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Understanding the molecular underpinnings of disease severity and progression in human studies is necessary to develop metabolism-related preventative strategies for severe COVID-19. Metabolites and metabolic pathways that predispose individuals to severe disease are not well understood. In this study, we generated comprehensive plasma metabolomic profiles in >550 patients from the Longitudinal EMR and Omics COVID-19 Cohort. Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis, representing 555 distinct patients, most of which had single timepoints. Regression models adjusted for demographics, risk factors, and comorbidities, were used to determine metabolites associated with predisposition to and/or persistent effects of COVID-19 severity, and metabolite changes that were transient/lingering over the disease course. Sphingolipids/phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were acutely elevated, reflecting the particular importance of pyrimidine metabolism in active COVID-19. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. Our results lay the groundwork for identifying putative biomarkers and preventive strategies for severe COVID-19. [ABSTRACT FROM AUTHOR]

Traditional approaches to understanding metabolomics in mental illness have focused on investigating a single disorder or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales. Furthermore, three of these four metabolites demonstrated a higher degree of alteration in men who reported poor scores in all three dimensions compared to men with poor scores in only one, suggesting the potential for shared underlying biology but a differing degree of perturbation when depression and anxiety symptoms co-occur. Our findings implicate pathways of interest relevant to the overlap of mental health conditions in aging veterans and could represent clinically translatable targets underlying poor mental health in this high-risk population. [ABSTRACT FROM AUTHOR]

Maternal infection and stress during the prenatal period have been associated with adverse neurodevelopmental outcomes in offspring, suggesting that biomarkers of increased inflammation in the mothers may associate with poorer developmental outcomes. In 491 mother–child pairs from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we investigated the association between maternal levels of two inflammatory biomarkers; interleukin-8 (IL-8) and C-Reactive Protein (CRP) during early (10–18 wks) and late (32–38 wks) pregnancy with offspring scores in the five domains of the Ages and Stages Questionnaire, a validated screening tool for assessing early life development. We identified a robust association between early pregnancy IL-8 levels and decreased fine-motor (β: −0.919, 95%CI: −1.425, −0.414, p = 3.9 × 10−4) and problem-solving skills at age two (β: −1.221, 95%CI: −1.904, −0.414, p = 4.9 × 10−4). Associations between IL-8 with other domains of development and those for CRP did not survive correction for multiple testing. Similarly, while there was some evidence that the detrimental effects of early pregnancy IL-8 were strongest in boys and in those who were not breastfed, these interactions were not robust to correction for multiple testing. However, further research is required to determine if other maternal inflammatory biomarkers associate with offspring neurodevelopment and work should continue to focus on the management of factors leading to increases in IL-8 levels in pregnant women. [ABSTRACT FROM AUTHOR]

To explore novel methods for the analysis of metabolomics data, we compared the ability of Partial Least Squares Discriminant Analysis (PLS-DA) and Bayesian networks (BN) to build predictive plasma metabolite models of age three asthma status in 411 three year olds (n = 59 cases and 352 controls) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) study. The standard PLS-DA approach had impressive accuracy for the prediction of age three asthma with an Area Under the Curve Convex Hull (AUCCH) of 81%. However, a permutation test indicated the possibility of overfitting. In contrast, a predictive Bayesian network including 42 metabolites had a significantly higher AUCCH of 92.1% (p for difference < 0.001), with no evidence that this accuracy was due to overfitting. Both models provided biologically informative insights into asthma; in particular, a role for dysregulated arginine metabolism and several exogenous metabolites that deserve further investigation as potential causative agents. As the BN model outperformed the PLS-DA model in both accuracy and decreased risk of overfitting, it may therefore represent a viable alternative to typical analytical approaches for the investigation of metabolomics data. [ABSTRACT FROM AUTHOR]

The in utero environment during pregnancy has important implications for the developing health of the child. We aim to examine the potential impact of maternal metabolome at two different timepoints in pregnancy on offspring respiratory health in early life. In 685 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial, we assessed the prospective associations between maternal metabolites at both baseline (10–18 weeks gestation) and third trimester (32–38 weeks gestation) and the risk of child asthma or recurrent wheeze by age three using logistic regression models accounting for confounding factors. Subgroup analyses were performed by child sex. Among 632 metabolites, 19 (3.0%) and 62 (9.8%) from baseline and third trimester, respectively, were associated with the outcome (p-value < 0.05). Coffee-related metabolites in the maternal metabolome appeared to be of particular importance. Caffeine, theophylline, trigonelline, quinate, and 3-hydroxypyridine sulfate were inversely associated with asthma risk at a minimum of one timepoint. Additional observations also highlight the roles of steroid and sphingolipid metabolites. Overall, there was a stronger relationship between the metabolome in later pregnancy and offspring asthma risk. Our results suggest that alterations in prenatal metabolites may act as drivers of the development of offspring asthma. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency contributes to a multitude of health conditions, but its biological mechanisms are not adequately understood. Untargeted metabolomics offers the opportunity to comprehensively examine the metabolic profile associated with variations in vitamin D concentrations. The objective of the current analysis was to identify metabolites and metabolic pathways associated with plasma 25-hydroxyvitamin D [25(OH)D] concentrations. The current study included children of pregnant women in the Vitamin D Antenatal Asthma Reduction Trial, who had 25(OH)D and global metabolomics data at age 1 and 3 years. We assessed the cross-sectional associations between individual metabolites and 25(OH)D using linear regression adjusting for confounding factors. Twelve metabolites were significantly associated with plasma 25(OH)D concentrations at both age 1 and 3 after correction for multiple comparisons, including three members of the n-6 polyunsaturated fatty acid (PUFA) metabolism pathway (linoleate, arachidonate, and docosapentaenoate) inversely associated with 25(OH)D. These PUFAs along with four other significant metabolites were replicated in the independent Childhood Asthma Management Program (CAMP) cohort. Both vitamin D and n-6 PUFAs are involved in inflammatory processes, and evidence from cell and animal studies demonstrate a plausible biological mechanism where the active form of 25(OH)D may influence n-6 PUFA metabolism. These relationships warrant further investigation in other populations. [ABSTRACT FROM AUTHOR]

It is not controversial that study design considerations and challenges must be addressed when investigating the linkage between single omic measurements and human phenotypes. It follows that such considerations are just as critical, if not more so, in the context of multi-omic studies. In this review, we discuss (1) epidemiologic principles of study design, including selection of biospecimen source(s) and the implications of the timing of sample collection, in the context of a multi-omic investigation, and (2) the strengths and limitations of various techniques of data integration across multi-omic data types that may arise in population-based studies utilizing metabolomic data. [ABSTRACT FROM AUTHOR]

