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1.
Front Immunol ; 15: 1397722, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957471

RESUMO

Rationale: Sepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms. Methods: Exosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms. Results: LPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150-5p in LPS-Exo compared to that in Exo, and exosomal miR-150-5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150-5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway. Conclusion: The current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150-5p as a novel molecular target for regulating immune hyperactivation during sepsis.


Assuntos
Exossomos , Proteínas Substratos do Receptor de Insulina , Lipopolissacarídeos , Macrófagos , Células-Tronco Mesenquimais , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Sepse , Transdução de Sinais , Serina-Treonina Quinases TOR , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Sepse/metabolismo , Sepse/imunologia , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Ativação de Macrófagos/efeitos dos fármacos , Modelos Animais de Doenças
2.
J Hazard Mater ; 476: 135120, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38976960

RESUMO

The decommissioning of nuclear reactors is a global concern, in part because of the generation of radioactive aerosols that can lead to internal radiation exposure. At present, radioactive aerosols generated during nuclear decommissioning have not been actively studied, and data collected from the actual decommissioning are limited. This paper presents a study of radioactive aerosols generated during the pre-decommission phase of an experimental shielding reactor. Among all the on-site operations, cutting resulted in the highest levels of radioactivity. Plasma arc cutting, in particular, had a maximum gross α and ß radioactivity over 0.10 and 0.14 Bq/m3, respectively. Assumed AMAD (activity median aerodynamic diameter) values are employed to assess the impact of particle size on the internal exposure dose resulting from the inhalation of 137Cs aerosols based on the Human Respiratory Tract Model of International Commission on Radiological Protection. When cutting stainless steel by plasma arc, the internal exposure dose caused by 137Cs aerosols with an AMAD of 0.1 µm is estimated to be nearly four times as that of aerosols with an AMAD of 10 µm. Results show that the internal exposure dose is highly dependent on the AMAD, implying the importance of measuring size-related parameters of radioactive aerosols in the future nuclear decommissioning. This study has revealed some characteristics of radioactive aerosols released in decommissioning operations, which can serve as a valuable reference for controlling and removing aerosols during the decommissioning of nuclear facilities.

3.
J Biotechnol ; 392: 139-151, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009230

RESUMO

Automatically finding novel pathways plays an important role in the initial designs of metabolic pathways in synthetic biology and metabolic engineering. Although path-finding methods have been successfully applied in identifying valuable synthetic pathways, few efforts have been made in fusing atom group tracking into building stoichiometry model to search metabolic pathways from arbitrary start compound via Mixed Integer Linear Programming (MILP). We propose a novel method called AFP to find metabolic pathways by incorporating atom group tracking into reaction stoichiometry via MILP. AFP tracks the movements of atom groups in the reaction stoichiometry to construct MILP model to search the pathways containing atom groups exchange in the reactions and adapts the MILP model to provide the options of searching pathways from an arbitrary or given compound to the target compound. Combining atom group tracking with reaction stoichiometry to build MILP model for pathfinding may promote the search of well-designed alternative pathways at the stoichiometric modeling level. The experimental comparisons to the known pathways show that our proposed method AFP is more effective to recover the known pathways than other existing methods and is capable of discovering biochemically feasible pathways producing the metabolites of interest.

4.
Eur Heart J Case Rep ; 8(7): ytae307, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39006212

RESUMO

Background: 17α-Hydroxylase deficiency, a rare form of congenital adrenal hyperplasia, presents diagnostic and treatment challenges because of the limited number of cases reported. Case summary: This report discusses the case of a 17-year-old Chinese girl who suffered from unexplained dizziness, headaches, and high blood pressure. She had amenorrhoea during puberty and had been diagnosed with ovarian delay. Initially, she was diagnosed with hypertension and received three antihypertensive medications. However, her blood pressure remained poorly controlled. Gene sequencing revealed 17α-hydroxylase deficiency caused by compound heterozygous mutations in CYP17A1. One of the mutation sites, potentially novel, has not been reported previously. Subsequently, dexamethasone therapy was initiated, her blood pressure was controlled, and the symptoms disappeared. During the 1-year follow-up, her blood pressure remained normal, and the symptoms did not recur. Discussion: 17α-Hydroxylase deficiency is a rare cause of secondary hypertension. Despite the low prevalence, it should not be overlooked in younger patients.

