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Abstract Background With the advancement of world population aging, age-related sarcopenia (SP) imposes enormous clinical burden on hospital. Clinical research of SP in non-geriatric wards has not been appreciated, necessitating further investigation. However, observational studies are susceptible to confounders. Mendelian randomization (MR) can effectively mitigate bias to assess causality. Objective To investigate the correlation between SP and comorbidities in orthopedic wards, and subsequently infer the causality, providing a theoretical basis for developing strategies in SP prevention and treatment. Methods Logistic regression models were employed to assess the correlation between SP and comorbidities. The MR analysis was mainly conducted with inverse variance weighted, utilizing data extracted from the UK and FinnGen biobank (Round 9). Results In the cross-sectional analysis, SP exhibited significant associations with malnutrition (P = 0.013) and some comorbidities, including osteoporosis (P = 0.014), body mass index (BMI) (P = 0.021), Charlson Comorbidity Index (CCI) (P = 0.006). The MR result also provided supporting evidence for the causality between SP and hypertension, osteoporosis and BMI. These results also withstood multiple sensitivity analyses assessing the validity of MR assumptions. Conclusion The result indicated a significant association between SP and BMI, CCI, malnutrition, and osteoporosis. We highlighted that SP and comorbidities deserved more attention in non-geriatric wards, urging further comprehensive investigation.

Abstract The window strategy, known for its flexibility and efficiency, is extensively used in dynamic path planning. To further enhance the performance of the Automated Guided Vehicles (AGVs) sorting system, the two processes of AGV movement and path planning can be executed concurrently based on the window strategy. Nonetheless, difficulties in matching the computing time of the planning server with the moving time of AGVs may cause delays or reduced path optimality. To address the problem, this paper proposes an optimal time reuse strategy. The proposed solution controls computing time by managing path length for each planning instance, ensuring alignment with the moving time of AGVs to maximize path optimality and avoid delays. To achieve this, two aspects need to be considered. Firstly, on a systemic level, we control the entry rate of AGVs by adjusting the replanning period, thus avoiding congestion caused by excessive AGVs and maintaining high system efficiency. Secondly, we reversely control the computing time by adjusting the path length that needs to be planned for each single planning, so that it matches the moving time of AGVs. Simulation results show that our method outperforms existing top-performing methods, achieving task completion rates 1.64, 1.57, and 1.12 times faster across various map sizes. This indicates its effectiveness in synchronizing planning and movement times. The method contributes significantly to dynamic path planning methodologies, offering a novel approach to time management in AGV systems.

Abstract Background Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. Methods In this study, all cases(n = 241) were enrolled from a tertiary women’s hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children’s neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. Results Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P

This study aimed to establish a time-resolved fluorescence immunoassay method for the simultaneous quantitative detection of fumonisin B1, B2 and B3 in corn. The EDC/NHS active ester method was used to prepare time-resolved fluorescent microspheres and fumonisin antibody conjugates. Fumonisin antigen was immobilized on a nitrocellulose membrane as the test line. By optimizing the number of test line, a competitive immunoassay method for detecting fumonisin was eventually established. Subsequently, the sensitivity, specificity, accuracy, precision, and correlation with the national standard method were evaluated for the established method. The detection limits of the established method by using two test line pattern were 107.68~168.28 μg/kg, and the quantification limits were 283.46~444.63 μg/kg. The cross-reactivity with fumonisin B1, fumonisin B2 and fumonisin B3 were 100%, 85.59% and 72.72%, respectively, and no significant cross-reactivity was observed with five other common mycotoxins. The recovery rates ranged from 88.37% to 117.42%, and the coefficients of variation were lower than 10%. The conformity of the results obtained by the established method, as compared to the immunoaffinity column purification-high performance liquid chromatography (IAC-HPLC) method specified in the national standard GB 5009.240-2016, fell within the range of 92.17% to 107.21%. The established time-resolved fluorescence immunoassay method meets the requirements for rapid on-site quantitative detection of fumonisin B1, B2 and B3 in corn.