We hypothesized metabolomic profiling could be utilized to identify children who scored poorly on the communication component of the Ages and Stages Questionnaire (ASQ); which assesses development in childhood, and to provide candidate biomarkers for autism spectrum disorders (ASD). In a population of three-year-old children, 15 plasma metabolites, were significantly (p < 0.05) different between children who were categorized as having communication skills that were "on schedule" (n = 365 (90.6%)) as compared to those "requiring further monitoring/evaluation" (n = 38 (9.4%)) according to multivariable regression models. Five of these metabolites, including three endocannabinoids, were also dysregulated at age one (n = 204 "on schedule", n = 24 "further monitoring/evaluation") in the same children. Stool metabolomic profiling identified 11 significant metabolites. Both the plasma and stool results implicated a role for tryptophan and tyrosine metabolism; in particular, higher levels of N-formylanthranilic acid were associated with an improved communication score in both biosample types. A model based on the significant plasma metabolites demonstrated high sensitivity (88.9%) and specificity (84.5%) for the prediction of autism by age 8. These results provide evidence that ASQ communication score and metabolomic profiling of plasma and/or stool may provide alternative approaches for early diagnosis of ASD, as well as insights into the pathobiology of these conditions. [ABSTRACT FROM AUTHOR]

As the economy develops and urbanization progresses, the amount of arable land continues to decline. In this context, the cultivation of double-season rice is particularly important for enhancing yield per unit area. However, research on the physiological mechanisms that contribute to high yields in double-season early rice varieties with short growing seasons is still limited. To address this gap, we conducted a field study using two early rice varieties, Zhongzu18 and Yongxian15, to examine their production characteristics, photosynthesis, fluorescence, and energy metabolism. The results indicate that Zhongzu18 has a significantly higher seed-setting rate, grain weight, and total grain yield compared to Yongxian15. Additionally, Zhongzu18 exhibits a higher head rice rate and a lower degree of chalkiness, along with a reduced chalky grain rate. Furthermore, the total dry matter weight and the ratio of panicle weight to total weight for Zhongzu18 were significantly greater than those for Yongxian15. After anthesis, Zhongzu18 also demonstrated a higher leaf net photosynthetic rate and actual fluorescence quantum efficiency compared to Yongxian15. Moreover, the levels of ATP and ATPase, as well as the activities of antioxidant enzymes and the expression of sucrose transport-related genes, were significantly increased in Zhongzu18 plants relative to Yongxian15. We conclude that the enhanced photosynthetic efficiency and energy production in Zhongzu18 lead to more effective assimilation and carbohydrate transport to the grains, resulting in higher grain yields and improved rice quality.

The transient plane source (TPS) method heat transfer model was established. A body-fitted coordinate system is proposed to transform the unstructured grid structure to improve the speed of solving the heat transfer direct problem of the winding probe. A parallel Bayesian optimization algorithm based on a multi-objective hybrid strategy (MHS) is proposed based on an inverse problem. The efficiency of the thermophysical properties inversion was improved. The results show that the meshing method of 30° is the best. The transformation of body-fitted mesh is related to the orthogonality and density of the mesh. Compared with parameter inversion the computational fluid dynamics (CFD) software, the absolute values of the relative deviations of different materials are less than 0.03%. The calculation speeds of the body-fitted grid program are more than 36% and 91% higher than those of the CFD and self-developed unstructured mesh programs, respectively. The application of body-fitted coordinate system effectively improves the calculation speed of the TPS method. The MHS is more competitive than other algorithms in parallel mode, both in terms of accuracy and speed. The accuracy of the inversion is less affected by the number of initial samples, time range, and parallel points. The number of parallel points increased from 2 to 6, reducing the computation time by 66.6%. Adding parallel points effectively accelerates the convergence of algorithms.

The manufacturing precision of electro-hydraulic servo valve sleeves is critical to the performance and longevity of the valves. To ensure the service life of these valves, the valve sleeve is typically made from high-hardness martensitic stainless steel, which is considered a hard-to-cut material. Current honing methods often suffer from inefficiency and instability. This study compares the honing processes using electroplated and sintered oilstones, emphasizing processing efficiency and surface quality. Initially, the morphology of the oilstones was examined. Equivalent honing depth and material removal rate per unit width were developed to characterized material removal. The influence of various parameters on honing depth and material removal rates was explored, along with the surface morphology and roughness after honing. The results indicated that electroplated oilstones achieved a material removal rate 2.5 times higher than sintered oilstones. In contrast, sintered oilstones produced superior surface quality. To optimize both surface quality and efficiency, we proposed a sequential honing method: using electroplated oilstones for significant material removal followed by sintered oilstones for surface finishing, which enhanced efficiency by 1.6 times. Electroplated oilstone has broad application prospects in the field of precision and efficient machining of hydraulic components.

Nuclear Factor Y A (NF-YA) transcription factors are widely involved in multiple plant biological processes, such as embryogenesis, abscisic acid signaling, and abiotic stress response. This study presents a comprehensive genome-wide identification and expression profiling of NF-YA transcription factors in blueberry ( Vaccinium corymbosum ), an important economic crop with good adaptability, under abiotic stress conditions. Given the economic significance and health benefits of blueberries, understanding their responses to environmental stresses, such as salt, drought, and temperature extremes, is crucial. A total of 24 NF-YA transcription factors were identified through bioinformatics analyses, including sequence alignment, phylogenetic tree construction, and conserved motif analysis. The expression patterns of these NF-YA genes were evaluated in various tissues (roots, stems, and leaves) and under different stress treatments (abscisic acid, salt, and cold) using quantitative real-time PCR (qRT-PCR). The results indicated that most VcNF-YA genes exhibited higher expression levels in stems and leaves compared to roots. Most VcNF-YA s were responsive to the stress treatment. Furthermore, cis -acting element analysis revealed that the promoters of VcNF-YA s were enriched with elements responsive to abiotic stress, suggesting their pivotal role in stress adaptation. This research unveils the expressional responses of NF-YA transcription factors in blueberry upon abiotic stresses and lays the groundwork for future studies on improving crop adaptation.

