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1.
Plant Physiol ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829837

ABSTRACT

Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.

2.
Nano Lett ; 24(10): 3213-3220, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38426819

ABSTRACT

Rational design of well-defined active sites is crucial for promoting sluggish oxygen reduction reactions. Herein, leveraging the surfactant-oriented and solvent-ligand effects, we develop a facile self-assembly strategy to construct a core-shell catalyst comprising a high-index Pt shell encapsulating a PtCu3 intermetallic core with efficient oxygen-reduction performance. Without undergoing a high-temperature route, the ordered PtCu3 is directly fabricated through the accelerated reduction of Cu2+, followed by the deposition of the remaining Pt precursor onto its surface, forming high-index steps oriented by the steric hindrance of surfactant. This approach results in a high half-wave potential of 0.911 V versus reversible hydrogen electrode, with negligible deactivation even after 15000-cycle operation. Operando spectroscopies identify that this core-shell catalyst facilitates the conversion of oxygen-involving intermediates and ensures antidissolution ability. Theoretical investigations rationalize that this improvement is attributed to reinforced electronic interactions around high-index Pt, stabilizing the binding strength of rate-determining OHads species.

3.
Chemistry ; 30(11): e202303602, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38093158

ABSTRACT

Developing stable and highly selective two-electron oxygen reduction reaction (2e- ORR) electrocatalysts for producing hydrogen peroxide (H2 O2 ) is considered a major challenge to replace the anthraquinone process and achieve a sustainable green economy. Here, we doped Sn into Ti4 O7 (D-Sn-Ti4 O7 ) by simple polymerization post-calcination method as a high-efficiency 2e- ORR electrocatalyst. In addition, we also applied plain calcination after the grinding method to load Sn on Ti4 O7 (L-Sn-Ti4 O7 ) as a comparison. However, the performance of L-Sn-Ti4 O7 is far inferior to that of the D-Sn-Ti4 O7 . D-Sn-Ti4 O7 exhibits a starting potential of 0.769 V (versus the reversible hydrogen electrode, RHE) and a high H2 O2 selectivity of 95.7 %. Excitingly, the catalyst can maintain a stable current density of 2.43 mA ⋅ cm-2 for 3600 s in our self-made H-type cell, and the cumulative H2 O2 production reaches 359.2 mg ⋅ L-1 within 50,000 s at 0.3 V. The performance of D-Sn-Ti4 O7 is better than that of the non-noble metal 2e- ORR catalysts reported so far. The doping of Sn not only improves the conductivity but also leads to the lattice distortion of Ti4 O7 , further forming more oxygen vacancies and Ti3+ , which greatly improves its 2e- ORR performance compared with the original Ti4 O7 . In contrast, since the Sn on the surface of L-Sn-Ti4 O7 displays a synergistic effect with Tin+ (3≤n≤4) of Ti4 O7 , the active center Tin+ dissociates the O=O bond, making it more inclined to 4e- ORR.

4.
Chemistry ; 30(2): e202303173, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37880198

ABSTRACT

The development of a stable and efficient non-noble metal catalyst with both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is paramount to achieving the widespread application of Zn-air batteries (ZABs) but remains a great challenge. Herein, a novel Co3 Fe7 alloy nanoparticle dispersed on Se, N co-doped graphitic carbon (denoted as CoFe/Se@CN) was prepared through a facile hydrothermal and pyrolysis process. The synthesized CoFe/Se@CN exhibits outstanding ORR and OER properties with an ultralow potential gap of 0.625 V, which is mainly attributed to the abundant porous structure, the rich structural defects formed by doping Se atoms, and the strong synergistic effects between the CoFe alloys and graphitic carbon nanosheet. Furthermore, the ZAB fabricated by CoFe/Se@CN shows a high peak power density of 160 mW cm-2 and a large specific capacity of 802 mA h g-1 with favorable cycling stability, outperforming that of Pt/C+RuO2 . Our study offers a plausible strategy to explore bifunctional carbon-based materials with efficient electrocatalytic properties for rechargeable ZABs.

5.
Pediatr Res ; 95(5): 1372-1378, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38200323

ABSTRACT

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

6.
Biomacromolecules ; 25(5): 3112-3121, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38651274

ABSTRACT

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Escherichia coli/drug effects , Animals , Microbial Sensitivity Tests , Polyelectrolytes/chemistry , Polyelectrolytes/pharmacology , Peptides/chemistry , Peptides/pharmacology , Protein Conformation, alpha-Helical , Micelles , Escherichia coli Infections/drug therapy , Hemolysis/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Mice , Polyglutamic Acid/chemistry , Polyglutamic Acid/analogs & derivatives , Polyglutamic Acid/pharmacology , Humans
7.
Pharmacol Res ; 203: 107164, 2024 May.
Article in English | MEDLINE | ID: mdl-38569981

ABSTRACT

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.


