Search

Abstract The Chinese cooking process, intricate and diverse, encompasses a wide range of dishes, generating substantial data that often poses significant challenges for automation. To address these challenges, this paper introduces a versatile, highly reliable, user-friendly, and intelligent data recorder specifically designed for Chinese cuisine-the Chinese Cuisine Intelligent Cooker Recorder-V1.0 (CCICR-V1.0). This device is intended to record data generated during the cooking process and provide essential support for intelligent cooking robot systems. The core of CCICR-V1.0 is a STM32 microcontroller, equipped with sensors that monitor temperature, pressure, and attitude. These sensors facilitate the intelligent collection of data related to dishes, ingredients, and the movements of cookware throughout the cooking process. To ensure efficient data acquisition and storage, CCICR-V1.0 employs a multi-task data buffering storage method that effectively allocates CPU resources. NAND Flash is used as the storage medium, guaranteeing secure storage, management, and preservation of high-frequency, multi-channel data. Experimental results demonstrate the effectiveness of CCICR-V1.0 in achieving multi-channel, high-frequency data acquisition and storage in complex environments. This leads to an increase in automation efficiency of 89.9%. The weighing module demonstrates a maximum relative error of only 0.288%, while the attitude sensor experiment shows an attitude information error of just 0.22°C. Furthermore, the non-contact infrared temperature measurement module exhibits impressive performance with a maximum absolute error of 0.258 $$^\circ C$$ ∘ C and a maximum relative error of 0.88%. Notably, this measurement module has achieved a cost reduction of approximately 91.7% and an accuracy improvement of around 40%. Additionally, the response time of CCICR-V1.0 is less than 3 ms. With its ability to effectively capture data related to Chinese cooking, CCICR-V1.0 holds commercial value for widespread adoption and application in the field of intelligent cooking.

Abstract Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12–16 weeks), GDM patients (24–28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12–16 and 24–28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM.

Abstract The NOD2 signaling pathway, which plays an important role in the mechanisms of inflammatory bowel disease (IBD) development, has been closely associated with ubiquitination. It was revealed in this study that NOD2 receptor activation could obviously affect the expression of 19 ubiquitination-related genes, with N4BP3 being the most prominently expressed and upregulated. In addition, N4BP3 knockdown was found to reduce the mRNA levels of MDP-induced inflammatory factors, while N4BP3 overexpression elevated their mRNA levels as well as the levels of phospho-ERK1/2, phospho-JNK, phospho-P38 and phospho-NF-κB P65 proteins. Immunoprecipitation tests showed that N4BP3 could pull down RIPK2 and promote its K63-linked ubiquitination. In human tissue specimen assays and mouse experiments, we found that the expression of N4BP3 was significantly elevated in Crohn’s disease (CD) patients and IBD mice, and N4BP3 knockdown reduced the dextran sulfate sodium-induced pathological score and the expression of inflammatory factors in the mouse colon tissue. In conclusion, N4BP3 is able to interact with RIPK2 and promote its K63-linked ubiquitination, to further promote the NOD2-MAPK/NF-κB pathway, thereby increasing promoting the release of inflammation factors and the degree of IBD inflammation.

Abstract Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABAACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABAACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABAACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABAACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABAACC neurons.

Abstract Background An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy. Methods This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord’ test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations. Results A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low. Conclusions This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.

Abstract As the new energy industry continues to progress, the health management of power batteries has become the key to ensuring the performance and safety of automobiles. Therefore, accurately predicting battery capacity decline is particularly important. A battery capacity degradation prediction model combining unscented particle filtering, particle swarm optimization, and SVR is constructed. It optimizes regression parameters through the introduced optimization strategy. Unscented particle filtering is used to improve particle swarm optimization and battery detection model. The study tested four various models of lithium-ion batteries. The model predicted a mean square error of 0.0011 for battery 5, 0.0007 for battery 6, 0.0022 for battery 7, and 0.0013 for battery 18. In the prediction of different battery types, the mean square error of the NIMH battery was reduced by 0.0008 compared with the particle swarm optimization-support vector regression algorithm, and by 0.0005 compared with the unscented particle filtering-regression vector regression algorithm. The mean square error of lithium-iron phosphate battery was reduced by 0.0008 and 0.0004 respectively compared with comparison models. The mean square error value of lithium titanate battery was reduced by 0.0007 and 0.0003 respectively in the research model compared with comparison models. It improves the prediction accuracy in lithium-ion batteries. Its application in battery health management can provide important technical support for improving battery performance and extending service cycles. The proposed method can be used for battery monitoring and management of power grid energy storage system. By accurately predicting the capacity decline of battery, the operation strategy of energy storage system can be optimized to ensure the efficient operation and long life of the system. The battery management system can be used for drones and aviation equipment to predict battery health and capacity decline in real time, ensuring the safety and reliability of flight missions.

Research into the pulmonary function of patients with transfusion-dependent thalassemia (TDT) is limited, with existing studies presenting conflicting results. We carried out a retrospective study involving 140 patients with TDT. The mean patient age was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (IQR: 2424.1–5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43 % (65 out of 140) of patients, primarily manifesting as diffusion dysfunction (26.43 %), followed by ventilatory dysfunction (5.0 %), and mixed pulmonary dysfunction (15.0 %). A serum ferritin level above 2500 ng/ml significantly correlated with the occurrence of these abnormalities(OR = 3.187, 95%CI:1.312–7.741, P = 0.010), while higher hemoglobin concentrations demonstrated a protective effect (OR = 0.966, 95%CI: 0.943–0.989, P = 0.004). Our study highlights diffusion dysfunction as the most prevalent type of pulmonary function abnormalities in TDT patients. Furthermore, it establishes a correlation between elevated serum ferritin levels and pulmonary dysfunction.

Mesenchymal stem cell-derived exosomes(MSCs-Exos) offer promising therapeutic potential for a wide range of tissues and organs such as bone/cartilage, nerves, skin, fat, and endocrine organs. In comparison to the application of mesenchymal stem cells (MSCs), MSCs-Exos address critical challenges related to rejection reactions and ethical concerns, positioning themselves as a promising cell-free therapy. As exosomes are extracellular vesicles, their effective delivery necessitates the use of carriers. Consequently, the selection of hydrogel materials as scaffolds for exosome delivery has become a focal point of contemporary research. The diversity of hydrogel scaffolds, which can take various forms such as injectable types, dressings, microneedles, and capsules, leads to differing choices among researchers for treating diseases within the same domain. This variability in hydrogel materials poses challenges for the translation of findings into clinical practice. The review highlights the potential of hydrogel-loaded exosomes in different fields and introduces the advantages and disadvantages of different forms of hydrogel applications. It aims to provide a multifunctional and highly recognized hydrogel scaffold option for tissue regeneration at specific sites, improve clinical translation efficiency, and benefit the majority of patients.