With the progress of society and the improvement of agricultural scientific technology, the single focus on high yield for rice production has gradually shifted to high quality. Coordinated development of grain yield and rice quality has become a core issue for researchers, and the underlying mechanisms remain to be solved. Two varieties, Zhongzheyou1 (ZZY1) and Zhongzheyou8 (ZZY8), were used as study materials under field conditions. The yield of ZZY1 was higher than that of ZZY8, which was mainly characterized by a higher seed-setting rate and grain weight. The rice quality of ZZY8 was better than that of ZZY1, primarily due to lower chalkiness and a higher head rice rate. The total dry matter weight of ZZY1 was lower than that of ZZY8, but the proportion of panicle dry matter weight or nonstructural carbohydrate to the total in the former was higher than that of the latter. The maximum grain-filling rate, average grain-filling rate, and key enzyme activities of ZZY1 were significantly higher than those of ZZY8, while the active grain-filling period was shorter than that of ZZY8. Furthermore, the ATP/ATPase content and energy charge values in the grains of ZZY1 were higher than those of ZZY8 at the early grain-filling stage. Transcriptome analysis showed that carbohydrate and energy metabolism were the main ways affecting the yield and quality of the two varieties. The energy production of ZZY1 was insufficient to simultaneously supply the needs thus leading to the discordant formation in its grain yield and rice quality formation.

Black soldier fly larvae ( Hermetia illucens ) (BSFL) are insect larvae with significant ecological and economic value. This study aims to investigate whether swill and manure had any effects on the transcriptome and metabolome of BSFL. Through high-throughput transcriptome sequencing, we found that larvae fed with swill exhibited higher levels of gene expression, especially with the upregulation of genes related to energy metabolism, amino acid metabolism, and redox reactions. Metabolomics analysis showed a significant increase in energy metabolism-related metabolites, such as organic acids and amino acids, in the swill-fed larvae. In contrast, gene expression and metabolic characteristics in the pig manure-fed group indicated a higher stress response, with relevant genes and metabolites (such as short-chain fatty acids and antioxidants) showing significant upregulation. GO and KEGG enrichment analyses further supported these results, suggesting that swill promotes larval growth and metabolism, whereas pig manure induces the activation of stress response mechanisms. These findings offer clear molecular and physiological insights into the optimization of substrate selection for enhancing the performance of BSFL in waste management.

A d 10 -Cd cluster containing sandwich-type arsenotungstate [C 3 H 12 N 2 ] 6 [Cd 4 Cl 2 (B- α -AsW 9 O 34 ) 2 ] was synthesized and its structure characterized through elemental analyses, X-ray powder diffraction (XRPD), IR spectroscopy, X-ray photoelectron spectroscopy (XPS), and single-crystal X-ray diffraction. The X-ray analysis revealed that the molecular unit of the compound consists of a captivating tetra-Cd-substituted sandwich-type polyoxoanion, accompanied by six elegantly protonated 1,2-diaminopropane as counter ions. The further novelty of the tetranuclear cadmium cluster lies in its occupied chlorine atom sites. This makes it highly susceptible to coordinate reactions with nitrogen on polycyclic aromatic hydrocarbons, thereby exhibiting different fluorescent signals that facilitate the identification and detection of these carcinogenic substances in methanol.

At present, China's coal mine permanent tunneling support commonly uses mechanized drilling and anchoring equipment; there are low support efficiency, labor intensity, and other issues. In order to further improve the support efficiency and liberate productivity, this paper further researches the trajectory planning of the drilling and anchoring materials of the robotic arm for the drilling machine "grasping-carrying-loading-unloading" on the basis of the drilling and anchoring robotic system designed by the team in the previous stage. Firstly, the kinematic model of the robotic arm with material was established by improving the D-H parameter method. Then, the working space of the robotic arm with the material was analyzed using the Monte Carlo method. The singular bit-shaped region of the robotic arm was restricted, and obstacles were removed from the working space. The inverse kinematics was utilized to solve the feasible domain of the robotic arm with material. Secondly, in order to avoid blind searching, the guidance of the Bi-RRT algorithm was improved by adding the target guidance factor, and the two-way tree connection strategy for determining the feasible domain was combined with the Bi-RRT algorithm's feasible domain judgment bi-directional tree connection strategy to improve the convergence speed of the Bi-RRT algorithm. Then, in order to adapt to the dynamic environment and avoid the global planning algorithm from falling into the local minima, on the basis of the above planning methods, an improved Bi-RRT trajectory planning algorithm incorporating the artificial potential field was proposed, which takes the planned paths as the guiding potential field of the artificial potential field to make full use of the global information and avoid falling into the local minimization. Finally, a simulation environment was built in a ROS environment to compare and analyze the planning effect of different algorithms. The simulation results showed that the improved Bi-RRT trajectory planning algorithm incorporating the artificial potential field improved the optimization speed by 69.8% and shortened the trajectory length by 46.6% compared with the traditional RRT algorithm.

Wireless neural signal transmission is essential for both neuroscience research and neural disorder therapies. However, conventional wireless systems are often constrained by low sampling rates, limited channel counts, and their support of only a single transmission mode. Here, we developed a wireless bi-directional brain-computer interface system featuring dual transmission modes. This system supports both low-power Bluetooth transmission and high-sampling-rate Wi-Fi transmission, providing flexibility for various application scenarios. The Bluetooth mode, with a maximum sampling rate of 14.4 kS/s, is well suited for detecting low-frequency signals, as demonstrated by both in vitro recordings of signals from 10 to 50 Hz and in vivo recordings of 16-channel local field potentials in mice. More importantly, the Wi-Fi mode, offering a maximum sampling rate of 56.8 kS/s, is optimized for recording high-frequency signals. This capability was validated through in vitro recordings of signals from 500 to 2000 Hz and in vivo recordings of single-neuron spike firings with amplitudes reaching hundreds of microvolts and high signal-to-noise ratios. Additionally, the system incorporates a wireless stimulation function capable of delivering current pulses up to 2.55 mA, with adjustable pulse width and polarity. Overall, this dual-mode system provides an efficient and flexible solution for both neural recording and stimulation applications.

Background: Protein secondary structure prediction (PSSP) is a critical task in computational biology, pivotal for understanding protein function and advancing medical diagnostics. Recently, approaches that integrate multiple amino acid sequence features have gained significant attention in PSSP research., Objectives: We aim to automatically extract additional features represented by evolutionary information from a large number of sequences while simultaneously incorporating positional information for more comprehensive sequence features. Additionally, we consider the interdependence between secondary structures during the prediction stage., Methods: To this end, we propose a deep neural network model, ILMCNet, which utilizes a language model and Conditional Random Field (CRF). Protein language models (PLMs) pre-trained on sequences from multiple large databases can provide sequence features that incorporate evolutionary information. ILMCNet uses positional encoding to ensure that the input features include positional information. To better utilize these features, we propose a hybrid network architecture that employs a Transformer Encoder to enhance features and integrates a feature extraction module combining a Convolutional Neural Network (CNN) with a Bidirectional Long Short-Term Memory Network (BiLSTM). This design enables deep extraction of localized features while capturing global bidirectional information. In the prediction stage, ILMCNet employs CRF to capture the interdependencies between secondary structures., Results: Experimental results on benchmark datasets such as CB513, TS115, NEW364, CASP11, and CASP12 demonstrate that the prediction performance of our method surpasses that of comparable approaches., Conclusions: This study proposes a new approach to PSSP research and is expected to play an important role in other protein-related research fields, such as protein tertiary structure prediction.