Subject(s)
Cardiovascular Diseases , Mitochondrial Proteins , Muscle Proteins , Humans , Animals , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/drug therapy , Muscle Proteins/metabolism , Muscle Proteins/genetics , Mitochondrial Proteins/metabolism , Mitochondria, Heart/metabolism , Mitochondria, Heart/drug effects
8.
Pulm Pharmacol Ther ; 84: 102285, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38191069

ABSTRACT

Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro. Meanwhile, the protein content of TGF-ß1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-ß1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-ß/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.


Subject(s)
Abietanes , Pulmonary Fibrosis , Animals , Rats , Bleomycin/toxicity , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta1/metabolism
9.
Inorg Chem ; 63(21): 10068-10078, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38758008

ABSTRACT

Antimony selenide is a promising P-type photocatalyst, but it has a large number of deep energy level defects, leading to severe carrier recombination. The construction of a heterojunction is a common way to resolve this problem. However, the conventional heterojunction system inevitably introduces interface defects. Herein, we employ in situ synthesis to epitaxially grow In2Se3 nanosheets on Sb2Se3 nanorods and form In-Sb covalent interfacial bonds. This petal-shaped heterostructure reduced interface defects and enhanced the efficiency of carrier separation and transport. In this work, the photocurrent density in the proposed Sb2Se3/In2Se3 photocathode is 0.485 mA cm-2 at 0 VRHE, which is 30 times higher than that of pristine Sb2Se3 and it has prominent long-term stability for 24 h without obvious decay. The results reveal that the synergy of the bidirectional built-in electric field constructed between In2Se3 and Sb2Se3 and the solid In-Sb interfacial bonds together build a high-efficiency transport channel for the photogenerated carriers that display enhanced photoelectrochemical (PEC) water-splitting performance. This work provides efficient guidance for reducing interface defects via the in situ synthesis and construction of interfacial bonds.

10.
Arch Virol ; 169(7): 134, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38834736

ABSTRACT

Anthrax is an acute infectious zoonotic disease caused by Bacillus anthracis, a bacterium that is considered a potential biological warfare agent. Bacillus bacteriophages shape the composition and evolution of bacterial communities in nature and therefore have important roles in the ecosystem community. B. anthracis phages are not only used in etiological diagnostics but also have promising prospects in clinical therapeutics or for disinfection in anthrax outbreaks. In this study, two temperate B. anthracis phages, vB_BanS_A16R1 (A16R1) and vB_BanS_A16R4 (A16R4), were isolated and showed siphovirus-like morphological characteristics. Genome sequencing showed that the genomes of phages A16R1 and A16R4 are 36,569 bp and 40,059 bp in length, respectively. A16R1 belongs to the genus Wbetavirus, while A16R4 belongs to the genus Hubeivirus and is the first phage of that genus found to lyse B. anthracis. Because these two phages can comparatively specifically lyse B. anthracis, they could be used as alternative diagnostic tools for identification of B. anthracis infections.


Subject(s)
Bacillus Phages , Bacillus anthracis , Genome, Viral , Bacillus anthracis/virology , Genome, Viral/genetics , Bacillus Phages/isolation & purification , Bacillus Phages/genetics , Bacillus Phages/classification , Siphoviridae/genetics , Siphoviridae/isolation & purification , Siphoviridae/classification , Phylogeny
11.
J Chem Inf Model ; 64(4): 1319-1330, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38346323

ABSTRACT

Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 µM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 µM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.


