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Abstract Embedded Dynamic RAM (eDRAM) has become a key solution for large-capacity cache in high-performance processors. A heterogeneous two transistor capacitorless eDRAM (2T-eDRAM) that combines silicon and molybdenum disulfide (MoS2) is reported to address the short retention issue in conventional gain cell (GC) eDRAMs meanwhile eliminate the pillar capacitor in one transistor and one capacitor (1T1C) eDRAMs. The MoS2 write transistor with low OFF current (IOFF) enables long data retention, while the Si read transistor offers high drive current and logic compatibility. This combination enhances data retention by 1000 times and sense margin by 100 times respectively compared to full Si and MoS2 counterparts. A three-dimensional (3D) design stacking MoS2 on Si is demonstrated with back-end-of-line (BEOL) process to double integration density. With 6000 s data retention, 35 μA/μm sense margin, 5 ns access speeds, 3D integration and CMOS logic compatibility, this Si-MoS2 eDRAM marks a significant advancement in memory technology.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use. Method PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024. Data extraction and evaluation were conducted using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). The Prediction model Risk Of Bias Assessment Tool (PROBAST) was employed to assess the risk of bias and applicability of the models. Results After deduplication and screening 5942 retrieved articles, 46 studies comprising 53 models were included. Of these, 17 (37.0%) studies developed from studies conducted in China. All models were based on cohort studies. Mortality was the predicted outcome in 27 (50.9%) models. Logistic regression was used in 41 (77.4%) models, while machine learning methods were employed in 9 (17.0%) models. The median (minimum, maximum) sample size for model development was 672 (106, 150,035). The median (minimum, maximum) number of predictors per model was 5 (2, 42). Frequently used predictors included age (n = 28), dyspnea severity scores (n = 12), and PaCO2 (n = 11). The pooled AUC was 0.80 for mortality prediction models and 0.84 for hospitalization-related outcomes. 52 models have a high overall risk of bias, and all models were judged to have low concern regarding applicability. Major sources of bias included insufficient sample sizes (83.0%), reliance on univariate analysis for predictor selection (73.6%), inappropriate internal and external validation methods (54.7%), inappropriate inclusion and exclusion criteria for study subjects (50.9%) and so on. The only model with low bias was the PEARL score. Conclusion Current prognostic risk prediction models for patients with AECOPD generally exhibit high bias. Future efforts should standardize model development and validation methods, and develop widely usable clinical models.

ABSTRACT Recent guidelines have recognized several factors, including blood pressure (BP), body mass index (BMI), low‐density lipoprotein cholesterol (LDL‐C), hemoglobin A1c (HbA1c), smoking, and physical activity, as key contributors to stroke risk. However, the impact of simultaneous management of these risk factors on stroke susceptibility in individuals with hypertension remains ambiguous. This study involved 238 388 participants from the UK Biobank, followed up from their recruitment date until April 1, 2023. Cox proportional hazard models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to illustrate the correlation between the joint modifiable risk factor control and the stroke risk. As the degree of risk factor control increased, a gradual reduction in stroke risk was observed. Hypertensive patients who had the optimal risk factor control (≥5 risk factor controls) had a 14.6% lower stroke risk than those who controlled 2 or fewer (HR: 0.854; 95% CI: 804–0.908; p < 0.001). The excess risk of stroke linked to hypertension slowly diminished as the number of controlled risk factors increased. However, the risk was still 25.1% higher for hypertensive patients with optimal risk factor control as compared to the non‐hypertensive population (HR: 1.251; 95% CI: 1.100–1.422; p < 0.001). The protective effect of joint risk factor control against the stroke risk due to hypertension was stronger in medicated hypertensive patients than in those not medicated. This finding leads to the conclusion that joint risk factor control combined with pharmacological treatment could potentially eliminate the excess risk of stroke associated with hypertension.

Abstract Resveratrol has been reported to promote immunity and decrease oxidative stress, but which demonstrates biphasic effects relied on the use concentration. In this study, the effects of diet supplement with a relative high concentration of resveratrol (0.32 mg/kg) on metabolism, antioxidation and apoptosis of liver were investigated in Siberian sturgeon. The results showed that resveratrol significantly increased the lipid synthesis and the apoptosis, but did not either activate the antioxidant NRF2/KEAP1 pathway or enhance the antioxidant enzyme activity. Transcriptome analysis revealed significant changes in regulatory pathways related to glycolipid, including PPAR signaling pathway, Insulin signaling pathway, Fatty acid biosynthesis, and Glycolysis/Gluconeogenesis. In addition, resveratrol significantly increased the lipid synthesis genes (accα and fas), fatty acid transport gene (fatp 6) and gluconeogenesis gene (gck), but decreased the survival-promoting genes (gadd45β and igf 1). These findings highlight a significant effect of resveratrol on glycolipid metabolism in Siberian sturgeon. Moreover, this study also demonstrated that 0.32 mg/kg resveratrol has physiological toxicity to the liver of Siberian sturgeon, indicating that this dose is too high for Siberian sturgeon. Thus, our study provides a valuable insight for future research and application of resveratrol in fish.

This study presents a cancer diagnostics method through the development of a graphitic carbon nitride (g-C3N4)-based electrochemical sensor for detecting circulating tumor cells (CTCs) in blood. Utilizing the unique properties of g-C3N4 nanosheets combined with gold nanoparticles functionalized with DNA aptamers, the sensor exhibits remarkable sensitivity and selectivity in CTC detection. The aptamers specifically target cell surface biomarkers, enabling the precise capture and quantification of CTCs. The sensor's detection limit is an impressive 5 cells/mL, with a broad detection range from 10 to 105 cells/mL. This high-performance sensing platform not only achieves rapid and accurate quantification of CTCs but also demonstrates robustness against interference from other cell types, making it highly suitable for clinical applications. The optimized conditions for aptamer-functionalized nanoparticle concentration and incubation time ensure the sensor's efficacy, as validated in spiked blood samples. This work provides a practical and efficient approach for non-invasive cancer diagnostics, offering significant improvements over existing methods in terms of simplicity, sensitivity, and specificity for early detection and monitoring of cancer progression.