Abstract The phenomenon of flexoelectricity, wherein mechanical deformation induces alterations in the electron configuration of metal oxides, has emerged as a promising avenue for regulating electron transport. Leveraging this mechanism, stress sensing can be optimized through precise modulation of electron transport. In this study, the electron transport in 2D ultra‐smooth In2O3 crystals is modulated via flexoelectricity. By subjecting cubic In2O3 (c‐In2O3) crystals to significant strain gradients using an atomic force microscope (AFM) tip, the crystal symmetry is broken, resulting in the separation of positive and negative charge centers. Upon applying nano‐scale stress up to 100 nN, the output voltage and power values reach their maximum, e.g. 2.2 mV and 0.2 pW, respectively. The flexoelectric coefficient and flexocoupling coefficient of c‐In2O3 are determined as ≈0.49 nC m−1 and 0.4 V, respectively. More importantly, the sensitivity of the nano‐stress sensor upon c‐In2O3 flexoelectric effect reaches 20 nN, which is four to six orders smaller than that fabricated with other low dimensional materials based on the piezoresistive, capacitive, and piezoelectric effect. Such a deformation‐induced polarization modulates the band structure of c‐In2O3, significantly reducing the Schottky barrier height (SBH), thereby regulating its electron transport. This finding highlights the potential of flexoelectricity in enabling high‐performance nano‐stress sensing through precise control of electron transport.

Abstract Background Bronchopleural fistula (BPF) is a rare but fatal complication after pneumonectomy. When a BPF occurs late (weeks to years postoperatively), direct resealing of the bronchial stump through the primary thoracic approach is challenging due to the risks of fibrothorax and injury to the pulmonary artery stump, and the surgical outcome is generally poor. Here, we report a case of late left BPF following left pneumonectomy successfully treated using a right thoracic approach assisted by extracorporeal membrane oxygenation (ECMO). Case presentation We report the case of a 57-year-old male patient who underwent left lower and left upper lobectomy, respectively, for heterochronic double primary lung cancer. A left BPF was diagnosed at the 22nd month postoperatively, and conservative treatment was ineffective. Finally, the left BPF was cured by minimally invasive BPF closure surgery via the right thoracic approach with the support of veno-venous extracorporeal membrane oxygenation (VV-ECMO). Conclusions Advanced BPF following left pneumonectomy can be achieved with an individualized treatment plan, and the right thoracic approach assisted by ECMO is a relatively simple and effective method, which could be considered as an additional treatment option for similar patients.

The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR−ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR−ILC3s. The study involved both in vivo and in vitro experiments. In the former, the frequencies of lung NCR−ILC3s and NKp46−IL-17A+ ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1β quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46−IL-17A+ ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45+Lin−CD127+ ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45+Lin−CD127+ ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR−ILC3s and NKp46−IL-17A+ ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46−IL-17A+ ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR−ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR−ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.

For sustainable energy management, soft computing can play an important role in developing a charging station planning for low carbon transition to address the challenges faced by electric vehicle (EV) infrastructure system. This article proposes a planning scheme for charging stations of electronic vehicles for low carbon transition using soft computing-based computational techniques in the transportation sector. The existing charging stations have many flaws which are acting as hindrance in the development and acceptance of electronic vehicles by consumers. These flaws include the unreasonable layout of charging terminals, difficulty in charging, consumption of time in charging, and consumer convenience. This paper proposes a novel planning model for charging electronic vehicles as an innovative solution for electronic vehicles for low carbon transition. The protection of the environment is important in this current era and switching to electronic vehicles is a mandate for low-carbon transitions in the transportation sector. The proposed method begins with the collection of data from diverse sites of charging stations using the existing charging infrastructure, and this data also analyzed for ascertaining the energy consumption patterns, availability of renewable energy options, flow of traffic, and consumer preferences. The proposed method aims to augment the deployment of convenient charging infrastructure to promote consumers to switch to electronic vehicles from fuel-based vehicles and to promote renewable energy solutions for electric vehicles (EVs) at economic costs. The location and capacity of charging terminals is also optimized with the aid of hybrid algorithm based on catfish and PSO algorithms in this proposed research work. The effectiveness of the proposed soft computing-based hybrid algorithm is tested by using standard statistical methods and respective results are presented in the result section of this article. The proposed research has practical implications in a real-world scenario where consumers can be promoted to use electric vehicles by optimizing the capacity and availability of the charging station infrastructure which can eventually reduce the carbon footprints from this world.

There is a relative lack of research aimed at developing a comprehensive index system for low-carbon development of power systems in load-intensive cities in China. First, this paper outlined the main challenges faced in the urban power system development process and determined development goals and key indexes that combined the macro goals and requirements of constructing new power systems with the development characteristics and trends of load-intensive urban power systems. Second, a comprehensive index system and evaluation method for the low-carbon development of power systems was proposed to consider the perspectives of safety, efficiency, clean energy, low carbon, and flexibility. Finally, the effectiveness of the proposed index system and evaluation method was verified by taking the development of actual power systems in ultra-large-load-intensive cities as an example, providing support for the development decision making of actual urban power system construction and transformation.

BackgroundAnnual declines in university students’ physical health have an impact on social stability and the nation’s long-term growth. Parenting style, which is crucial to a child’s growth and development, may have a big influence on physical health. This study delves into the effects of different parenting styles on the physical fitness of Chinese college students under gender differences.MethodsThrough random allocation and stratified sampling methods, this study comprehensively investigated 3,151 undergraduate students (male = 1,365; female = 1786) with an average age of 18.44 years (SD = 1.46), from a university in Jiangsu Province, China. Parenting styles of college students were evaluated by the Parental Bonding Instrument (PBI). Physical fitness tests were based on the Chinese National Student Physical Fitness Standards including body mass index, lung capacity, standing-long-jump, bent-leg-sit-up, seated forward bend, pull-ups, 50 m sprint, and 800/1,000 m run. Further investigations focused on the relationship between parenting styles and physical health by statistical analysis methods such as Pearson correlation and multiple linear regression.ResultsSignificant differences were identified in gender, family members, and academic majors in most of the correlation indicators between different parenting styles and physical health among college students. Further analysis showed that the parenting styles of democratic and authoritative mothers and democratic fathers were more conducive to the promotion of physical health among female university students. The combination of a democratic fathering style and a permissive mothering style is considered an ideal parenting model for male students.ConclusionThis study confirmed that different parenting styles have a significant impact on the physical health of college students. Positive parenting styles may improve physical health, while negative ones are likely to have adverse effects, especially among female students. It is also important to notice differentiated parenting styles with respect to male and female university students. Therefore, more attention should be raised on parenting styles to enhance physical health of the student population.