Subject(s)
COVID-19 , Coronavirus 3C Proteases , Humans , SARS-CoV-2/metabolism , Medicine, Chinese Traditional , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/chemistry
12.
Macromol Rapid Commun ; 45(2): e2300457, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37831810

ABSTRACT

Ionogels possess high conductivity, stretchability, and adhesion, making them promising as flexible sensors. However, it remains challenging to fabricate an ionogel which integrates excellent environment endurance, superior mechanical strength, high self-healing efficiency, and super adhesion. Herein, a supramolecular ionic liquid is synthesized using calcium chloride and 1-butyl-3-methylimidazolium chloride. An advanced ionogel based on this supramolecular ionic liquid is conveniently constructed by a one-pot method with acrylamide and acrylic acid as monomers. The supramolecular cross-linking network, formed by affluent coordination interactions, hydrogen bonds, and electrostatic interactions, provides the ionogel with ideal mechanical strength (tensile strength up to 1.7 MPa), high self-healing efficiency (up to 149%), super adhesion (up to 358 kPa on aluminum), excellent solvent tolerance (less than 10% weight increase, high mechanical and sensing performance retention after being soaked in organic solvents), and low-temperature endurance (breaking elongation can reach 87% at -30 °C). The supramolecular ionogels can function as multi-mode sensors, capable of monitoring strain and different amplitudes of human movements in real-time. Moreover, the sensing performance of ionogels remains unaffected even after being self-healed or exposure to organic solvents. It is expected that this study could offer valuable design ideas to construct advanced gel materials applicable in complicated environment.


Subject(s)
Ionic Liquids , Humans , Acrylamide , Cold Temperature , Electric Conductivity , Hydrogen Bonding
13.
Cereb Cortex ; 33(9): 5055-5065, 2023 04 25.
Article in English | MEDLINE | ID: mdl-36190444

ABSTRACT

Females are considered the more empathic sex. This conventional view, however, has been challenged in the past few decades with mixed findings. These heterogeneous findings could be caused by the fact that empathy is a complex and multifaceted construct. To clarify whether sex differences exist in certain dimensions of empathy and whether they are associated with specific neural bases, this study measured trait empathy using the interpersonal reactivity index (IRI) and collected brain structural and functional magnetic resonance imaging data in a large sample of healthy participants (206 males vs. 302 females). We found that females scored higher in the personal distress (PD) subscale than males, but they were comparable to males in other IRI subscales. Sex difference in PD was encoded by brain structural (e.g. gray matter volume in left anterior insula [AI]) and functional (e.g. resting-state functional connectivity between left AI and temporoparietal junction/inferior frontal gyrus) characteristics. Notably, the relationship between sex and PD was indirect-only and serially mediated by AI-associated structural and functional characteristics. Altogether, our results suggested that sex difference existed in self-oriented affective empathy (i.e. PD) and highlighted the importance of the AI, both structurally and functionally, in mediating the sex difference in trait empathy.


Subject(s)
Empathy , Sex Characteristics , Humans , Male , Female , Cerebral Cortex , Brain , Brain Mapping
14.
Ecotoxicol Environ Saf ; 276: 116315, 2024 May.
Article in English | MEDLINE | ID: mdl-38614001

ABSTRACT

This study explores the role of endogenous indole-3-acetic acid (IAA) in modulating plant responses to pollution stress and its effect on pollutant accumulation, with a focus on fluoranthene (Flu) in ryegrass. To elucidate the mechanism, we employed an IAA promoter (α-aminobutyric acid [α-AB]) and an IAA inhibitor (naphthylphthalamic acid [NPA]) to regulate IAA levels and analyze Flu uptake characteristics. The experimental setup included a Flu treatment group (ryegrass with Flu addition) and a control group (ryegrass without Flu). Our findings demonstrate that Flu treatment enhanced IAA content and plant growth in ryegrass compared to the control. The Flu+AB treatment further enhanced these effects, while the Flu+NPA treatment exhibited a contrasting trend. Moreover, Flu+AB treatment led to increased Flu accumulation, in contrast to the inhibitory effect observed with Flu+NPA treatment. Flu treatment also enhanced the activities of key antioxidant enzymes (SOD, POD, CAT) and increased soluble sugar and protein levels, indicative of enzymatic and nonenzymatic defense responses, respectively. The Flu+AB treatment amplified these responses, whereas the Flu+NPA treatment attenuated them. Significantly, Flu treatment raised H+-ATPase activity compared to the control, an effect further elevated by Flu+AB treatment and diminished by Flu+NPA treatment. A random forest analysis suggested that Flu accumulation dependency varied under different treatments: it relied more on H+-ATPase activity under Flu+AB treatment and more on SOD activity under Flu+NPA treatment. Additionally, Flu+AB treatment boosted the transpiration rate in ryegrass, thereby increasing the Flu translocation factor, a trend reversed by Flu+NPA treatment. This research highlights crucial factors influencing Flu accumulation in ryegrass, offering potential new avenues for controlling the gathering of contaminants within plant systems.