Abstract Background Considering the age relevance of prostate cancer (PCa) and the involvement of the cGAS-STING pathway in aging and cancer, we aim to classify PCa into distinct molecular subtypes and identify key genes from the novel perspective of the cGAS-STING pathway. It is of significance to guide personalized intervention of cancer-targeting therapy based on genetic evidence. Methods The 430 patients with PCa from the TCGA database were included. We integrated 29 key genes involved in cGAS-STING pathway and analyzed differentially expressed genes and biochemical recurrence (BCR)-free survival-related genes. The assessments of tumor stemness and heterogeneity and tumor microenvironment (TME) were conducted to reveal potential mechanisms. Results PCa patients were classified into two distinct subtypes using AURKB, TREX1, and STAT6, and subtype 1 had a worse prognosis than subtype 2 (HR: 21.19, p

Currently, chemicals and waste are recognized as key drivers of habitat degradation and biodiversity loss in aquatic ecosystems. To ensure vibrant habitats for aquatic species and maintain a sustainable aquatic food supply system, Japan promulgated its Environmental Quality Standards for the Conservation of Aquatic Life (EQS-CAL), based on its own aquatic life water quality criteria (ALWQC) derivation method and application mechanism. Here we overview Japan's EQS-CAL framework and highlight their best practices by examining the framework systems and related policies. Key experiences from Japan's EQS-CAL system include: (1) Classifying six types of aquatic organisms according to their adaptability to habitat status; (2) Using a risk-based chemical screening system for three groups of chemical pollutants; (3) Recommending a five-step method for determining ALWQC values based on the most sensitive life stage of the most sensitive species; (4) Applying site-specific implementation mechanisms through a series of Plan-Do-Check-Act loops. This paper offers scientific references for other jurisdictions, aiding in the development of more resilient ALWQC systems that can maintain healthy environments for aquatic life and potentially mitigate ongoing threats to human societies and global aquatic biodiversity.

In environments with high humidity or water exposure, the performance of polyurethane materials could be adversely affected by water and its penetration, which could compromise their long-term utility. The influence of water on polyurethane materials is affected by water transport and various factors. This article summarizes the factors affecting the water absorption of polyurethane, introduces research methods for water transport in polyurethane, analyzes the pathways of water transport, and reviews the influence of water on the mechanical properties of polyurethane and its composite materials. The ultimate goal of this paper is to furnish a comprehensive theoretical foundation and a valuable reference for the research and practical application of polyurethane materials in water environments.

ObjectiveTo understand the status and influencing factors of human papillomavirus (HPV) vaccination knowledge and recommendation behaviors among healthcare workers and teachers in Ordos city, Inner Mongolia Autonomous Region. MethodsUsing a typical sampling method and a self-designed questionnaire, we conducted an online survey among 415 healthcare workers and teachers recruited in one district and one banner of Ordos City, Inner Mongolia Autonomous Region in July 2023. Participants′ information on knowledge of HPV and its vaccines, and beliefs about HPV vaccination based on the health belief model (HBM) were collected. Univariate logistic regression and unconditional multivariate logistic regression were used to analyze the factors influencing HPV vaccination recommendation behavior. ResultsOf the 243 health care workers and 86 teachers ultimately included in the analysis, 201 and 56, respectively, had recommended HPV vaccination. The median of HPV knowledge score was 7 out of a total score of 11 for healthcare workers and 6 for teachers. Multivariate unconditional logistic regression model analysis showed that among healthcare workers, those with the following characteristics were more likely to recommend HPV vaccination: living in the banner (odds ratio [OR] = 17.042, 95% confidence interval [95%CI]: 2.778 – 104.544), having a higher HPV knowledge score (OR = 10.194, 95%CI: 3.076 – 33.778), having a higher HPV vaccination knowledge score (OR = 4.510, 95%CI: 1.451 – 14.015), having a higher score of perceived favorable factors for recommending HPV vaccination (OR = 17.492, 95% CI: 3.054 – 100.178), and having a high perception of susceptibility to HPV infection (OR = 100.407, 95%CI: 15.087 – 668.239); while those who were married were less likely to recommend HPV vaccination (OR = 0.050, 95%CI: 0.006 – 0.404); the teachers with high perception of susceptibility to HPV infection were more likely to recommend HPV vaccination (OR = 4.947, 95%CI: 1.322 – 18.516). ConclusionHealthcare workers and teachers in Ordos city had good knowledge of HPV vaccination. Region of residence, marital status, HPV knowledge, perceived favorable factors for recommending HPV vaccination, and perceived susceptibility to HPV infection were the main factors influencing the recommendation behavior of healthcare workers, while perceived susceptibility to HPV infection was the main factor influencing the recommendation behavior of teachers.

Abstract Background In aquaculture, sturgeons are generally maintained in the confined spaces, which not only hinders sturgeon movement, but also threatens their flesh quality that seriously concerned by aquaculture industry. As a typical antioxidant, resveratrol can improve the flesh quality of livestock and poultry. However, the mechanism of resveratrol’s effect on the muscle of Siberian sturgeon is still unclear. Results In this study, the dietary resveratrol increased the myofiber diameter, the content of the amino acids, antioxidant capacity markers (CAT, LDH and SOD) levels and the expression levels of mTORC1 and MYH9 in muscle of Siberian sturgeon. Further transcriptome analysis displayed that ROS production-related pathways (“Oxidative phosphorylation” and “Chemical carcinogenes-reactive oxygen species”) were enriched in KEGG analysis, and the expression levels of genes related to the production of ROS (COX4, COX6A, ATPeF1A, etc.) in mitochondria were significantly down-regulated, while the expression levels of genes related to scavenging ROS (SOD1) were up-regulated. Conclusions In summary, this study reveals that resveratrol may promote the flesh quality of Siberian sturgeon probably by enhancing myofiber growth, nutritional value and the antioxidant capacity of muscle, which has certain reference significance for the development of a new type of feed for Siberian sturgeon.

Abstract Artemisinin is primarily synthesized and stored in the subepidermal space of the glandular trichomes of Artemisia annua. The augmentation of trichome density has been demonstrated to enhance artemisinin yield. However, existing literature lacks insights into the correlation between the stratum corneum and trichomes. This study aims to unravel the involvement of TrichomeLess Regulator 3 (TLR3), which encodes the transcription factor, in artemisinin biosynthesis and its potential association with the stratum corneum. TLR3 was identified as a candidate gene through transcriptome analysis. The role of TLR3 in trichome development and morphology was investigated using yeast two-hybrid, pull-down analysis, and RNA electrophoresis mobility assay. Our research revealed that TLR3 negatively regulates trichome development. It modulates the morphology of Arabidopsis thaliana trichomes by inhibiting branching and inducing the formation of abnormal trichomes in Artemisia annua. Overexpression of the TLR3 gene disrupts the arrangement of the stratum corneum and reduces artemisinin content. Simultaneously, TLR3 possesses the capacity to regulate stratum corneum development and trichome follicle morphology by interacting with TRICHOME AND ARTEMISININ REGULATOR 1, and CycTL. Consequently, our findings underscore the pivotal role of TLR3 in the development of glandular trichomes and stratum corneum biosynthesis, thereby influencing the morphology of Artemisia annua trichomes.

Immune checkpoint inhibitors (ICIs) are monoclonal antibody antagonists, which can block cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1/ligand-1 (PD-1/PD-L1) pathways, and other molecules exploited by tumor cells to evade T cell-mediated immune response. ICIs have transformed the treatment landscape for various cancers due to their amazing efficacy. Many anti-tumor therapies, including targeted therapy, radiotherapy, and chemotherapy, combine ICIs to make the treatment more effective. However, the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ systems. Among irAEs, cardiotoxicity induced by ICIs, uncommon but fatal, has greatly offset survival benefits from ICIs, which is heartbreaking for both patients and clinicians. Consequently, such cardiotoxicity requires special vigilance, and it has become a common challenge both for patients and clinicians. This article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clinicians, elaborated on the underlying mechanisms in conjunction with animal studies, and then attempted to propose management strategies from a cardio-immuno-oncology multidisciplinary perspective.

