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Abstract The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Abstract The increasing incidence of autism spectrum disorder (ASD) worldwide poses serious social and family problems. Various risk factors for ASD are gradually being recognized, and there are also various options for the treatment of ASD. It is worth noting that dietary interventions have been shown to have a positive effect in terms of mitigating and preventing some psychiatric disorders, such as epilepsy, Parkinson's disease, and ASD, and they are gradually receiving attention as a safe adjuvant treatment. In this review, based on the current understanding of the pathogenic factors and intervention strategies for ASD, different dietary patterns that can be selected for children with ASD are discussed in depth. Moreover, a review was conducted on the use of dietary factors, such as natural products from food sources, prebiotics, and probiotics, as effective supplements to existing dietary patterns. As increasing evidence shows that maternal risk factors, such as obesity, diabetes, and hypertension, are associated with an increased risk of ASD in offspring, dietary suggestions are also made for pregnant woman with ASD‐related risk factors to counteract the impact of these risk factors. With compensation from food‐derived natural products, prebiotics, and probiotics, suitable dietary patterns can further enhance the effectiveness of dietary interventions for ASD. In addition, dietary recommendations for pregnant woman may reduce the potential impact of obesity, diabetes, and hypertension and may help to prevent the occurrence of ASD to the maximum extent possible.

Abstract The viscosity of fracturing fluid and in-situ stress difference are the two important factors that affect the hydraulic fracturing pressure and propagation morphology. In this study, raw coal was used to prepare coal samples for experiments, and clean fracturing fluid samples were prepared using CTAB surfactant. A series of hydraulic fracturing tests were conducted with an in-house developed triaxial hydraulic fracturing simulator and the fracturing process was monitored with an acoustic emission instrument to analyze the influences of fracturing fluid viscosity and horizontal in-situ stress difference on coal fracture propagation. The results show that the number of branched fractures decreased, the fracture pattern became simpler, the fractures width increased obviously, and the distribution of AE event points was concentrated with the increase of the fracturing fluid viscosity or the horizontal in-situ stress difference. The acoustic emission energy decreases with the increase of fracturing fluid viscosity and increases with the increase of horizontal in situ stress difference. The low viscosity clean fracturing fluid has strong elasticity and is easy to be compressed into the tip of fractures, resulting in complex fractures. The high viscosity clean fracturing fluids are the opposite. Our experimental results provide a reference and scientific basis for the design and optimization of field hydraulic fracturing parameters.

Abstract Background Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. Results By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. Conclusions Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

Abstract Disease modeling with isogenic Induced Pluripotent Stem Cell (iPSC)-differentiated organoids serves as a powerful technique for studying disease mechanisms. Multiplexed coculture is crucial to mitigate batch effects when studying the genetic effects of disease-causing variants in differentiated iPSCs or organoids, and demultiplexing at the single-cell level can be conveniently achieved by assessing natural genetic barcodes. Here, to enable cost-efficient time-series experimental designs via multiplexed bulk and single-cell RNA-seq of hybrids, we introduce a computational method in our Vireo Suite, Vireo-bulk, to effectively deconvolve pooled bulk RNA-seq data by genotype reference, and thereby quantify donor abundance over the course of differentiation and identify differentially expressed genes among donors. Furthermore, with multiplexed scRNA-seq and bulk RNA-seq, we demonstrate the usefulness and necessity of a pooled design to reveal donor iPSC line heterogeneity during macrophage cell differentiation and to model rare WT1 mutation-driven kidney disease with chimeric organoids. Our work provides an experimental and analytic pipeline for dissecting disease mechanisms with chimeric organoids.

Abstract Rare-earth engineering is an effective way to introduce and tune magnetism in topological kagome materials, which have been acting as a fertile platform to investigate the quantum interactions between geometry, topology, spin, and correlation. Here, we report the synthesis, structure, and physical properties of titanium-based kagome metals RETi3Bi4 (RE = Yb, Pr, and Nd) with various magnetic states. They all crystallize in the orthogonal space group Fmmm (No. 69), featuring distorted titanium kagome lattices and rare-earth zig-zag chains. By changing the rare earth atoms in the zig-zag chains, the magnetism can be tuned from nonmagnetic YbTi3Bi4 to short-range ordered PrTi3Bi4 (T anomaly ~ 8.2 K), and finally to ferromagnetic NdTi3Bi4 (T c ~ 8.5 K). In-situ resistance measurements of NdTi3Bi4 under high pressure further reveal a tunable ferromagnetic ordering temperature. These results highlight RETi3Bi4 as a promising family of kagome metals to explore nontrivial band topology and exotic phases.

This study investigated the effects of different dilution concentrations of azoxystrobin and thiophanate-methyl on the preservation of postharvest litchi fruit at ambient temperature. By analyzing the physiological indicators of litchi fruit during storage, the optimal fungicide formulation was selected, verified, and dietary exposure assessed thus the preservation method of extending shelf life for litchi at ambient temperature was obtained. The results showed that the litchi fruit treated with a 1600-fold dilution of 25% azoxystrobin (M1600), or a 1600-fold dilution of 25% azoxystrobin mixed with a 700-fold dilution of 70% thiophanate-methyl (M1600+J700) significantly inhibited the respiratory rate of litchi fruit, decreased the relative conductivity of pericarp and decay rate of litchi fruit (P

Abstract This study aims to establish a rapid diagnostic method for Streptococcus agalactiae (GBS) based on recombinase polymerase amplification (RPA) and lateral flow strips (LFS). The best primer pairs designed by SIP gene were screened according to the basic RPA reaction, then the probe was designed. The reaction condition was optimized based on the color development of the LFS detection line. To ascertain the reaction specificity, 10 common clinical pathogens and 10 clinical specimens of GBS were tested. Furthermore, the reaction sensitivity was assessed by utilizing a tenfold gradient dilution of GBS genomic DNA as templates. RPA–LFS method was compared to the qPCR assay and biochemical culture method for the Kappa consistency test. The RPA–LFS technique was able to complete the amplification process within 30 min and the results were observed on lateral flow strips. The method is highly sensitive, with a minimum detection limit of 1.31 ng for GBS. The RPA–LFS method showed consistent accuracy of results compared to qPCR and the culture–biochemical method. The establishment of this method is conducive to the development of on-site immediate detection, which can provide information for the timely development of a reasonable antimicrobial treatment plan, and has a greater potential for clinical application.

Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion: The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Abstract The joints are existing throughout the underground rock mass. It is of great significance to investigate the shear performance of the rock mass to maintain the stability of the underground structure. In this study, we conducted orthogonal tests to determine the proportion of rock-like materials, and used JRC curves to make specimen molds and then prepare the specimens. We conducted straight shear tests and uniaxial compression tests to determine the various mechanical parameters of the rock-like materials. Next, we carried out the compression and shear tests to investigate the shear characteristics of the specimens, and study the damage pattern and shear strength of the jointed rock mass under different confining pressures and roughness levels. The mesoscopic displacements in the shear process of joints were analyzed by using ABAQUS. The test results show that the effect of the confining pressure on the shear strength of the joint plane is relatively obvious, and a larger confining pressure indicates a larger shear strength. The effects of different joint plane roughness and shear rated on the shear characteristics of the joint plane are also significant. The mesoscopic displacement difference inside the joint plane with higher roughness is relatively large, and the stress concentration phenomenon is obvious and lasts longer, which leads to the faster destruction of the specimen with higher roughness and the higher destruction degree. Therefore, we suggest that the priority should be given to the reinforcement of jointed rock mass with high roughness during the construction to prevent sudden destabilization and failure.

Abstract Background Suicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data. Methods In this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared. Results Patients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p

Abstract In recent years, intelligent robots are extensively applied in the field of the industry and intelligent rehabilitation, wherein the human‐robot interaction (HRI) control strategy is a momentous part that needs to be ameliorated. Specially, the efficacy and robustness of the HRI control algorithm in the presence of unknown external disturbances deserve to be addressed. To deal with these urgent issues, in this study, artificial systems, computational experiments and a parallel execution intelligent control framework are constructed for the HRI control. The upper limb‐robotic exoskeleton system is re‐modelled as an artificial system. Depending on surface electromyogram‐based subject's active motion intention in the practical system, a non‐convex function activated anti‐disturbance zeroing neurodynamic (NC‐ADZND) controller is devised in the artificial system for parallel interaction and HRI control with the practical system. Furthermore, the linear activation function‐based zeroing neurodynamic (LAF‐ZND) controller and proportional‐derivative (posterior deltoid (PD)) controller are presented and compared. Theoretical results substantiate the global convergence and robustness of the proposed controller in the presence of different external disturbances. In addition, the simulation results verify that the NC‐ADZND controller is better than the LAF‐ZND and the PD controllers in respect of convergence order and anti‐disturbance characteristics.

Abstract Double-sided microlens arrays (DSMLAs) include combinations of two single-sided MLAs to overcome positioning errors and greatly improve light transmissivity compared to other types of lenses. Precision glass molding (PGM) is used to fabricate DSMLAs, but controlling alignment errors during this process is challenging. In this paper, a mold assembly was manufactured with a novel combination of materials to improve the alignment accuracy of mold cores during PGM by using the nonlinear thermal expansion characteristics of the various materials to improve the DSMLA alignment accuracy. By establishing a mathematical model of the DSMLA alignment error and a thermal expansion model of the mold-sleeve pair, the relationship between the maximum alignment error of the DSMLA and the mold-sleeve gap was determined. This research provides a method to optimize the mold-sleeve gap and minimize the alignment error of the DSMLA. The measured DSMLA alignment error was 10.56 μm, which is similar to the predicted maximum alignment error. Optical measurements showed that the uniformity of the homogenized beam spot was 97.81%, and the effective homogeneous area accounted for 91.66% of the total area. This proposed method provides a novel strategy to improve the performance of DSMLAs.

Abstract Background Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. Methods Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. Results Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. Conclusions Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

The field of person re-identification (re-ID) encounters challenges such as inter-person similarity and occlusion. In this paper, we introduce an occluded pedestrian re-ID method based on Multiple Fusion and Semantic feature Mining (MFSM) to mitigate the adverse effects of occlusion on feature representation. Specifically, we devise a Multi-branch Strategic Enhancement Module (SEM) to bolster the robustness of data augmentation in addressing the issues posed by data memorization more consistently. This module emulates various real-world disturbances by implementing distinct and independent augmentation strategies. Furthermore, we propose the Triplet Cross Unit (TCU) to comprehensively exploit and consolidate both regional and relational visual cues, as well as multi-level features. The TCU facilitates transformers in acquiring an early understanding of translation invariance in images by transferring local patterns such as edges, textures, and colors from the lower CNN layers to the shallower transformer layers. Simultaneously, deeper transformer features offer more abstracted semantic visual representations that complement CNN's high-level semantic features. Lastly, we introduce the Global Squeeze-Excitation Fusion (GSEF) module to address the challenge of global feature segregation across different models in final outputs. The GSEF selectively merges features based on attention mechanisms, prioritizing the comprehensive utilization of valid global features. Extensive experiments demonstrate the state-of-the-art performance of our model in handling pedestrian occlusion, thus validating the efficacy of our method.

Background Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.Methods Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.Results Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of Ad-AURKA/CDK7 promoted the induction and maturation of dendritic cell subsets and augmented multifunctional CD8+ T-cell antitumor immunity. Furthermore, the vaccine induced a long-lasting antitumor effect by promoting the generation of memory CD8+ T cells. Tumor recovery on CD8+ T-cell depletion underscored the indispensable role of these cells in the observed therapeutic effects. The potent efficacy of the Ad-AURKA/CDK7 vaccine was consistently demonstrated in lung metastasis, orthotopic, and humanized tumor models by inducing multifunctional CD8+ T-cell antitumor immune responses.Conclusions Our findings illustrate that the Ad-AURKA/CDK7 vaccine targeting dual kinases AURKA and CDK7 emerges as a promising and effective therapeutic approach for the treatment of solid tumors.

