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1.
Article in English | MEDLINE | ID: mdl-38781436

ABSTRACT

BACKGROUND: Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD). OBJECTIVE: To assess coronary CT angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB. METHODS: Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as development set. They were divided into training and internal testing in an 8:2 ratio. Patients from 4 other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centerline (MB CL), proximal MB CL (pMB CL), MB cross section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). RESULTS: 295 patients were included in the development (n=192; median age, 54±11 years; 137 men) and external validation sets (n=103; median age, 57±9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC=0.78, 0.75, 0.75) than the clinical and anatomical model (all p<0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (p=0.002), along with enhanced NRI (0.76 [0.37-1.14], p<0.001) and IDI (0.17 [0.07-0.26], p<0.001) in the external validation set. CONCLUSION: The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB.

2.
Front Immunol ; 15: 1340702, 2024.
Article in English | MEDLINE | ID: mdl-38690275

ABSTRACT

The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.


Subject(s)
Extracellular Matrix , Neoplasms , T-Lymphocytes , Tumor Microenvironment , Tumor Microenvironment/immunology , Humans , Extracellular Matrix/metabolism , Extracellular Matrix/immunology , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/metabolism , Neoplasms/therapy , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , Cell Communication/immunology , Immunotherapy/methods
3.
Mol Oral Microbiol ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757737

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. METHODS: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot. RESULTS: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6. CONCLUSIONS: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.

4.
J Ethnopharmacol ; 332: 118363, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38763373

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). AIM OF THE STUDY: To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. MATERIALS AND METHODS: PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. RESULTS: GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (p<0.01 or p<0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (p<0.01 or p<0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (p<0.01). CONCLUSION: GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.

5.
ACS Appl Bio Mater ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790078

ABSTRACT

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

6.
Acta Biomater ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38735374

ABSTRACT

The limited mechanical properties of pure Zn, such as its low strength and ductility, hinder its application as a material for biodegradable implants. Addressing this challenge, the current study focuses on the development of biodegradable Zn-based alloys, employing innovative alloy design and processing strategies. Here, alloys with compositions ranging from 0.02 to 0.10 weight percent (wt%) Cu, 1.22 to 1.80 wt% Ti, and 0.04 to 0.06 wt% Mo were produced utilizing a high-throughput gradient continuous casting process. This study highlights three specific alloys: Zn1.82Cu0.10Ti0.05Mo (HR8), Zn0.08Cu1.86Ti0Mo (HR7), and Zn1.26Cu0.13Ti0.06Mo (HR6), which were extensively evaluated for their microstructure, mechanical properties, electrochemical performance, potential as bioimplants, and cytotoxicity. These alloys were found to exhibit enhanced mechanical strength, optimal degradation rates, and superior biocompatibility, evidenced by in-vivo experiments with SD rats, positioning them as promising candidates for medical implants. This research not only introduces a significant advancement in biodegradable alloy development but also proposes an efficient method for their production, marking a pivotal step forward in biomedical engineering. STATEMENT OF SIGNIFICANCE: The limited mechanical properties of pure Zn have hindered its application in biodegradable implants. Our research primarily focuses on the alloy design and process strategies of biodegradable Zn-based alloys. We explore the ZnCuxTixMox alloys. This study introduces a high-throughput experimental approach for efficient screening of multi-component alloy systems with optimal properties. The ZnCuxTixMox alloys were designed and processed through gradient continuous casting, followed by homogenization and hot rolling. Our findings indicate that the Zn1.82Cu0.10Ti0.05Mo alloy demonstrates superior tensile, mechanical, and corrosion properties post hot rolling. The study suggests that Zn0.13Cu1.26Ti0.06Mo, Zn0.08Cu1.86Ti0Mo, and Zn1.82Cu0.10Ti0.05Mo alloys hold significant potential as biodegradable materials.