Abstract We investigate the entanglement harvesting phenomenon for static detectors that locally interact with massless scalar fields in the cosmic string spacetime, which, though locally flat, features a conical structure defined by a deficit angle. Specifically, we analyze three detector alignments relative to the string: parallel and orthogonal alignments with detectors on the same side of the string, and an orthogonal alignment with detectors on opposite sides of the string. For the alignments on the same side of the string, we observe that the cosmic string’s presence can either aid or hinder entanglement harvesting, affecting both the extent of entanglement harvested and the achievable range of interdetector separation. This effect depends on the distance between the detectors and the string and differs markedly from scenarios in a locally flat spacetime with a reflecting boundary, where the boundary invariably extends the harvesting-achievable range. Conversely, for the alignment with detectors on opposite sides of the string, we find that detectors consistently harvest more entanglement than those in a flat spacetime devoid of a cosmic string. This starkly contrasts the behavior observed with detectors on the same side. Interestingly, the presence of a cosmic string expands the harvesting-achievable range for detectors in orthogonal alignment only when near the string, whereas it invariably reduces the achievable range for detectors in parallel alignment.

Abstract Metal‐enzyme integrated catalysts (MEICs) that combine metal and enzyme offer great potential for sustainable chemoenzymatic cascade catalysis. However, rational design and construction of optimal microenvironments and accessible active sites for metal and enzyme in individual nanostructures are necessary but still challenging. Herein, Pd nanoparticles (NPs) and Candida antarctica lipase B (CALB) are co‐immobilized into the pores and surfaces of covalent organic frameworks (COFs) with tunable functional groups, affording Pd/COF‐X/CALB (X = ONa, OH, OMe) MEICs. This strategy can regulate the microenvironment around Pd NPs and CALB, and their interactions with substrates. As a result, the activity of the COF‐based MEICs in catalyzing dynamic kinetic resolution of primary amines is enhanced and followed COF‐OMe > COF‐OH > COF‐ONa. The experimental and simulation results demonstrated that functional groups of COFs modulated the conformation of CALB, the electronic states of Pd NPs, and the affinity of the integrated catalysts to the substrate, which contributed to the improvement of the catalytic activity of MEICs. Further, the MEICs are prepared using COF with hollow structure as support material, which increased accessible active sites and mass transfer efficiency, thus improving catalytic performance. This work provides a blueprint for rational design and preparation of highly active MEICs.

Abstract Background Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. Methods The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. Results RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. Conclusion RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Abstract Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

Abstract On-site and real-time non-destructive measurement of elastic constants for materials of a component in a in-service structure is a challenge due to structural complexities, such as ambiguous boundary, variable thickness, nonuniform material properties. This work develops for the first time a method that uses ultrasound echo groups and artificial neural network (ANN) for reliable on-site real-time identification of material parameters. The use of echo groups allows the use of lower frequencies, and hence more accommodative to structural complexity. To train the ANNs, a numerical model is established that is capable of computing the waveform of ultrasonic echo groups for any given set of material properties of a given structure. The waveform of an ultrasonic echo groups at an interest location on the surface the structure with material parameters varying in a predefined range are then computed using the numerical model. This results in a set of dataset for training the ANN model. Once the ANN is trained, the material parameters can be identified simultaneously using the actual measured echo waveform as input to the ANN. Intensive tests have been conducted both numerically and experimentally to evaluate the effectiveness and accuracy of the currently proposed method. The results show that the maximum identification error of numerical example is less than 2%, and the maximum identification error of experimental test is less than 7%. Compared with currently prevailing methods and equipment, the proposefy the density and thickness, in addition to the elastic constants. Moreover, the reliability and accuracy of inverse prediction is significantly improved. Thus, it has broad applications and enables real-time field measurements, which has not been fulfilled by any other available methods or equipment.

Abstract Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. Methods We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. Results The most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. Conclusions Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1 P409L , ADGRA2 and ADRB3) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

ABSTRACTPaxilline (PAX) is a tremorgenic mycotoxin that is thought to be associated with various syndromes in animals. To facilitate the determination of this toxin, a hapten was chemically synthesized and then respectively conjugated to Bovine Thyroglobulin (BTG) and Bovine serum albumin (BSA) for antibody production. Monoclonal antibody (mAb) 4F8 was finally obtained and used to establish an accurate and sensitive indirect competitive ELISA (icELISA). Various parameters that could impact the performance of icELISA were optimized, including the ion concentration, pH value and organic solvent. Under optimal condition, this assay exhibits an IC50 value as low as 0.84 µg L−1. The limit of detection (LOD) of the established icELISA method for PAX was 0.03–0.3 µg L−1. In conclusion, this study provided a rapid, sensitive, and high-throughput immunoassay for the detection of PAX in grains.

