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1.
RSC Adv ; 14(22): 15647-15655, 2024 May 10.
Article En | MEDLINE | ID: mdl-38746837

A reversible two-channel fluorescent nanocomposite with fluorescence resonance energy transfer (FRET) effect was designed for the development, analysis, and characterization of latent fingerprints (LFPs). For the construction of the FRET probe, a core of mesoporous silicas (MSNs) were used to encapsulate the organic dye rhodamine 6G (RhD-6) as an acceptor, while green-emitting monodisperse phenolic resin nanoparticles (PFR NPs) were selected as a donor. The up-conversion material (UC) of NaYF4:Yb,Er was synthesized using a simple hydrothermal method, and the MSNs-RhD-6/PFR (PRM) was electrostatically adsorbed onto the UC nanoparticles using a layer-by-layer method to obtain MSNs-RhD-6/PFR-UC (PMU). Compared to ordinary single-channel materials, PMU can be excited by different light sources (365 nm UV/980 nm laser) and its fluorescence can be reversibly switched between yellow and green, demonstrating excellent light reversibility. The PMU composites were successfully used to visualize and detect LFPs on various substrate surfaces using a simple powder coating method. Due to the existing FRET effect and dual-channel characteristics, this composite material displays excellent contrast, outperforming commercially available products for wider applicability. Even on complex backgrounds and after aging or washing treatments, it still clearly recognizes fingerprints in first-, second-, and third-level details, showing its great potential in latent fingerprint detection.

2.
Sci Rep ; 14(1): 11012, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745104

Considering the influence of thermal stress and material property variations, this study employs the Navier-Stokes equations and Fourier heat conduction law to establish a semi-implicit time-domain numerical analysis method for hypersonic aerothermal-structural coupling. Study the temporal variation pattern of different regions of the composite material wing under aerodynamic heating. Using the obtained transient temperature field of the wing, the thermal modal of the wing at different time points is calculated using the finite element method. Additionally, it conducts an analysis and discussion on the factors influencing the thermal modal. Composites can be effectively utilized as thermal protection materials for aircraft. During the aerodynamic heating process, the leading edge temperature reaches thermal equilibrium first, followed by the trailing edge, and the belly plate experiences a slower thermal response. Temperature rise significantly affects higher-order modes, with the change in material properties during the early stages of heating being the dominant factor. This leads to a faster decrease in natural frequency. As heat conduction progresses, the influencing factors of thermal stresses gradually increase, and the natural frequency decreases slowly or even rises.

3.
New Phytol ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38715078

Cultivated spinach (Spinacia oleracea) is a dioecious species. We report high-quality genome sequences for its two closest wild relatives, Spinacia turkestanica and Spinacia tetrandra, which are also dioecious, and are used to study the genetics of spinach domestication. Using a combination of genomic approaches, we assembled genomes of both these species and analyzed them in comparison with the previously assembled S. oleracea genome. These species diverged c. 6.3 million years ago (Ma), while cultivated spinach split from S. turkestanica 0.8 Ma. In all three species, all six chromosomes include very large gene-poor, repeat-rich regions, which, in S. oleracea, are pericentromeric regions with very low recombination rates in both male and female genetic maps. We describe population genomic evidence that the similar regions in the wild species also recombine rarely. We characterized 282 structural variants (SVs) that have been selected during domestication. These regions include genes associated with leaf margin type and flowering time. We also describe evidence that the downy mildew resistance loci of cultivated spinach are derived from introgression from both wild spinach species. Collectively, this study reveals the genome architecture of spinach assemblies and highlights the importance of SVs during the domestication of cultivated spinach.

4.
Article En | MEDLINE | ID: mdl-38652611

The issue of traffic congestion poses a significant obstacle to the development of global cities. One promising solution to tackle this problem is intelligent traffic signal control (TSC). Recently, TSC strategies leveraging reinforcement learning (RL) have garnered attention among researchers. However, the evaluation of these models has primarily relied on fixed metrics like reward and queue length. This limited evaluation approach provides only a narrow view of the model's decision-making process, impeding its practical implementation. Moreover, effective TSC necessitates coordinated actions across multiple intersections. Existing visual analysis solutions fall short when applied in multi-agent settings. In this study, we delve into the challenge of interpretability in multi-agent reinforcement learning (MARL), particularly within the context of TSC. We propose MARLens, a visual analytics system tailored to understand MARL-based TSC. Our system serves as a versatile platform for both RL and TSC researchers. It empowers them to explore the model's features from various perspectives, revealing its decision-making processes and shedding light on interactions among different agents. To facilitate quick identification of critical states, we have devised multiple visualization views, complemented by a traffic simulation module that allows users to replay specific training scenarios. To validate the utility of our proposed system, we present three comprehensive case studies, incorporate insights from domain experts through interviews, and conduct a user study. These collective efforts underscore the feasibility and effectiveness of MARLens in enhancing our understanding of MARL-based TSC systems and pave the way for more informed and efficient traffic management strategies.