7.
Viruses ; 16(5)2024 04 25.
Article in English | MEDLINE | ID: mdl-38793556

ABSTRACT

Yunnan province in China shares its borders with three neighboring countries: Myanmar, Vietnam, and Laos. The region is characterized by a diverse climate and is known to be a suitable habitat for various arthropods, including midges which are notorious for transmitting diseases which pose significant health burdens affecting both human and animal health. A total of 431,100 midges were collected from 15 different locations in the border region of Yunnan province from 2015 to 2020. These midges were divided into 37 groups according to the collection year and sampling site. These 37 groups of midges were then homogenized to extract nucleic acid. Metatranscriptomics were used to analyze their viromes. Based on the obtained cytochrome C oxidase I gene (COI) sequences, three genera were identified, including one species of Forcipomyia, one species of Dasyhelea, and twenty-five species of Culicoides. We identified a total of 3199 viruses in five orders and 12 families, including 1305 single-stranded positive-stranded RNA viruses (+ssRNA) in two orders and seven families, 175 single-stranded negative-stranded RNA viruses (-ssRNA) in two orders and one family, and 1719 double-stranded RNA viruses in five families. Six arboviruses of economic importance were identified, namely Banna virus (BAV), Japanese encephalitis virus (JEV), Akabane virus (AKV), Bluetongue virus (BTV), Tibetan circovirus (TIBOV), and Epizootic hemorrhagic disease virus (EHDV), all of which are capable, to varying extents, of causing disease in humans and/or animals. The survey sites in this study basically covered the current distribution area of midges in Yunnan province, which helps to predict the geographic expansion of midge species. The complexity and diversity of the viral spectrum carried by midges identified in the study calls for more in-depth research, which can be utilized to monitor arthropod vectors and to predict the emergence and spread of zoonoses and animal epidemics, which is of great significance for the control of vector-borne diseases.


Subject(s)
Ceratopogonidae , Phylogeny , Animals , China , Ceratopogonidae/virology , Ceratopogonidae/genetics , RNA Viruses/genetics , RNA Viruses/classification , RNA Viruses/isolation & purification , Transcriptome , Insect Vectors/virology , Virome/genetics , Humans
8.
Front Pharmacol ; 15: 1386565, 2024.
Article in English | MEDLINE | ID: mdl-38770002

ABSTRACT

The blood-spinal cord barrier (BSCB) is disrupted within minutes of spinal cord injury, leading to increased permeability and secondary spinal cord injury, resulting in more severe neurological damage. The preservation of blood-spinal cord barrier following spinal cord injury plays a crucial role in determining the prognosis. Teriparatide, widely used in clinical treatment for osteoporosis and promoting fracture healing, has been found in our previous study to have the effect of inhibiting the expression of MMP9 and alleviating blood-brain barrier disruption after ischemic stroke, thereby improving neurological damage symptoms. However, there are limited research on whether it has the potential to improve the prognosis of spinal cord injury. This article summarizes the main pathological mechanisms of blood-spinal cord barrier disruption after spinal cord injury and its relationship with Teriparatide, and explores the therapeutic potential of Teriparatide in improving the prognosis of spinal cord injury by reducing blood-spinal cord barrier disruption.

9.
Acta Radiol ; 65(5): 422-431, 2024 May.
Article in English | MEDLINE | ID: mdl-38584372

ABSTRACT

BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.


Subject(s)
Contrast Media , Gallbladder Neoplasms , Gallbladder , Tomography, X-Ray Computed , Humans , Male , Female , Gallbladder Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Middle Aged , Aged , Diagnosis, Differential , Adult , Gallbladder/diagnostic imaging , Retrospective Studies , Aged, 80 and over , Nomograms , Radiographic Image Enhancement/methods , Reproducibility of Results , Sensitivity and Specificity , Radiomics
10.
Ophthalmol Ther ; 13(6): 1589-1599, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38587772

ABSTRACT

INTRODUCTION: Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. METHODS: Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. RESULTS: Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. CONCLUSIONS: Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment.

11.
Neuroradiology ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676749

ABSTRACT

PURPOSE: The Centiloid project helps calibrate the quantitative amyloid-ß (Aß) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aß deposition in CL using [18F]Flutemetamol and evaluate regional Aß deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aß deposition by measuring regional CL in equivocal cases showing negative global CL. METHODS: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aß positivity. RESULTS: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aß deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aß positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. CONCLUSION: The expression of regional brain Aß deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aß deposition that can be detected by measuring regional CL.