Subject(s)
Fluorenes , Indoleacetic Acids , Lolium , Superoxide Dismutase , Fluorenes/toxicity , Lolium/drug effects , Lolium/growth & development , Indoleacetic Acids/metabolism , Superoxide Dismutase/metabolism , Soil Pollutants/toxicity , Plant Growth Regulators , Antioxidants/metabolism
15.
Sensors (Basel) ; 24(4)2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38400345

ABSTRACT

Hyperspectral image (HSI) classification is a highly challenging task, particularly in fields like crop yield prediction and agricultural infrastructure detection. These applications often involve complex image types, such as soil, vegetation, water bodies, and urban structures, encompassing a variety of surface features. In HSI, the strong correlation between adjacent bands leads to redundancy in spectral information, while using image patches as the basic unit of classification causes redundancy in spatial information. To more effectively extract key information from this massive redundancy for classification, we innovatively proposed the CESA-MCFormer model, building upon the transformer architecture with the introduction of the Center Enhanced Spatial Attention (CESA) module and Morphological Convolution (MC). The CESA module combines hard coding and soft coding to provide the model with prior spatial information before the mixing of spatial features, introducing comprehensive spatial information. MC employs a series of learnable pooling operations, not only extracting key details in both spatial and spectral dimensions but also effectively merging this information. By integrating the CESA module and MC, the CESA-MCFormer model employs a "Selection-Extraction" feature processing strategy, enabling it to achieve precise classification with minimal samples, without relying on dimension reduction techniques such as PCA. To thoroughly evaluate our method, we conducted extensive experiments on the IP, UP, and Chikusei datasets, comparing our method with the latest advanced approaches. The experimental results demonstrate that the CESA-MCFormer achieved outstanding performance on all three test datasets, with Kappa coefficients of 96.38%, 98.24%, and 99.53%, respectively.

16.
Mol Cancer ; 22(1): 99, 2023 06 23.
Article in English | MEDLINE | ID: mdl-37353784

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood. METHODS: This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored. RESULTS: We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m6A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients. CONCLUSIONS: Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Methylation , Ecosystem , Endothelial Cells , Phosphatidylinositol 3-Kinases , Neoplasm Recurrence, Local , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics , Tumor Microenvironment , RNA-Binding Proteins/genetics
17.
Hum Brain Mapp ; 44(2): 315-326, 2023 02 01.
Article in English | MEDLINE | ID: mdl-35972315

ABSTRACT

Dance is unique in that it is a sport and an art simultaneously. Beyond improving sensorimotor functions, dance training could benefit high-level emotional and cognitive functions. Duo dances also confer the possibility for dancers to develop the abilities to recognize, understand, and share the thoughts and feelings of their dance partners during the long-term dance training. To test this possibility, we collected high-resolution structural and resting-state functional magnetic resonance imaging (MRI) data from 43 expert-level ballroom dancers (a model of long-term exposure to duo dance training) and 40 age-matched and sex-matched nondancers, and measured their empathic ability using a self-report trait empathy scale. We found that ballroom dancers showed higher scores of empathic concern (EC) than controls. The EC scores were positively correlated with years with dance partners but negatively correlated with the number of dance partners for ballroom dancers. These behavioral results were supported by the structural and functional MRI data. Structurally, we observed that the gray matter volumes in the subgenual anterior cingulate cortex (ACC) and EC scores were positively correlated. Functionally, the connectivity between ACC and occipital gyrus was positively correlated with both EC scores and years with dance partners. In addition, the relationship between years with dance partners and EC scores was indirect-only mediated by the ACC-occipital gyrus functional connectivity. Therefore, our findings provided solid evidence for the close link between long-term ballroom dance training and empathy, which deepens our understanding of the neural mechanisms underlying this phenomenon.


Subject(s)
Dancing , Humans , Dancing/psychology , Empathy , Brain/diagnostic imaging , Magnetic Resonance Imaging , Brain Mapping
18.
Small ; 19(39): e2301751, 2023 09.
Article in English | MEDLINE | ID: mdl-37259675