5.
Circulation ; 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38686562

BACKGROUND: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear. METHODS: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N6-methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF. RESULTS: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury. CONCLUSIONS: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions.

6.
Nat Commun ; 15(1): 3169, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38609353

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Ecosystem , Phylogeography , Liver Neoplasms/genetics , Gene Expression Profiling
7.
Front Genet ; 15: 1381690, 2024.
Article En | MEDLINE | ID: mdl-38650857

The ALOG (Arabidopsis LSH1 and Oryza G1) family proteins, namely, DUF640 domain-containing proteins, have been reported to function as transcription factors in various plants. However, the understanding of the response and function of ALOG family genes during reproductive development and under abiotic stress is still largely limited. In this study, we comprehensively analyzed the structural characteristics of ALOG family proteins and their expression profiles during inflorescence development and under abiotic stress in rice. The results showed that OsG1/OsG1L1/2/3/4/5/6/7/8/9 all had four conserved helical structures and an inserted Zinc-Ribbon (ZnR), the other four proteins OsG1L10/11/12/13 lacked complete Helix-1 and Helix-2. In the ALOG gene promoters, there were abundant cis-acting elements, including ABA, MeJA, and drought-responsive elements. Most ALOG genes show a decrease in expression levels within 24 h under ABA and drought treatments, while OsG1L2 expression levels show an upregulated trend under ABA and drought treatments. The expression analysis at different stages of inflorescence development indicated that OsG1L1/2/3/8/11 were mainly expressed in the P1 stage; in the P4 stage, OsG1/OsG1L4/5/9/12 had a higher expression level. These results lay a good foundation for further studying the expression of rice ALOG family genes under abiotic stresses, and provide important experimental support for their functional research.

8.
Ital J Pediatr ; 50(1): 63, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38589916

BACKGROUND: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. METHODS: This observational study uses data from the National Survey of Children's Health (2020-2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. RESULTS: A total of 85,314 children aged 0-17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs. CONCLUSIONS: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs.


Heart Defects, Congenital , Language Disorders , Neurodevelopmental Disorders , Premature Birth , Child , Female , Humans , Infant, Newborn , Heart Defects, Congenital/epidemiology , Heart Defects, Congenital/genetics , Mendelian Randomization Analysis , Neurodevelopmental Disorders/epidemiology , Neurodevelopmental Disorders/genetics , Infant , Child, Preschool , Adolescent , Male
9.
Nat Commun ; 15(1): 2930, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38575640

Gradient matters with hierarchical structures endow the natural world with excellent integrity and diversity. Currently, direct ink writing 3D printing is attracting tremendous interest, and has been used to explore the fabrication of 1D and 2D hierarchical structures by adjusting the diameter, spacing, and angle between filaments. However, it is difficult to generate complex 3D gradient matters owing to the inherent limitations of existing methods in terms of available gradient dimension, gradient resolution, and shape fidelity. Here, we report a filament diameter-adjustable 3D printing strategy that enables conventional extrusion 3D printers to produce 1D, 2D, and 3D gradient matters with tunable heterogeneous structures by continuously varying the volume of deposited ink on the printing trajectory. In detail, we develop diameter-programmable filaments by customizing the printing velocity and height. To achieve high shape fidelity, we specially add supporting layers at needed locations. Finally, we showcase multi-disciplinary applications of our strategy in creating horizontal, radial, and axial gradient structures, letter-embedded structures, metastructures, tissue-mimicking scaffolds, flexible electronics, and time-driven devices. By showing the potential of this strategy, we anticipate that it could be easily extended to a variety of filament-based additive manufacturing technologies and facilitate the development of functionally graded structures.