12.
Int J Biol Macromol ; 267(Pt 1): 131436, 2024 May.
Article in English | MEDLINE | ID: mdl-38593897

ABSTRACT

Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the perspective of block polymer molecular sequence design, which would provide theoretical guidance for subsequent clinical applications. This study aims to investigate the structural stability of drug-loading micelles formed by two diblock/triblock polymers with various block sequences through coarse-grained dissipative particle dynamics (DPD) simulations. From the perspectives of the binding strength of poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) in nanoparticles, hydrophilic bead surface coverage, and the morphological alteration of nanoparticles induced by shear force, the ratio of hydrophilic/hydrophobic sequence length has been observed to affect the stability of nanoparticles. We have found that for diblock polymers, PEG3kda-PLLA2kda has the best stability (corresponding hydrophilic coverage ratio is 0.832), while PEG4kda-PLLA5kda has the worst (coverage ratio 0.578). For triblock polymers, PEG4kda-PLLA2kda-PEG4kda has the best stability (0.838), while PEG4kda-PLLA5kda-PEG4kda possesses the worst performance (0.731), and the average performance on stability is better than nanoparticles composed of diblock polymers.


Subject(s)
Atorvastatin , Hydrophobic and Hydrophilic Interactions , Lactates , Nanoparticles , Polyethylene Glycols , Atorvastatin/chemistry , Polyethylene Glycols/chemistry , Nanoparticles/chemistry , Drug Carriers/chemistry , Micelles , Polyesters/chemistry , Drug Compounding , Molecular Dynamics Simulation
13.
Plant Physiol ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630866

ABSTRACT

Ginkgo (Ginkgo biloba L.) is one of the earliest extant species in seed plant phylogeny. Embryo development patterns can provide fundamental evidence for the origin, evolution, and adaptation of seeds. However, the architectural and morphological dynamics during embryogenesis in Ginkgo biloba (G. biloba) remain elusive. Herein, we obtained over 2200 visual slices from three stages of embryo development using micro-computed tomography imaging with improved staining methods. Based on 3D spatio-temporal pattern analysis, we found that a shoot apical meristem with seven highly differentiated leaf primordia, including apical and axillary leaf buds, is present in mature Ginkgo embryos. 3D rendering from the front, top, and side views showed two separate transport systems of tracheids located in the hypocotyl and cotyledon, representing a unique pattern of embryogenesis. Furthermore, the morphological dynamic analysis of secretory cavities indicated their strong association with cotyledons during development. In addition, we identified genes GbLBD25a (lateral organ boundaries domain 25a), GbCESA2a (cellulose synthase 2a), GbMYB74c (myeloblastosis 74c), GbPIN2 (PIN-FORMED 2) associated with vascular development regulation, and GbWRKY1 (WRKYGOK 1), GbbHLH12a (basic helix-loop-helix 12a), GbJAZ4 (jasmonate zim-domain 4) potentially involved in the formation of secretory cavities. Moreover, we found that flavonoid accumulation in mature embryos could enhance post-germinative growth and seedling establishment in harsh environments. Our 3D spatial reconstruction technique combined with multi-omics analysis opens avenues for investigating developmental architecture and molecular mechanisms during embryogenesis and lays the foundation for evolutionary studies of embryo development and maturation.

14.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1564-1569, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621940

ABSTRACT

Various separation methods in combination with spectral data analysis, X-ray single crystal diffraction analysis, and litera-ture data comparison were employed to clarify the chemical constituents of Itea yunnanensis. Seven compounds were obtained from I. yunnanensis, which were identified as(S)-3-[1-(4-hydroxyphenyl)propane-2-yl]-4-methoxybenzoate methyl ester(1), iteafuranal B(2), syringaresinol(3), dihydrokaempferol(4), trimethoxybenzene(5), eicosane(6), and nonacosane(7), respectively. Among them, compound 1 was a new nor-neolignan compound named iteanorneoligan A, and the rest of the compounds were identified from I. yunnanensis for the first time. The anti-hepatocellular carcinoma effect of the compound was evaluated based on Sk-hep-1 cells model via MTT assay, and compound 2 showed a significant inhibitory effect on the proliferation of Sk-hep-1 cells with an IC_(50) of 9.4 µmol·L~(-1). The antioxidant capacity was determined via DPPH, ABTS~(·+), and O■ radical scavenging ability, and compound 1 exhibited a significant ABTS~(·+) radical scavenging effect with an IC_(50) of 0.178 mg·mL~(-1).