It is very important to clarify the optimization method of the rock-like material ratio for accurately characterizing mechanical properties similar to the original rock. In order to explore the optimal ratio of rock-like materials in gneissic granite, the water-paste ratio, iron powder content and coarse sand content were selected as the influencing factors of the ratio. An orthogonal test design and sensitivity analysis of variance were used to obtain the significant influencing factors of the ratio factors on seven macroscopic mechanical parameters, including compressive strength σ c , tensile strength σ t , shear strength τ f , elastic modulus E , Poisson's ratio ν , internal friction angle φ and cohesion c. A multivariate linear regression equation was constructed to obtain the quantitative relationship between the significant ratio factors and the macroscopic mechanical parameters. Finally, a rock-like material ratio optimization program based on genetic algorithm inversion was written. The results show that the water-paste ratio had extremely significant effects on σ c , σ t , τ f , E , ν and c. The iron powder content had a highly significant effect on σ c , σ t , τ f and c , and it had a significant effect on ν and φ . Coarse sand content had a significant effect on σ c , E and c. The multiple linear regression model has good reliability after testing, which can provide theoretical support for predicting the macroscopic mechanical parameters of rock-like materials to a certain extent. After testing, the ratio optimization program works well. When the water-paste ratio is 0.5325, the iron powder content is 3.975% and the coarse sand content is 15.967%, it is the optimal ratio of rock-like materials.

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. The progressive HIV infection is marked by the increasing size and diversity of latent HIV reservoirs until an effective immune response is mobilized, which can control but not eliminate HIV infection. The stalemate between HIV replication and the immune response is manifested by the establishment of a viral set point. ART initiation during the early stage limits HIV reservoir development, preserves immune function, improves the quality of life, and may lead to ART-free viral remission in a few people living with HIV (PLWH). However, for the overwhelming majority of PLWH, early ART initiation alone does not cure HIV, and lifelong ART is needed to sustain viral suppression. A critical area of research is focused on determining whether HIV could be functionally cured if additional treatments are provided alongside early ART. Several HIV interventions including Block and Lock, Shock and Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell therapy, and gene therapy have demonstrated delayed viral rebound and/or viral remission in animal models and/or some PLWH. Whether or not their application during early infection can improve the success of HIV remission is less studied. Herein, we review the current state of clinical and investigative HIV interventions and discuss their potential to improve the likelihood of post-treatment remission if initiated during early infection.

Phenazine natural products are a class of colored nitrogen-containing heterocycles produced by various microorganisms mainly originating from marine and terrestrial sources. The tricyclic ring molecules show various chemical structures and the decorating groups dedicate extensive pharmacological activities, including antimicrobial, anticancer, antiparasitic, anti-inflammatory, and insecticidal. These secondary metabolites provide natural materials for screening and developing medicinal compounds in the field of medicine and agriculture due to biological activities. The review presents a systematic summary of the literature on natural phenazines in the past decade, including over 150 compounds, such as hydroxylated, O -methylated, N -methylated, N -oxide, terpenoid, halogenated, glycosylated phenazines, saphenic acid derivatives, and other phenazine derivatives, along with their characterized antimicrobial and anticancer activities. This review may provide guidance for the investigation of phenazines in the future.

The ongoing obesity epidemic has raised awareness of the complex physiology of adipose tissue. Abnormal adipocyte differentiation results in the development of systemic metabolic disorders such as insulin resistance and diabetes. The conjugation of NEDD8 (neural precursor cell expressed, developmentally downregulated 8) to target protein, termed neddylation, has been shown to mediate adipogenesis. However, much remains unknown about its role in adipogenesis. Here, we demonstrated that neddylation and its targets, the cullin (CUL) family members, are differentially regulated during mouse and human adipogenesis. Inhibition of neddylation by MLN4924 significantly reduced adipogenesis of 3T3-L1 and human stromal vascular cells. Deletion of NAE1, a subunit of the only NEDD8 E1 enzyme, suppressed neddylation and impaired adipogenesis. Neddylation deficiency did not affect mitotic cell expansion. Instead, it disrupted CREB/CEBPβ/PPARγ signaling, essential for adipogenesis. Interestingly, among the neddylation-targeted CUL family members, deletion of CUL3, but not CUL1, CUL2, or CUL4A, largely replicated the adipogenic defects observed with neddylation deficiency. A PPARγ agonist minimally rescued the adipogenic defects caused by the deletion of NAE1 and CUL3. In conclusion, our study demonstrates that neddylation and its targeted CUL3 are crucial for adipogenesis. These findings provide potential targets for therapeutic intervention in obesity and metabolic disorders.

Chinese cabbage ( Brassica rapa L. ssp. pekinensis ) ranks among the most cultivated and consumed vegetables in China. A major threat to its production is Plasmodiophora brassicae, which causes large root tumors, obstructing nutrient and water absorption and resulting in plant withering. This study used a widely targeted metabolome technique to identify resistance-related metabolites in resistant (DH40R) and susceptible (DH199S) Chinese cabbage varieties after inoculation with P. brassicae . This study analyzed disease-related metabolites during different periods, identifying 257 metabolites linked to resistance, enriched in the phenylpropanoid biosynthesis pathway, and 248 metabolites linked to susceptibility, enriched in the arachidonic acid metabolism pathway. Key metabolites and genes in the phenylpropanoid pathway were upregulated at 5 days post-inoculation (DPI), suggesting their role in disease resistance. In the arachidonic acid pathway, linoleic acid and gamma-linolenic acid were upregulated at 5 and 22 DPI in resistant plants, while arachidonic acid was upregulated at 22 DPI in susceptible plants, leading to the conclusion that arachidonic acid may be a response substance in susceptible plants after inoculation. Many genes enriched in these pathways were differentially expressed in DH40R and DH199S. The research provided insights into the defense mechanisms of Chinese cabbage against P. brassicae through combined metabolome and transcriptome analysis.

