weight loss, endocrine and follicle size, could influence the outcome.

ABSTRACTChanges in crop mix significantly affect the carbon emissions from cropping systems, thus underscoring their importance in achieving sustainable agriculture development. This article aims to offer new insights into the relationship between crop mix changes and carbon emissions from cropping systems. Based on provincial statistical data on crop production, this study analyzed the spatiotemporal dynamics of crop mix and the subsequent effect on the carbon emissions from cropping systems in China from 2005 to 2020. The crop-mix type identification rules, emission-factor approach, and grey incidence analysis were applied. The results showed clear changes in crop mix and obvious transitions from grain crops to cash crops in southern provinces. Among crops, the abundance of maize, vegetables, and melons increased remarkably. Besides, the carbon emission intensity (CI) from cropping systems generally showed an upward trend in most provinces, with a spatial pattern of gradual decrease from southeast to northwest. The changes in CI were most closely correlated with rice, maize, vegetables, and melon, with coefficients of 0.808, 0.773, 0.814, and 0.792, respectively. Additionally, the growth of maize and vegetables ratios played a significant role in the CI increases in most provinces. To optimize crop cultivation and mitigate carbon emissions, possible strategies including rational crop production layout, land transfer, and clean production technologies were proposed.

ABSTRACTThe insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.

IntroductionMetabolic dysfunction-associated steatohepatitis (MASH) is increasingly becoming a prevalent cause of hepatocellular carcinoma (HCC). Our study examines the burden of MASH-related HCC globally, regionally, and nationally, along with associated risk factors from 1990 to 2019, considering variables such as age, sex, and socioeconomic status.ObjectiveWe aimed to report the global, regional, and national burden of liver cancer due to MASH and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index (SDI).MethodsUtilizing the Global Burden of Disease 2019 project, we analyzed data on prevalence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to MASH across 204 countries. We provided counts and rates per 100,000 population, including 95% uncertainty intervals.ResultsIn 2019, there were 46.8 thousand cases of MASH-related HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs globally. While the prevalence increased by 19.8% since 1990, the death and DALY rates decreased by 5.3% and 15.1%, respectively. The highest prevalence was in High-income Asia Pacific, with the greatest increases observed in Australasia, Central Asia, and High-income North America. Southern Sub-Saharan Africa reported the highest death rate, while the lowest rates were in parts of Latin America, Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin America.DiscussionThe burden of MASH-related HCC is expected to rise slightly over the next decade. This disease, which is not associated with the SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position MASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It is imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with MASH.

BackgroundMitochondria have always been considered too be closely related to the occurrence and development of malignant tumors. However, the bioinformatic analysis of mitochondria in lung adenocarcinoma (LUAD) has not been reported yet.MethodsIn the present study, we constructed a novel and reliable algorithm, comprising a consensus cluster analysis and risk assessment model, to predict the survival outcomes and tumor immunity for patients with terminal LUAD.ResultsPatients with LUAD were classified into three clusters, and patients in cluster 1 exhibited the best survival outcomes. The patients in cluster 3 had the highest expression of PDL1 (encoding programmed cell death 1 ligand 11) and HAVCR2 (encoding Hepatitis A virus cellular receptor 2), and the highest tumor mutation burden (TMB). In the risk assessment model, patients in the low-risk group tended to have a significantly better survival outcome. Furthermore, the risk score combined with stage could act as a reliable independent prognostic indicator for patients with LUAD. The prognostic signature is a novel and effective biomarker to select anti-tumor drugs. Low-risk patients tended to have a higher expression of CTLA4 (encoding cytotoxic T-lymphocyte associated protein 4) and HAVCR2. Moreover, patients in the high-risk group were more sensitive to Cisplatin, Docetaxel, Erlotinib, Gemcitabine, and Paclitaxel, while low-risk patients would probably benefit more from Gefitinib.ConclusionWe constructed a novel and reliable algorithm comprising a consensus cluster analysis and risk assessment model to predict survival outcomes, which functions as a reliable guideline for anti-tumor drug treatment for patients with terminal LUAD.

Summary: Background: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. Methods: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice. Findings: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. Interpretation: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC. Funding: The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the “European Union Next Generation EU/PRTR,” the Regional Government of Castile and León (CSI144P20), European Union.