Abstract Objective In this study, multimodal magnetic resonance imaging (MRI) imaging was used to deeply analyze the changes of hippocampal subfields perfusion and function in patients with type 2 diabetes mellitus (T2DM), aiming to provide image basis for the diagnosis of hippocampal‐related nerve injury in patients with T2DM. Methods We recruited 35 patients with T2DM and 40 healthy control subjects (HCs). They underwent resting‐state functional MRI (rs‐fMRI), arterial spin labeling (ASL) scans, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low‐frequency fluctuation (ALFF) value, and regional homogeneity (ReHo) value of the bilateral hippocampus subfields. Results The CBF values of cornu ammonis area 1 (CA1), dentate gyrus (DG), and subiculum in the right hippocampus of T2DM group were significantly lower than those of HCs. The ALFF values of left hippocampal CA3, subiculum, and bilateral hippocampus amygdala transition area (HATA) were higher than those of HCs in T2DM group. The ReHo values of CA3, DG, subiculum, and HATA in the left hippocampus of T2DM group were higher than those of HCs. In the T2DM group, HbAc1 and FINS were negatively correlated with imaging characteristics in some hippocampal subregions. Conclusion This study indicates that T2DM patients had decreased perfusion in the CA1, DG, and subiculum of the right hippocampus, and the right hippocampus subiculum was associated with chronic hyperglycemia. Additionally, we observed an increase in spontaneous neural activity within the left hippocampal CA3, subiculum, and bilateral HATA regions, as well as an enhanced local neural coordination in the left hippocampal CA3, DG, HATA, and subiculum among patients with type 2 diabetes, which may reflect an adaptive compensation for cognitive decline. However, this compensation may decline with the exacerbation of metabolic disorders.

BackgroundThe gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure.ObjectivesTo elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress.MethodsA cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale.ResultsAlpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, anti-inflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients.ConclusionsDKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD.

The incidence of multiple primary tumors(MPTs) is on the rise in recent years, but patients having four or more primary tumors is still rare. Lynch syndrome (LS) patients have a high risk of developing MPTs. NGS sequencing could identify the genetic alterations in different tumors to make a definite diagnosis of uncommon cases in clinical practice. Here, we report the case of a 66-year-old female patient who develops four MPTS between the ages of 41 and 66, that is sigmoid colon cancer, acute non-lymphocytic leukemia, urothelial carcinoma and ascending colon cancer. She has survived for more than 26 years since the first discovery of tumor. Targeted sequencing indicates that she has a pathogenic germline mutation in the exon 13 of MSH2, and her 2020 ureteral cancer sample and 2023 colon cancer sample have completely different mutation profiles. To the best of our knowledge, this is the first case of multiple primary tumors with an acute non-lymphocytic leukemia in LS patients.

Abstract The formation of tribolayers may play significant influences on fretting wear. At elevated temperature, the adhesion among wear debris and the increased diffusion rate facilitate the formation of tribolayers. However, the intensification of oxidation at elevated temperature and the low diffusion rate in oxides may play an adverse role. The present study aims to investigate the role of temperature in tribolayers in fretting wear using a γ-TiAl alloy. Scanning electron microscope, energy dispersive spectrometer, Raman spectrometer, transmission electron microscope and nanoindentation were utilized to investigate the wear debris, tribolayers, and wear scars. The fretting tests showed that, compared with that at room temperature (RT) and 350 °C, significant reduction in wear rate and decrease in the fluctuation of friction coefficient occurred at 550 and 750 °C. It was further revealed that when temperature raised from room temperature (RT) to 750 °C, the oxidation of the wear debris increased slightly and the diffusion coefficients increased prominently, which facilities the formation of well tribo-sintered tribolayers. The well tribo-sintered tribolayers presented homogenous structure, nanocrystalline grains with excellent mechanical properties, and resulted in the improvement in the fretting wear resistance of the γ-TiAl alloy at 550 and 750 °C.

Objectives. Until now, limited knowledge remains regarding the association among childhood obesity, cognitive behavior, and brain networks. Utilizing a publicly available dataset, we aimed to investigate the relationships between childhood obesity and functional networks during the stop-signal task. Results. Given the huge conflict-monitoring and inhibitory control demands of the task, both enhanced network connectivity and properties were observed under the “No-go” compared to the “Go” condition for both obese and non-obese preadolescents. Obese preadolescents exhibited significantly increased frontal-parietal, frontal-occipital, and frontal-temporal linkages, as well as heightened network efficiency under both “Go” and “No-go” conditions compared to non-obese counterparts. Additionally, significant correlations were found between network connectivity and properties and preadolescents’ body mass index (BMI), with their combination predicting BMI scores successfully. Conclusions. These findings support that childhood obesity is not simply a deviant habit with restricted physical health consequences, but rather associated with the atypical development of frontal-based networks involved in inhibitory control and cognitive performance.

This paper investigates the synchronization problem for multiplex networks with the stochastic perturbations via intermittent control. In the control schemes, the topologies of different layers of multiplex networks can be different, the control strategy adopts aperiodically intermittent and pinning control methods, and the number of pinned nodes can be different in different layers. Based on the stochastic theory and the Lyapunov stability theory, linear feedback and adaptive controllers are constructed respectively, some sufficient conditions are derived for guaranteeing synchronization of multiplex networks. Furthermore, for the different connectivity of multiplex networks, the conditions for achieving synchronization are discussed. Finally, two numerical simulations are provided to verify the theoretical results.

Capturing finer and discriminative difference features (DFs) is key to obtaining a high-quality change detection (CD) map. However, there is still significant scope for further study on fine-grained detection, especially concerning terms of improving structural integrity and reducing internal holes or sticking in DF. To this end, we propose a progressive difference amplification network (PDANet) with edge sensitivity to detect changed areas in optical remote sensing images (RSIs), where the key point is to amplify DF and reinforce edge detail to improve CD accuracy. The edge sensitivity (ES) encoder is designed to capture the long-distance dependency, which compensates for the limited receptive fields of the convolutional neural network with fixed kernels. Meanwhile, we introduce the prior edge in the network training stage, which collaborates with the ESE to improve the structural integrity of the changed areas. On the other hand, the difference amplification decoder is proposed to enhance the representation of the changed areas, and it is achieved by integrating multiscale DF and reconstructing the original single RSI using DF as full-stage guidance. Finally, the CD map and edge map are predicted based on the reconstructed feature and the maximum scale DF. Extensive experiments on one instance dataset and three CD benchmark datasets demonstrate that PDANet outperforms the state-of-the-art CD competitors both qualitatively and quantitatively.

Bistatic synthetic aperture radar (BiSAR) can perform remote imaging at any position, thus playing a crucial role in remote sensing applications. In BiSAR imaging with complex trajectory, an inevitable issue is the complicated correspondence between the geometry space and signal space, which will cause Doppler parameters mismatch and affect the imaging performance. To address this problem, the spatial inverse mapping relationship is skillfully constructed through the method of series reverse, which accurately describes the specific correspondence between the geometry space and signal space. On this basis, an extended time scaling algorithm is proposed. Its innovation is compensating for spatially variant Doppler phase that causes image distortion and defocusing by introducing the preprocessing and scaling functions in the time and frequency domains, respectively. Simulation experiments validate the effectiveness of the proposed method.