The electrospinning of pure chitosan nanofibers is highly sensitive to environmental humidity, which limits their production consistency and applicability. This study investigates the addition of sodium chloride (NaCl) to chitosan solutions to enhance spinnability and mitigate the effigurefects of low humidity. NaCl was incorporated into the electrospun chitosan solution, leading to increased conductivity and decreased viscosity. These modifications improved the electrospinning process. Comparative analyses between chitosan membranes (CM) and sodium-chloride-added chitosan membranes (SCM) revealed no significant differences in chemical structure, mechanical strength, or in vitro cell proliferation. This indicates that the addition of 1% ( w / v ) NaCl does not adversely affect the fundamental properties of the chitosan membranes. The findings demonstrate that NaCl addition is a viable strategy for producing electrospun chitosan nanofibers in low-humidity environments, maintaining their physicochemical properties while enhancing spinnability.

Background/objectives: Nitrogen is an essential macroelement for plant growth and productivity. Calcium (Ca 2+ ) acts as a critical second messenger in numerous adaptations and developmental processes in plants. The Calcineurin B-like protein (CBL)-interacting protein kinase (CIPK) signaling pathway has been demonstrated to be involved in multiple intracellular ion homeostasis of plants in response to stresses. However, whether CIPKs are involved in nitrate deficiency stress remains largely unknown., Methods: In this study, we screened Arabidopsis thaliana T-DNA insertion mutants of the CIPK family under nitrate deficiency conditions by a reverse genetic strategy., Results: We found that the cipk1 mutant showed a shorter primary root and had a lower fresh weight and total N content compared with wildtype (WT) plants under nitrate deficiency. The CIPK1 complementation lines completely rescued the sensitive phenotype. Additionally, CIPK1 mutation caused nitrogen-starvation marker genes to be decreased under nitrate deficiency. We further found that CIPK1 interacted with teosintebranched 1/cycloidea/proliferating cell factor 1-20 (TCP20) in a yeast two-hybrid system., Conclusions: Collectively, our results reveal a novel role of CIPK1 in response to nitrate deficiency in Arabidopsis .

Cytokinins (CKs) are a group of phytohormones that are involved in plant growth, development, and disease resistance. The isopentenyl transferase (IPT) and cytokinin oxidase/dehydrogenase (CKX) families comprise key enzymes controlling CK biosynthesis and degradation. However, an integrated analysis of these two gene families in radish has not yet been explored. In this study, 13 RsIPT and 12 RsCKX genes were identified and characterized, most of which had four copies in Brassica napus and two copies in radish and other diploid Brassica species. Promoter analysis indicated that the genes contained at least one phytohormone or defense and stress responsiveness cis-acting element. RsIPTs and RsCKXs were expanded through segmental duplication. Moreover, strong purifying selection drove the evolution of the two gene families. The expression of the RsIPT and RsCKX genes distinctly showed diversity in different tissues and developmental stages of the root. Expression profiling showed that RsCKX1-1/1-2/1-3 was significantly upregulated in club-resistant materials during primary infection, suggesting their vital function in clubroot resistance. The interaction network of CKX proteins with similar 3D structures also reflected the important role of RsCKX genes in disease resistance. This study provides a foundation for further functional study on the IPT and CKX genes for clubroot resistance improvement in Raphanus .

γ-valerolactone (GVL), derived from biomass, is a crucial platform compound for biofuel synthesis and various industrial applications. Current methods for synthesizing GVL involve expensive catalysts and high-pressure hydrogen, prompting the search for greener alternatives. This study focuses on a novel zirconium phosphate (ZrP)-pillared zeolite MCM-36 derivative catalyst for converting levulinic acid (LA) to GVL using alcohol as a hydrogen source. The incorporation of ZrP significantly contributes to mesoporosity and greatly enhances the acidity of the catalysts. Additionally, we employed 31 P MAS NMR to comprehensively investigate the influence of phosphorus species on both the acidity and the catalytic conversion of LA to GVL. By adjusting the Zr-to-P ratios, we synthesized catalysts with enhanced acidity, achieving high conversion of LA and selectivity for GVL. The catalyst exhibited high recyclability, showing only minor deactivation over the course of five cycles. Furthermore, the catalyst was successfully applied to the one-pot conversion of furfural to GVL, showcasing its versatility in biomass conversion. This study highlights the potential of the MCM-ZrP1 catalyst for sustainable biomass conversion and offers insights for future research in renewable energy technologies.

Jaundice is a symptom of high blood bilirubin levels affecting about 80% of neonates. In neonates fed with breast milk, jaundice is particularly prevalent and severe, which is likely multifactorial. With the development of genomics and metagenomics, a deeper understanding of the neonatal gut microbiota has been achieved. We find there are accumulating evidence to indicate the importance of the gut microbiota in the mechanism of jaundice. In this paper, we present new comprehensive insight into the relationship between the microbiota and jaundice. In the new perspective, the gut is a crucial crossroad of bilirubin excretion, and bacteria colonizing the gut could play different roles in the excretion of bilirubin, including Escherichia coli as the main traffic jam causers, some Clostridium and Bacteroides strains as the traffic police, and most probiotic Bifidobacterium and Lactobacillus strains as bystanders with no effect or only a secondary indirect effect on the metabolism of bilirubin. This insight could explain why breast milk jaundice causes a longer duration of blood bilirubin and why most probiotics have limited effects on neonatal jaundice. With the encouragement of breastmilk feeding, our perspective could guide the development of new therapy methods to prevent this side effect of breastfeeding.

In this paper, a Cr coating was prepared by induction heating and pack-cementation chromizing on AISI 304 austenitic stainless steel. Then, the cold-rolling deformation and annealing treatment were introduced to refine the coarse matrix grains caused by pack-chromizing and improve the overall performance of 304 austenitic stainless steel. The phase composition, element distribution, and microstructure of the coating were carefully characterized. The microhardness, wear resistance, and corrosion resistance of the coating were tested. The results show that the Cr coating with a thickness of 100 μm is mainly composed of a (Cr,Fe) 23 C 6 , (Cr,Fe) 7 C 3 , and α-Fe-Cr solid solution. After the cold-rolling deformation and subsequent annealing treatment, the grains are significantly refined and the Cr coating is divided into two layers, consisting of carbon-chromium compounds such as Cr 23 C 6 , Cr 7 C 3 , Cr 2 C, and Cr 3 C 2 in the surface layer and a Fe-Cr solid solution in the subsurface layer. The cold-rolling deformation and annealing treatment significantly improved the microhardness and wear resistance of the coated sample, and the corrosion resistance was also better than that of the uncoated sample.