10.
Int J Biol Macromol ; 266(Pt 2): 131076, 2024 May.
Article En | MEDLINE | ID: mdl-38531522

Physically crosslinked hydrogels have shown great potential as excellent and eco-friendly matrices for wound management. Herein, we demonstrate the development of a thermosensitive chitosan hydrogel system using CaCO3 as a gelling agent, followed by CaCO3 mineralization to fine-tune its properties. The chitosan hydrogel effectively gelled at 37 °C and above after an incubation period of at least 2 h, facilitated by the CaCO3-mediated slow deprotonation of primary amine groups on chitosan polymers. Through synthesizing and characterizing various chitosan hydrogel compositions, we found that mineralization played a key role in enhancing the hydrogels' mechanical strength, viscosity, and thermal inertia. Moreover, thorough in vitro and in vivo assessments of the chitosan-based hydrogels, whether modified with mineralization or not, demonstrated their outstanding hemostatic activity (reducing coagulation time by >41 %), biocompatibility with minimal inflammation, and biodegradability. Importantly, in vivo evaluations using a rat burn wound model unveiled a clear wound healing promotion property of the chitosan hydrogels, and the mineralized form outperformed its precursor, with a reduction of >7 days in wound closure time. This study presents the first-time utilization of chitosan/CaCO3 as a thermogelation formulation, offering a promising prototype for a new family of thermosensitive hydrogels highly suited for wound care applications.


Calcium Carbonate , Chitosan , Hydrogels , Wound Healing , Chitosan/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Calcium Carbonate/chemistry , Wound Healing/drug effects , Rats , Temperature , Male , Viscosity , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Burns/drug therapy , Burns/therapy
11.
ACS Appl Mater Interfaces ; 16(12): 15165-15176, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38476078

Amine-functionalized silica aerogel globules (AFSAGs) were first synthesized via a simple ball drop casting method followed by amine grafting. The effect of grafting time on the structure and CO2 adsorption performance of the AFSAGs was investigated. The CO2 adsorption performance was comprehensively studied by breakthrough curves, adsorption capacity and rates, surface amine loading and density, amine efficiency, adsorption halftime, and cyclic stability. The results demonstrate that prolonging the grafting time does not lead to a significant increase in surface amine content owing to pore space blockage by superabundant amine groups. The CO2 adsorption performance shows obvious dependence on surface amine density, determined by both the surface amine content and specific surface area, and working temperature. AFSAGs with a grafting time of 24 h (AFSAG24) with a moderate surface amine density have optimal CO2 adsorption capacities, which are 1.78 and 2.14 mmol/g at 25 °C with dry and humid 400 ppm CO2, respectively. The amine efficiency of AFSAG24 with low CO2 concentrations, 0.38-0.63 with dry 400 ppm-1% CO2, is the highest among the reported amine-functionalized adsorbents. After estimation with different diffusion models, the CO2 adsorption process of AFSAG24 is governed by film diffusion and intraparticle diffusion. In the range of 1-4 mm, the ball size does not affect the CO2 adsorption capacity of AFSAG24 obviously. AFSAG24 offers significant advantages for practical direct air capture compared with its state-of-the-art counterparts, such as high dynamic adsorption capacity and amine efficiency, excellent stability, and outstanding adaptation to the environment.

12.
Adv Mater ; : e2400110, 2024 Mar 17.
Article En | MEDLINE | ID: mdl-38494761

Bioelectronics, which converges biology and electronics, has attracted great attention due to their vital applications in human-machine interfaces. While traditional bioelectronic devices utilize nonliving organic and/or inorganic materials to achieve flexibility and stretchability, a biological mismatch is often encountered because human tissues are characterized not only by softness and stretchability but also by biodynamic and adaptive properties. Recently, a notable paradigm shift has emerged in bioelectronics, where living cells, and even viruses, modified via gene editing within synthetic biology, are used as core components in a new hybrid electronics paradigm. These devices are defined as "living synthelectronics," and they offer enhanced potential for interfacing with human tissues at informational and substance exchange levels. In this Perspective, the recent advances in living synthelectronics are summarized. First, opportunities brought to electronics by synthetic biology are briefly introduced. Then, strategic approaches to designing and making electronic devices using living cells/viruses as the building blocks, sensing components, or power sources are reviewed. Finally, the challenges faced by living synthelectronics are raised. It is believed that this paradigm shift will significantly contribute to the real integration of bioelectronics with human tissues.

13.
Plant J ; 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38525917

With global climate change, the high-temperature environment has severely impacted the community structure and phenotype of marine diatoms. Phaeodactylum tricornutum, a model species of marine diatom, is sensitive to high temperature, which grow slowly under high temperature. However, the regulatory mechanism of P. tricornutum in response to high-temperature is still unclear. In this study, we found that the expression level of the HSP70A in the wild type (WT) increased 28 times when exposed to high temperature (26°C) for 1 h, indicating that HSP70A plays a role in high temperature in P. tricornutum. Furthermore, overexpression and interference of HSP70A have great impact on the exponential growth phase of P. tricornutum under 26°C. Moreover, the results of Co-immunoprecipitation (Co-IP) suggested that HSP70A potentially involved in the correct folding of the photosynthetic system-related proteins (D1/D2), preventing aggregation. The photosynthetic activity results demonstrated that overexpression of HSP70A improves non-photochemical quenching (NPQ) activity under high-temperature stress. These results reveal that HSP70A regulates the photosynthetic activity of P. tricornutum under high temperatures. This study not only helps us to understand the photosynthetic activity of marine diatoms to high temperature but also provides a molecular mechanism for HSP70A in P. tricornutum under high-temperature stress.