Abstract Polyethers play a crucial role in the development of anticancer drugs. To enhance the anticancer efficacy and reduce the toxicity of these compounds, thereby advancing their application in cancer treatment, herein, guided by the structure‐activity relationships of aglycone polyethers, novel aglycone polyethers are rationally redesigned with potentially improved efficacy and reduced toxicity against tumors. To realize the biosynthesis of the novel aglycone polyethers, the gene clusters and the post‐polyketide synthase tailoring pathways for aglycone polyethers endusamycin and lenoremycin are identified and subjected to combinatorial biosynthesis studies, resulting in the creation of a novel aglycone polyether termed End‐16, which demonstrates significant potential for treating bladder cancer (BLCA). End‐16 demonstrates the ability to suppress the proliferation, migration, invasion, and cellular protrusions formation of BLCA cells, as well as induce cell cycle arrest in the G1 phase in vitro. Notably, End‐16 exhibits superior inhibitory activity and fewer side effects against BLCA compared to the frontline anti‐BLCA drug cisplatin in vivo, thereby warranting further preclinical studies. This study highlights the significant potential of integrating combinatorial biosynthesis strategies with rational design to create unnatural products with enhanced pharmacological properties.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored. Method: We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated. Results: Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence. Conclusions: This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.

Abstract The mechanism involved in major depressive disorder (MDD) is well‐studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single‐cell RNA‐sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA‐seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen‐activated protein kinases (MAPK) pathway is identified. E‐twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

Aims To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO).Methods 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG.Results A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p

Background and objectiveDepression is a widespread mental health condition that can impact both mental and physical well-being. Prior research has shown that high levels of copper in the blood and low levels of folate are linked to depression. This study aimed to explore whether serum folate levels, independently or in combination with serum copper levels, associated with the risk of depression.MethodsData from participants aged 18–80 years in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016 were analyzed to examine the role of trace elements. Depression was assessed using the nine-item Patient Health Questionnaire (PHQ-9). Logistic regression analyses were employed to evaluate the main effect of serum copper and folate levels on depression. Three indices, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze the interaction effect.ResultsAmong the 4,847 participants selected for this study, 429 (8.9%) had PHQ-9 scores above 10, which we defined as having depressive symptoms. After adjusting for all confounding factors, higher serum copper levels [≥15.5 vs.

Abstract Wilms tumor‐1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single‐cell chromatin accessibility and gene expression maps of foetal kidneys and kidney organoids are generated. Functional implications of WT1‐targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1‐mediated transcriptional regulation during podocyte development, cultured and implanted patient‐derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single‐cell RNA sequencing (scRNA‐seq) and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR‐Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1‐related epigenomic landscape with respect to human podocyte development and identifies the disease‐causing role of a WT1 mutation.

Integrating RGB and Event (RGBE) multi-domain information obtained by high-dynamic-range and temporal-resolution event cameras has been considered an effective scheme for robust object tracking. However, existing RGBE tracking methods have overlooked the unique spatio-temporal features over different domains, leading to object tracking failure and inefficiency, especally for objects against complex backgrounds. To address this problem, we propose a novel tracker based on adaptive-time feature extraction hybrid networks, namely Siamese Event Frame Tracker (SiamEFT), which focuses on the effective representation and utilization of the diverse spatio-temporal features of RGBE. We first design an adaptive-time attention module to aggregate event data into frames based on adaptive-time weights to enhance information representation. Subsequently, the SiamEF module and cross-network fusion module combining artificial neural networks and spiking neural networks hybrid network are designed to effectively extract and fuse the spatio-temporal features of RGBE. Extensive experiments on two RGBE datasets (VisEvent and COESOT) show that the SiamEFT achieves a success rate of 0.456 and 0.574, outperforming the state-of-the-art competing methods and exhibiting a 2.3-fold enhancement in efficiency. These results validate the superior accuracy and efficiency of SiamEFT in diverse and challenging scenes.

BackgroundProlonged postoperative hospital stay following gastric cancer (GC) surgery is an important risk factor affecting patients’ mood and increasing complications. We aimed to develop a nomogram to predict risk factors associated with prolonged postoperative length of stay (PLOS) in patients undergoing gastric cancer resection.MethodsData were collected from 404 patients. The least absolute shrinkage and selection operator (LASSO) was used for variable screening, and a nomogram was designed. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). The consistency between the predicted and actual values was evaluated via a calibration map, and the clinical application value was evaluated via decision curve analysis (DCA) and clinical impact curve analysis (CICA).ResultsA total of 404 patients were included in this study. Among these patients, 287 were assigned to the training cohort, and 117 were assigned to the validation cohort. According to the PLOS quartile distance, 103 patients were defined as having prolonged PLOS. LASSO regression and logistic multivariate analysis revealed that 4 clinical characteristics, the neutrophil–lymphocyte ratio (NLR) on postoperative day one, the NLR on postoperative day three, the preoperative prognostic nutrition index and the first time anal exhaust was performed, were associated with the PLOS and were included in the construction of the nomogram. The AUC of the nomogram prediction model was 0.990 for the training set and 0.983 for the validation set. The calibration curve indicated good correlation between the predicted results and the actual results. The Hosmer-Lemeshow test revealed that the P values for the training and validation sets were 0.444 and 0.607, respectively, indicating that the model had good goodness of fit. The decision curve analysis and clinical impact curve of this model showed good clinical practicability for both cohorts.ConclusionWe explored the risk factors for prolonged PLOS in GC patients via the enhanced recovery after surgery (ERAS) program and developed a predictive model. The designed nomogram is expected to be an accurate and personalized tool for predicting the risk and prognosis of PLOS in GC patients via ERAS measures.