Photodetectors (PDs) are crucial in modern society as they enable the detection of a diverse range of light-based signals. With the exponential increase in their development, materials are being used to create a wide range of PDs that play critical roles in enabling various applications and technologies. Image sensor technology has been hindered due to the lack of a universal system that can integrate all types of PDs with silicon-based readout integrated circuits (ROICs). To address this issue, we conducted experiments adopting two-dimensional materials as an example. High-performance MoS2-/MoTe2-based PDs were fabricated in the current work and the most suitable ROICs were identified to pair with them. This established a solid foundation for further researches in the field of image sensors. We developed and implemented a versatile testing system that uses a printed circuit board to connect the PD and ROIC. After the ROIC generates the sampled signal, it is collected and processed by algorithms, which overcome device uniformity limitations and produce a high-quality image that is visible to the naked eye. This universal system can be used with a wide range of PD and ROIC types made from different materials, making it highly convenient for diverse testing applications and the development of diverse image sensor types. This robust new platform is expected to spur further innovation and advancements in this rapidly developing field.

Grapefruit and stem detection play a crucial role in automated grape harvesting. However, the dense arrangement of fruits in vineyards and the similarity in color between grape stems and branches pose challenges, often leading to missed or false detections in most existing models. Furthermore, these models’ substantial parameters and computational demands result in slow detection speeds and difficulty deploying them on mobile devices. Therefore, we propose a lightweight TiGra-YOLOv8 model based on YOLOv8n. Initially, we integrated the Attentional Scale Fusion (ASF) module into the Neck, enhancing the network’s ability to extract grape features in dense orchards. Subsequently, we employed Adaptive Training Sample Selection (ATSS) as the label-matching strategy to improve the quality of positive samples and address the challenge of detecting grape stems with similar colors. We then utilized the Weighted Interpolation of Sequential Evidence for Intersection over Union (Wise-IoU) loss function to overcome the limitations of CIoU, which does not consider the geometric attributes of targets, thereby enhancing detection efficiency. Finally, the model’s size was reduced through channel pruning. The results indicate that the TiGra-YOLOv8 model’s mAP(0.5) increased by 3.33% compared to YOLOv8n, with a 7.49% improvement in detection speed (FPS), a 52.19% reduction in parameter count, and a 51.72% decrease in computational demand, while also reducing the model size by 45.76%. The TiGra-YOLOv8 model not only improves the detection accuracy for dense and challenging targets but also reduces model parameters and speeds up detection, offering significant benefits for grape detection.

In the field of biomedical research, rats are widely used as experimental animals due to their short gestation period and strong reproductive ability. Accurate monitoring of the estrous cycle is crucial for the success of experiments. Traditional methods are time-consuming and rely on the subjective judgment of professionals, which limits the efficiency and accuracy of experiments. This study proposes an EfficientNet model to automate the recognition of the estrous cycle of female rats using deep learning techniques. The model optimizes performance through systematic scaling of the network depth, width, and image resolution. A large dataset of physiological data from female rats was used for training and validation. The improved EfficientNet model effectively recognized different stages of the estrous cycle. The model demonstrated high-precision feature capture and significantly improved recognition accuracy compared to conventional methods. The proposed technique enhances experimental efficiency and reduces human error in recognizing the estrous cycle. This study highlights the potential of deep learning to optimize data processing and achieve high-precision recognition in biomedical research. Future work should focus on further validation with larger datasets and integration into experimental workflows.

In recent years, the periodic outbreak of green tides in the coastal areas of China, caused by the combined effects of environmental changes and human activities, has been attracting extensive attention due to the serious negative impacts on the coastal marine ecosystem. In the study, the samples of Ulva linza, a green tide species, were cultivated under two light intensities (LL: 80 μmol photons m-2 s-1; HL: 300 μmol photons m-2 s-1) and three stocking densities (LD: 0.2 g L-1; MD:1 g L-1; HD:2 g L-1) to explore the photosynthetic physiological responses and nutrients absorption capacity. The results showed that high light and low density significantly increased the growth rate of U. linza. Under the HLLD, the maximum growth rate of U. linza was 43.13% day-1 and the energy captured per unit reaction center for electron transfer (ET0/RC) was the highest. The higher density significantly decreased the maximum relative electron transfer rate (rETRmax) of U. linza, especially among groups subjected to high-light condition. Under HL condition, HD also significantly decreased light utilization efficiency (α) in U. linza. The contents of chlorophyll a, b and carotenoids of U. linza were significantly lower in HLLD group compared to other treatment groups. The P uptake of U. linza was prominently inhibited by higher density, and the maximum P uptake and minimum P uptake was 17.94 μM g-1 FW day-1 in LLLD group and 2.74 μM g-1 FW day-1 in LLHD group, respectively. Lower density improved N uptake of U. linza, but high light had no effect on it. These results suggest that high light and lower density synergistically promote the growth of U. linza, which is likely due to enhanced photosynthetic efficiency and nutrient uptake. And the inhibitory effects of higher densities on growth, particularly under high-light conditions, may be due to increased competition for light and nutrients. In the late stage of the green tides outbreak, an increase in accumulation density could help to suppress the sustained outbreak of the green tides, particularly in high-light condition.

Background Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients’ complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH.Methods We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People’s Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence.Results Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability.Conclusions The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.

BackgroundAlthough prognostic models based on pyroptosis-related genes (PRGs) have been constructed in bladder cancer (BLCA), the comprehensive impact of these genes on tumor microenvironment (TME) and immunotherapeutic response has yet to be investigated.MethodsBased on expression profiles of 52 PRGs, we utilized the unsupervised clustering algorithm to identify PRGs subtypes and ssGSEA to quantify immune cells and hallmark pathways. Moreover, we screened feature genes of distinct PRGs subtypes and validated the associations with immune infiltrations in tissue using the multiplex immunofluorescence. Univariate, LASSO, and multivariate Cox regression analyses were employed to construct the scoring scheme.ResultsFour PRGs clusters were identified, samples in cluster C1 were infiltrated with more immune cells than those in others, implying a favorable response to immunotherapy. While the cluster C2, which shows an extremely low level of most immune cells, do not respond to immunotherapy. CXCL9/CXCL10 and SPINK1/DHSR2 were identified as feature genes of cluster C1 and C2, and the specimen with high CXCL9/CXCL10 was characterized by more CD8 + T cells, macrophages and less Tregs. Based on differentially expressed genes (DEGs) among PRGs subtypes, a predictive model (termed as PRGs score) including five genes (CACNA1D, PTK2B, APOL6, CDK6, ANXA2) was built. Survival probability of patients with low-PRGs score was significantly higher than those with high-PRGs score. Moreover, patients with low-PRGs score were more likely to benefit from anti-PD1/PD-L1 regimens.ConclusionPRGs are closely associated with TME and oncogenic pathways. PRGs score is a promising indicator for predicting clinical outcome and immunotherapy response.