Abstract Increased sequencing depth can improve the detection rate of noninvasive prenatal testing (NIPT) for chromosome aneuploidies and copy number variations (CNVs). However, due to the technical limitations of NIPT, false-positives and false-negatives are inevitable. False-positives for aneuploidy and CNVs have been widely reported, but few missed cases have been reported. In this study, we report 3 patients missed by NIPT, which were still missed after increasing the sequencing depth. To verify the detection efficiency of the platform, the results of NIPT in 32,796 patients treated in Yulin Women and Children Health Care Hospital from 2020 to 2022 were retrospectively analyzed. Data on false-negative cases found by postnatal follow-up or amniocentesis were collected, and the sequencing data, pregnancy examination data, and postnatal follow-up results of these missed patients were summarized. Five patients missed by NIPT were found, and they were missed again by retesting or increasing the sequencing depth. Except for hypospadias found in 1 patient, ultrasonography of the other 4 patients showed no obvious abnormalities during the whole pregnancy. Our results suggest that pregnant women should be fully informed of the benefits and limitations of NIPT before undergoing the examination to avoid unnecessary medical disputes.

Abstract Background Screen time and physical activity behaviors undergo development during early childhood and impact mental health. However, there is limited knowledge regarding the associations between physical activity, screen time, and mental health problems (MHP) in preschoolers. This study examines these associations using a large sample size and brief measures. Methods A multistage cluster stratified sampling method was used to conduct an observational cross-sectional study of 19,015 Chinese preschoolers in 2020. Information on physical activity, and screen time was collected by a self-administered questionnaire; MHP was assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Logistic regression models were used to obtain the odds ratios (ORs) and 95% confidence intervals (95% CIs) of preschoolers’ MHP associated with screen time, total physical activities, moderate to vigorous physical activity (MVPA), and outdoor physical activities. Results A total of 19,015 participants from the 19,548 recruited population were included in the analyses (missing rate: 2.73%), 52.60% were boys. 64.01%, 57.96%, 35.98%, and 82.64% of preschoolers were reported to meet total physical activities, MVPA, and outdoor activities with screen time recommendations level. The results of multivariable-adjusted ORs (95% CIs) of preschoolers’ MHP for comparisons of different levels of screen time (

Abstract Introduction Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians. Methods A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis. Results No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features. Conclusion This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.

Abstract Background Atelectasis after anesthesia induction in most patients undergoing general anesthesia may lead to postoperative pulmonary complications (PPCs) and affect postoperative outcomes. However, there is still no existing effective method used for the prevention of perioperative atelectasis. S-ketamine may prevent atelectasis due to airway smooth muscle relaxation and anti-inflammatory effects. Lung ultrasound is a portable and reliable bedside imaging technology for diagnosing anesthesia-induced atelectasis. The primary objective of this study is to assess whether a small dose of S-ketamine can reduce the incidence of atelectasis after intubation, and further investigate the effects of preventing the early formation of perioperative atelectasis and PPCs. Methods This is a single-institution, prospective, randomized controlled, parallel grouping, and double-blind study. From October 2020 to March 2022, 100 patients (18–60 years old) scheduled for elective surgery will be recruited from Beijing Tiantan Hospital, Capital Medical University, and randomly assigned to the S-ketamine group (group 1) and the normal saline group (group 2) at a ratio of 1:1. The label-masked agents will be administered 5 min before induction, and all patients will undergo a standardized general anesthesia protocol. Related data will be collected at three time points: after radial artery puncture (T1), 15 min after tracheal intubation (T2), and before extubation (T3). The primary outcome will be the total lung ultrasound scores (LUS) at T2. Secondary outcomes will include LUS in six chest regions at T2, total LUS at T3, arterial blood gas analysis results (PaCO2, PaO2) and PaO2/FiO2 at T2 and T3, and plateau pressure (Pplat) and dynamic lung compliance (Cdyn) at T2 and T3. The incidence of postoperative complications associated with S-ketamine and PPCs at 2 h and 24 h after surgery will be recorded. Discussion This trial aims to explore whether a simple and feasible application of S-ketamine before the induction of general anesthesia can prevent atelectasis. The results of this study may provide new ideas and direct clinical evidence for the prevention and treatment of perioperative pulmonary complications during anesthesia. Trial registration ClinicalTrials.gov NCT04745286. Registered on February 9, 2021.

Abstract Background The bimolecular fluorescence complementation (BiFC) assay is commonly used for investigating protein–protein interactions. While several BiFC detection systems have been developed, there is a limited amount of research focused on using laser scanning confocal microscope (LSCM) techniques to observe protoplasts. Protoplasts are more susceptible to damage and instability compared to their original cell state due to the preparation treatments they undergo, which makes it challenging for researchers to manipulate them during observation under LSCMs. Therefore, it is crucial to utilize microscope techniques properly and efficiently in BiFC assays. Results When the target fluorescence is weak, the autofluorescence of chloroplast particles in protoplasts can interfere with the detection of BiFC signals localized in the nuclear region. Spectrum analysis revealed that chloroplast autofluorescence can be excited by lasers of various types, with the highest fluorescence signal observed at around 660 nm. Furthermore, our investigation into the impact of different pipette tips on the integrity of protoplast samples indicated that the utilization of cut tips with larger openings can mitigate cell breakage. We presented a workflow of LSCM techniques for investigating protoplast BiFC and discussed the microscopic manipulation involved in sample preparation and image capturing. Conclusion When the BiFC signals are weak, they may be affected by chloroplast autofluorescence. However, when used properly, the autofluorescence of chloroplasts can serve as an excellent internal marker for effectively distinguishing other signals. In combination with other findings, this study can provide valuable reference for researchers conducting BiFC assays and related studies.

Abstract The cellular prion protein (PrPC) is required for skeletal muscle function. Here, we report that a higher level of PrPC accumulates in the cytoplasm of the skeletal muscle of six myopathy patients compared to controls. PrPC inhibits skeletal muscle cell autophagy, and blocks myoblast differentiation. PrPC selectively binds to a subset of miRNAs during myoblast differentiation, and the colocalization of PrPC and miR-214-3p was observed in the skeletal muscle of six myopathy patients with excessive PrPC. We demonstrate that PrPC is overexpressed in skeletal muscle cells under pathological conditions, inhibits muscle cell differentiation by physically interacting with a subset of miRNAs, and selectively recruits these miRNAs into its phase-separated condensate in living myoblasts, which in turn enhances liquid–liquid phase separation of PrPC, promotes pathological aggregation of PrP, and results in the inhibition of autophagy-related protein 5-dependent autophagy and muscle bundle formation in myopathy patients characterized by incomplete muscle regeneration.