In order to reveal the mechanism of sleeved stud connectors, 15 push-out specimens were designed, and static loading tests were conducted to evaluate the mechanical performance. The shear performance differences between the novel sleeved studs and conventional welded studs were compared. Referring to the experimental results, an Abaqus nonlinear finite element model was established to study the shear mechanism of sleeved stud connectors. Parametric analysis was conducted to investigate the effects of stud height, sleeve filling material, and sleeve diameter on the mechanical performance of the connectors. The experimental and finite element analysis results indicated that the ultimate shear bearing capacity and shear stiffness of the sleeved stud connectors were higher than those of ordinary welded studs, and the maximum slip was relatively small. Compared to conventional welded studs, the ultimate bearing capacity of sleeved studs increased by 4% to 8%, and the shear stiffness increased by 25% to 35%. Since the shear behavior of sleeved studs mainly occurred at the base of the studs, the influence of stud height on shear performance was relatively small. However, sleeve and stud diameter have a great influence on bearing capacity and stiffness. As the Ultra-High Performance Concrete (UHPC) near the base of the stud effectively enhanced the shear carrying capacity of the sleeved stud connectors, the shear carrying capacity and shear stiffness increased with the increase in the sleeve diameter.

Nanogenerators possess the capability to harvest faint energy from the environment. Among them, thermoelectric (TE), triboelectric, piezoelectric (PE), and moisture-enabled nanogenerators represent promising approaches to micro-nano energy collection. These nanogenerators have seen considerable progress in material optimization and structural design. Printing technology has facilitated the large-scale manufacturing of nanogenerators. Although inks can be compatible with most traditional functional materials, this inevitably leads to a decrease in the electrical performance of the materials, necessitating control over the rheological properties of the inks. Furthermore, printing technology offers increased structural design flexibility. This review provides a comprehensive framework for ink-based nanogenerators, encompassing ink material optimization and device structural design, including improvements in ink performance, control of rheological properties, and efficient energy harvesting structures. Additionally, it highlights ink-based nanogenerators that incorporate textile technology and hybrid energy technologies, reviewing their latest advancements in energy collection and self-powered sensing. The discussion also addresses the main challenges faced and future directions for development.

The mechanical properties and microstructure of the cemented paste backfill (CPB) in dry-wet cycle environments are particularly critical in backfill mining. In this study, coal gangue, fly ash, cement, glass fiber, and nano-SiO 2 were used to prepare CPB, and dry-wet cycle tests on CPB specimens with different curing ages were conducted. The compressive, tensile, and shear strength of CPB specimens with different curing ages under different dry-wet cycles were analyzed, and the microstructural damage of the specimens was observed by scanning electron microscopy (SEM). The results show that compared with the specimens without dry-wet cycles, the uniaxial compressive strength, tensile strength, and shear strength of the specimens with a curing age of 7 d after seven dry-wet cycles were the smallest, being reduced by 40.22%, 58.25%, and 66.8%, respectively. After seven dry-wet cycles, the compressive, tensile, and shear strength of the specimens with the curing age of 28 d decreased slightly. The SEM results show that with the increasing number of dry-wet cycles, the internal structure of the specimen becomes more and more loose and fragile, and the damage degree of the structural skeleton gradually increases, leading to the poor mechanical properties of CPB specimens. The number of cracks and pores on the specimen surface is relatively limited after a curing age of 28 d, while the occurrence of internal structural damage within the specimen remains insignificant. Therefore, the dry-wet cycle has an important influence on the both mechanical properties and microstructure of CPB. This study provides a reference for the treatment of coal-based solid waste and facilitates the understanding of the mechanical properties of backfill materials under dry-wet cycling conditions.

One-step carbonization was explored to prepare biochar using the residue of a traditional Chinese herbal medicine, Atropa belladonna L. (ABL), as the raw material. The resulting biochar, known as ABLB4, was evaluated for its potential as a sustainable material for norfloxacin (NOR) adsorption in water. Subsequently, a comprehensive analysis of adsorption isotherms, kinetics, and thermodynamics was conducted through batch adsorption experiments. The maximum calculated NOR adsorption capacity was 252.0 mg/g at 298 K, and the spontaneous and exothermic adsorption of NOR on ABLB4 could be better suited to a pseudo-first-order kinetic model and Langmuir model. The adsorption process observed is influenced by pore diffusion, π-π interaction, electrostatic interaction, and hydrogen bonding between ABLB4 and NOR molecules. Moreover, the utilization of response surface modeling (RSM) facilitated the optimization of the removal efficiency of NOR, yielding a maximum removal rate of 97.4% at a temperature of 304.8 K, an initial concentration of 67.1 mg/L, and a pH of 7.4. Furthermore, the biochar demonstrated favorable economic advantages, with a payback of 852.5 USD/t. More importantly, even after undergoing five cycles, ABLB4 exhibited a consistently high NOR removal rate, indicating its significant potential for application in NOR adsorption.

Desirable characteristics of electrospun chitosan membranes (ESCM) for guided bone regeneration are their nanofiber structure that mimics the extracellular fiber matrix and porosity for the exchange of signals between bone and soft tissue compartments. However, ESCM are susceptible to swelling and loss of nanofiber and porous structure in physiological environments. A novel post-electrospinning method using di-tert-butyl dicarbonate (tBOC) prevents swelling and loss of nanofibrous structure better than sodium carbonate treatments. This study aimed to evaluate the hypothesis that retention of nanofiber morphology and high porosity of tBOC-modified ESCM (tBOC-ESCM) would support more bone mineralization in osteoblast-fibroblast co-cultures compared to Na 2 CO 3 treated membranes (Na 2 CO 3 -ESCM) and solution-cast chitosan solid films (CM-film). The results showed that only the tBOC-ESCM retained the nanofibrous structure and had approximately 14 times more pore volume than Na 2 CO 3 -ESCM and thousands of times more pore volume than CM-films, respectively. In co-cultures, the tBOC-ESCM resulted in a significantly greater calcium-phosphate deposition by osteoblasts than either the Na 2 CO 3 -ESCM or CM-film ( p < 0.05). This work supports the study hypothesis that tBOC-ESCM with nanofiber structure and high porosity promotes the exchange of signals between osteoblasts and fibroblasts, leading to improved mineralization in vitro and thus potentially improved bone healing and regeneration in guided bone regeneration applications., Competing Interests: Authors Hengjie Su, Tomoko Fujiwara and Joel D Bumgardner have a patent on the TEA/tBOC-ESCMs that were used in this study (U.S. Patent No. 11,878,088; Chitosan Nanofiber Compositions, Compositions Comprising Modified Chitosan, and Methods of Use).