Combining multiple data sources, Digital Earth is an integrated observation platform based on air–space–ground–sea monitoring systems. Among these data sources, the Inverse Synthetic Aperture Radar (ISAR) is a crucial observation method. ISAR is typically utilized to monitor both military and civilian ships due to its all-day and all-weather superiority. However, in complex scenarios, multiple targets may exist within the same radar antenna beam, resulting in severe defocusing due to different motion conditions. Therefore, this paper proposes a multiple-target ISAR imaging method with the removal of micro-motion connections based on the integration of joint constraints. The fully motion-compensated targets exhibit low rank and local similarity in the high-resolution range profile (HRRP) domain, while the micro-motion components possess sparsity. Additionally, targets display sparsity in the image domain. Inspired by this, we formulate a novel optimization by promoting the low-rank, the Laplacian, and the sparsity constraints of targets and the sparsity constraints of the micro-motion components. This optimization problem is solved by the linearized alternative direction method with adaptive penalty (LADMAP). Furthermore, the different motions of various targets degrade their inherent characteristics. Therefore, we integrate motion compensation transformation into the optimization, accordingly achieving the separation of rigid bodies and the micro-motion components of different targets. Experiments based on simulated data demonstrate the effectiveness of the proposed method.

According to the equilibrium crystal shape of α-U, the surface of α-U (110) is more stable and has a larger area fraction than α-U (001). Therefore, the adsorption, dissociation, and diffusion behaviors of H atoms and H2 molecules on the α-U (110) surface were systematically studied by first-principles calculations. The results show that there are only two stable adsorption sites for the H atom: the surface short-bridge site (SB1) and the subsurface short-bridge site (SB2). The adsorption of H2 molecules is divided into chemical adsorption of dissociated H2 molecules and physical adsorption of undissociated H2 molecules, and the LB2-ParL adsorption configuration is the most stable adsorption configuration for H2 molecule adsorption, with an adsorption energy of −0.250 eV. The work function and charge transfer show that adsorption of the H atom or H2 molecule leads to an increase in the work function value of the α-U (110) surface, which enhances the electronic stability of the α-U (110) surface. The projected density of states shows that when the H atom or H2 molecule is close to the α-U (110) surface, the 1s orbital electrons of the H atom will hybridize with the 5f/6d orbital electrons of the nearby surface and subsurface U atoms, and new hybridized orbital peaks appear near the −4.5 eV or −7.3 eV energy level. The climbing image nudged elastic band study shows that the surface free H atoms are very easy to diffuse between the surface short-bridge sites and the subsurface short-bridge sites but the diffusion between the short-bridge site and the triangular center site is extremely difficult.

The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle.

Strontium (Sr), a trace element with a long history and a significant presence in the Earth’s crust, plays a critical yet often overlooked role in various biological processes affecting human health. This comprehensive review explores the multifaceted implications of Sr, especially in the context of non-communicable diseases (NCDs) such as cardiovascular diseases, osteoporosis, hypertension, and diabetes mellitus. Sr is predominantly acquired through diet and water and has shown promise as a clinical marker for calcium absorption studies. It contributes to the mitigation of several NCDs by inhibiting oxidative stress, showcasing antioxidant properties, and suppressing inflammatory cytokines. The review delves deep into the mechanisms through which Sr interacts with human physiology, emphasizing its uptake, metabolism, and potential to prevent chronic conditions. Despite its apparent benefits in managing bone fractures, hypertension, and diabetes, current research on Sr’s role in human health is not exhaustive. The review underscores the need for more comprehensive studies to solidify Sr’s beneficial associations and address the gaps in understanding Sr intake and its optimal levels for human health.

Time-of-use pricing of electric energy, as an important part of the national policy of energy conservation and emission reduction, requires accurate electric energy data as support. However, due to various reasons, the electric energy data are often missing. To address this thorny problem, this paper constructs a CNN and GRU-based recovery model (RCNN-BiGRU) for electric energy data by taking the missing data as the output and the historical data of the neighboring moments as the input. Firstly, a convolutional network with a residual structure is used to capture the local dependence and periodic patterns of the input data, and then a bidirectional GRU network utilizes the extracted potential features to model the temporal relationships of the data. Aiming at the difficult selection of network structure parameters and training process parameters, an accelerated adaptive differential evolution (AADE) algorithm is proposed to optimize the electrical energy data recovery model. The algorithm designs an accelerated mutation operator and at the same time adopts an adaptive strategy to set the two key parameters. A large amount of real grid data are selected as samples to train the network, and the comparison results verify that the proposed combined model outperforms the related CNN and GRU networks. The comparison experimental results with other optimization algorithms also show that the AADE algorithm proposed in this paper has better data recovery performance on the training set and significantly better performance on the test set.

Magnaporthe oryzae, one of the most destructive rice pathogens, causes significant losses during the rice harvest every year. Bacillus amyloliquefaciens has been explored in many crops as a potential biocontrol agent. However, the mechanisms of B. amyloliquefaciens controled rice blast are not fully understood. Here, a biocontrol strain LM-1, isolated from a contaminated medium, was identified as B. amyloliquefaciens using morphological observation, physiological and biochemical tests, and 16S rDNA sequencing. LM-1 inhibited the growth and pathogenicity of M. oryzae and Bipolaris oryzae (Breda de Haan) Shoem. The mycelia of M. oryzae co-cultured with LM-1 were enlarged and broken by fluorescence microscopy using calcofluor white. LM-1 inhibited the mycelia of M. oryzae from producing conidia. Genes itu, srf, and fenB were detected in LM-1. Furthermore, the supernatant of LM-1 interfered with the appressorium formation of M. oryzae, blocked conidial cell death, and reduced autophagy degradation but did not affect the normal germination of rice seeds and seeding growth. Additionally, we observed hypersensitivity reactions, reactive oxygen species, and iron accumulation reduction in rice cells inoculated with supernatant. Our study reveals that LM-1 has a control effect on rice blast and affects cell wall integrity, sporulation, appressorium formation, cell death, and autophagy.

Detecting and localizing standing dead trees (SDTs) is crucial for effective forest management and conservation. Due to challenges posed by mountainous terrain and road conditions, conducting a swift and comprehensive survey of SDTs through traditional manual inventory methods is considerably difficult. In recent years, advancements in deep learning and remote sensing technology have facilitated real-time and efficient detection of dead trees. Nevertheless, challenges persist in identifying individual dead trees in airborne remote sensing images, attributed to factors such as small target size, mutual occlusion and complex backgrounds. These aspects collectively contribute to the increased difficulty of detecting dead trees at a single-tree scale. To address this issue, the paper introduces an improved You Only Look Once version 7 (YOLOv7) model that incorporates the Simple Parameter-Free Attention Module (SimAM), an unparameterized attention mechanism. This improvement aims to enhance the network’s feature extraction capabilities and increase the model’s sensitivity to small target dead trees. To validate the superiority of SimAM_YOLOv7, we compared it with four widely adopted attention mechanisms. Additionally, a method to enhance model robustness is presented, involving the replacement of the Complete Intersection over Union (CIoU) loss in the original YOLOv7 model with the Wise-IoU (WIoU) loss function. Following these, we evaluated detection accuracy using a self-developed dataset of SDTs in forests. The results indicate that the improved YOLOv7 model can effectively identify dead trees in airborne remote sensing images, achieving precision, recall and mAP@0.5 values of 94.31%, 93.13% and 98.03%, respectively. These values are 3.67%, 2.28% and 1.56% higher than those of the original YOLOv7 model. This improvement model provides a convenient solution for forest management.