IntroductionPhysical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures.MethodsThe Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran’s Q test, and weighted median were employed.ResultsAt the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable.DiscussionThe results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

BackgroundCurrently, no food frequency questionnaire is available to be administered exclusively to ethnic minorities in China. This study aimed to evaluate the reproducibility and validity of a culturally tailored semi-quantitative food frequency questionnaire (FFQ) designed for pregnant women belonging to the Miao ethnic group in China.MethodsA total of 74 questions in the FFQ were administered to collect dietary information from Miao women in China during their pregnancy. This study included 153 and 127 pregnant women, respectively, for testing the validity and reproducibility of the results. Baseline FFQ data (FFQ1) were collected initially, followed by the administration of a repeated FFQ 4–6 weeks later (FFQ2). Two 24-h recalls (24HR) were used as references to compare food groups and nutrient intake. Pearson/Spearman's coefficients were used to measure the validity and reproducibility of the FFQ. Quartile cross-classification, weighted kappa coefficients, and Bland–Altman plots were employed to assess the agreement.ResultsMost food groups and nutrient intake estimated by the FFQ were higher than those estimated by the 24HR. Food groups and nutrients' correlations for FFQ vs. 24HR after being energy-adjusted and de-attenuated, respectively, were 0.10 (vegetables) to 0.45 (grains/tubers) and 0.15 (iron) to 0.52 (riboflavin). Comparatively, correlation coefficients for FFQ1 vs. FFQ2 ranged from 0.41 (fruit) to 0.71 (vegetables) and from 0.45 (energy) to 0.64 (calcium). The percentage of pregnant women classified in the same or adjacent quartiles ranged from 64.08% (vegetables) to 95.29% (sour soup) and from 68.88% (vitamin E) to 78.81% (energy). Weighted kappa coefficients exceeded 0.2 for food groups and most nutrients, and Bland–Altman plots demonstrated acceptable agreement between the two tools.ConclusionsThis study provides novel information on the validation of FFQ. It demonstrates that the FFQ exhibits ideal reproducibility and acceptable validity in estimating and ranking the intake of food groups and most nutrients among pregnant women belonging to the Chinese Miao ethnic group.

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de |log2fold change| > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Background: The association between bone morphogenetic protein 10 (BMP10) and atrial fibrillation (AF) has been widely investigated by observational studies, but their causal relationships remain inconclusive. Here, we aimed to evaluate the causal effect of BMP10 on the risk of AF through single-nucleotide polymorphisms. Methods: A Mendelian randomization (MR) analytic framework was applied to data from two BMP10-specific genome-wide association studies comprising a total of 11,036,163 single-nucleotide polymorphisms of European ancestry. Instrument genetic variants associated with BMP10 were selected. A total of 12 AF-specific genome-wide association studies comprising a total of 5,095,117 European participants were included. Summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were used. Pleiotropy and sensitivity were assessed. Results: Specific to AF-specific genome-wide association studies, we found that BMP10 was not associated with AF among different methods (all P > 0.05). We further identified no significant horizontal pleiotropy (all P > 0.05) and no fundamental impact among various data. Conclusions: This large-scale population study upon data from BMP10- and AF-specific genome-wide association studies and a longitudinal biobank cohort indicates plausible non-causal associations between BMP10 and AF in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.

Modern data centers provide the foundational infrastructure of cloud computing. Workload generation, which involves simulating or constructing tasks and transactions to replicate the actual resource usage patterns of real-world systems or applications, plays essential role for efficient resource management in these centers. Data center traces, rich in information about workload execution and resource utilization, are thus ideal data for workload generation. Traditional traces provide detailed temporal resource usage data to enable fine-grained workload generation. However, modern data centers tend to favor tracing statistical metrics to reduce overhead. Therefore the accurate reconstruction of temporal resource consumption without detailed, temporized trace information become a major challenge for trace-based workload generation. To address this challenge, we propose STWGEN, a novel method that leverages statistical trace data for workload generation. STWGEN is specifically designed to generate the batch task workloads based on Alibaba trace. STWGEN contains two key components: a suite of C program-based flexible workload building blocks and a heuristic strategy to assemble building blocks for workload generation. Both components are carefully designed to reproduce synthetic batch tasks that closely replicate the observed resource usage patterns in a representative data center. Experimental results demonstrate that STWGEN outperforms state-of-the-art workload generation methods as it emulates workload-level and machine-level resource usage in much higher accuracy.

The growth environment significantly influences the intestinal microbiota of aquatic organisms. We investigated the composition and functional differences in the intestinal microbiota of red claw crayfish (Cherax quadricarinatus) in rice fields (RB) and ponds (PB) by 16S rDNA high-throughput sequencing technology. The results indicate that the Shannon, Simpson, Sobs, Chao1, and ACE indices of PB are all higher than those of RB, demonstrating greater diversity and richness of intestinal microbiota. The dominant phyla in the intestinal microbiota of the Cherax quadricarinatus were Proteobacteria, Tenericutes, and Firmicutes. Tenericutes and Proteobacteria were significantly more abundant in the RB than in the PB, while Planctomycetes and Firmicutes were significantly more abundant in the PB than in the RB. The results of network correlation analysis indicate that Proteobacteria and Firmicutes exhibit strong connectivity with other microbial groups in the gut microbiota of Cherax quadricarinatus, showing significant centrality. They play an important role in the interactions within the gut microbiota community. The dominant bacterial genera in the Cherax quadricarinatus’s gut were Citrobacter, Candidatus_Bacilloplasma, and Clostridium_sensu_stricto_1. The abundance of the genus Clostridium was significantly higher in the PB than in the RB, whereas the abundance of Candidatus_Hepatoplasma and Vibrio was significantly lower in the PB than in the RB. The prediction function of KEGG enrichment showed that the abundance of Amino acid metabolism, Biosynthesis of Other Secondary Metabolites, Transport and Catabolism, Cancers, and Nervous System, Substance Dependence were significantly higher in the PB, while the infectious diseases pathway was enriched in the RB. In summary, our results revealed significant differences in the composition and diversity of intestinal microbiota in the Cherax quadricarinatus between rice paddy and pond farming environments. The intestinal microbiota of the Cherax quadricarinatus grown in pond environments exhibit higher diversity and stability, manifested by an increase in beneficial bacteria abundance and a decrease in opportunistic pathogens. These findings significantly improve understanding of the complex relationship among Cherax quadricarinatus, intestinal microbiota, and the environment.