Study region: Yellow River Basin (YRB) in China. Study focus: This study attempts to shed new light on regional land-atmosphere coupling and relevant impacts on basin-scale water resource management. Specifically, the objectives are to investigate the driving factors and physical mechanisms of SM changes via land-atmosphere coupling. New hydrological insights for the region: Ecological conservation and the high-quality development in the YRB stand as a pivotal national strategy. The equilibrium of water availability (PME，precipitation minus evapotranspiration) poses a significant challenge to the sustainability of the basin's ecosystem. Unfortunately, a comprehensive examination of the regional response, spatiotemporal heterogeneity, and the mechanism governing soil moisture (SM) in response to PME remains limited. An enhanced multiple linear regression method is implemented to quantify monthly sensitivity coefficients, revealing a notable correlation: reduced SM in arid regions correlates with heightened PME. This decline in SM triggers a decrease in evapotranspiration, attenuates the cooling effect of evapotranspiration, and amplifies temperature disparities. Consequently, this process results in an intensified boundary layer and tropospheric ascending motion, thereby increasing water vapor transport. This feedback loop is most pronounced during drought conditions, particularly in summer arid areas (sensitivity coefficient =-0.27). The findings underscore the intricate interplay between land and atmosphere, elucidating the discernible impact of climate change on water resources at a sub-basin scale.

Dual-comb photoacoustic spectroscopy (DC-PAS) advances spectral measurements by offering high-sensitivity and compact size in a wavelength-independent manner. Here, we present a novel cantilever-enhanced DC-PAS scheme, employing a high-sensitivity fiber-optic acoustic sensor based on an optical cantilever and a non-resonant photoacoustic cell (PAC) featuring a flat-response characteristic. The dual comb is down-converted to the audio frequency range, and the resulting multiheterodyne sound waves from the photoacoustic effect, are mapped into the response frequency region of the optical cantilever microphone. This cantilever-enhanced DC-PAS method provides advantages such as high sensitivity, compact design, and immunity to electromagnetic interference. Through 10 seconds averaging time, the proposed approach experimentally achieved a minimum detection limit of 860 ppb for acetylene. This technology presents outstanding opportunities for highly sensitive detection of trace gases in a wavelength-independent manner, all within a compact volume.

Phytoplankton blooms have become a global concern due to their negative impacts on public health, aquaculture, tourism, and the economic stability of coastal regions. Therefore, elucidating the shifts in phytoplankton community structure and abundance, as well as their environmental drivers, is crucial. However, existing studies often fail to capture the detailed dynamics of phytoplankton blooms and their environmental triggers due to low temporal observation resolution. In this study, high temporal resolution (daily) samples were collected over 43 days to investigate the influence of environmental factors on phytoplankton in Qinhuangdao in the summer. During the observation period, a total of 45 phytoplankton species were identified, comprising 26 Bacillariophyta species, 16 Dinophyta species, 2 Euglenophyta species, and 1 Chromophyta species. Interestingly, a lag bloom pattern of phytoplankton behind freshwater input was observed across day-to-day samples. Phytoplankton blooms typically lagged 1–3 days behind periods of decreased salinity and nutrient input, suggesting that freshwater influx provides the foundational materials and benefits for these blooms. Moreover, the phytoplankton blooms were triggered by six dominant species, i.e., Chaetoceros spp., Pseudo-nitzschia delicatissima, Skeletonema costatum, Protoperdinium spp., Leptocylindrus minimus, Pseudo-nitzschia pungens, and Thalassiosira spp. Consequently, the succession of phytoplankton showed a predominant genera shift in the following sequence: Nitzschia, Protoperdinium, and Prorocentrum – Skeletonema – Pseudo-nitzschia – Gymnodinium – Leptocylindrus. Besides that, a deterministic process dominated phytoplankton community assembly across time series, and DIP is a key factor in shifting the phytoplankton community structures in this area. In summary, our study offers high-resolution observations on the succession of phytoplankton communities and sheds light on the complex and differentiated responses of phytoplankton to environmental factors. These findings enhance our understanding of the dynamics of phytoplankton blooms and their environmental drivers, which is essential for the effective management and mitigation of their adverse impacts.

Abstract Prussian blue analogs (PBAs) are considered as one of the most potential electrode materials in capacitive deionization (CDI) due to their unique 3D framework structure. However, their practical applications suffer from low desalination capacity and poor cyclic stability. Here, an entropy engineering strategy is proposed that incorporates high‐entropy (HE) concept into PBAs to address the unfavorable multistage phase transitions during CDI desalination. By introducing five or more metals, which share N coordination site, high‐entropy hexacyanoferrate (HE‐HCF) is constructed, thereby increasing the configurational entropy of the system to above 1.5R and placing it into the high‐entropy category. As a result, the developed HE‐HCF demonstrates remarkable cycling performance, with a capacity retention rate of over 97% after undergoing 350 ultralong‐life cycles of adsorption/desorption. Additionally, it exhibits a high desalination capacity of 77.24 mg g−1 at 1.2 V. Structural characterization and theoretical calculation reveal that high configurational entropy not only helps to restrain phase transition and strengthen structural stability, but also optimizes Na+ ions diffusion path and energy barrier, accelerates reaction kinetics and thus improves performance. This research introduces a new approach for designing electrodes with high performance, low cost, and long‐lasting durability for capacitive deionization applications.

Background: Tripterygium glycosides (TG) is extracted from the roots of Tripterygium wilfordii Hook F (Lei gong teng, a traditional Chinese medicine). It is widely used in China to treat immunoglobulin A vasculitis nephritis (IgAVN), which is a common secondary glomerular disease. As there are no guidelines for the rational application of TG, we performed this study to evaluate the efficacy and safety of different doses of TG and to determine the optimal treatment for IgAVN. Methods: Ten databases were searched from their inception to April 2023 for randomised controlled trials (RCTs) using TG, TG combined with glucocorticoids (GC), or TG combined with traditional Chinese medicine (TCM) to treat IgAVN. A network meta-analysis was performed following the protocol (CRD42023401645). Results: Forty-four eligible RCTs involving 3402 patients were included. For effective rate, TG 1.5 mg/kg/d (TG1.5) + TCM was ranked as the best intervention, followed by TG 1.0 mg/kg/d (TG1.0) + TCM, TG1.5, TG1.0+GC, TG1.0, TCM, GC, and routine treatment (RT). TG1.0+TCM ranked best in reducing recurrence, followed by TG1.0+GC, GC, TG1.5, and RT. Compared with TG1.0, TG1.0+TCM and TG1.5+TCM effectively reduced liver injury events. Compared with TG1.5, TG1.5+TCM and TG1.0+TCM effectively reduced leukopenia events. No significant differences in the reduction of gastrointestinal events were observed between the interventions. Subgroup analyses explored the effects of the participants’ age. The intervention rankings of the outcomes generally remained consistent. Only a small difference was observed in gastrointestinal events. TCM was the best treatment for reducing gastrointestinal events in paediatric patients. Conclusions: The results showed a positive correlation between dose and efficacy, whereas no relationship was found between dose and adverse events. TCM can boost the efficacy and reduce adverse events when combined with TG. In conclusion, we consider TG1.5+TCM as the best treatment for IgAVN. However, further research is required to confirm these findings.