IntroductionWheat is a food crop with a large global cultivation area, and the content and quality of wheat glutenin accumulation are important indicators of the quality of wheat flour.MethodsTo elucidate the gene expression regulation and metabolic characteristics related to the gluten content during wheat grain formation, transcriptomic and metabolomic analyses were performed for the high gluten content of the Xinchun 26 cultivar and the low proteins content of the Xinchun 34 cultivar at three periods (7 d, 14 d and 21 d) after flowering.ResultsTranscriptomic analysis revealed that 5573 unique differentially expressed genes (DEGs) were divided into two categories according to their expression patterns during the three periods. The metabolites detected were mainly divided into 12 classes. Lipid and lipid-like molecule levels and phenylpropanoid and polyketide levels were the highest, and the difference analysis revealed a total of 10 differentially regulated metabolites (DRMs) over the three periods. Joint analysis revealed that the DEGs and DRMs were significantly enriched in starch and sucrose metabolism; the citrate cycle; carbon fixation in photosynthetic organisms; and alanine, aspartate and glutamate metabolism pathways. The genes and contents of the sucrose and gluten synthesis pathways were analysed, and the correlation between gluten content and its related genes was calculated. Based on weighted correlation network analysis (WGCNA), by constructing a coexpression network, a total of 5 specific modules and 8 candidate genes that were strongly correlated with the three developmental stages of wheat grain were identified.DiscussionThis study provides new insights into the role of glutenin content in wheat grain formation and reveals potential regulatory pathways and candidate genes involved in this developmental process.

BackgroundThe application of virtual reality (VR) in health care has grown rapidly in China, where approximately half of the population is directly exposed to secondhand smoke (SHS). As VR headsets have become increasingly popular and short video platforms have incorporated 360° videos in China, new formats and opportunities for health campaigns about SHS have emerged. ObjectiveIn a simulated environment of exposure to SHS, this study aims to explore the emotional and behavioral responses to enhanced social presence brought about by VR in contrast to flat-screen videos. It also aims to examine whether and to what extent video modality (360° video vs flat-screen video) and contextual cues (high threat vs low threat) influence psychometric and intentional variables among viewers. MethodsA total of 245 undergraduate and graduate students who were nonsmokers and from a large university in China participated in this study between October 2020 and January 2021. This study created 4 different versions of a SHS experience in a café with a 2 (360° video on a head-mounted display vs flat-screen display) × 2 (high threat vs low threat) experimental design. It developed and tested a path model examining the effects of experience modality and threat levels on social presence, emotions (anger and disgust), and eventually behavioral intentions (staying away and asking for help). ResultsWe found that both video modality (P

Abstract Background Intraperitoneal paclitaxel is proved to be efficient for peritoneal metastasis of gastric cancer. It remains uncertain the efficacy and safety of the triplets regimen which combined intraperitoneal high‐dose paclitaxel with systemic SOX in gastric cancer patients with peritoneal metastasis. This study aimed to evaluate the efficacy and safety of intraperitoneal administration of high‐dose paclitaxel, intravenous oxaliplatin and S‐1 in patients with peritoneal metastatic gastric cancer. Methods This single‐center, prospective, single‐arm phase II study was conducted between January 2017 and May 2019 in West China Hospital, Sichuan University. Patients diagnosed with primary gastric cancer by histopathology and confirmed synchronous peritoneal metastasis were enrolled. This study aimed to evaluate efficacy and safety of intraperitoneal administration of high‐dose paclitaxel (80 mg/m2, d1), intravenous oxaliplatin (100 mg/m2, d1), and S‐1 (80 mg/m2, d1‐14) of patients. The primary endpoint was 1‐year overall survival rate, and the second endpoints were progression‐free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events. Results In this single‐arm phase II clinical trial, 49 patients received SOX combined intraperitoneal high‐dose paclitaxel treatment. One‐year survival rate was 81.6% (95% CI, 68.6–90.0%). Median PFS and OS were 6.50 months (95% CI, 2.89–10.11) and 16.9 months (95% CI, 13.58 to 20.22), respectively; ORR was 55.3% (95% CI, 41.3–68.6) and DCR was 76.6% (95% CI, 62.8–86.4). Thirteen patients underwent second laparoscopic detection, but only nine ultimately underwent radical gastrectomy. Subgroup analysis showed that sPCI ≤12 was a good index for a favorable prognosis. The most frequent grade 3/4 toxicities were neutropenia (40.8%), anemia (22.4%), leukopenia (18.4%), nausea (14.3%), and vomiting (12.2%). None of the patients had any intraperitoneal catheter‐related complications. Conclusions Intraperitoneal high‐dose paclitaxel with systemic SOX is an effective and tolerable first‐line treatment for patients with peritoneal metastatic gastric cancer and patients with sPCI≤12 scores might be recommended crowd for this regimen as conversion therapy.

In order to solve the problem of worse recognition performance under the multi-classification scenarios of existing cryptosystem identification, this paper proposes a block cryptosystem recognition scheme based on Hamming weight distribution. A feature extraction method based on Hamming weight distribution is designed to extract the cipher text features, and the cryptosystem is further described. XGBoost-RFE feature selection algorithm is proposed to filter invalid features. In order to better adapt to the characteristics of complex ciphertext data and difficult fitting in multi classification scenarios, XGB-LGBM ensemble learning model with multi-layer fusion structure is designed to further improve the accuracy and generalization of recognition. The experiment carried out mixed identification of 10 common block cipher algorithm, and the overall recognition accuracy reached 89.65%.

Abstract Background Maintaining osmotic equilibrium plays an important role in the survival of cold-water fishes. Heat stress has been proven to reduce the activity of Na+/K+-ATPase in the gill tissue, leading to destruction of the osmotic equilibrium. However, the mechanism of megatemperature affecting gill osmoregulation has not been fully elucidated. Results In this study, Siberian sturgeon (Acipenser baerii) was used to analyze histopathological change, plasma ion level, and transcriptome of gill tissue subjected to 20℃, 24℃and 28℃. The results showed that ROS level and damage were increased in gill tissue with the increasing of heat stress temperature. Plasma Cl− level at 28℃ was distinctly lower than that at 20℃ and 24℃, while no significant difference was found in Na+ and K+ ion levels among different groups. Transcriptome analysis displayed that osmoregulation-, DNA-repair- and apoptosis-related terms or pathways were enriched in GO and KEGG analysis. Moreover, 194 osmoregulation-related genes were identified. Amongst, the expression of genes limiting ion outflow, occluding (OCLN), and ion absorption, solute carrier family 4, member 2 (AE2) solute carrier family 9, member 3 (NHE3) chloride channel 2 (CLC-2) were increased, while Na+/K+-ATPase alpha (NKA-a) expression was decreased after heat stress. Conclusions This study reveals for the first time that the effect of heat stress on damage and osmotic regulation in gill tissue of cold-water fishes. Heat stress increases the permeability of fish’s gill tissue, and induces the gill tissue to keep ion balance through active ion absorption and passive ion outflow. Our study will contribute to research of global-warming-caused effects on cold-water fishes.