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

Image denoising is a fundamental tool in the fields of image processing and computer vision. With the rapid development of multimedia and cloud computing, it has become popular for resource-constrained users to outsource the storage and denoising of massive images. However, it may cause privacy concerns and response delays. In this scenario, we propose an ef F icient priv A cy-prese R ving I mage de N oising sch E me (FARINE) for outsourcing digital images. By introducing a key conversion mechanism, FARINE allows removing noise from a given noisy image using a non-local mean way without leaking any information about the plaintext content. Due to its low computational latency/communication cost, edge computing is considered to improve the user experience. To achieve a dynamic user set efficiently, we design a fine-grained access control mechanism to support user authorization and revocation in multi-user scenarios. Extensive experiments over several benchmark data sets show that FARINE obtains comparable performance to plaintext image denoising.

Abstract Rock salt is considered a suitable medium for the permanent disposal of heat‐generating radioactive waste due to its isolation properties. However, excavation damage and heating induce complex and heterogeneous thermal‐hydrological‐mechanical (THM) processes across different zones. Quantifying this heterogeneity is crucial for accurate long‐term performance assessment models, but traditional methods lack the necessary resolution. This study employs 4D electrical resistivity tomography (ERT) monitoring during controlled heating experiments in a salt formation to unravel the spatiotemporal dynamics of THM processes. Advanced time‐lapse inversion and clustering analysis quantify subsurface properties and map the heterogeneity of THM dynamics. The ERT results can estimate subsurface properties and delineate the damaged and intact zones, enabling appropriate parameterization and representation of processes for long‐term modeling. This approach may be used in further improving the predictive models and ensuring the safe long‐term disposal of radioactive waste in rock salt.

Candidatus Accumulibacter, a prominent polyphosphate-accumulating organism (PAO) in wastewater treatment, plays a crucial role in enhanced biological phosphorus removal (EBPR). The genetic underpinnings of its polyphosphate accumulation capabilities, however, remain largely unknown. Here, we conducted a comprehensive genomic analysis of Ca. Accumulibacter-PAOs and their relatives within the Rhodocyclaceae family, identifying 124 core genes acquired via horizontal gene transfer (HGT) at its least common ancestor. Metatranscriptomic analysis of an enrichment culture of Ca. Accumulibacter revealed active transcription of 44 of these genes during an EBPR cycle, notably including the polyphosphate kinase 2 (PPK2) gene instead of the commonly recognized polyphosphate kinase 1 (PPK1) gene. Intriguingly, the phosphate regulon (Pho) genes showed minimal transcriptions, pointing to a distinctive fact of Pho dysregulation, where PhoU, the phosphate signaling complex protein, was not regulating the high-affinity phosphate transport (Pst) system, resulting in continuous phosphate uptake. To prevent phosphate toxicity, Ca. Accumulibacter utilized the laterally acquired PPK2 to condense phosphate into polyphosphate, resulting in the polyphosphate-accumulating feature. This study provides novel insights into the evolutionary emergence of the polyphosphate-accumulating trait in Ca. Accumulibacter, offering potential advancements in understanding the PAO phenotype in the EBPR process.

Different spatial positions lead to inconsistent fermentation effects and flavors, however, the spatial heterogeneity of Qingxiangxing (QXX) Baijiu remains unknown. We investigated the microbes, flavors, and physicochemical properties of different layers in fermented grains of QXX Baijiu using Illumina HiSeq sequencing, two-dimensional gas chromatography–mass spectrometry (GC × GC–MS) and ultra-high performance liquid chromatography-mass (UHPLC-MS). A total of 79 volatiles, 1596 metabolites, 50 bacterial genera, and 52 fungal genera were identified. The contents distribution followed the order: upper layer > bottom layer > middle layer. Organic acids and derivatives were the main differential metabolites across the three layers. Starch, pH, and reducing sugar levels increased from the upper to bottom layer. Saccharomyces and Lactobacillus were dominant microbes. Pediococcus, the biomarker of upper layer, showed positive correlations with formic acid, ethyl lactate, acetic acid, ethyl linoleate, and ethyl oleate. These findings deepen our understanding of the fermentation and flavor formation mechanisms of QXX Baijiu.