BackgroundMajor depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC).MethodsIn this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4–8 Hz; alpha, 8–12 Hz; beta1, 12–16 Hz; beta2, 16–24 Hz; and beta3, 24–40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17).ResultsDuring the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked.ConclusionOur study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression.LimitationsThe study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD.

IntroductionFew minimally invasive options for sampling the small intestinal (SI) luminal fluid exist to study the SI microbiota in health and disease. To address the lack of tools and methods to study GI regions that are difficult to access, Nimble Science developed a fully autonomous and passive sampling method, the Small Intestine MicroBiome Aspiration (SIMBA™) capsule, for convenient, high-quality, and reliable sampling to study the diet-microbiota interactions in the SI. MethodsThe sealing efficacy and microbial DNA preservation capacity of the SIMBA capsules was first validated through in vitro simulation assays. Then, a clinical study was conducted with 20 healthy participants to validate the in vivo use of SIMBA capsules to reliably capture samples for SI microbiome analysis before and after an intervention (NCT04489329). Briefly, participants ingested the capsules at baseline and 7 days later, with a probiotic capsule containing a blend of L. rhamnosus R0011 and B. longum R0175. Following baseline SIMBA capsule ingestion, multiple low-dosage x-ray scans were performed to track the sampling location. Fecal samples corresponding with the baseline and intervention capsule were analyzed for comparison. ResultsThe SIMBA capsules’ performance in vitro demonstrated the potential for contamination-free sampling with preservation of the microbial communities. Within the clinical study, the capsules performed safely and reliably for collection of SI content. X-ray tracking confirmed that 97.2% of the capsules completed sample collection in the SI regions before reaching the colon. Importantly, our data showed that the capsules sampled in the right area of the intestines and that baseline SIMBA microbiome profile is significantly different from fecal microbiome profile. SIMBA successfully detected a concurrent probiotic intervention in the small intestine, which was not detectable using stool samples. DiscussionsThe high accuracy of sampling location and sealing efficacy of the SIMBA capsules makes them potentially useful research tools in clinical trials for studying diet-microbiota interactions in health and disease, and perhaps eventually for the clinical diagnosis of GI tract conditions affecting the SI such as SIBO.

Sjögren’s Syndrome (SS) is an autoimmune disorder characterized by dysfunction of exocrine glands. Primarily affected are the salivary glands, which exhibit the most frequent pathological changes. The pathogenesis involves susceptibility genes, non-genetic factors such as infections, immune cells-including T and B cells, macrophage, dendritic cells, and salivary gland epithelial cells. Inflammatory mediators such as autoantibodies, cytokines, and chemokines also play a critical role. Key signaling pathways activated include IFN, TLR, BAFF/BAFF-R, PI3K/Akt/mTOR, among others. Comprehensive understanding of these mechanisms is crucial for developing targeted therapeutic interventions. Thus, this study explores the cellular and molecular mechanisms underlying SS-related salivary gland damage, aiming to propose novel targeted therapeutic approaches.

IntroductionLucerne (Medicago sativa), is a cornerstone of China’s livestock industry, however, due to the backward agronomic strategies and technology, lucerne in China faces cultivation challenges that result in lower productivity and quality than global standards. Therefore, we undertook a meta-analysis to evaluate the impact of five distinct fertilization types on lucerne yield and nutritional quality in various locations in China. The fertilizer practices included manure application, combined mineral fertilizer and manure application (FM), biological fertilizer application, unbalanced application of two or more mineral fertilizer types, and balanced mineral fertilizer application. Furthermore, we investigate influential factors of yield and quality of lucerne under fertilization, including climatic variables (mean annual precipitation, mean annual temperature), initial soil properties (soil organic carbon; total nitrogen, pH), and agronomic factors (seeding rate, harvest frequency, and lucerne stand age).MethodsOur study analyzed 53 published papers to discern the most beneficial fertilizer for enhancing lucerne yield and nutritional quality.Results and discussionThe results showed that the fertilizer practices, on average, significantly improved yield by 31.72% and crude protein content by 11.29%, with FM emerging as the most effective, this is because mineral fertilizers provide available nutrients for lucerne, manure provides essential organic matter for microorganisms and improve soil properties. In addition, the fertilizer practices significantly reduced neutral and acid detergent fiber contents by 6.28% and 8.50%, respectively, while increasing ash content and relative feeding value. Furthermore, climatic variables, soil properties, and planting system factors such as sowing date and harvest frequency significantly affected yield and nutritional quality. The practical implications of our results emphasize the need for balanced and strategic fertilizer application to optimize lucerne production and highlight the potential to adjust cultivation practices according to environmental conditions. Balanced and strategic fertilizer application can simultaneously improve soil properties, enhance soil carbon sequestration, and reduce the emission of greenhouse gases from the soil, which is a vital measure for realizing sustainable agricultural development.

In recent years, the ever-rising penetration of distributed photovoltaics (PV) power has presented substantial challenges in power system dispatch due to its inherent randomness and unpredictability. To bridge this gap, this paper proposes a two-stage robust optimization method for power system security dispatch considering traditional generators as well as flexible resources, such as load demand response and energy storage systems. Specifically, a price-based demand response model is established to optimize the system’s load curve during a day. On this basis, a two-stage optimization problem for day-ahead and intra-day power system dispatch model is proposed. The dispatch objective is to minimize the overall cost in worst-case scenarios through properly scheduling unit commitment (UC) as well as flexible resources in each dispatch interval. Column and constraint generation (C&CG) algorithm is adopted for problem solving. The effectiveness of the proposed method is validated by case studies based on a modified 6-node system and a 24-node system. Simulation results indicate that through appropriately scheduling the energy storage system and load demand response, the proposed dispatch method can significantly reduce the total operation cost of a PV rich power system, which in turn facilitates the integration of PV power.