Summary: PTEN loss in fetal liver hematopoietic stem cells (HSCs) leads to alterations in myeloid, T-, and B-lineage potentials and T-lineage acute lymphoblastic leukemia (T-ALL) development. To explore the mechanism underlying PTEN-regulated hematopoietic lineage choices, we carry out integrated assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell RNA-seq, and in vitro culture analyses using in vivo-isolated mouse pre-leukemic HSCs and progenitors. We find that PTEN loss alters chromatin accessibility of key lineage transcription factor (TF) binding sites at the prepro-B stage, corresponding to increased myeloid and T-lineage potentials and reduced B-lineage potential. Importantly, we find that PU.1 is an essential TF downstream of PTEN and that altering PU.1 levels can reprogram the chromatin accessibility landscape and myeloid, T-, and B-lineage potentials in Ptennull prepro-B cells. Our study discovers prepro-B as the key developmental stage underlying PTEN-regulated hematopoietic lineage choices and suggests a critical role of PU.1 in modulating the epigenetic state and lineage plasticity of prepro-B progenitors.

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of autoimmune diseases with various clinical manifestations, treatment responses, and prognoses. According to the clinical manifestations and presence of different myositis-specific autoantibodies (MSAs), IIM is classified into several major subgroups, including PM, DM, IBM, ASS, IMNM, and CADM. However, the pathogenic mechanisms of these subgroups remain unclear and need to be investigated. Here, we applied MALDI-TOF-MS to examine the serum metabolome of 144 patients with IIM and analyze differentially expressed metabolites among IIM subgroups or MSA groups. The results showed that the DM subgroup had lower activation of the steroid hormone biosynthesis pathway, while the non-MDA5 MSA group had higher activation of the arachidonic acid metabolism pathway. Our study may provide some insights into the heterogeneous mechanisms of IIM subgroups, potential biomarkers, and management of IIM.

Chronic heat stress caused by global warming can have serious implications for fish survival. The kidney plays a central role in many homeostatic functions, including water and electrolyte regulation. However, there is limited knowledge about the effect of heat stress on fish kidneys. In this study, water temperatures were increased from 20 °C to 24 °C and 28 °C in 8 days at a warming rate of 1 °C/d, and then maintained for 12 days. We investigated the effects of mild heat stress (24 °C) and high heat stress (28 °C) on Siberian Sturgeon (Acipenser baerii) kidneys using histological observation, flow cytometry detection, and RT-qPCR. Our histological observations revealed that heat stress caused significant infiltration of inflammatory cells in the kidney, especially at 28 °C. The flow cytometry assay demonstrated a significant increase in the number of apoptotic cells after heat stress at 28 °C compared to a control group at 20 °C (p = 0.033). The level of plasma creatinine was significantly increased in the 28 °C group compared to the control group (p = 0.001). In addition, the mRNA expression levels of heat shock protein GRP75 increased (p = 0.009). The results indicate that heat stress at 28 °C caused damage to the kidneys of A. baerii and triggered the protective response of heat shock proteins. In conclusion, this study contributes to the understanding of the coping strategies of the kidney of A. baerii for chronic heat stress.

Abstract Stable interface adhesion and bending durability of flexible organic solar cells (FOSCs) is a basic requirement for its real application in wearable electronics. Unfortunately, the device performance always degraded during continuous bending. Here, we revealed the weak interface adhesion force between MoO3 hole transporting layer (HTL) and the organic photoactive layer was the main reason of poor bending durability. The insertion of an interface bonding layer with a thermoplastic elastomer, polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS) effectively improved the interface adhesion force of MoO3 HTL and the active layer and decreased the modulus, which ensured higher than 90% of the initial efficiency remaining after 10000 bending. Meanwhile, the FOSCs gave an efficiency of 14.18% and 16.15% for the PM6:Y6 and PM6:L8-BO devices, which was among the highest performance of FOSCs. These results demonstrated the potential of improving the mechanical durability of FOSCs through thermoplastic elastomer interface modification.

Osteocalcin (Ocn), also known as bone Gla protein, is synthesized by osteoblasts and thought to regulate energy metabolism, testosterone synthesis and brain development. However, its function in bone is not fully understood. Mice have three Ocn genes: Bglap, Bglap2 and Bglap3. Due to the long span of these genes in the mouse genome and the low expression of Bglap3 in bone, researchers commonly use Bglap and Bglap2 knockout mice to investigate the function of Ocn. However, it is unclear whether Bglap3 has any compensatory mechanisms when Bglap and Bglap2 are knocked out. Considering the controversy surrounding the role of Ocn in bone, we constructed an Ocn-deficient mouse model by knocking out all three genes (Ocn−/−) and analyzed bone quality by Raman spectroscopy (RS), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and MicroCT (μCT). The RS test showed that the alignment of hydroxyapatite crystals and collagen fibers was significantly poorer in Ocn−/− mice than in wild-type (WT) mice. Ocn deficiency resulted in a looser surface structure of bone particles and a larger gap area proportion. FTIR analysis showed few differences in bone mineral index between WT and Ocn−/− mice, while μCT analysis showed no significant difference in cortical and trabecular regions. However, under tail-suspension simulating bone loss condition, the disorder of hydroxyapatite and collagen fiber alignment in Ocn−/− mice led to more obvious changes in bone mineral composition. Collectively, our results revealed that Ocn is necessary for regulating the alignment of minerals parallel to collagen fibrils.

BackgroundSpinal schwannomas (SSs) are benign tumors affecting the nerve sheath, accounting for 25% of spinal nerve root tumors. Surgery represents the mainstay of treatment for SS patients. Following surgery, approximately 30% of patients experienced developed new or worsening neurological deterioration, which probably represented an inevitable complication of nerve sheath tumor surgery. The objective of this study was to identify the rates of new or worsening neurological deterioration in our center and accurately predict the neurological outcomes of patients with SS by developing a new scoring model.MethodsA total of 203 patients were retrospectively enrolled at our center. Risk factors associated with postoperative neurological deterioration were identified by multivariate logistic regression analysis. β–coefficients for independent risk factors were used to define a numerical score to generate a scoring model. The validation cohort at our center was used to verify the accuracy and reliability of the scoring model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the scoring model.ResultsIn this study, five measured variables were selected for the scoring model: duration of preoperative symptoms (1 point), radiating pain (2 points), tumor size (2 points), tumor site (1 point), and dumbbell tumor (1 point). The scoring model divided the spinal schwannoma patients into three categories: low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-7 points), with predicted risks of neurological deterioration of 8.7%, 36%, and 87.5%, respectively. And the validation cohort confirmed the model with the predicted risks of 8.6%, 46.4%, and 66.6%, respectively.ConclusionThe new scoring model might intuitively and individually predict the risk of neurological deterioration and may aid individualized treatment decision-making for SS patients.