The grid integration of large-scale photovoltaic and other distributed energy sources is an effective solution for addressing power supply shortages and environmental pollution. However, the widespread adoption of photovoltaics and grid integration presents various technological and management challenges. To fulfill the demands of grid management and ensure safe operations, the exchange of information between different terminals is continuously escalating. Use of diverse communication standards creates the problem of “information islands” among terminals. Hence, a standardized information model is crucial for describing the photovoltaic grid integration business and enhancing the efficiency of related software platform research and development. This study extends the IEC 61970/61968 standards and presents a common information model for the integration of photovoltaic systems into the grid. Initially, the operational procedures for integrating photovoltaic systems into the grid are analyzed, and UML modeling tools are employed for business modeling purposes. Subsequently, leveraging the outcomes of the business modeling and the content of the IEC 61970/61968 standards, the development of the common information model is executed. Lastly, causal analysis is conducted along with the modeling of communication standard extensions specifically targeted for the integration of photovoltaic systems into the grid, culminating in the finalization of the construction of the common information model for photovoltaic grid connection.

The aim of this study was to isolate biocontrol bacteria that could antagonize brown rot of Dendrocalamus latiflorus, optimize the culture conditions, and develop an effective biocontrol preparation for brown rot of D. latiflorus. This study isolated a bacterium with an antagonistic effect on bamboo brown rot from healthy D. latiflorus rhizosphere soil. Morphology, molecular biology, and physiological biochemistry methods identified it as Bacillus siamensis. The following culturing media and conditions improved the inhibition effect of B. siamensis: the best culturing media were 2% sucrose, 1.5% yeast extract, and 0.7% potassium chloride; the optimal culturing time, temperature, pH, and inoculation amount were 48 h, 30°C, 6, and 20%. The optimum formula of the applying bacterial suspension was 14% sodium dodecyl benzene sulfonate emulsifier, 4% Na2HPO4·2H2O, 0.3% hydroxypropyl methylcellulose thickener, and 20% B. siamensis. The pot experiment results showed the control effect of applying bacterial suspension, diluted 1,000 times is still better than that of 24% fenbuconazole suspension. The applying bacterial suspension enables reliable control of brown rot in D. latiflorus.

The use of the plasma-enhanced atomic layer deposition (ALD) technique for the deposition of HfO2-based ferroelectrics has received attention in recent years primarily due to wake-up free operation. However, these studies have primarily focused on metal-ferroelectric-metal (MFM) structures. In this work, we investigate the characteristics of ferroelectric field-effect transistors (FEFETs) in which the ferroelectric Hf0.5Zr0.5O2 (HZO) gate stack is deposited using the plasma-enhanced atomic layer deposition (PEALD) technique. We observe that PEALD FEFET requires a higher write voltage for the same memory window compared to an equivalent FEFET with thermal ALD (THALD)-grown HZO. The increase in write voltage in PEALD FEFET occurs primarily due to the increase of the interfacial oxide layer using the plasma process. In addition, we observe that the SiO2 interfacial layer underneath the ferroelectric (FE) HZO layer eliminates the wake-up behavior in both THALD and PEALD FEFETs.

To at the low robustness of the existing model for occluded object detection, an occluded object detection algorithm based on fuzzy sample anchor box IoU Matching degree Deviation Aware(IoU_MDA)is proposed. Firstly, fuzzy samples are defined based on Anchor-based, which reflects the degree of object occlusion. Secondly, IoU_MDA is proposed to quantify the degree of interference experienced by fuzzy samples. Then, IoU_MDA_Loss is constructed based on IoU_MDA, combined with IoU and the balance parameter $\Phi$ . To address class imbalance issues and enhance model generality, intra-class and inter-class fuzzy weights, and fuzzy sample focusing parameters are designed on the basis of the initial IoU_MDA_Loss. An occluded object training scheme is designed based on IoU perception, and non-fuzzy sample weight balancing parameters are constructed. Finally, IoU_MDA_Loss is merged with Focal Loss to obtain IoU_MDA_Focal Loss, simultaneously enhancing the detection performance of fuzzy samples and difficult-to-distinguish samples. The experimental results on the WiderPerson and VOC2007 datasets show that the mAP of IoU_MDA_Loss has increased by 2.04%, 2.36%, and IoU_MDA_Focal Loss has increased by 1.82%, 2.65%, respectively, compared to the baseline model. The detection performance surpasses current mainstream algorithms.