The satellite–ground bistatic configuration, which uses geosynchronous synthetic aperture radar (GEO SAR) for illumination and ground equipment for reception, can achieve wide coverage, high revisit, and continuous illumination of interest areas. Based on the analysis of the signal characteristics of GEO satellite–ground bistatic SAR (GEO SG-BiSAR), it is found that the bistatic echo signal has problems of azimuth spectrum aliasing and 2-D spatial variability. Therefore, to overcome those problems, a novel SAR imaging method for a GEO SG-BiSAR system with severe azimuth spectrum aliasing and 2-D spatial variability is proposed. Firstly, based on the geometric configuration of the GEO SG-BiSAR system, the time-domain and frequency-domain expressions of the signal are derived in detail. Secondly, in order to avoid the increasing cost caused by traditional multi-channel reception technology and the processing burden caused by inter-channel errors, the azimuth deramping is executed to solve the azimuth spectrum aliasing of the signal under the special geometric structure of GEO SG-BiSAR. Thirdly, based on the investigation of azimuth and range spatial variability characteristics of GEO SG-BiSAR in the Range Doppler (RD) domain, the azimuth spatial variability correction strategy is proposed. The signal corrected by the correction strategy has the same migration characteristics as monostatic radar. Therefore, the traditional chirp scaling function (CSF) is also modified to solve the range spatial variability of the signal. Finally, the two-dimensional spectrum of GEO SG-BiSAR with modified chirp scaling processing is derived, followed by the SPECAN operation to obtain the focused SAR image. Furthermore, the completed flowchart is also given to display the main composed parts for GEO SG-BiSAR imaging. Both azimuth spectrum aliasing and 2-D spatial variability are taken into account in the imaging method. The simulated data and the real data obtained by the Beidou navigation satellite are used to verify the effectiveness of the proposed method.

In this study, headspace solid phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) was used to determine the volatile flavor compounds of sundried Ulva spp., including U. prolifera collected from Xiamen (sample X), U. linza collected from Yantai (sample Y) and U. clathrata collected from Ningbo (sample N). A total of 61 volatile compounds including 19 aldehydes, 9 ketones, 6 alcohols, 8 acids, 3 esters, 2 sulfur compounds, and 14 other compounds were detected. The content of sulfur compounds was reaching 40.39%~58.09%. Meanwhile, relative odor activity value (ROAV) and sensory evaluation were employed to identify the aroma active components of Ulva spp.. The results revealed that dimethyl sulfide (onion, garlic, sulfur) and β-ionone (violet, floral) were the key aroma active components of dried Ulva spp.. Besides, dimethyl sulfoxide, 4-methyl-3-penten-2-one, benzaldehyde and 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-2(4H)-benzofuranone were the important aroma active components of three Ulva spp.. Among three tested Ulva spp., sample N contained the most abundant volatile compounds especially in aldehydes and ketones, and (E)-2-butenal, (E)-2-octenal, (E)-2,6-nondialdehyde and 1-octene-3-ol were considered as the key volatile substances. Aroma active compounds including 4-ethylbenzaldehyde, (5Z)-1,5-octadiene-3-ol, and 5-methyl furfural were only detected in sample Y, which might correlate to its unique green and fruity flavor. For sample X, the sensory analysis reulst revealed significant fishy smell (P

Abstract Rheumatoid arthritis (RA) is a common chronic inflammatory disorder that usually affects joints. It was found that roburic acid (RBA), an ingredient from anti-RA herb Gentiana macrophylla Pall., displayed strong anti-inflammatory activity. However, its medical application is limited by its hydrophobicity, lack of targeting capability and unclear functional mechanism. Here, we constructed a pH responsive dual-target drug delivery system hitchhiking RBA (RBA-NPs) that targeted both CD44 and folate receptors, and investigated its pharmacological mechanism. In rat RA model, the nanocarriers effectively delivered RBA to inflammatory sites and significantly enhanced the therapeutic outcomes compared with free RBA, as well as strongly reducing inflammatory cytokine levels and promoting tissue repair. Following analysis revealed that M1 macrophages in the joints were reprogrammed to M2 phenotype by RBA. Since the balance of pro- and anti-inflammatory macrophages play important roles in maintaining immune homeostasis and preventing excessive inflammation in RA, this reprogramming is likely responsible for the anti-RA effect. Furthermore, we revealed that RBA-NPs drove M1-to-M2 phenotypic switch by down-regulating the glycolysis level via blocking ERK/HIF-1α/GLUT1 pathway. Thus, our work not only developed a targeting delivery system that remarkably improved the anti-RA efficiency of RBA, but also identified a potential molecular target to reversely reprogram macrophages though energy metabolism regulation.

Regional green technology innovation (RGTI) carries ecological and technological externalities, serving as a crucial force in aligning economic development with the imperative of environmental preservation. Industrial digitalization (indig) exhibits innovative, quality-enhancing, and efficiency-enhancing traits. Yet, the exact effects of indig on RGTI have not been extensively studied. In this study, based on provincial data from 2013-2019 in China, we investigated the linear and nonlinear relationships, spatial characteristics and underlying mechanisms between indig and RGTI through a Hansen threshold model and a mediating effect model. The results showed that: i. indig fluctuates while RGTI increases steadily, both displaying evident spatial agglomeration traits and a unipolar characteristic of regional heterogeneity; ii. indig has effectively boosted RGTI at both national and regional levels, with the exception of the northeastern region; iii. There was a single threshold for industrial digitalization and the positive driving trend exhibited a “marginally increasing” characteristic; iv. Two critical elements, namely industrial structure advancement and marketization, have partial intermediary roles. Basing on these results, this study presents several policy recommendations.

Microfracture density in fault damage zones can reflect spatial variability that decays in intensity as a function of distance from the fault, which is crucial in understanding the mechanical, seismological, and fluid-flow properties of the fault system. However, few studies explored the characteristics of fracture density between the two sides of active dip-slip faults due to rare field observations. Here, we measured and modeled microfractures across an active thrust fault associated with the 2008 Mw 7.9 Wenchuan earthquake in the Longmen Shan, eastern Tibetan Plateau. The results showed that the microfracture density at the Qingping site developed more intensely in the hanging wall than in the footwall for an exposed thrust fault, indicating an asymmetrical pattern. The hidden thrust fault at the Jushui site showed that microfractures developed more intensely in vertical planes in the hanging wall than in the footwall, whereas microfractures developed similarly in horizontal planes within the two sides, indicating a quasiasymmetrical pattern. Comparing the data at the two sites with computational modeling, we suggest that fault geometry might exert a first-order control of the asymmetrical microfracture density pattern, which is helpful for revealing different deformational behaviors of rock masses in the fault damage zones and better understanding the hanging-wall effect for evaluating seismic hazards on active thrust faults.

BackgroundPreclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC).MethodsPatients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190.ResultsThis study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths.ConclusionIn patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities.

