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1.
Adv Sci (Weinh) ; : e2403771, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961647

ABSTRACT

The rational design of visible-light-responsive catalysts is crucial for converting solar energy into hydrogen energy to promote sustainable energy development. In this work, a C─S─C bond is introduced into g-C3N4 (CN) through S doping. With the help of the flexible C─S─C bond under specific stimuli, a hollow coral-like porous structure of S-doped g-C3N4 (S-CN) is synthesized for the first time. And an S-doped g-C3N4/ZnIn2S4 (S-CN/ZIS) heterojunction catalyst is in situ synthesized based on S-CN. S0.5-CN/ZIS exhibits excellent photocatalytic hydrogen evolution (PHE) efficiency (19.25 mmol g-1 h-1), which is 2.7 times higher than that of the g-C3N4/ZnIn2S4 (CN/ZIS) catalyst (8.46 mmol g-1 h-1), with a high surface quantum efficiency (AQE) of 34.43% at 420 nm. Experiments and theoretical calculations demonstrate that the excellent photocatalytic performance is attributed to the larger specific surface area and porosity, enhanced interfacial electric field (IEF) effect, and appropriate hydrogen adsorption Gibbs free energy (ΔGH*). The synergistic effect of S doping and S-scheme heterojunction contributes to the above advancement. This study provides new insights and theoretical basis for the design of CN-based photocatalysts.

2.
Methods ; 229: 125-132, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964595

ABSTRACT

DNase I hypersensitive sites (DHSs) are chromatin regions highly sensitive to DNase I enzymes. Studying DHSs is crucial for understanding complex transcriptional regulation mechanisms and localizing cis-regulatory elements (CREs). Numerous studies have indicated that disease-related loci are often enriched in DHSs regions, underscoring the importance of identifying DHSs. Although wet experiments exist for DHSs identification, they are often labor-intensive. Therefore, there is a strong need to develop computational methods for this purpose. In this study, we used experimental data to construct a benchmark dataset. Seven feature extraction methods were employed to capture information about human DHSs. The F-score was applied to filter the features. By comparing the prediction performance of various classification algorithms through five-fold cross-validation, random forest was proposed to perform the final model construction. The model could produce an overall prediction accuracy of 0.859 with an AUC value of 0.837. We hope that this model can assist scholars conducting DNase research in identifying these sites.

3.
PNAS Nexus ; 3(6): pgae215, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38919269

ABSTRACT

Fireflies were believed to originally evolve their novel bioluminescence as warning signals to advertise their toxicity to predators, which was later adopted in adult mating. Although the evolution of bioluminescence has been investigated extensively, the warning signal hypothesis of its origin has not been tested. In this study, we test this hypothesis by systematically determining the presence or absence of firefly toxin lucibufagins (LBGs) across firefly species and inferring the time of origin of LBGs. We confirm the presence of LBGs in the subfamily Lampyrinae, but more importantly, we reveal the absence of LBGs in other lineages, including the subfamilies of Luciolinae, Ototretinae, and Psilocladinae, two incertae sedis lineages, and the Rhagophthalmidae family. Ancestral state reconstructions for LBGs based on firefly phylogeny constructed using genomic data suggest that the presence of LBGs in the common ancestor of the Lampyrinae subfamily is highly supported but unsupported in more ancient nodes, including firefly common ancestors. Our results suggest that firefly LBGs probably evolved much later than the evolution of bioluminescence. We thus conclude that firefly bioluminescence did not originally evolve as direct warning signals for toxic LBGs and advise that future studies should focus on other hypotheses. Moreover, LBG toxins are known to directly target and inhibit the α subunit of Na+, K+-ATPase (ATPα). We further examine the effects of amino acid substitutions in firefly ATPα on its interactions with LBGs. We find that ATPα in LBG-containing fireflies is relatively insensitive to LBGs, which suggests that target-site insensitivity contributes to LBG-containing fireflies' ability to deal with their own toxins.