Abstract Background miR390s is an ancient family with a high level of conservation among plant miRNAs. Through the auxin signal transduction pathway, miR390 participates in diverse biological processes of plant growth and development. As an important Chinese traditional orchid, Cymbidium goeringii has unique flower shape and elegant fragrance. But its development has been greatly restricted because of the low flower bud differentiation and the difficult reproduction. This study aims to provide guidance for the role of cgo-miR390 in reproductive organ development to enhance the ornamental and economic value of Cymbidium. Results MIR390a, MIR390b and MIR390c of C. goeringii were cloned, and their length ranged from 130 to 150 nt. Each precursor sequence of cgo-miR390 contains 2 to 3 mature miRNAs. Three kinds of cgo-miR390s displayed distinct temporal and spatial expression patterns during floral development in C. goeringii. The overexpression of MIR390s alters morphology and function of stamens and pistils in Arabidopsis, such as enlargement of anther aspect ratio and separation of stylar and stigmas, which affects the development of fruits and seeds. In particular, the pollen amount decreased and the seed abortion rate increased in cgo-MIR390c-overexpressed plants. Conclusions cgo-miR390 family affected the development of reproductive organs in transgenic Arabidopsis. The study provides references for the genetic improvement for orchid with potentially great economic benefit.

Drought stress is one of the major abiotic stresses to wheat worldwide, with negative effects on wheat growth and yield. Assessing genetic variation and drought stress tolerance of key agronomic and physiological traits of spring wheat and screening germplasm resources for higher drought tolerance and yield stability are a prerequisite for developing new, better-adapted spring wheat varieties. This study evaluated nine important agronomic and physiological traits in 152 spring wheat cultivars under non-stress (NS) and drought-stress (DS) conditions. Under DS conditions, grain yield per plot (GYP) and grain weight per spike (GWE) were significantly reduced by 33.8% and 31.7%, and their drought-tolerance indexes (DIs) were only 0.66 and 0.69, respectively, indicating that GYP and GWE are the most susceptible traits to drought stress. The SPAD value of flag leave at flowering stage decreased by 13.9% under DS conditions, and the DI of SPAD was 0.86. In addition, DI-SPAD was significantly positively correlated with DIs of plant height (PH), grain number per spikelet (GPS), grain number per spike (GNS), GWE and GYP, indicating that the drought tolerance and yield of wheat are closely related to chlorophyll retention. Six wheat germplasm accessions were identified for their ability to sustain grain yield and improve drought tolerance simultaneously. These results provide insights into the genetic co-variation between grain yield and drought stress tolerance and provide a theoretical basis for the development of new wheat cultivars with excellent drought tolerance and high yields in the presence and absence of drought.

These years, disease-causing and disabling diseases have caused great concern. Neurological musculoskeletal disorders are diverse and affect people of a wide range of ages. And the lack of comprehensive diagnostic methods places a huge burden on healthcare systems and social economies. In this paper, the current status of clinical research on neuromuscular diseases is introduced, and the advantages of magnetic field measurement compared with clinical diagnostic methods are illustrated. A comprehensive description of the related technology of superconducting quantum interference devices (SQUIDs), magnetic field detection noise suppression scheme, the development trend of the sensor detection system, and the application and model establishment of the neuromuscular magnetic field is also given in this paper. The current research and development trends worldwide are compared simultaneously, and finally the conclusions and outlook are put forward. Based on the description of the existing literature and the ideas of other researchers, the next development trends and my own research ideas are presented in this paper, that is, starting from the establishment of a neuromuscular model, combining medical and industrial work, designing a sensor system that meets clinical needs, and laying the foundation for the clinical application of a bio-magnetic system. This review promotes a combination between medicine and industry, and guides researchers on considering the challenges of sensor development in terms of clinical needs. In addition, in this paper, the development trends are described, including the establishment of the model, the clinical demand for sensors, and the challenges of system development so as to give certain guidance to researchers.

Limited response to immune checkpoint inhibitors has been reported in patients with castration-resistant prostate cancer. Here the authors show that intermittent, but not continuous, treatment with an anti-PI3Kα/β/δ-inhibitor promotes anti-tumor immunity and response to PD-1 blockade in a preclinical Pten-null model of prostate cancer.

Cancer therapies have made tremendous progress in the last decade, but monotherapy still has apparent limitations and lacks therapeutic efficacy. Thus, the simultaneous administration of multiple drugs has been widely explored and has shown better outcomes. Exosomes, deriving from almost all living cells, are natural nanocarriers designed to deliver drugs to tumor sites. Therefore, combinational antitumor therapies based on exosomes, such as engineered exosomes and different combinations of chemotherapeutic agents, therapeutic nucleic acids, photosensitizers, immunotherapy and phytochemicals, have considerable prospects and potential for clinical translation. Here, we summarize current strategies of cancer combination therapy in exosomes and propose opportunities and challenges in the future.

Abstract Background Cymbidium goeringii, belonging to the Orchidaceae family, is an important ornamental plant with striking petals and lips. Extremely diversified floral patterns and morphologies make C. goeringii good research material to examine floral development of orchids. However, no floral organ-specific protein has been identified yet. To screen floral development associated proteins, four proteomes from petal (PE), lip (LI), gynostemium (GY), and sepal (SE) were analyzed using Tandem Mass Tag-based proteomic analysis. Results A total of 6626 unique peptides encoding 2331 proteins were identified in our study. Proteins in several primary metabolic pathways, including amino acid metabolism, energy metabolism, and lipid metabolism, were identified as differentially expressed proteins. Interestingly, most of the energy metabolism-related proteins highly expressed in SE, indicating that SE is an important photosynthetic organ of C. goeringii flower. Furthermore, a number of phytohormone-related proteins and transcription factors (TFs) were identified in C. goeringii flowers. Expression analysis showed that 1-aminocyclopropane-1-carboxylate oxidase highly expressed in GY, IAA-amino acid hydrolase ILR1-like 4 and gibberellin receptor 1 C greatly expressed in LI, and auxin-binding protein ABP20 significantly expressed in SE, suggesting a significant role of hormones in the regulation of flower morphogenesis and development. For TFs, GY-highly expressed bHLH13, PE-highly expressed WRKY33, and GY-highly expressed VIP1, were identified. Conclusions Mining of floral organ differential expressed enzymes and TFs helps us to excavate candidate proteins related to floral organ development and to accelerate the breeding of Cymbidium plants.

Here, the authors demonstrate the application of machine learning to optimize the device fabrication process for wafer-scale 2D semiconductors, and eventually fabricate digital, analog, and optoelectrical circuits.