Electricity theft presents a significant financial burden to utility companies globally, amounting to trillions of dollars annually. This pressing issue underscores the need for transformative measures within the electrical grid. Accordingly, our study explores the integration of block chain technology into smart grids to combat electricity theft, improve grid efficiency, and facilitate renewable energy integration. Block chain's core principles of decentralization, transparency, and immutability align seamlessly with the objectives of modernizing power systems and securing transactions within the electricity grid. However, as smart grids advance, they also become more vulnerable to attacks, particularly from smart meters, compared to traditional mechanical meters. Our research aims to introduce an advanced approach to identifying energy theft while prioritizing user privacy, a critical aspect often neglected in existing methodologies that mandate the disclosure of sensitive user data. To achieve this goal, we introduce three distributed algorithms: lower-upper decomposition (LUD), lower-upper decomposition with partial pivoting (LUDP), and optimized LUD composition (OLUD), tailored specifically for peer-to-peer (P2P) computing in smart grids. These algorithms are meticulously crafted to solve linear systems of equations and calculate users' "honesty coefficients," providing a robust mechanism for detecting fraudulent activities. Through extensive simulations, we showcase the efficiency and accuracy of our algorithms in identifying deceitful users while safeguarding data confidentiality. This innovative approach not only bolsters the security of smart grids against energy theft, but also addresses privacy and security concerns inherent in conventional energy-theft detection methods.

Using sodium lignosulfonate as feedstock, ZnCl 2 and NaHCO 3 co-activated the hierarchical porous carbons (HPCs) were prepared by one-pot pyrolysis with different NaHCO 3 dosages (0-4 g) and carbonization temperatures (400-600 °C). Subsequently, phosphotungstate (HPW) was supported with the resulting biochar for the α-pinene hydration reaction to produce α-terpineol. The optimum preparation conditions were determined according to the yield of α-terpineol. The formation mechanism and physicochemical properties of HPCs were analyzed through TG, SEM, XPS, XRD, FT-IR, and N 2 adsorption-desorption isotherms. The results demonstrated that NaHCO 3 underwent a two-step reaction which liberated a substantial quantity of CO 2 , thereby enhancing activated carbon's macroporous and mesoporous structures. Simultaneously, NaHCO 3 mitigated strong acid gas (HCl) emissions during ZnCl 2 activation. Compared with AC450-4:8:0 prepared by ZnCl 2 activation alone, the total pore volume of AC450-4:8:2 prepared by co-activation is increased from 0.595 mL/g to 0.754 mL/g and the mesopore rate from 47.7% to 77.8%, which is conducive to reducing the steric hindrance of the hydration reaction and improving the selectivity. Hydration experiments show that the selectivity of α-terpineol is 55.7% under HPW/AC450-4:8:2 catalysis, higher than 31.0% for HPW and 47.4% for HPW/AC450-4:8:0.

Heart development is a spatiotemporally regulated process that extends from the embryonic phase to postnatal stages. Disruption of this highly orchestrated process can lead to congenital heart disease or predispose the heart to cardiomyopathy or heart failure. Consequently, gaining an in-depth understanding of the molecular mechanisms governing cardiac development holds considerable promise for the development of innovative therapies for various cardiac ailments. While significant progress in uncovering novel transcriptional and epigenetic regulators of heart development has been made, the exploration of post-translational mechanisms that influence this process has lagged. Culling-RING E3 ubiquitin ligases (CRLs), the largest family of ubiquitin ligases, control the ubiquitination and degradation of ~20% of intracellular proteins. Emerging evidence has uncovered the critical roles of CRLs in the regulation of a wide range of cellular, physiological, and pathological processes. In this review, we summarize current findings on the versatile regulation of cardiac morphogenesis and maturation by CRLs and present future perspectives to advance our comprehensive understanding of how CRLs govern cardiac developmental processes.

Disordered immunity, aging, human immunodeficiency virus type one (HIV-1) infection, and responses to antiretroviral therapy are linked. However, how each factor is linked with the other(s) remains incompletely understood. It has been reported that accelerated aging, advanced HIV-1 infection, inflammation, and host genetic factors are associated with host cellular, mitochondrial, and metabolic alterations. However, the underlying mechanism remains elusive. With these questions in mind, we used chronically HIV-1-infected CD34-NSG humanized mice (hu-mice) to model older people living with HIV and uncover associations between HIV-1 infection and aging. Adult humanized mice were infected with HIV-1 at the age of 20 weeks and maintained for another 40 weeks before sacrifice. Animal brains were collected and subjected to transcriptomics, qPCR, and immunofluorescence assays to uncover immune disease-based biomarkers. CD4+ T cell decline was associated with viral level and age. Upregulated C1QA, CD163, and CXCL16 and downregulated LMNA and CLU were identified as age-associated genes tied to HIV-1 infection. Ingenuity pathway analysis affirmed links to innate immune activation, pyroptosis signaling, neuroinflammation, mitochondrial dysfunction, cellular senescence, and neuronal dysfunction. In summary, CD34-NSG humanized mice are identified as a valuable model for studying HIV-1-associated aging. Biomarkers of immune senescence and neuronal signaling are both age- and virus-associated. By exploring the underlying biological mechanisms that are linked to these biomarkers, interventions for next generation HIV-1-infected patients can be realized.

In the research of robot systems, path planning and obstacle avoidance are important research directions, especially in unknown dynamic environments where flexibility and rapid decision makings are required. In this paper, a state attention network (SAN) was developed to extract features to represent the interaction between an intelligent robot and its obstacles. An auxiliary actor discriminator (AAD) was developed to calculate the probability of a collision. Goal-directed and gap-based navigation strategies were proposed to guide robotic exploration. The proposed policy was trained through simulated scenarios and updated by the Soft Actor-Critic (SAC) algorithm. The robot executed the action depending on the AAD output. Heuristic knowledge (HK) was developed to prevent blind exploration of the robot. Compared to other methods, adopting our approach in robot systems can help robots converge towards an optimal action strategy. Furthermore, it enables them to explore paths in unknown environments with fewer moving steps (showing a decrease of 33.9%) and achieve higher average rewards (showning an increase of 29.15%).