4.
Gastroenterol Rep (Oxf) ; 12: goae066, 2024.
Article in English | MEDLINE | ID: mdl-38912038

ABSTRACT

During liver ischemia-reperfusion injury, existing mechanisms involved oxidative stress, calcium overload, and the activation of inflammatory responses involve mitochondrial injury. Mitochondrial autophagy, a process that maintains the normal physiological activity of mitochondria, promotes cellular metabolism, improves cellular function, and facilitates organelle renewal. Mitochondrial autophagy is involved in oxidative stress and apoptosis, of which the PINK1-Parkin pathway is a major regulatory pathway, and the deletion of PINK1 and Parkin increases mitochondrial damage, reactive oxygen species production, and inflammatory response, playing an important role in mitochondrial quality regulation. In addition, proper mitochondrial permeability translational cycle regulation can help maintain mitochondrial stability and mitigate hepatocyte death during ischemia-reperfusion injury. This mechanism is also closely related to oxidative stress, calcium overload, and the aforementioned autophagy pathway, all of which leads to the augmentation of the mitochondrial membrane permeability transition pore opening and cause apoptosis. Moreover, the release of mitochondrial DNA (mtDNA) due to oxidative stress further aggravates mitochondrial function impairment. Mitochondrial fission and fusion are non-negligible processes required to maintain the dynamic renewal of mitochondria and are essential to the dynamic stability of these organelles. The Bcl-2 protein family also plays an important regulatory role in the mitochondrial apoptosis signaling pathway. A series of complex mechanisms work together to cause hepatic ischemia-reperfusion injury (HIRI). This article reviews the role of mitochondria in HIRI, hoping to provide new therapeutic clues for alleviating HIRI in clinical practice.

5.
Front Surg ; 11: 1404513, 2024.
Article in English | MEDLINE | ID: mdl-38859999

ABSTRACT

Objective: To investigate the short-term clinical efficacy of robot-assisted retrograde drilling and arthroscopic microfracture for osteochondral lesions of the talus (OCLT). Methods: This study was divided into two groups: experimental group: robot-assisted retrograde drilling group; control group: arthroscopic microfracture group. A total of 6 OCLT patients who were treated with robot navigation-assisted retrograde drilling and 10 OCLT patients who were treated with arthroscopic microfracture between October 2020 and October 2021 were retrospectively analyzed. There were 11 males and five females, with a mean age of 36 years. The patients were followed up for 6-12 months to compare the changes in the OCLT lesion area by magnetic resonance imaging (MRI), visual analogue scale/score (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) before and after surgery. Results: All 16 patients were followed up for an average of 8 months, and no complications such as joint infection, nerve injury, or active bleeding occurred during the follow-up period. Only one patient suffered discomfort involving transient postoperative pain in the operative area, but did not experience long-term numbness or chronic pain. Postoperative MRI revealed that none of the patients had severe signs of osteonecrosis, osteolysis or cystic changes of the talus, with lesion areas smaller than those before surgery. The difference was statistically significant (P < 0.01). The patients in the experimental group showed a more significant improvement in the last 3 months than in the first 3 months of the follow-up period. At the last follow-up, the VAS score was 3 points in the experimental group and 2.2 points in the control group, and the AOFAS score was 88.6 points in the experimental group and 88 points in the control group, all of which were significantly higher than those before operation, and the differences were statistically significant, but there was no statistically significant difference between the groups. Conclusion: Both robot navigation-assisted retrograde drilling and arthroscopic microfracture for bone marrow stimulation (BMS) to treat OCLT in all patients obtained satisfactory effects in the short term. In addition, the follow-up revealed that with excellent efficacy and few complications, robot navigation-assisted retrograde drilling was safe and minimally invasive, and greatly reduced operative time. Consequently, robot navigation-assisted retrograde drilling for BMS was a safe and effective procedure for the treatment of OCLT.

6.
Int J Surg ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884274

ABSTRACT

OBJECTIVES: Exploring the efficacy of an artificial intelligence (AI) model derived from the analysis of CT images to precisely forecast the therapeutic outcomes of singular-session extracorporeal shock wave lithotripsy (ESWL) in the management of ureteral stones. METHODS: A total of 317 patients diagnosed clinically with ureteral stones were included in this investigation. Unenhanced CT was administered to the participants within the initial fortnight preceding the inaugural ESWL. The internal cohort consisted of 250 individuals from a local healthcare facility, whereas the external cohort comprised 67 participants from another local medical institution. The proposed framework comprises three main components: an automated semantic segmentation model developed using 3D U-Net, a feature extractor that integrates radiomics and autoencoder techniques, and an ESWL efficacy prediction model trained with various machine learning algorithms. All participants underwent thorough postoperative follow-up examinations four weeks hence. The efficacy of ESWL was defined by the absence of stones or residual fragments measuring ≤2 mm in KUB X-ray assessments. Model stability and generalizability were judiciously validated through a fivefold cross-validation approach and a multi-center external test strategy. Moreover, Shapley Additive Explanations (SHAP) values for individual features were computed to elucidate the nuanced contributions of each feature to the model's decision-making process. RESULTS: The semantic segmentation model we constructed exhibited an average Dice coefficient of 0.88 ± 0.08 on the external testing set. ESWL classifiers built using Support Vector Machine (SVM), Random Forest (RF), XGBoost (XB), and CatBoost (CB) achieved AUROC values of 0.78, 0.84, 0.85, and 0.90, respectively, on the internal validation set. For the external testing set, SVM, RF, XB, and CB predicted ESWL with AUROC values of 0.68, 0.79, 0.80, and 0.83, respectively, with the last one being the optimal algorithm. The radiomics features and auto-encoder features made significant contributions to the decision-making process of the classification model. CONCLUSIONS: This investigation unmistakably underscores the remarkable predictive prowess exhibited by a scrupulously crafted AI model using CT images to precisely anticipate the therapeutic results of a singular session of extracorporeal shock wave lithotripsy for ureteral stones.