Subject(s)
Lignans , Molecular Structure , Benzothiazoles , Sulfonic Acids , Antioxidants/pharmacology , Antioxidants/chemistry
15.
Appl Microbiol Biotechnol ; 108(1): 304, 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38643456

ABSTRACT

Tobramycin is an essential and extensively used broad-spectrum aminoglycoside antibiotic obtained through alkaline hydrolysis of carbamoyltobramycin, one of the fermentation products of Streptoalloteichus tenebrarius. To simplify the composition of fermentation products from industrial strain, the main byproduct apramycin was blocked by gene disruption and constructed a mutant mainly producing carbamoyltobramycin. The generation of antibiotics is significantly affected by the secondary metabolism of actinomycetes which could be controlled by modifying the pathway-specific regulatory proteins within the cluster. Within the tobramycin biosynthesis cluster, a transcriptional regulatory factor TobR belonging to the Lrp/AsnC family was identified. Based on the sequence and structural characteristics, tobR might encode a pathway-specific transcriptional regulatory factor during biosynthesis. Knockout and overexpression strains of tobR were constructed to investigate its role in carbamoyltobramycin production. Results showed that knockout of TobR increased carbamoyltobramycin biosynthesis by 22.35%, whereas its overexpression decreased carbamoyltobramycin production by 10.23%. In vitro electrophoretic mobility shift assay (EMSA) experiments confirmed that TobR interacts with DNA at the adjacent tobO promoter position. Strains overexpressing tobO with ermEp* promoter exhibited 36.36% increase, and tobO with kasOp* promoter exhibited 22.84% increase in carbamoyltobramycin titer. When the overexpressing of tobO and the knockout of tobR were combined, the production of carbamoyltobramycin was further enhanced. In the shake-flask fermentation, the titer reached 3.76 g/L, which was 42.42% higher than that of starting strain. Understanding the role of Lrp/AsnC family transcription regulators would be useful for other antibiotic biosynthesis in other actinomycetes. KEY POINTS: • The transcriptional regulator TobR belonging to the Lrp/AsnC family was identified.  • An oxygenase TobO was identified within the tobramycin biosynthesis cluster. • TobO and TobR have significant effects on the synthesis of carbamoyltobramycin.


Subject(s)
Actinobacteria , Actinomycetales , Metabolic Engineering , Anti-Bacterial Agents , Tobramycin
16.
Materials (Basel) ; 17(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38612088

ABSTRACT

The multifunctional development in the field of face masks and the growing demand for scalable manufacturing have become increasingly prominent. In this study, we utilized high-vacuum magnetron sputtering technology to deposit a 5 nm ultra-thin Ag-Cu film on non-woven fabric and fabricated ultra-thin Ag-Cu film face masks. The antibacterial rates against Escherichia coli and Staphylococcus aureus were 99.996% and 99.978%, respectively, while the antiviral activity against influenza A virus H1N1 was 99.02%. Furthermore, the mask's ability to monitor respiratory system diseases was achieved through color change (from brownish-yellow to grey-white). The low cost and scalability potential of ultra-thin silver-copper film masks offer new possibilities for practical applications of multifunctional masks.

17.
Small ; : e2400855, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563589

ABSTRACT

The transition metal oxides/sulfides are considered promising catalysts due to their abundant resources, facile synthesis, and reasonable electrocatalytic activity. Herein, a significantly improved intrinsic catalytic activity is achieved for constructing a Co-based nanocrystal (Co-S@NC) with the coordination of Co─S, Co─S─C, and Co─Nx─C. The calculational and experimental results demonstrate that the diversified chemical environment of Co-cations induces the transition of 3d orbitals to a high spin-state that exhibits the coexistence of Co2+ with fully occupied dπ orbitals and Co3+ with unpaired electrons in dπ orbitals. The diverse dπ orbitals occupation contributes to an elevated d-band center of Co ions, which accelerates oxygen reduction reaction and oxygen evolution reaction electrocatalytic kinetics of the Co-S@NC nanocrystal. Therefore, the Li-O2 batteries with Co-S@NC as cathode catalyst exhibit 300 cycles at the current density of 500 mA g-1 with a cut-off capacity of 1000 mAh g-1. Moreover, the ultrahigh discharge specific capacity of 34 587 mAh g-1 is obtained at a current density of 1000 mA g-1, corresponding to the energy density 949 Wh kg-1 of a prototype Li-O2 battery. The study on 3d orbital regulation of nanocrystals provides an innovative strategy for bifunctional electrocatalysts toward the practical application of metal-air batteries.