BackgroundWe compared the real-world efficacy and safety of neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with stage III non-small-cell lung cancer (NSCLC).Participants and methodsA total of 59 consecutive patients were finally selected and divided into two groups: the neoadjuvant chemotherapy group (n = 33) and the neoadjuvant chemoimmunotherapy group (n = 26). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, and adverse events. All patients were followed up to collect perioperative pathology and clinical data.ResultsThe objective response rate (ORR), pathological complete response (pCR), and major pathological response (MPR) were significantly higher in the neoadjuvant chemoimmunotherapy group than in the neoadjuvant chemotherapy group (73.1% vs. 45.5%, 34.6% vs. 3.0%, and 65.3% vs. 15.1%, respectively; P < 0.05). There was no statistically significant difference in disease-free survival between the neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy groups (P = 0.129). Patients in the neoadjuvant chemoimmunotherapy group had a higher rate of tumor regression than those in neoadjuvant chemotherapy group (37.0% [25 patients] vs. 29.0% [33 patients], P = 0.018). However, no discernible correlation between MPR achievement and the degree of tumor shrinkage was observed in either group (P > 0.05). The cumulative MPR rates were 42.3, 50, and 65.3% for 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemoimmunotherapy group and 9.1, 12.1, and 15.1% for ≤ 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemotherapy group. Moreover, No statistical difference was observed between the two groups regarding postoperative complications, resection range, operation time, surgical method, and extent of resection (P > 0.05). Although the incidence of grades III–IV adverse events was higher in the neoadjuvant chemotherapy group than in the neoadjuvant chemoimmunotherapy group (33.3% vs. 4.6%, P = 0.042), there was no significant difference in the incidence of adverse events between the two groups (64.6% vs. 83.6%, P = 0.072).ConclusionIn stage III NSCLC, neoadjuvant chemoimmunotherapy achieved higher pathological and clinical remission rates than chemotherapy alone, with compromising safety, making it an attractive choice for neoadjuvant therapy.

ABSTRACTThe evolution of immune profile from primary tumors to distant and local metastases in non-small cell lung cancer (NSCLC), as well as the impact of the immune background of primary tumors on metastatic potential, remains unclear. To address this, we performed whole-exome sequencing and immunohistochemistry for 73 paired primary and metastatic tumor samples from 41 NSCLC patients, and analyzed the change of immune profile from primary tumors to metastases and involved genetic factors. We found that distant metastases tended to have a decreased CD8+ T cell level along with an increased chromosomal instability (CIN) compared with primary tumors, which was partially ascribed to acquired DNA damage repair (DDR) deficiency. Distant metastases were characterized by immunosuppression (low CD8+ T cell level) and immune evasion (high PD-L1 level) whereas local metastases (pleura) were immune-competent with high CD8+ T cell, low CD4+ T cell and low PD-L1 level. Primary tumors with high levels of CD4+ T cells were associated with distant metastases rather than local metastases. Analysis of TCGA data and a single-cell RNA-sequencing dataset revealed a decreasing trend of major immune cells, such as CD8+ T cells, and an increasing trend of CD4 T helper cells (Th2 and Th1) in primary tumors with metastases from local to distant sites. Our study indicates that there are differences in the immune evolution between distant and local metastases, and that acquired DDR deficiency contributes to the immunosuppression in distant metastases of NSCLC. Moreover, the immune background of primary tumors may affect their metastatic potential.

Brown-rot fungus is one of the important medicinal mushrooms, which include some species within the genus Fomitopsis. This study identified wild macrofungi collected from a broad-leaved tree in Liaoning Province as Fomitopsis palustris using both morphological and molecular methods. To elucidate the potential medicinal and economic value of F. palustris, we conducted single-factor and orthogonal tests to optimize its mycelium culture conditions. Subsequently, we completed liquid culture and domestic cultivation based on these findings. Furthermore, crude polysaccharides were extracted from the cultivated fruiting bodies of F. palustris and their antioxidant activity was evaluated using chemical methods and cell-based models. The results showed that the optimal culture conditions for F. palustris mycelium were glucose as the carbon source, yeast extract powder as the nitrogen source, pH 6.0, and a temperature of 35 °C. Moreover, temperature was found to have the most significant impact on mycelial growth. The liquid strains were fermented for 6 days and then inoculated into a cultivation substrate composed of broadleaf sawdust, resulting in mature fruiting bodies in approximately 60 days. The crude polysaccharides extracted from the cultivated fruiting bodies of F. palustris (FPPs) possess in vitro scavenging abilities against DPPH radicals and OH radicals, as well as a certain ferric-reducing antioxidant power. Additionally, FPPs effectively mitigated H2O2-induced oxidative stress in RAW264.7cells by enhancing the intracellular activity of antioxidant enzymes such as SOD and CAT, scavenging excess ROS, and reducing MDA levels. This study provides preliminarily evidence of the potential medicinal and economic value of F. palustris and offers initial data for the future development and utilization of this species.

Essential macronutrient nitrogen (N) is crucial for plant growth and yield, but excessive chemical N fertilizer not only increases unnecessary production costs but also causes environmental pollution. Therefore, reducing N fertilizer use by increasing organic fertilizer use is crucial for sustainable agriculture. In this study, we investigated the effects of three nitrogen levels—the recommended rate (N), a 20.0% reduced rate (0.8N), and a 40.0% reduced rate (0.6N)—and two levels of organic fertilizer—a normal dose (M) and a four-times the normal dose (4M)—combined with root application of the beneficial element silicon (Si) on the photosynthetic characteristics, yield, and fruit quality of the tomato cultivar ‘Tianxi No. 5’. Compared with M + N treatment, the longitudinal diameter, transverse diameter, fruit weight, and fruit yield of tomato fruit in 4M + 0.6N treatment significantly increased by 12.4%, 14.6%, 14.5%, and 12.8%, respectively, while the yield was further improved with Si application. In addition, a reduction in N fertilizer and an increase in organic fertilizer, combined with Si application, improved fruit quality parameters such as concentrations of vitamin C, lycopene, phenols, flavonoids, sucrose, fructose, etc., and promoted sugar metabolism-related enzyme activity (sucrose synthase, invertase, and sucrose phosphate synthase) and the accumulation of N in the fruit. The principal component analysis and three-factor analysis of variance (ANOVA) of the fruit quality and yield indices showed that nitrogen fertilizer, organic fertilizer, silicon fertilizer, and the interaction of the three had significant effects on the quality and yield of tomato fruits, and that the 4M + 0.6N + Si treatment had the best combined effect on the yield and quality of the tomatoes. Thus, a moderate reduction in chemical N fertilizer, combined with increased organic fertilizer and Si, could be an effective agronomic practice for improving the yield and quality of tomatoes.