ABSTRACT

Sustained oral uncoupler 2,4-dinitrophenol (DNP) administration exerts prominent anti-obesity effects, but the adipose tissue off-target disadvantage leads to systemic adverse effects. A novel non-cardiotoxicity DNP delivery method using a biocompatible microneedles patch containing the amphiphilic tetradecanoic acid-DNP ester (TADNP) is described, which is synthesized via esterification on the phenolic hydroxyl of DNP. The TADNP is self-assembled as nanomicelles, which enhance the endocytosis rate of DNP by adipocytes and its permeation in isolated adipose tissues. The microenvironment of adipose tissues promotes the massive release of DNP and plasma and simulated gastrointestinal fluids. The microneedles-delivered TADNP nanomicelles (MN-TADNP) effectively deliver DNP in treated adipose tissues and reduce DNP content in off-target organs. Both oral and MN patch-delivered TADNP micelles effectively exert anti-obesity effects in a mouse model of high-fat diet-induced obesity; and noteworthily, MN-TADNP exhibit more satisfactory biosafety than oral administration. Here, a smart MN patch loaded with tetradecanoic acid-modified DNP is reported, which enhances its accumulation in adipose tissues and exerts an anti-obesity effect without causing any systemic toxicity.


Subject(s)
2,4-Dinitrophenol , Lipogenesis , Mice , Animals , 2,4-Dinitrophenol/pharmacology , Myristic Acid/pharmacology , Esters/pharmacology , Obesity/drug therapy , Adipocytes , Dinitrophenols/pharmacology
19.
Mod Pathol ; 36(6): 100148, 2023 06.
Article in English | MEDLINE | ID: mdl-36841435

ABSTRACT

As the most common type of human papillomavirus-independent endocervical adenocarcinomas (ECAs), gastric-type endocervical adenocarcinomas (GEAs) account for approximately 10% of all ECAs. Although anti-HER2 therapy has been proven effective in many cancers, it has not been used in ECAs, including GEAs, which is at least partly due to the lack of a well-defined guideline. Limited available data regarding HER2 in GEAs and ECAs have considerable variations likely caused by variations in the tumor type selection, testing methods, and scoring criteria. Here, we selected 58 GEA cases to examine the HER2 status using immunohistochemistry and fluorescent in situ hybridization and investigate the prognostic value and their association with other known or potential prognostic factors. When strong complete or lateral/basolateral membranous reactivity in ≥10% tumor cells was used to define HER2 positivity, relatively high prevalence of HER2 overexpression (10/58[17.2%]) and amplification (9/58 [15.5%]), as well as high immunohistochemistry-fluorescent in situ hybridization concordance rate (9/10 [90%]) was found in GEAs. A lateral/basolateral staining pattern ("U-shaped") was observed, at least focally, in most of HER2-positive (3+) and equivocal (2+) tumors. Notably, considerable heterogeneity of HER2 expression was observed in HER2 positive and equivocal cases (80.0% and 83.3%, respectively). HER2 overexpression and amplification were associated with worse progression-free survival (P = .047 and P = .032, respectively). Programmed death-ligand 1 expression was associated with worse progression-free survival (P = .032), whereas mutant-type p53 demonstrated no prognostic significance. Our work laid a solid foundation for the eventual development of a future standard HER2 testing guideline for GEAs.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Uterine Cervical Neoplasms , Female , Humans , In Situ Hybridization, Fluorescence , Prognosis , Stomach Neoplasms/pathology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/pathology , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Biomarkers, Tumor/genetics , Gene Amplification
20.
J Med Virol ; 95(12): e29296, 2023 12.
Article in English | MEDLINE | ID: mdl-38054540

ABSTRACT

Mpox is still spreading globally and is mostly reported to be transmitted by skin and mucosal contact. However, transmission through contact with fomites, contaminated objects, or surfaces has been reported in general population. Evaluation of the stability of mpox virus (MPXV) on different surfaces is important to minimize mpox transmission. In the study, the stability of MPXV on different kinds of commonly contacted surfaces was determined. MPXV was observed to have a surface-dependent stability pattern. Viable virus was detected on both glass and stainless steel for up to 5 days, and on plastic surfaces for up to 3 days. In contrast, no viable MPXV was detected on wooden board and cardboard, which are porous and water-absorbent surfaces, after 1 and 2 days of incubation, respectively. In addition, MPXV nucleic acids were more stable and showed better correlation with viral titers on stainless steel, plastic, and glass. The results indicate that fomite transmission of MPXV is plausible. Moreover, the stability of MPXV was highly surface-dependent and more stable on smooth surfaces, which could provide more information for minimizing the transmission of mpox and emphasize the significance of environmental disinfection in mpox prevention and control.


Subject(s)
Mpox (monkeypox) , Humans , Monkeypox virus , Stainless Steel , Disinfection , Fomites
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