18.
Nat Ecol Evol ; 8(5): 947-959, 2024 May.
Article in English | MEDLINE | ID: mdl-38519631

ABSTRACT

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.


Subject(s)
Culicidae , Mosquito Vectors , Virome , Animals , Culicidae/virology , China , Mosquito Vectors/virology , Metagenomics , Arboviruses/genetics , Arboviruses/classification , Phylogeny , Biodiversity
19.
Theriogenology ; 221: 47-58, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38554613

ABSTRACT

Zinc, an essential trace mineral, exerts a pivotal influence in various biological processes. Through zinc concentration analysis, we found that the zinc concentration in the bovine embryo in vitro culture (IVC) medium was significantly lower than that in bovine follicular fluid. Therefore, this study explored the impact of zinc sulfate on IVC bovine embryo development and investigated the underlying mechanism. The results revealed a significant decline in zygote cleavage and blastocyst development rates when zinc deficiency was induced using zinc chelator N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) in culture medium during embryo in vitro culture. The influence of zinc-deficiency was time-dependent. Conversely, supplementing 0.8 µg/mL zinc sulfate to culture medium (CM) increased the cleavage and blastocyst formation rate significantly. Moreover, this supplementation reduced reactive oxygen species (ROS) levels, elevated the glutathione (GSH) levels in blastocysts, upregulated the mRNA expression of antioxidase-related genes, and activated the Nrf2-Keap1-ARE signaling pathways. Furthermore, 0.8 µg/mL zinc sulfate enhanced mitochondrial membrane potential, maintained DNA stability, and enhanced the quality of bovine (in vitro fertilization) IVF blastocysts. In conclusion, the addition of 0.8 µg/mL zinc sulfate to CM could enhance the antioxidant capacity, activates the Nrf2-Keap1-ARE signaling pathways, augment mitochondrial membrane potential, and stabilizes DNA, ultimately improving blastocyst quality and in vitro bovine embryo development.


Subject(s)
Antioxidants , Zinc , Female , Animals , Cattle , Antioxidants/pharmacology , Antioxidants/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Zinc/pharmacology , Zinc/metabolism , Zinc Sulfate/pharmacology , NF-E2-Related Factor 2/metabolism , Embryo Culture Techniques/veterinary , Embryonic Development , Fertilization in Vitro/veterinary , Blastocyst/physiology , Glutathione/metabolism , DNA/metabolism
20.
World J Pediatr ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38526835

ABSTRACT

BACKGROUND: Preschooling is a critical time for intervention in children with autism spectrum disorder (ASD); thus, we analyzed brain tissue component volumes (BTCVs) and clinical indicators in preschool children with ASD to identify new biomarkers for early screening. METHODS: Eighty preschool children (3-6 years) with ASD were retrospectively included. The whole-brain myelin content (MyC), white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging (SyMRI). Clinical data, such as intelligence scores, autism diagnostic observation schedule-calibrated severity scores, age at first production of single words (AFSW), age at first production of phrases (AFP), and age at walking onset (AWO), were also collected. The correlation between the BTCV and clinical data was evaluated, and the effect of BTCVs on clinical data was assessed by a regression model. RESULTS: WM and GM volumes were positively correlated with intelligence scores (both P < 0.001), but WM and GM did not affect intelligence scores (P = 0.116, P = 0.290). AWO was positively correlated with AFSW and AFP (both P < 0.001). The multivariate linear regression analysis revealed that MyC, AFSW, AFP, and AWO were significantly different (P = 0.005, P < 0.001, P < 0.001). CONCLUSIONS: This study revealed positive correlations between WM and GM volumes and intelligence scores. Whole-brain MyC affected AFSW, AFP, and AWO in preschool children with ASD. Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker (abnormal MyC) for early ASD screening in preschool children.

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