14.
Nanoscale ; 16(13): 6402-6428, 2024 Mar 28.
Article En | MEDLINE | ID: mdl-38488215

The peripheral nervous and muscular system, a cornerstone of human physiology, plays a pivotal role in ensuring the seamless functioning of the human body. This intricate network, comprising nerves and muscles extending throughout the body, is essential for motor control, sensory feedback, and the regulation of autonomic bodily functions. The qualified implantable peripheral interface can accurately monitor the biopotential of the target tissue and conduct treatment with stimulation, enhancing the human-machine interaction and new achievements in disease cure. Implantable electrodes have revolutionized the field of neuromuscular interfaces, offering precise bidirectional communication between the neuromuscular system and external devices. They enable natural control for individuals with limb loss, bridging the gap between mind and machine and aiding neuromuscular rehabilitation. In research and medical diagnostics, implantable electrodes provide invaluable tools for studying neuromuscular function and the development of therapies. However, traditional rigid electrodes face challenges due to the dynamic nature of the peripheral neuromuscular system. Flexible and stretchable devices show immense promise in accommodating dynamic alterations, offering adaptability, and accurate monitoring of electrophysiological signals. This review delves into the challenges associated with the peripheral interface, primarily focusing on monitoring and stimulation. It then provides a summary of common materials and structural design optimizations, discusses technologies for enhancing interface adhesion and surface functionalization, and explores encapsulation methods for implanted devices. Recent advancements in energy supply and the applications of implantable, flexible, and stretchable devices are also comprehensively reviewed, with due consideration given to ethical concerns and signal analysis. The promising directions are finally presented to provide enlightenment for high-performance sensor-tissue interfaces in the future, which will promote profound progress in clinical and human-machine interaction research. Flexible and stretchable devices are at the forefront of healthcare, with the potential to transform the treatment of neuromuscular disorders and enhance human augmentation, blurring the lines between natural and artificial limbs. They represent a promising avenue for the future, with exciting applications in healthcare, science, and technology, promising to bring us closer to the seamless integration of human and machine in the realm of neuromuscular interfaces.


Artificial Limbs , Wearable Electronic Devices , Humans , Electrodes, Implanted , Electrophysiology
15.
Front Endocrinol (Lausanne) ; 15: 1340604, 2024.
Article En | MEDLINE | ID: mdl-38444589

Aim: This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. Methods: This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. Results: A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Conclusion: Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.


Diabetes Mellitus, Type 2 , Humans , Young Adult , Adult , Diabetes Mellitus, Type 2/epidemiology , Nutrition Surveys , Cross-Sectional Studies , Alanine Transaminase , Liver
16.
PLoS One ; 19(3): e0296701, 2024.
Article En | MEDLINE | ID: mdl-38427644

BACKGROUND: Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits. METHODS: The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits. RESULTS: Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified. CONCLUSIONS: WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding.


Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/genetics , Insulin Resistance/genetics , Mendelian Randomization Analysis , Genome-Wide Association Study , Glucose , Basophils
17.
Synth Syst Biotechnol ; 9(2): 259-268, 2024 Jun.
Article En | MEDLINE | ID: mdl-38450325

Descriptors play a pivotal role in enzyme design for the greener synthesis of biochemicals, as they could characterize enzymes and chemicals from the physicochemical and evolutionary perspective. This study examined the effects of various descriptors on the performance of Random Forest model used for enzyme-chemical relationships prediction. We curated activity data of seven specific enzyme families from the literature and developed the pipeline for evaluation the machine learning model performance using 10-fold cross-validation. The influence of protein and chemical descriptors was assessed in three scenarios, which were predicting the activity of unknown relations between known enzymes and known chemicals (new relationship evaluation), predicting the activity of novel enzymes on known chemicals (new enzyme evaluation), and predicting the activity of new chemicals on known enzymes (new chemical evaluation). The results showed that protein descriptors significantly enhanced the classification performance of model on new enzyme evaluation in three out of the seven datasets with the greatest number of enzymes, whereas chemical descriptors appear no effect. A variety of sequence-based and structure-based protein descriptors were constructed, among which the esm-2 descriptor achieved the best results. Using enzyme families as labels showed that descriptors could cluster proteins well, which could explain the contributions of descriptors to the machine learning model. As a counterpart, in the new chemical evaluation, chemical descriptors made significant improvement in four out of the seven datasets, while protein descriptors appear no effect. We attempted to evaluate the generalization ability of the model by correlating the statistics of the datasets with the performance of the models. The results showed that datasets with higher sequence similarity were more likely to get better results in the new enzyme evaluation and datasets with more enzymes were more likely beneficial from the protein descriptor strategy. This work provides guidance for the development of machine learning models for specific enzyme families.