7.
Materials (Basel) ; 17(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38894020

ABSTRACT

Analytical modeling of the squeezing force for aircraft wings and fuselage panels in the existing literature usually assumes uniform deformation of the rivets, while in reality, the deformation of the rivets is non-uniform. To achieve high-quality squeezing force modeling, this paper introduces Coulomb's friction and four critical adjustments to the original equation: the non-uniform rivet/sheet interference along the sheet's hole axial ordinate; the barreling effect when calculating the driven head's volume; the spring-back of the driven head's dimensions; the modified height of the driven head; and the modified sheet-hole expanded diameter considering the convex structure of the driven head. The calculated values of the proposed new model demonstrate an improved level of accuracy, particularly under squeeze ratios commonly encountered in the aerospace industry.

8.
Plants (Basel) ; 13(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38891343

ABSTRACT

While it is well known that plants interpret UV-B as an environmental cue and a potential stressor influencing their growth and development, the specific effects of UV-B-induced oxidative stress on the dynamics of membrane lipids and proteins remain underexplored. Here, we demonstrate that UV-B exposure notably increases the formation of ordered lipid domains on the plasma membrane (PM) and significantly alters the behavior of the Glycine max nodule autoregulation receptor kinase (GmNARK) protein in Arabidopsis leaves. The GmNARK protein was located on the PM and accumulated as small particles in the cytoplasm. We found that UV-B irradiation interrupted the lateral diffusion of GmNARK proteins on the PM. Furthermore, UV-B light decreases the efficiency of surface molecule internalization by clathrin-mediated endocytosis (CME). In brief, UV-B irradiation increased the proportion of the ordered lipid phase and disrupted clathrin-dependent endocytosis; thus, the endocytic trafficking and lateral mobility of GmNARK protein on the plasma membrane are crucial for nodule formation tuning. Our results revealed a novel role of low-intensity UV-B stress in altering the organization of the plasma membrane and the dynamics of membrane-associated proteins.

9.
Adv Mater ; : e2404309, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837485

ABSTRACT

Developing high-performance polarization-sensitive ultraviolet photodetectors is crucial for their application in military remote sensing, detection, bio-inspired navigation, and machine vision. However, the significant absorption in the visible light range severely limits the application of polarization-sensitive ultraviolet photodetectors, such as high-quality anti-interference imaging. Here, based on a wide-bandgap organic semiconductor single crystal (trans-1,2-bis(5-phenyldithieno[2,3-b:3',2'-d]thiophen-2-yl)ethene, BPTTE), high-performance polarization-sensitive solar-blind ultraviolet photodetectors with a dichroic ratio close to 4.26 are demonstrated. The strong anisotropy of 2D grown BPTTE single crystals in molecular vibration and optical absorption is characterized by various techniques. Under voltage modulation, stable and efficient detection of polarized light is demonstrated, attributed to the intrinsic anisotropy of transition dipole moment in the bc crystal plane, rather than other factors. Finally, high-contrast polarimetric imaging and anti-interference imaging are successfully demonstrated based on BPTTE single crystal photodetectors, highlighting the potential of organic semiconductors for polarization-sensitive solar-blind ultraviolet photodetectors.