Abstract Background In many cardiac diseases, myocardial scar tissue detected by late gadolinium enhancement (LGE) is a risk factor for cardiac arrhythmia and sudden cardiac death. Previous studies in athletes reported an increased risk for cardiac events in this group of ostensibly healthy subjects. However, the currently available longitudinal studies on this topic included fairly old marathon runners with a mean age of 57 ± 6 years or represent a case–control study in athletes with preexisting ventricular arrhythmia. The purpose of this prospective study was to analyze the prognostic relevance of LGE cardiac magnetic resonance (CMR) in middle-aged endurance athletes without known preexisting cardiac disorders. Methods Three-hundred and twelve apparently healthy athletes were prospectively enrolled. Inclusion criteria were a training for a minimum of 10 h per week and regularly participation in competitions. LGE CMR was obtained at baseline in all athletes and presence of LGE was classified visually according to established criteria as ischemic LGE, major or minor non-ischemic LGE or absent LGE. Follow-up consisted of a standardized questionnaire and an additional phone call in case of incomplete data. An event was defined as fatal myocardial infarction, ventricular tachycardia, ventricular fibrillation or sudden cardiac death (SCD). Results Complete follow-up was available for 293/312 athletes (94%) including 145 triathletes, 74 marathon runners and 74 cyclists after a median of 5.6 [quartiles 4,3, 6,4] years. Median age was 44 [35, 50] years at study enrollment. Spiroergometry did not reveal heart rhythm disturbances or significant ECG changes in the study population. LGE CMR revealed myocardial scar/focal fibrosis in 80 of 293 athletes (27%) including 7 athletes (2%) with ischemic subendocardial LGE of the left ventricle (LV), 16 athletes (6%) with major non-ischemic LGE of the LV and 57 athletes (19%) with minor non-ischemic LGE. During follow-up, two athletes experienced SCD. One marathon runner died during a training run and one cyclist died suddenly at rest. Both athletes had ischemic LGE of the LV. The event rate for SCD was 0.7% in the entire study population and 28% in the 7 athletes with ischemic LGE (p

Abstract Background Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics. Results Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation. Conclusions Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.

Abstract Curiosity, or novelty seeking, is a fundamental mechanism motivating animals to explore and exploit environments to improve survival, and is also positively associated with cognitive, intrapersonal and interpersonal well-being in humans. However, curiosity declines as humans age, and the decline even positively predicts the extent of cognitive decline in Alzheimer’s disease patients. Therefore, determining the underlying mechanism, which is currently unknown, is an urgent task for the present aging society that is growing at an unprecedented rate. This study finds that seeking behaviors for both social and inanimate novelties are compromised in aged mice, suggesting that the aging-related decline in curiosity and novelty-seeking is a biological process. This study further identifies an aging-related reduction in the activity (manifesting as a reduction in spontaneous firing) of dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Finally, this study establishes that this reduction in activity causally underlies the aging-related decline in novelty-seeking behaviors. This study potentially provides an interventional strategy for maintaining high curiosity in the aged population, i.e., compensating for the reduced activity of VTA/SNc dopaminergic neurons, enabling the aged population to cope more smoothly with the present growing aging society, physically, cognitively and socioeconomically.