Methamphetamine (METH) abuse inflicts both physical and psychological harm. While our previous research has established the regulatory role of miR-29c-3p in behavior sensitization, the underlying mechanisms and target genes remain incompletely understood. In this study, we employed the isobaric tags for relative and absolute quantitation (iTRAQ) technique in conjunction with Ingenuity pathway analysis (IPA) to probe the putative molecular mechanisms of METH sensitization through miR-29c-3p inhibition. Through a microinjection of AAV-anti-miR-29c-3p into the nucleus accumbens (NAc) of mice, we observed the attenuation of METH-induced locomotor effects. Subsequent iTRAQ analysis identified 70 differentially expressed proteins (DEPs), with 22 up-regulated potential target proteins identified through miR-29c-3p target gene prediction and IPA analysis. Our focus extended to the number of neuronal branches, the excitatory synapse count, and locomotion-related pathways. Notably, GPR37, NPC1, and IREB2 emerged as potential target molecules for miR-29c-3p regulation, suggesting their involvement in the modulation of METH sensitization. Quantitative PCR confirmed the METH-induced aberrant expression of Gpr37 , Npc1 , and Ireb2 in the NAc of mice. Specifically, the over-expression of miR-29c-3p led to a significant reduction in the mRNA level of Gpr37 , while the inhibition of miR-29c-3p resulted in a significant increase in the mRNA level of Gpr37 , consistent with the regulatory principle of miRNAs modulating target gene expression. This suggests that miR-29c-3p potentially influences METH sensitization through its regulation of neuroplasticity. Our research indicates that miR-29c-3p plays a crucial role in regulating METH-induced sensitization, and it identified the potential molecular of miR-29c-3p in regulating METH-induced sensitization.

This paper proposes a non-contact current measurement method for three-phase rectangular busbars based on TMR (tunneling magneto-resistance) sensors, due to their advantages of large dynamic range, wide bandwidth, light weight, and easy installation. A non-contact current sensor composed of only three TMR sensors is developed and the TMR sensors are respectively placed at a location with a certain distance from the surface of each rectangular busbar to measure the magnetic fields generated by the busbar currents. To calibrate the developed current sensor, i.e., to establish the relationship between the magnetic fields measured by the TMR sensors and the currents flowing in the three-phase rectangular busbars, we designed a thyristor-controlled resistive load as a calibrator, which is connected to a downstream branch of the distribution cabinet. By switching the resistive load, a calibration current, which can be identified from the background current, is generated in one rectangular busbar and its value is measured at the location of the calibrator, and transmitted wirelessly to the location of the TMR sensors. A new and robust method is proposed to extract the voltage components, corresponding to the calibration current, from the voltage waveforms of the TMR sensors. By calculating the proportional coefficients between the calibration currents and the extracted voltage components, online calibration of the current sensor is achieved. We designed and implemented a current measurement system consisting of a current sensor using TMR sensors, a thyristor-controlled resistive load for current sensor calibration, and a data acquisition circuit based on a multi-channel analog-to-digital converter (ADC). Current measurement experiments were performed in a practical distribution cabinet installed in our laboratory. Compared to the measurement results using a commercial current probe with an accuracy of 1%, the relative error of the measured currents in RMS is less than 2.5% and the phase error is less than 1°, while the nonlinearity error of the current sensor is better than 0.8%.

Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 ( n = 7) or endoglin ( n = 7) deleted in the endothelial cells or brain focally ( n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.

Taxus , a vital source of the anticancer drug paclitaxel, grapples with a pronounced supply-demand gap. Current efforts to alleviate the paclitaxel shortage involve expanding Taxus cultivation through cutting propagation. However, traditional cutting propagation of Taxus is difficult to root and time-consuming. Obtaining the roots with high paclitaxel content will cause tree death and resource destruction, which is not conducive to the development of the Taxus industry. To address this, establishing rapid and efficient stem rooting systems emerges as a key solution for Taxus propagation, facilitating direct and continuous root utilization. In this study, Agrobacterium rhizogenes were induced in the 1-3-year-old branches of Taxus × media Rehder, which has the highest paclitaxel content. The research delves into the rooting efficiency induced by different A. rhizogenes strains, with MSU440 and C58 exhibiting superior effects. Transcriptome and metabolome analyses revealed A. rhizogenes ' impact on hormone signal transduction, amino acid metabolism, zeatin synthesis, and secondary metabolite synthesis pathways in roots. LC-MS-targeted quantitative detection showed no significant difference in paclitaxel and baccatin III content between naturally formed and induced roots. These findings underpin the theoretical framework for T. media rapid propagation, contributing to the sustainable advancement of the Taxus industry.

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) ( B. dorsalis ) is an important agricultural, major invasive, and quarantine pest that can cause significant damage to the economic value of the fruit and vegetable industry. Male bait is one of the most effective methods of surveying, monitoring, and controlling B. dorsalis . In our study, we constructed cDNA libraries using total RNA extracted independently from the antennae, mouthparts, and thoracic legs of male and female adults and the ovipositors of female adults and screened out four aldehyde-oxidase-related genes (AOX-related), C58800 , C66700 , C67485 , and C67698 . Molecular docking predictions showed that eight compounds, including 3,4-dimethoxycinnamyl alcohol, 3,4-dimethoxy-cinnamaldehyde, deet, ethyl N-acetyl-N-butyl-β-alaninate, n-butyl butyrate, n-butyl butyrate, ethyl butyrate, methyl eugenol, and ethyl acetate, could combine with proteins encoded by the four B. dorsalis AOX-related genes. Furthermore, QPCR was performed to confirm that four compounds, including 3,4-dimethoxy cinnamic aldehyde, butyl levulinic acid ethyl ester (mosquito repellent), butyl butyrate, and methyl eugenol, induced significant changes in the AOX-related genes of B. dorsalis . These results provide useful information and guidance for the batch screening of potentially useful compounds and the search for effective attractants of B. dorsalis .

Root rot of Paris polyphylla has received widespread attention due to its threat to yield and leads to serious economic losses. However, the relationship among the rhizosphere microbial community, metabolites and root rot disease remained largely unexplored. Herein, we used integrated 16S rRNA, ITS, RNA sequencing and UPLC-MS/MS to systematically investigate the differences between healthy and diseased P. polyphylla . We found that root rot reduced the microbial diversity in the diseased P. polyphylla compared with the healthy control. The relative abundance of the bacterial phylum Actinobacteria increased in the diseased rhizome of P. polyphylla . For the fungal community, root rot disease contributed to an increased relative abundance of Ascomycota and decreased Glomeromycota at the phylum level. The transcriptomic results showed that the differently expressed genes were significantly enriched in the "Biosynthesis of various alkaloids", "flavonoid biosynthesis" and "isoflavonoid biosynthesis" and "Phenylpropanoid biosynthesis" was dramatically enriched in healthy P. polyphylla compared with that in diseased P. polyphylla. Likewise, the metabolomic results showed that the biosynthesis of secondary metabolites and metabolic pathways was found to be significantly enriched by differential metabolites. Taken together, the study of combining metabolomics with microbiomes can help us enhance our understanding of the mechanisms of plant resistance to root rot disease, thereby discovering specific metabolites and microorganisms that can resist pathogen infection in P. polyphylla .