10.
BMC Genomics ; 25(1): 563, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840042

ABSTRACT

BACKGROUND: Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals (HMs). Effective scientific cultivation management, which enhances the yield and quality of B. papyrifera, necessitates an understanding of its regulatory mechanisms in response to HM stress. RESULTS: Twelve Metallothionein (MT) genes were identified in B. papyrifera. Their open reading frames ranged from 186 to 372 bp, encoding proteins of 61 to 123 amino acids with molecular weights between 15,473.77 and 29,546.96 Da, and theoretical isoelectric points from 5.24 to 5.32. Phylogenetic analysis classified these BpMTs into three subclasses: MT1, MT2, and MT3, with MT2 containing seven members and MT3 only one. The expression of most BpMT genes was inducible by Cd, Mn, Cu, Zn, and abscisic acid (ABA) treatments, particularly BpMT2e, BpMT2d, BpMT2c, and BpMT1c, which showed significant responses and warrant further study. Yeast cells expressing these BpMT genes exhibited enhanced tolerance to Cd, Mn, Cu, and Zn stresses compared to control cells. Yeasts harboring BpMT1c, BpMT2e, and BpMT2d demonstrated higher accumulation of Cd, Cu, Mn, and Zn, suggesting a chelation and binding capacity of BpMTs towards HMs. Site-directed mutagenesis of cysteine (Cys) residues indicated that mutations in the C domain of type 1 BpMT led to increased sensitivity to HMs and reduced HM accumulation in yeast cells; While in type 2 BpMTs, the contribution of N and C domain to HMs' chelation possibly corelated to the quantity of Cys residues. CONCLUSION: The BpMT genes are crucial in responding to diverse HM stresses and are involved in ABA signaling. The Cys-rich domains of BpMTs are pivotal for HM tolerance and chelation. This study offers new insights into the structure-function relationships and metal-binding capabilities of type-1 and - 2 plant MTs, enhancing our understanding of their roles in plant adaptation to HM stresses.


Subject(s)
Broussonetia , Metallothionein , Metals, Heavy , Phylogeny , Metallothionein/genetics , Metallothionein/metabolism , Metallothionein/chemistry , Metals, Heavy/metabolism , Broussonetia/genetics , Broussonetia/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Stress, Physiological , Amino Acid Sequence , Protein Binding
11.
J Mol Biol ; : 168653, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38871176

ABSTRACT

Meiotic recombination plays a pivotal role in genetic evolution. Genetic variation induced by recombination is a crucial factor in generating biodiversity and a driving force for evolution. At present, the development of recombination hotspot prediction methods has encountered challenges related to insufficient feature extraction and limited generalization capabilities. This paper focused on the research of recombination hotspot prediction methods. We explored deep learning-based recombination hotspot prediction and scrutinized the shortcomings of prevalent models in addressing the challenge of recombination hotspot prediction. To addressing these deficiencies, an automated machine learning approach was utilized to construct recombination hotspot prediction model. The model combined sequence information with physicochemical properties by employing TF-IDF-Kmer and DNA composition components to acquire more effective feature data. Experimental results validate the effectiveness of the feature extraction method and automated machine learning technology used in this study. The final model was validated on three distinct datasets and yielded accuracy rates of 97.14%, 79.71%, and 98.73%, surpassing the current leading models by 2%, 2.56%, and 4%, respectively. In addition, we incorporated tools such as SHAP and AutoGluon to analyze the interpretability of black-box models, delved into the impact of individual features on the results, and investigated the reasons behind misclassification of samples. Finally, an application of recombination hotspot prediction was established to facilitate easy access to necessary information and tools for researchers. The research outcomes of this paper underscore the enormous potential of automated machine learning methods in gene sequence prediction.

12.
Small ; : e2401110, 2024 Jun 14.
Article in Catalan | MEDLINE | ID: mdl-38874051

ABSTRACT

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O2 and 1O2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition.

13.
J Med Chem ; 67(11): 9104-9123, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38829030

ABSTRACT

Amyloid-ß oligomers (AßOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aß plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AßOs, aimed at early AD diagnosis. An initial screening identified compound 18 as being highly selective for AßOs. Subsequent analysis revealed that compound 20 improved serum stability while retaining affinity for AßOs. The most promising iteration, compound 37, demonstrated exceptional qualities: a high affinity for AßOs, emission in the near-infrared region, and good biocompatibility. Significantly, ex vivo double staining indicated that compound 37 detected AßOs in AD mouse brain and in vivo imaging experiments showed that compound 37 could differentiate between 4-month-old AD mice and age-matched wild-type mice. Therefore, compound 37 has emerged as a valuable NIRF probe for early detection of AD and a useful tool in exploring AD's pathological mechanisms.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Drug Design , Early Diagnosis , Fluorescent Dyes , Alzheimer Disease/diagnosis , Alzheimer Disease/diagnostic imaging , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Animals , Amyloid beta-Peptides/metabolism , Mice , Humans , Brain/diagnostic imaging , Brain/metabolism , Mice, Transgenic
14.
Article in English | MEDLINE | ID: mdl-38878896