Based on the project portfolio selection and scheduling problem (PPSS), the development of a systematic and scientific project scheduling plan necessitates comprehensive consideration of individual preferences and multiple realistic constraints, rendering it an NP-hard problem. Simultaneously, accurately and swiftly evaluating the value of projects as a complex entity poses a challenging issue that requires urgent attention. This paper introduces a novel qualitative evaluation-based project value assessment process that significantly reduces the cost and complexity of project value assessment, upon which a preference-based deep reinforcement learning method is presented for computing and solving project subsets and time scheduling plans. This paper first determines the key parameter values of the algorithm through specific examples. Then, using the method of controlling variables, it explores the sensitivity of the algorithm to changes in problem size and dimensionality. Finally, the proposed algorithm is compared with two classical algorithms and two heuristic algorithms across different instances. The experimental results demonstrate that the proposed algorithm exhibits higher effectiveness and accuracy.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Many medical conditions, including hypertension, diabetes, obesity, sleep apnea, and heart failure (HF), increase the risk for AF. Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production. Significant changes occur in myocardial metabolism in AF. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus (T2DM) and obesity. GLP-1RAs have also been shown to reduce oxidative stress, inflammation, autonomic nervous system modulation, and mitochondrial function. This article reviews the changes in metabolic characteristics in cardiomyocytes in AF. Although the clinical trial outcomes are unsatisfactory, the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors, lowering the incidence of AF.

Current investigations have illuminated the essential roles played by circular RNAs (circRNAs) in driving breast cancer (BC) tumorigenesis. However, the functional implications and molecular underpinnings of most circRNAs in BC are not well characterized. Here, Circular RNA (circRNA) expression profiles were analyzed in four surgically resected BC cases along with adjacent non-cancerous tissues applying RNA microarray analysis. The levels and prognostic implications of circRREB1 in BC were subjected to quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Experimental manipulation of circRREB1 levels in both in vivo and in vitro settings further delineated its role in BC cell growth, invasion, and metastasis. The mechanical verification of circRREB1's interaction with GNB4 was established through RNA pull-down, mass spectrometry, Western blot analysis, RNA immunoprecipitation assays (RIP), fluorescence ISH (FISH), and rescue experiments. We found that circRREB1 exhibited significant upregulation in BC tissues and cells, implicating its association with an unfavorable prognosis in BC patients. CircRREB1 knockdown elicited anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in BC cells, whereas its upregulation exerted opposing influences. Follow-up mechanistic examinations suggested that circRREB1 might interact with GNB4 directly, inducing the activation of Erk1/2 signaling and driving BC progression. Our findings collectively indicate that the interplay of circRREB1 with GNB4 promotes Erk1/2 signaling, thereby fostering BC progression, and positioning circRREB1 as a candidate therapeutic target for intervention in BC.

Abstract Headwater catchments play a vital role in regional water supply and ecohydrology, and a quantitative understanding of the hydrological partitioning in these catchments is critically needed, particularly under a changing climate. Recent studies have highlighted the importance of subsurface critical zone (CZ) structure in modulating the partitioning of precipitation in mountainous catchments; however, few existing studies have explicitly taken into account the 3D subsurface CZ structure. In this study, we designed realistic synthetic catchment models based on seismic velocity‐estimated 3D subsurface CZ structures. Integrated hydrologic modeling is then used to study the effects of the shape of the weathered bedrock and the associated storage capacity on various hydrologic fluxes and storages in mountainous headwater catchments. Numerical results show that the weathered bedrock affects not only the magnitude but also the peak time of both streamflow and subsurface dynamic storage.

With the demand for communication, imaging, spectroscopy, and other applications, broadband detection has always been a particularly popular direction. However, the current photodetectors have the problems of relatively narrow response bands, a low sensitivity, a slow response speed, and complex manufacturing processes. In this article, the alloy material InBiSe3 is proposed to manufacture a wideband photodetector from visible to terahertz at room temperature. The noise equivalent power (NEP) of the detector is 1.37 × 10−10 W Hz−1/2 at 635 nm, 1.2 × 10−10 W Hz−1/2 at 808 nm, and 1.56 × 10−10 W Hz−1/2 at 980 nm. The device also exhibits a good response in the terahertz and millimeter-wave bands, with a NEP of 8.33 × 10−15 W Hz−1/2 at 0.023 THz, 7.03 × 10−14 W Hz−1/2 at 0.14 THz, 6.14 × 10−15 W Hz−1/2 at 0.171 THz, 1.91 × 10−14 W Hz−1/2 at 0.35 THz, and 4.04 × 10−14 W Hz−1/2 at 0.5 THz based on the electromagnetic induced potential wells effect. The response time is as fast as 10 µs. Our results demonstrate the promise of the InBiSe3 alloy for photoelectric applications and provide a method for the high performance of broadband photodetectors.

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ.Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation.Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX.Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.