Background Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN.Aims The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN.Methods In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline.Results Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN.Conclusions Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

BackgroundFor patients with hilar cholangiocarcinoma (HC) undergoing hemi-hepatectomy, there are controversies regarding the requirement of, indications for, and timing of preoperative biliary drainage (PBD). Dynamic three-dimensional volume reconstruction could effectively evaluate the regeneration of liver after surgery, which may provide assistance for exploring indications for PBD and optimal preoperative bilirubin value. The purpose of this study was to explore the indications for PBD and the optimal preoperative bilirubin value to improve prognosis for HC patients undergoing hemi-hepatectomy.MethodsWe retrospectively analyzed the data of HC patients who underwent hemi-hepatectomy in the First Affiliated Hospital of China Medical University from 2012 to 2023. The liver regeneration rate was calculated using three-dimensional volume reconstruction. We analyzed the factors affecting the liver regeneration rate and occurrence of postoperative liver insufficiency.ResultsThis study involved 83 patients with HC, which were divided into PBD group (n=36) and non-PBD group (n=47). The preoperative bilirubin level may be an independent risk factor affecting the liver regeneration rate (P=0.014) and postoperative liver insufficiency (P=0.016, odds ratio=1.016, β=0.016, 95% CI=1.003–1.029). For patients whose initial bilirubin level was >200 μmol/L (n=45), PBD resulted in better liver regeneration in the early stage (P=0.006) and reduced the incidence of postoperative liver insufficiency [P=0.012, odds ratio=0.144, 95% confidence interval (CI)=0.031–0.657]. The cut-off value of bilirubin was 103.15 μmol/L based on the liver regeneration rate. Patients with a preoperative bilirubin level of ≤103.15 μmol/L shown a better liver regeneration (P200 μmol/L, PBD may result in better liver regeneration and reduce the incidence of postoperative liver insufficiency. Preoperative bilirubin levels ≤103.15 μmol/L maybe recommended for leading to a better liver regeneration and lower incidence of postoperative hepatic insufficiency.

ContextCabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC).ObjectivesWe performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC.MethodsWe extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials.ResultsA total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR in randomized controlled trials was [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p < 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p < 0.0001].ConclusionCabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events.Systematic Review Registration:identifier CRD42023455878.

Objective To investigate the mechanisms of mitochondrial dysfunction-induced vitiligo based on bioinformatics. Methods The vitiligo target genes were obtained from CTD/Gene Cards/OMIM/NCBI Gene databases, while mitochondrial dysfunction target genes were downloaded from the MITOMAP database, followed by intersection analysis to identify the common genes. The latter were subjected to GO and KEGG enrichment analysis. The core genes were screened by analysis of protein-protein interaction. The NetworkAnalyst and Toppgene databases were used to predict the core gene-related transcription factors, miRNAs and the treatments. Results There were 90 common genes in vitiligo and mitochondrial dysfunction, and 13 core genes were screened by analysis of protein-protein interaction. The biological processes of the common genes were mainly enriched in mitochondrial respiratory chain complex assembly, while the cellular components were mainly enriched in mitochondria. The molecular functions were mainly enriched in the activities of redox-driven transmembrane transporter and oxidoreductase, and KEGG was mainly enriched in respiratory electron transport. The transcription factors with high degree of interactions with the core genes included ATF1, KDM5A, KDM5B and PHF8, and the miRNAs with high interaction with core genes included hsa-mir-1-3p and hsa-mir-16-5p. The predicted effective drugs were lipoic acid and ubiquinols. Conclusions Mitochondrial dysfunction may contribute to pathogenesis of vitiligo by affecting biological processes, such as complex assembly and electron transport in the mitochondrial respiratory chain. Transcription factors, such as ATF1 and KDM5, and miRNAs, including miR-1 and miR-493, may play an important pathogenic role in vitiligo by interaction with key genes, such as NDUFA9, SURF1, NDUFS1, NDUFS4 and LRPPRC.

AbstractThe R-spondin protein family comprises four members (RSPO1-4), which are agonists of the canonical Wnt/β-catenin pathway. Emerging evidence revealed that RSPOs should not only be viewed as agonists of the Wnt/β-catenin pathway but also as regulators for tumor development and progression. Aberrant expression of RSPOs is related to tumorigenesis and tumor development in multiple cancers and their expression of RSPOs has also been correlated with anticancer immune cell signatures. More importantly, the role of RSPOs as potential target therapies and their implication in cancer progressions has been studied in the preclinical and clinical settings. These findings highlight the possible therapeutic value of RSPOs in cancer medicine. However, the expression pattern, effects, and mechanisms of RSPO proteins in cancer remain elusive. Investigating the many roles of RSPOs is likely to expand and improve our understanding of the oncogenic mechanisms mediated by RSPOs. Here, we reviewed the recent advances in the functions and underlying molecular mechanisms of RSPOs in tumor development, cancer microenvironment regulation, and immunity, and discussed the therapeutic potential of targeting RSPOs for cancer treatment. In addition, we also explored the biological feature and clinical relevance of RSPOs in cancer mutagenesis, transcriptional regulation, and immune correlation by bioinformatics analysis.KEY MESSAGESAberrant expressions of RSPOs are detected in various human malignancies and are always correlated with oncogenesis.Although extensive studies of RSPOs have been conducted, their precise molecular mechanism remains poorly understood.Bioinformatic analysis revealed that RSPOs may play a part in the development of the immune composition of the tumor microenvironment.