ABSTRACT

OBJECTIVE: The aim of the present study is to explore the impact of the tet(A) type I variant (tetA-v1) on its fitness effect in Klebsiella pneumoniae. METHODS: Clinical K. pneumoniae strains were utilized as parental strains to generate strains carrying only the plasmid vector (pBBR1MCS-5) or the tetA-v1 recombinant plasmid (ptetA-v1). Antimicrobial susceptibility testing was conducted to estimate the contribution of tetA-v1 to drug resistance. Plasmid stability was evaluated by serial passage over 10 consecutive days in the absence of tigecycline. Biological fitness was examined through growth curve analysis, in vitro competition assays and a neutropenic mouse thigh infection model. RESULTS: A 2-4-fold increase in tigecycline MIC was observed following the acquisition of tetA-v1. Without tigecycline treatment, the stability of ptetA-v1 plasmids has been decreasing since day 1. The ptetA-v1 plasmid in Kp89, Kp91, and Kp93 exhibited a decrease of about 20% compared to the pBBR1MCS-5 plasmid. The acquisition of the tetA-v1 gene could inhibit the growth ability of K. pneumoniae strains both in vitro and in vivo. tetA-v1 gene imposed a fitness cost in K. pneumoniae, particularly in the CRKP strain Kp51, with a W value of approximately 0.56. CONCLUSION: The presence of tetA-v1 is associated with a significant fitness cost in K. pneumoniae in the absence of tigecycline, both in vitro and in vivo.

15.
Nat Comput Sci ; 4(6): 394-395, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38877121
16.
Clin Immunol ; 265: 110291, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908771

ABSTRACT

Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LAB, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.

17.
Infect Genet Evol ; 122: 105605, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38759940

ABSTRACT

Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) is a promising candidate target for the development of multi-component vaccines. Therefore, determining the genetic variation pattern of Pvmsp8 is essential in providing a reference for the rational design of the P. vivax malaria vaccines. This study delves into the genetic characteristics of the Pvmsp8 gene, specifically focusing on samples from the China-Myanmar border (CMB) region, and contrasts these findings with broader global patterns. The study uncovers that Pvmsp8 exhibits a notable level of conservation across different populations, with limited polymorphisms and relatively low nucleotide diversity (0.00023-0.00120). This conservation contrasts starkly with the high polymorphisms found in other P. vivax antigens such as Pvmsp1. A total of 25 haplotypes and 14 amino acid mutation sites were identified in the global populations, and all mutation sites were confined to non-functional regions. The study also notes that most CMB Pvmsp8 haplotypes are shared among Burmese, Cambodian, Thai, and Vietnamese populations, indicating less geographical variance, but differ notably from those found in Pacific island regions or the Panama. The findings underscore the importance of considering regional genetic diversity in P. vivax when developing targeted malaria vaccines. Non departure from neutral evolution were found by Tajima's D test, however, statistically significant differences were observed between the kn/ks rates. The study's findings are crucial in understanding the evolution and population structure of the Pvmsp8 gene, particularly during regional malaria elimination efforts. The highly conserved nature of Pvmsp8, combined with the lack of mutations in its functional domain, presents it as a promising candidate for developing a broad and effective P. vivax vaccine. This research thus lays a foundation for the rational development of multivalent malaria vaccines targeting this genetically stable antigen.


Subject(s)
Genetic Variation , Haplotypes , Malaria, Vivax , Plasmodium vivax , Protozoan Proteins , Selection, Genetic , Plasmodium vivax/genetics , Protozoan Proteins/genetics , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/epidemiology , Malaria, Vivax/prevention & control , Mutation , Phylogeny , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology
18.
Article in English | MEDLINE | ID: mdl-38761998

ABSTRACT

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

19.
Nat Genet ; 56(6): 1245-1256, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38778242

ABSTRACT

The maize root system has been reshaped by indirect selection during global adaptation to new agricultural environments. In this study, we characterized the root systems of more than 9,000 global maize accessions and its wild relatives, defining the geographical signature and genomic basis of variation in seminal root number. We demonstrate that seminal root number has increased during maize domestication followed by a decrease in response to limited water availability in locally adapted varieties. By combining environmental and phenotypic association analyses with linkage mapping, we identified genes linking environmental variation and seminal root number. Functional characterization of the transcription factor ZmHb77 and in silico root modeling provides evidence that reshaping root system architecture by reducing the number of seminal roots and promoting lateral root density is beneficial for the resilience of maize seedlings to drought.


Subject(s)
Adaptation, Physiological , Domestication , Droughts , Plant Roots , Seedlings , Water , Zea mays , Zea mays/genetics , Zea mays/physiology , Plant Roots/genetics , Plant Roots/growth & development , Adaptation, Physiological/genetics , Seedlings/genetics , Water/metabolism , Chromosome Mapping , Phenotype , Gene Expression Regulation, Plant , Plant Proteins/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
20.
Burns ; 50(6): 1711-1712, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38789336
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