Loop closure detection is a crucial technique supporting localization and navigation in autonomous vehicles. Existing research focuses on feature extraction in global scenes while neglecting considerations for local dense environments. In such local scenes, there are a large number of buildings, vehicles, and traffic signs, characterized by abundant objects, dense distribution, and interlaced near and far. The current methods only employ a single strategy for constructing descriptors, which fails to provide a detailed representation of the feature distribution in dense scenes, leading to inadequate discrimination of descriptors. Therefore, this paper proposes a multi-information point cloud descriptor to address the aforementioned issues. This descriptor integrates three types of environmental features: object density, region density, and distance, enhancing the recognition capability in local dense scenes. Additionally, we incorporated wavelet transforms and invariant moments from the image domain, designing wavelet invariant moments with rotation and translation invariance. This approach resolves the issue of point cloud mismatch caused by LiDAR viewpoint variations. In the experimental part, We collected data from dense scenes and conducted targeted experiments, demonstrating that our method achieves excellent loop closure detection performance in these scenes. Finally, the method is applied to a complete SLAM system, achieving accurate mapping.

BackgroundResearch on the mental health and quality of life (hereafter QOL) among fire service recruits after the end of the COVID-19 restrictions is lacking. This study explored the network structure of depression, anxiety and insomnia, and their interconnections with QOL among fire service recruits in the post-COVID-19 era.MethodsThis cross-sectional study used a consecutive sampling of fire service recruits across China. We measured the severity of depression, anxiety and insomnia symptoms, and overall QOL using the nine-item Patient Health Questionnaire (PHQ-9), seven-item Generalized Anxiety Disorder scale (GAD-7), Insomnia Severity Index (ISI) questionnaire, and World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. We estimated the most central symptoms using the centrality index of expected influence (EI), and the symptoms connecting depression, anxiety and insomnia symptoms using bridge EI.ResultsIn total, 1,560 fire service recruits participated in the study. The prevalence of depression (PHQ-9 ≥ 5) was 15.2% (95% CI: 13.5–17.1%), while the prevalence of anxiety (GAD-7 ≥ 5) was 11.2% (95% CI: 9.6–12.8%). GAD4 (“Trouble relaxing”) had the highest EI in the whole network model, followed by ISI5 (“Interference with daytime functioning”) and GAD6 (“Irritability”). In contrast, PHQ4 (“Fatigue”) had the highest bridge EI values in the network, followed by GAD4 (“Trouble relaxing”) and ISI5 (“Interference with daytime functioning”). Additionally, ISI4 “Sleep dissatisfaction” (average edge weight = −1.335), which was the central symptom with the highest intensity value, had the strongest negative correlation with QOL.ConclusionDepression and anxiety were important mental health issues to address among fire service recruits in the post-COVID-19 era in China. Targeting central and bridge symptoms identified in network analysis could help address depression and anxiety among fire service recruits in the post-COVID-19 era.

In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO2, TiO2 and SiO2 NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO2 NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO2 NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO2 NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO2 and SiO2 NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO2 NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO2 and TiO2 NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.

Background The role of phytoestrogens in asthma/wheeze and lung function remains controversial. Thus, we aimed to examine whether phytoestrogens have beneficial effects on asthma/wheeze, lung function for subgroups and mortality.Methods Participants in this study were individuals aged 20 years or older from the National Health and Nutrition Examination Survey. Multivariate logistic regression models were fitted to examine the associations of urinary phytoestrogens with the risk of asthma/wheeze and lung function in individuals with and without asthma/wheeze. Cox proportional hazards regression was used to examine the relationship between urinary phytoestrogens and all-cause mortality. Stratified analyses were conducted based on gender and smoking status.Results We included 2465 individuals in this study. Enterolactone levels in the highest quartile were associated with a lower risk of asthma than those in the lowest quartile. As compared with the lowest quartile, the highest quartile of enterodiol and enterolactone was associated with a lower risk of wheeze. Significant associations were observed between subtypes of phytoestrogens (equol and enterolactone) and lung function (forced vital capacity (FVC) and forced expiratory volume in 1 s). Besides, FVC was higher in individuals with higher levels of enterodiol. The results were consistent in subpopulations without asthma/wheeze, while the significant difference was not observed in individuals with asthma/wheeze. The stratified analyses revealed that the associations between phytoestrogens and lung function differed by gender and smoking status among subgroups. No significant association was found between urinary phytoestrogens and all-cause mortality.Conclusion In summary, subtypes of phytoestrogens were associated with lower risk of asthma/wheeze and beneficial for lung function improvement in individuals without asthma/wheeze. Furthermore, gender and smoking may interact in the relationship between phytoestrogens and asthma/wheeze, and lung function. Further researches are needed to confirm these associations and explain the results of stratified analyses.