Abstract We explore correlations harvesting by two static detectors locally interacting with vacuum massless scalar fields in the presence of an infinite perfectly reflecting boundary. We study the phenomena of mutual information harvesting and entanglement harvesting for two detector-boundary alignments, i.e., parallel-to-boundary and orthogonal-to-boundary alignments. Our results show that the presence of the boundary generally inhibits mutual information harvesting relative to that in flat spacetime without any boundaries. In contrast, the boundary may play a doubled-edged role in entanglement harvesting, i.e., inhibiting entanglement harvesting in the near zone of the boundary while assisting it in the far zone of the boundary. Moreover, there exists an optimal detector energy gap difference between two nonidentical detectors that makes such detectors advantageous in correlations harvesting as long as the interdetector separation is large enough. The value of the optimal detector energy gap difference depends on both the interdetector separation and the detector-to-boundary distance. A comparison of the correlations harvesting in two different alignments shows that although correlations harvesting share qualitatively the same properties, they also display quantitative differences in that the detectors in orthogonal-to-boundary alignment always harvest comparatively more mutual information than the parallel-to-boundary ones, while they harvest comparatively more entanglement only near the boundary.

Abstract Multiple evidence indicates that perinatal factors make impact on immune development and affect offspring allergic rhinitis (AR) risk. In this systematic review and meta-analysis, we examined available published studies to clarify the relationship between cesarean section (C-section) and offspring AR in children. To explore the relationship between C-section, especially the special attention was paid to different cesarean delivery mode, and the risk of AR in children. Articles were searched using PubMed, Web of Science, EMBASE, Cochrane Library, China knowledge Network, Wanfang, and China Science and Technology Journal databases. A meta-analysis of 22 studies published before August 1, 2022, which included 1,464,868 participants, was conducted for statistical analysis with RevMan5.4. The correlation strength between C-section and offspring AR was determined by combining odds ratio (OR) and 95% confidence interval (95% CI). Meta-regression and subgroup analyses were used to explore potential sources of heterogeneity. Publication bias was detected using the funnel chart and Egger tests. Meta-analysis revealed that there was a significant correlation between C-section and children AR (OR = 1.19, 95% CI: 1.12–1.27, P

Abstract Cold surge events in the South China Sea (over 110–117.5° E longitude at 15° N latitude) from 1979 to 2019 are divided into four types depending on their correlation with North Pacific extratropical cyclones (ECs). Climatologic relationships between the two phenomena reveal that 92% (39%) of all cold surges are accompanied by ECs (explosive extratropical cyclones, abbreviated as EC‐E), while 31% of ECs are accompanied by cold surges. The occurrence and development of ECs favour eruptions of cold air from higher latitudes, which in turn produce conditions conducive to cold surges. In the North Pacific, ECs travel in a northeastward direction, ultimately contributing to the Aleutian low. Meanwhile, the westerly jet is observed to strengthen following cold surge events. Both actions drive further EC activity, which in turn facilitates subsequent cold surges. Therefore, when ECs occur before and after cold surges, the cold surge event itself tends to be relatively strong and long lived. The transmission of energy by ECs is a primary link between the high and middle latitudes and contributes to the impact of cold surges on low latitudes. This study also explores the respective influences of the Siberia High and Aleutian Low on cold surges. The majority of cold surges that do not involve ECs occur in the context of the weaker Siberia High and Aleutian Low. Cold surges accompanied with ECs can be even stronger and longer lasting when the Siberia High and Aleutian Low strengthen.