Cecal microflora plays a key role in the production performance and immune function of chickens. White Leghorn (WL) is a well-known commercial layer line chicken with high egg production rate. In contrast, Silky Fowl (SF), a Chinese native chicken variety, has a low egg production rate, but good immune performance. This study analyzed the composition of cecal microbiota, metabolism, and gene expression in intestinal tissue of these varieties and the correlations among them. Significant differences were observed in the cecal microbes: Bacteroides was significantly enriched in WL, whereas Veillonellaceae and Parabacteroides were significantly enriched in SF. Carbohydrate biosynthesis and metabolism pathways were significantly upregulated in WL cecum, which might provide more energy to the host, leading to persistently high levels of egg production. The higher Parabacteroides abundance in SF increased volicitin content, enhanced α-linolenic acid metabolism, and significantly negatively correlated with metabolites of propanoate metabolism and carbohydrate metabolism. Genes related to lipid metabolism, immunity, and melanogenesis were significantly upregulated in the SF cecum, regulating lipid metabolism, and participating in the immune response, while genes related to glucose metabolism and bile acid metabolism were expressed at higher levels in WL, benefiting energy support. This study provided a mechanism for intestinal microorganisms and metabolic pathways to regulate chicken egg-laying performance and immunity.

Background Fasting has been widely used to improve various metabolic diseases in humans. Adaptive fasting is necessary for metabolic adaptation during prolonged fasting, which could overcome the great advantages of short-term fasting. The liver is the main organ responsible for energy metabolism and metabolic homeostasis. To date, we lack literature that describes the physiologically relevant adaptations of the liver during prolonged fasting and refeeding. For that reason, this study aims to evaluate the response of the liver of Sprague-Dawley (SD) rats to prolonged fasting and refeeding. Methods Sixty-six male SD rats were divided into the fasting groups, which were fasted for 0, 4, 8, 12, 24, 48, 72, or 96 h, and the refeeding groups, which were refed for 1, 3, or 6 days after 96 h of fasting. Serum glucose, TG, FFA, β-hydroxybutyrate, insulin, glucagon, leptin, adiponectin and FGF21 levels were assessed. The glucose content, PEPCK activity, TG concentration and FFA content were measured in liver tissue, and the expression of genes involved in gluconeogenesis (PEPCK and G6Pase), ketogenesis (PPARα, CPT-1a and HMGCS2) and the protein expression of nutrient-sensing signaling molecules (AMPK, mTOR and SIRT1) were determined by RT-qPCR and western blotting, respectively. Results Fasting significantly decreased the body weight, which was totally recovered to baseline after 3 days of refeeding. A 4-day fast triggered an energy metabolic substrate shift from glucose to ketones and caused serum hormone changes and changes in the protein expression levels of nutrient-sensing signaling molecules. Glycogenolysis served as the primary fuel source during the first 24 h of fasting, while gluconeogenesis supplied the most glucose thereafter. Serum FFA concentrations increased significantly with 48 h of fasting. Serum FFAs partly caused high serum β-hydroxybutyrate levels, which became an important energy source with the prolongation of the fasting duration. One day of refeeding quickly reversed the energy substrate switch. Nutrient-sensing signaling molecules (AMPK and SIRT1 but not mTOR signaling) were highly expressed at the beginning of fasting (in the first 4 h). Serum insulin and leptin decreased with fasting initiation, and serum glucagon increased, but adiponectin and FGF21 showed no significant changes. Herein, we depicted in detail the timing of the metabolic response and adaptation of the liver to a 4-day water-only fast and subsequent refeeding in rats, which provides helpful support for the design of safe prolonged and intermittent fasting regimens.

Abstract Background Clear‐cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts in understanding the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) was involved in the development of varied tumors. However, a comprehensive analysis of the prognostic model based on lncRNA‐miRNA‐mRNA ceRNA regulatory network of ccRCC with large‐scale sample size and RNA‐sequencing expression data is still limited. Methods RNA‐sequencing expression data were taken out from GTEx database and TCGA database, a total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC‐specific genes were obtained by WGCNA and differential expression analysis. Following, the communication of mRNAs and lncRNAs with targeted miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was further constructed by univariate Cox regression, Lasso methods, and multivariate Cox regression analysis. Results A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dysregulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature including eight genes based on this ceRNA was determined followed by the development of a nomogram predicting 1‐, 3‐, and 5‐year survival probability for ccRCC. Conclusion It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.

In standard computing architectures, memory and logic circuits are separated, a feature that slows matrix operations vital to deep learning algorithms. Here, the authors present an alternate in-memory architecture and demonstrate a feasible approach for analog matrix multiplication.

Egg production rate in chicken is related to the continuity of follicle development. In this study, we found that the numbers of white prehierarchical, dominant, and yellow preovulatory follicles in the high-yielding layer breed, White Leghorn (WL), were significantly higher than those in the low egg-yielding variety, Silky Fowl (SF). The proliferation and differentiation of granulosa cells (GCs) play an important role in follicle maturation. Histological observation revealed a large number of melanocytes in the outer granulosa layer of follicles in SF but not in WL. Finally, RNA-sequencing was used to analyze the gene expression profiles and pathways of the GC layer in the follicles in both WL and SF hens. Transcriptome analysis of prehierarchical GCs (phGCs) and preovulatory GCs (poGCs) between WL and SF showed that steroid hormone-, oxytocin synthesis-, tight junction-, and endocytosis-related genes were expressed at higher levels in WL phGCs than in SF phGCs, whereas the insulin signaling pathway- and vascular smooth muscle contraction-related genes were upregulated in SF phGCs. Fatty acid synthesis, calcium signaling, and Wnt signaling pathway-related genes were expressed at higher levels in WL poGCs than in SF poGCs; however, adrenergic signaling, cGMP-PKG, and melanogenesis-related genes were upregulated in SF poGCs. These results indicate that genes that promote GC proliferation and secretion of various sex hormones are more active in WL than in SF hens. The upregulated signaling pathways in SF help in providing energy to GCs and for angiogenesis and melanogenesis. In vitro experiments confirmed that both the proliferation of poGCs and synthesis of reproductive hormones were higher in WL than in SF hens.

The Grain-for-Green Program (GFGP) in China, one of the largest payment fot ecosystem services (PES) programs, has been regarded as an effective approach to achieving sustainable development. However, empirical research on factors motivating GFGP participation willingness remains limited and the comparison of the influencing pathways under different compensation scenarios is lacked. In this case study of farm households’ willingness of participation in Mulan Paddock, China, based on a participatory rural appraisal with 11 sample towns and 438 valid questionnaires, the structural equation model was applied to identify key factors influencing participation in GFGP in Mulan Paddock before (2000) and after (2014) the program under different compensation scenarios (i.e. with or without subsidies). It was found that 84.28% of farm households had increased income after the implementation of the GFGP. When the government provided subsidies, the past program support would dominate the willingness to participate in the program. When the government did not provide subsidies, subjective perceptions about the ecological and economic benefits and awareness of landscape protection were further supplemented as the most important factors for household participation. Under the subsidized scenario, neighborhood behavior could enhance household participation in the GFGP, while the participation decision was negatively influenced without subsidies. The findings provide guidance for better implementation of the next round GFGPs in China, and also for investigating the correlation between PES and social welfare in other non-developed areas.