BackgroundThe early adversity is associated with a series of negative outcomes in adulthood, and the impact on the cerebral cortex may be one of the fundamental causes of these adverse consequences in adulthood. In this study, we aim to investigate the causal relationship between early adversity and changes in cerebral cortex structure using Mendelian randomization (MR) analysis.MethodsThe GWAS summary statistics of 6 early adversity traits were obtained from individuals of European ancestry in the UK Biobank. The GWAS summary statistics of 34 known functional cortical regions were obtained from the ENIGMA Consortium. Causal relationships between the adversity factors and brain cortical structure were assessed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods, with IVW being the primary evaluation method. Cochran’s Q-test, MR-PRESSO, leave-one-out analysis, and funnel plot examination were employed to detect potential heterogeneity and pleiotropy, as well as to identify and exclude outliers.ResultsAt a global level, no causal relationship was found between early adversity and cortical thickness (TH) or surface area (SA) of the brain. However, at the regional level, early adversity was found to potentially influence the TH of the caudal anterior cingulate, superior temporal, entorhinal, paracentral, lateral occipital, banks of the superior temporal sulcus, and supramarginal regions, as well as the SA of the pars triangularis, lateral occipital, parahippocampal, medial orbitofrontal, and isthmus cingulate regions. All findings were nominally significant and passed sensitivity analyses, with no significant heterogeneity or pleiotropy detected.DiscussionOur study provides evidence for the association between early adversity and alterations in brain cortical structure, which may serve as a foundation for certain mental disorders. Furthermore, magnetic resonance imaging (MRI) might be considered as a promising tool to aid healthcare professionals in identifying individuals with a history of adverse experiences, allowing for early interventions.

Background: Previous researches have demonstrated a connection between psychiatric disorders and cardiovascular diseases (CVDs), but the cause-and-effect relationship is still unclear. To that goal, the mendelian randomization (MR) method was used to study the causal link between psychiatric disorders and CVDs. Methods: Genome-wide association studies (GWAS) data were collected for four CVDs, including coronary artery disease (n = 547,261), atrial fibrillation (n = 537,409), heart failure (n = 977,323) and ischemic stroke (n = 440,328). Summary data for four psychiatric disorders, including bipolar disorder (n = 51,710), major depressive disorder (n = 480,359), schizophrenia (n = 127,906) and attention deficit hyperactivity disorder (n = 55,374), came from the Psychiatric Genomics Consortium (PGC). All participants were European. The IVW method was mainly used, and the reliability of the results was increased using sensitivity analyses such as MR-Egger, Cochrane's Q test, MR-PRESSO and leave-one-out. Results: MR revealed that the attention deficit hyperactivity disorder was linked to an increased risk of atrial fibrillation (OR, 1.085; 95% CI, 1.021–1.153; P = 0.008), heart failure (OR, 1.117; 95% CI, 1.044–1.195; P = 0.001), and ischemic stroke (OR, 1.146; 95% CI, 1.052–1.248; P = 0.002). The schizophrenia was linked to an increased risk of heart failure (OR, 1.035; 95% CI, 1.006–1.066; P = 0.017), but was found to be suggestively inverse associated with coronary artery disease (OR, 0.969; 95% CI, 0.941–0.997; P = 0.03). The major depressive disorder was associated with higher odds of coronary artery disease (OR, 1.109; 95% CI, 1.018–1.208; P = 0.018), while the bipolar disorder was linked to a reduced incidence of coronary artery disease (OR, 0.894; 95% CI, 0.831–0.961; P = 0.002) and heart failure (OR, 0.889; 95% CI, 0.829–0.955; P = 0.001). There were no clear relationships between other psychiatric disorders and CVDs. Conclusion: The results provide genetic proof of a possible causal relationship between psychiatric disorders and CVDs. These results imply that psychiatric disorders may be the cause of some CVDs, and that some abnormal mental states may increase or reduce the likelihood of CVDs, providing guidance for the CVDs prevention.

Cartilage homeostasis is essential for chondrocytes to maintain proper phenotype and metabolism. Because adult articular cartilage is avascular, chondrocytes must survive in low oxygen conditions, and changing oxygen tension can significantly affect metabolism and proteoglycan synthesis in these cells. However, whether long noncoding RNA participate in cartilage homeostasis under hypoxia has not been reported yet. Here, we first identified LncZFHX2 as a lncRNA upregulated under physiological hypoxia in cartilage, specifically by HIF‐1α. LncZFHX2 knockdown simultaneously accelerated cellular senescence, targeted multiple components of extracellular matrix metabolism, and increased DNA damage in chondrocytes. Through a series of in vitro and in vivo experiments, we identified that LncZFHX2 performed a novel function that regulated RIF1 expression through forming a transcription complex with KLF4 and promoting chondrocyte DNA repair. Moreover, chondrocyte-conditional knockout of LncZFHX2 accelerated injury-induced cartilage degeneration in vivo. In conclusion, we identified a hypoxia-activated DNA repair pathway that maintains matrix homeostasis in osteoarthritis cartilage.

The 3D plotting of gold solubility and gold fineness aims to illustrate how to quantify their correlations with ore-forming conditions in hydrothermal gold deposits. The thermodynamic calculation of the Au-Ag solid solutions in Mathematica and the 3D plotting in MATLAB are used to build isopleths of gold solubility and gold fineness at different temperatures (200℃, 400℃), pressures (0.1, 5 kbar), salinities (1, 40 wt% NaCl eq.), and sulfur concentrations (0.01, 0.5 mol/kg). The plot indicates that the ore-forming conditions have different correlations with gold solubility and gold fineness. Average rates of change for the correlations are quantified, showing distinct values in the four pH-logfO2 fields of (I) HSO4−, (II) SO42−, (III) H2S, and (IV) HS−, where dominant gold and silver complexes have different dependencies on the conditions. The quantification of the plots illustrates that a decrease in gold solubility by one order of magnitude is possibly caused by a decrease in temperature of ≥40℃, the salinity of ≥9.6 wt% NaCl eq. or sulfur concentration of ≥0.14 mol/kg, or an increase in pressure of ≥3 kbar, while a decrease in gold fineness by 100 units is possibly caused by a decrease in temperature of ≥14 ℃, pressure of ≥1.4 kbar, or salinity of ≥4 wt% NaCl eq., or an increase in sulfur concentration of ≥0.07 mol/kg. Quantification results suggest that a sharp decrease in temperature may result in large-scale gold mineralization and a great variation in gold fineness. In addition, the quantification reveals that the correlation between gold solubility and gold fineness can be expressed by a function, providing a rapid method for 3D plotting.

Background: The severe acute respiratory syndrome coronavirus in 2019 (COVID-19) is still spreading and causing deaths worldwide, which further increased the burden of chronic diseases. Dyslipidemia is a common metabolic syndrome, which is a major risk factor for cardiovascular disease. However, studies on whether there is a direct causal relationship between COVID-19 and the exacerbation of hyperlipidemia are still scarce. Methods: Two-sample Mendelian randomization was conducted using publicly available summary statistics from independent cohorts of European ancestry. For COVID-19 and hyperlipidemia, we used data from the ieu open GWAS project database. Inverse variance-weighted, mendelian randomization Egger, weighted median, simple mode, and weighted mode mendelian randomization analyses were performed, together with a range of sensitivity analyses. Results: There is no direct causal relationship between COVID-19 and dyslipidemia, regardless of COVID-19 severity or either dyslipidemic outcome. In combination with previous studies, the reason for the clinical outcome that COVID-19 increased the burden of dyslipidemia may be due to the exacerbation of pre-existing disease caused by COVID-19. Conclusions: COVID-19 has no direct causal relationship with dyslipidemia.