Accurate identification of apple leaf diseases is of great significance for improving apple yield. The lesion area of the apple leaf disease image is small and vulnerable to background interference, which easily leads to low recognition accuracy. To solve this problem, a lightweight bilinear convolutional neural network (CNN) model named BLSENet based on attention mechanism is designed. The model consists of two subnetworks, and each subnetwork is embedded with a Squeeze-and-Excitation (SE) module. By using the feature extraction ability of the two subnetworks and combining the bilinear feature CONCAT operation, the multiscale features of the image are obtained. Compared with the unimproved model LeNet-5 (84.63%), BLSENet has higher accuracy in the test set, which indicates that SE module and bilinear feature fusion have a positive effect on the performance of the model, and BLSENet has the ability to identify apple leaf diseases. The model has achieved the expected goal and can provide technical support for accurate identification and real-time monitoring of apple disease images.

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In the wake of the dual-carbon objective, the call for low-carbon attributes in integrated energy systems is ascending, with an amplified imperative to integrate wind and solar power efficiently. This study introduces an advanced low-carbon optimization framework for integrated energy systems, incorporating a sophisticated time-differentiated carbon accounting mechanism attentive to consumer emissions. A nuanced carbon accounting model is crafted to assess consumer emissions with greater accuracy. Predicated on these emissions, a refined low-carbon demand response model is articulated, factoring in the influence of carbon emission factors pertinent to electricity and heat procurement on user conduct. This model integrates the consideration of heat reclaimed from methanation processes, which in turn informs the carbon emission factors associated with purchased heat, and evaluates the subsequent optimization impact on the system. The proposed model is designed to curtail the system’s operational expenditures and is operationalized via the CPLEX solver. Through the establishment of various scenarios for evaluative comparison, the model is corroborated to substantially augment the system’s proficiency in assimilating wind and solar energy, markedly curtail carbon emissions, and facilitate a sustainable and cost-efficient operation of the integrated energy system.

The applications of adjuvant chemotherapy and targeted drugs have greatly improved the prognosis of patients with advanced cancer, however the rapid emergence of drug resistance and the subsequent rapid progress of the disease have always been the unmet challenges in the field of cancer treatment. Adaptive therapy (AT) combined with Darwinian evolutionary dynamics is a new treatment concept different from the traditional maximum tolerated dose (MTD), which is expected to overturn the treatment paradigm of advanced cancer and achieve long-term low load tumor bearing survival. This paper reviewed the theory of AT and the important role of mathematical models in optimizing adaptive treatment strategies, then briefly described other tumor treatment strategies based on Darwinian dynamics, in order to provide new ideas for clinicians in the game with advanced cancer.

Polyinosinic-polycytidylic acid (poly I:C) is a synthesized analogue of viral double-strand RNA and considered as a potential immunostimulant in aquaculture. MicroRNAs (miRNAs) have been reported to play important roles in the development of the immune system and in regulation of host antiviral responses. In our earlier study, it was found that poly I:C pre-treatment could stimulate the resistance against cyprinid herpesvirus 2 (CyHV-2) infection and enhance the antiviral immune response in gibel carp. To understand the role of miRNAs in regulating the host response to poly I:C treatment, we investigated the expression profiles of miRNAs in the head kidney of poly I:C-treated gibel carp with small RNA sequencing technology. When compared with the untreated group, a total of 24 differentially expressed miRNAs were identified in the poly I:C-stimulated fish, among which, 7 and 17 miRNAs were upregulated and downregulated, respectively. Analysis of target genes of these differentially expressed miRNAs found that most targeted mRNAs were involved in catalytic activity, peptidase activity and endopeptidase activity, and were enriched in the metabolic, protein processing in endoplasmic reticulum and oxidative phosphorylation signaling pathways, suggesting that poly I:C could alter the expression of metabolism-related miRNAs in the kidney of gibel carp. Besides, it was noted that some immune-related miRNAs, including inflammation-related miRNAs (miR-192 and miR-731) and interferon-related miRNAs (miR-194a and miR-122), were downregulated after poly I:C treatment. In summary, it was found that poly I:C could regulate the cellular levels of specific miRNAs involved in metabolism and immune responses in the head kidney of gibel carp, which may increase the capacity of the immune cells to fight against pathogens infection.

Streamer discharge theory does not consider the influence of airflow on discharge. However, it is found experimentally that the airflow causes a great change in the breakdown process, especially in a nonuniform field. In this paper, a physical model of spark discharge in airflow is established considering the combined effect of the decrease in airflow density and the blowing away of positive ions and electrons on the breakdown process. Furthermore, the classic streamer breakdown criteria both in uniform field and nonuniform field are modified. This model extends the classic streamer breakdown criterion for static gases to the airflow environment.