【Objective】Lateolabrax maculatus iridovirus (LMIV) is a serious threat to the safety of Lateolabrax maculatus aquaculture industry, and there are no specific prevention and control drugs. Early diagnosis plays an importantrole in the prevention and control of LMIV. The study intends to establish a simple, fast and accurate on-site rapid diagnosis method to provide technical support for the primary layer diagnosis of LMIV.【Method】Cross priming amplification (CPA) was used to design CPA primers for the highly conserved region of ATPase gene of LMIV. The constructed ATPase recombinant plasmid was used as a positive template to optimize the primer concentration ratio, Bst DNA polymerase, Betaine, MgSO4, dNTPs, concentration reaction temperature and time in the reaction system. Combined with the disposable nucleic acid test strip technology, the visual detection of LMIV was established by LMIV-CPA.【Result】The results showed that the optimal primer concentration ratio was 1.0 μmol/L for the cross-primer CPF, 0.4 μmol/L for the stripping primers F3 and B3, and 0.8 μmol/L for the probe primers B1 (FAM) and B2 (Biotin); Concentrations of MgSO4, Betaine, dNTPs and Bst DNA polymerase were 6 mmol/L, 0.4 mol/L, 0.6 mmol/L and 0.256 U/μL; The reaction temperature was 62 ℃ and the optimum reaction time was 45 min. The amplified product of this experiment was trapezoidal band by gel electrophoresis, the reaction product with probe was detected by a disposable nucleic acid test strip detection device, and the reaction result could be visualized by the presence or absence of a characteristic band within 3 to 5 minutes. LMIV could be detected specifically by this method without cross-reaction with other aquatic viruses and pathogenic bacteria. A total of 156 clinical samples were detected by the LMIV-CPA method and the conventional PCR method. The positive detection rate of LMIV-CPA was 93.30%, and that of the conventional PCR method was 85.83%. The detection limit of LMIV-CPA was 102 copies/μL and the sensitivity was 10 times that of conventional PCR, revealing that LMIV-CPA was better than PCR.【Conclusion】LMIV-CPA detection method does not rely on expensive instruments and professional technicians. It can be applied to the on-site rapid detection of LMIV, which provides technical support for accurate and rapid diagnosis as well as effective prevention and control of LMIV.

Abstract Colorectal cancer (CRC) is a heterogeneous disease and one of the most prevalent malignancies worldwide. Previous research has indicated that phosphatase and tensin homolog (PTEN)‐related genes found in CRC may serve as potential biomarkers for individualized treatment options. The present study aimed to examine the association between PTEN‐related genes and the prognosis of CRC patients by evaluating the significance of PTEN‐related hub genes and determining potential mechanisms and genes associated with them. Gene expression profiles and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. At present, PTEN mutations have been identified in 7% of CRC patients, according to the most recent TCGA data. Differential expression analysis revealed 54 genes as differentially expressed genes (DEGs) between PTEN‐related genes and GEO databases (GSE39582 and GSE6263). Further gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on PTEN‐related DEGs. The prognostic efficacy of the PTEN‐related DEG signature was assessed using Kaplan–Meier survival and receiver operating characteristic curve analyses. Bioinformatics methods were utilized to analyze the correlation between PTEN‐related DEGs and CRC prognosis, survival, and drug efficacy. Through these analyses, eight prognostic‐related PTEN‐related hub genes (PPARGC1A, NTRK2, ANK2, PLCB4, STC2, PLAU, CDKN1A, and HPGDS) were identified and a risk prognosis model was constructed. Notably, NTRK2 and HPGDS were found to affect drug treatment response in CRC. Targeting these prognostic‐related PTEN‐related hub genes can regulate cell death signaling, which may benefit the prognosis of CRC patients and improve drug sensitivity.

Introduction This study analyzes the impact of active smoking and secondhand smoke on the ischemic stroke burden of Pakistan, 1990–2019. Methods We used data from the Global Burden of Disease (GBD) database to conduct a comprehensive evaluation of ischemic stroke-related indicators in Pakistan, including the number of deaths, mortality rates, disability-adjusted life years (DALYs), DALY rates, and the estimated annual percentage change (EAPC). Joinpoint analysis was applied to assess sex-specific temporal trends in the burden of active smoking and secondhand smoke in Pakistan and regions of Pakistan. These assessments incorporated the Socio-Demographic Index (SDI) and we have made comparative analyses of epidemiological differences between active smoking and secondhand smoke exposure. Results The burden of ischemic stroke related to tobacco use is presented in terms of the age-standardized mortality rate (ASMR) and the age-standardized disabilityadjusted life year rate (ASDR) per 100000 population. The results (ASMR/ ASDR) for Pakistan were 6.04/130.81, in the middle SDI region 7.69/176.54, and low-middle SDI region 5.64/124.22. Pakistan’s ASMR is higher than the global average of 5.85, while ASDR is lower than the global average of 140.23. From 1990 to 2019, a downward trend in both ASMR and ASDR was observed, indicating progress in controlling tobacco-related stroke burdens. Individuals aged ≥70 years experienced the highest rates of stroke (ASMR: 66.31; ASDR: 1091.20). Gender disparities were evident: men were more affected by active smoking (ASMR: 3.08; ASDR: 78.47) than women (ASMR: 0.79; ASDR: 20.76), while women faced a higher burden from secondhand smoke (ASMR: 0.66; ASDR: 16.33) compared to men (ASMR: 0.79; ASDR: 9.93). Regional differences within Pakistan show fluctuating death and DALY rates. Notably, an increasing trend in female ASDR due to secondhand smoke in the Khyber Pakhtunkhwa Region (annual percentage change, APC=0.17 from 2010 to 2019) calls for focused health interventions. Conclusions The study finds ASMR for tobacco-related ischemic stroke in Pakistan exceeds global averages, with significant gender and age disparities in exposure to smoke, highlighting the need for targeted health interventions.

Abstract Background Timely and accurate identification of pathogens is crucial for appropriate treatment and prognosis of infectious diseases. As an increasingly popular pathogen detection method, the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens in febrile patients with suspected infection requires further exploration. Methods This study included 368 febrile patients with suspected infections who were admitted to the Infectious Disease Department of Qilu Hospital, Shandong University between January 5, 2021 and April 14, 2023. Both mNGS testing and conventional culture were performed in all patients. Clinical data of enrolled patients were collected, and the diagnostic performances of mNGS and culture were compared. Results Of the 368 enrolled patients, 231 were finally diagnosed with infection and 137 were with diseases other than infection. The sensitivity (58.01% vs. 21.65%, p

Abstract Conventional food production is restricted by energy conversion efficiency of natural photosynthesis and demand for natural resources. Solar-driven artificial food synthesis from CO2 provides an intriguing approach to overcome the limitations of natural photosynthesis while promoting carbon-neutral economy, however, it remains very challenging. Here, we report the design of a hybrid electrocatalytic−biocatalytic flow system, coupling photovoltaics-powered electrocatalysis (CO2 to formate) with five-enzyme cascade platform (formate to sugar) engineered via genetic mutation and bioinformatics, which achieves conversion of CO2 to C6 sugar (L-sorbose) with a solar-to-food energy conversion efficiency of 3.5%, outperforming natural photosynthesis by over three-fold. This flow system can in principle be programmed by coupling with diverse enzymes toward production of multifarious food from CO2. This work opens a promising avenue for artificial food synthesis from CO2 under confined environments.