18.
Arch Virol ; 169(4): 80, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38519825

Here, we report a novel wheat-infecting marafivirus, tentatively named "Triticum aestivum marafivirus" (TaMRV). The full-length genome sequence of TaMRV comprises 6,437 nucleotides, excluding the poly(A) tail. Pairwise sequence comparisons and phylogenetic analysis revealed that TaMRV may represent a novel species within the genus Marafivirus in the family Tymoviridae. We also observed a mass of isometric particles with a diameter of about 30 nm in ultrathin sections of infected wheat leaf tissue. In addition, the leafhopper Psammotettix alienus was identified as a vector for this virus. This is the first report of the occurrence of a wheat-infecting marafivirus.


Hemiptera , Tymoviridae , Animals , Tymoviridae/genetics , Triticum , RNA, Viral/genetics , Phylogeny , Genome, Viral , Genomics
19.
Vet Med Sci ; 10(3): e1412, 2024 05.
Article En | MEDLINE | ID: mdl-38504633

BACKGROUND: Lipopolysaccharide (LPS) can induce systemic inflammation and affect the growth and development of poultry. As a kind of traditional Chinese medicine, polysaccharide of Atractylodes macrocephala Koidz (PAMK) can effectively improve the growth performance of animals and improve the immunity of animal bodies. OBJECTIVES: The purpose of this study was to investigate the effects of PAMK on LPS-induced inflammatory response, proliferation, differentiation and apoptosis of chicken embryonic myogenic cells. METHODS: We used chicken embryonic myogenic cells as a model by detecting EdU/MYHC immunofluorescence, the expression of inflammation, proliferation, differentiation-related genes and proteins and the number of apoptotic cells in the condition of adding LPS, PAMK, belnacasan (an inhibitor of Caspase1) or their combinations. RESULTS: The results showed that LPS stimulation increased the expression of inflammatory factors, inhibited proliferation and differentiation, and excessive apoptosis in chicken embryonic myogenic cells, and PAMK alleviated these adverse effects induced by LPS. After the addition of belnacasan (inhibitor of Caspase1), apoptosis in myogenic cells was inhibited, and therefore, the number of apoptotic cells and the expression of pro-apoptotic genes Caspase1 and Caspase3 were increased. In addition, belnacasan inhibited the increased expression of inflammatory factors, inhibited proliferation, differentiation and excessive apoptosis in chicken embryonic myogenic cells induced by LPS. CONCLUSIONS: This study provides a theoretical basis for further exploring the mechanism of action of PAMK and exogenous LPS on chicken embryonic myogenic cells and lays the foundation for the development and application of green feed additives in animal husbandry industry.


Atractylodes , Lipopolysaccharides , Animals , Lipopolysaccharides/toxicity , Chickens , Polysaccharides/pharmacology , Apoptosis , Cell Proliferation , Inflammation/veterinary
20.
Cereb Cortex ; 34(2)2024 01 31.
Article En | MEDLINE | ID: mdl-38372291

The ecological validity of bilingual code-switching has garnered increasing attention in recent years. Contrary to traditional studies that have focused on forced language switching, emerging theories posit that voluntary switching may not incur such a cost. To test these claims and understand differences between forced and voluntary switching, the present study conducted a systematic comparison through both behavioral and neural perspectives. Utilizing fMRI alongside picture-naming tasks, our findings diverge from prior work. Voluntary language switching not only demonstrated switching costs at the behavioral level but also significantly activated brain regions associated with inhibitory control. Direct comparisons of voluntary and forced language switching revealed no significant behavioral differences in switching costs, and both shared several common brain regions that were activated. On the other hand, a nuanced difference between the two types of language switching was revealed by whole-brain analysis: voluntary switching engaged fewer language control regions than forced switching. These findings offer a comprehensive view of the neural and behavioral dynamics involved in bilingual language switching, challenging prior claims that voluntary switching imposes no behavioral or neural costs, and thus providing behavioral and neuroimaging evidence for the involvement of inhibitory control in voluntary language switching.


Magnetic Resonance Imaging , Multilingualism , Humans , Language , Cognition , China
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