Background: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common bone and joint disease. There is currently a lack of effective treatment for GIONFH, and the disease progression may lead to total hip arthroplasty (THA). The exact mechanism of GIONFH pathogenesis remains unsettled, and emerging evidence indicates that the overactivation of osteoclasts plays a pivotal role in the occurrence and progression of this condition. Our previous study has shown that cycloastragenol (CAG), a triterpenoid saponin with multiple bioactivities, is a natural osteoclast inhibitor and has a protective effect on bone loss. However, its effect on GIONFH remains unclear. Methods: In this study, methylprednisolone (MPS) (20 mg/kg) was administered via gluteal muscle injection to female Sprague–Dawley (SD) rats to induce GIONFH, and different doses of CAG (5 and 15 mg/kg) were dispensed intraperitoneally for intervention. Micro-CT screening and angiography were applied to determine the shaping of necrotic lesions, the loss of trabecular bone, and the change in the local blood supply. The molecular mechanism was established by Real-time qPCR and Western blotting. Hematoxylin and eosin (H&E) staining was performed to identify empty lacunae in the femoral head. Results: CAG treatment shanked the necrotic lesion area, inhibited the trabecular bone loss, and improved the local blood supply in the femoral head. In addition, CAG medication lowered the ratio of Tnfsf11 (encoding RANKL) to Tnfrsf11b (encoding OPG) and the expression of osteoclast-specific genes, including Acp5 and Ctsk. Consistently, CAG treatment exhibited a dose-dependent weakening effect on the expression of osteoclastogenesis and bone resorption-related proteins, including TRAP, CTSK, and MMP9. CAG addition also alleviated the occurrence of empty lacunae in the subchondral region. Conclusion: Our discoveries demonstrate that CAG is a potential option for hip preservation therapy in GIONFH patients. Translational potential of this article: The protective effect of CAG on rats with GIONFH can be translated into clinical use.

The mechanical behaviors and microstructure evolutions of different aluminum materials including high-purity aluminum, 7075 aluminum alloy and selective laser melted (SLM) AlSi10Mg alloy under shock loading were investigated through plate impact experiments and microstructure characterization. The results show that the Hugoniot elastic limit stress has nothing to do with impact velocity, but is related to material type; the peak shock stress significantly increases with increasing impact velocity and is somewhat affected by material type. The microstructure variation is highly dependent on the material type. In the 7075 aluminum alloy and selectively laser melted (SLM) AlSi10Mg alloy with relatively high strengths, the microstructure, including the grain size, grain shape and misorientation angle, is slightly influenced by the impact velocity. In high-purity aluminum with low strength, the microstructure is closely related to the impact velocity. As the impact velocity increases, dislocations, elongated subgrains, equiaxed subgrains and a fraction of low angle grain boundaries (LAGBs) first increase and then decrease, accompanied by the formation of numerous ultrafine equiaxed grains with sizes in the range of 1–5 μm. The limited adiabatic temperature rise during high-velocity impact cannot affect the microstructure. High rate loading was confirmed as an effective and promising method to refine grain structure for low strength materials.

Abstract Background The host–microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, and microbial tryptophan metabolites are potent modulators of host physiology. However, whether and how these metabolites mediate host–microbiota interactions, particularly in terms of inter-microbial communication, remains unclear. Results Here, we have demonstrated that indole-3-lactic acid (ILA) is a key molecule produced by Lactobacillus in protecting against intestinal inflammation and correcting microbial dysbiosis. Specifically, Lactobacillus metabolizes tryptophan into ILA, thereby augmenting the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Notably, ILA, IPA, and IAA possess the ability to mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10−/− spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria (e.g., Clostridium), as well as the mRNA expression of acyl-CoA dehydrogenase and indolelactate dehydrogenase in vivo and in vitro, resulting in an augmented production of IPA and IAA. Furthermore, a mutant strain of Lactobacillus fails to protect against inflammation and producing other derivatives. ILA-mediated microbial cross-feeding was microbiota-dependent and specifically enhanced indole derivatives production under conditions of dysbiosis induced by Citrobacter rodentium or DSS, but not of microbiota disruption with antibiotics. Conclusion Taken together, we highlight mechanisms by which microbiome-host crosstalk cooperatively control intestinal homoeostasis through microbiota-derived indoles mediating the inter-microbial communication. These findings may contribute to the development of microbiota-derived metabolites or targeted “postbiotic” as potential interventions for the treatment or prevention of dysbiosis-driven diseases. Video Abstract

Codebooks with small cross-correlation amplitude have extensive applications in many fields including code division multiple access (CDMA) communications systems, space-time codes, and compressed sensing. In this paper, a class of asymptotically optimal codebooks was constructed, and the maximum inner-product of these presented codebooks was determined by using properties of character sums over finite fields. Furthermore, these codebooks provided new parameters.

Abstract The conservative treatment for Kohler's disease will take several months, but some patients still have flatfoot and persistent pain. From October 2013 to July 2015, 3 children with Kohler's disease underwent navicular decompression and micro-circulation reconstruction surgery in our hospital. All the patients have received conservative treatment for more than 3 months and the effect was poor. X-ray showed the bone density of navicular increased significantly. All patients were followed up over 1 year. The 3 patients recovered well. VAS score decreased from 7.0 to 2.6 at 1 month after the operation. The pain symptom disappeared completely on 3 months after surgery. The density of navicular bone recovered to normal. Navicular decompression and micro-circulation reconstruction surgery may quickly improve the ischemic status of navicular bone, alleviate pain symptom and enable patients to resume normal activity as soon as possible.