5.
Front Pharmacol ; 15: 1404092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027338

RESUMO

All-trans retinoic acid (ATRA) plays a role in tissue development, neural function, reproduction, vision, cell growth and differentiation, tumor immunity, and apoptosis. ATRA can act by inducing autophagic signaling, angiogenesis, cell differentiation, apoptosis, and immune function. In the blood system ATRA was first used with great success in acute promyelocytic leukemia (APL), where ATRA differentiated leukemia cells into mature granulocytes. ATRA can play a role not only in APL, but may also play a role in other hematologic diseases such as immune thrombocytopenia (ITP), myelodysplastic syndromes (MDS), non-APL acute myeloid leukemia (AML), aplastic anemia (AA), multiple myeloma (MM), etc., especially by regulating mesenchymal stem cells and regulatory T cells for the treatment of ITP. ATRA can also increase the expression of CD38 expressed by tumor cells, thus improving the efficacy of daratumumab and CD38-CART. In this review, we focus on the mechanism of action of ATRA, its role in various hematologic diseases, drug combinations, and ongoing clinical trials.

6.
Biotechnol Biofuels Bioprod ; 17(1): 81, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886802

RESUMO

BACKGROUND: Non-conventional yeasts hold significant potential as biorefinery cell factories for microbial bioproduction. Currently, gene editing systems used for these yeasts rely on antibiotic and auxotrophic selection mechanisms. However, the drawbacks of antibiotics, including high costs, environmental concerns, and the dissemination of resistance genes, make them unsuitable for large-scale industrial fermentation. For auxotrophic selection system, the engineered strains harboring auxotrophic marker genes are typically supplemented with complex nutrient-rich components instead of precisely defined synthetic media in large-scale industrial fermentations, thus lack selection pressure to ensure the stability of heterologous metabolic pathways. Therefore, it is a critical to explore alternative selection systems that can be adapted for large-scale industrial fermentation. RESULTS: Here, a novel glucose-dependent selection system was developed in a high pullulan-producing non-conventional strain A. melanogenum P16. The system comprised a glucose-deficient chassis cell Δpfk obtained through the knockout of the phosphofructokinase gene (PFK) and a series of chromosomal integration plasmids carrying a selection marker PFK controlled by different strength promoters. Utilizing the green fluorescent protein gene (GFP) as a reporter gene, this system achieved a 100% positive rate of transformation, and the chromosomal integration numbers of GFP showed an inverse relationship with promoter strength, with a customizable copy number ranging from 2 to 54. More importantly, the chromosomal integration numbers of target genes remained stable during successive inoculation and fermentation process, facilitated simply by using glucose as a cost-effective and environmental-friendly selectable molecule to maintain a constant and rigorous screening pressure. Moreover, this glucose-dependent selection system exhibited no significant effect on cell growth and product synthesis, and the glucose-deficient related selectable marker PFK has universal application potential in non-conventional yeasts. CONCLUSION: Here, we have developed a novel glucose-dependent selection system to achieve customizable and stable multilocus chromosomal integration of target genes. Therefore, this study presents a promising new tool for genetic manipulation and strain enhancement in non-conventional yeasts, particularly tailored for industrial fermentation applications.

7.
J Food Sci ; 89(7): 3917-3934, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38829741

RESUMO

Extrusion-based three-dimensional (3D) printing has been extensively studied in the food manufacturing industry. This technology places particular emphasis on the rheological properties of the printing ink. Gel system is the most suitable ink system and benefits from the composition of plant raw materials and gel properties of multiple components; green, healthy aspects of the advantages of the development of plant-based gel system has achieved a great deal of attention. However, the relevant treatment technologies are still only at the laboratory stage. With a view toward encouraging further optimization of ink printing performance and advances in this field, in this review, we present a comprehensive overview of the application of diverse plant-based gel systems in 3D food printing and emphasize the utilization of different treatment methods to enhance the printability of these gel systems. The treatment technologies described in this review are categorized into three distinct groups, physical, chemical, and physicochemical synergistic treatments. We comprehensively assess the specific application of these technologies in various plant-based gel 3D printing systems and present valuable insights regarding the challenges and opportunities for further advances in this field.


Assuntos
Géis , Impressão Tridimensional , Reologia , Géis/química , Tinta , Plantas/química , Manipulação de Alimentos/métodos
8.
J Orthop Surg Res ; 19(1): 340, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849937

RESUMO

BACKGROUND: Lumbar spondylolysis is a bone defect in the pars interarticularis of the lumbar vertebral, which is a common cause of low back pain in youth. Although non-surgical treatment is a mainstream option, surgery is necessary for patients with persistent symptoms. Buck technique is widely used as a classical direct repair technique, but it cannot achieve reduction of low-grade spondylolisthesis and reconstruction of lumbosacral sagittal balance. We have described a novel surgical procedure based on Buck technique with temporary intersegmental pedicle screw fixation, and report a series of clinical outcomes in 5 patients to provide a reference for the clinical treatment of young lumbar spondylolysis. METHODS: Five young patients with symptomatic lumbar spondylolysis with a mean age of 19.20 ± 5.41 years underwent surgical treatment after an average of 7.60 ± 1.52 months of failure to respond to conservative treatment, using a new surgical procedure based on Buck technique combined with temporary intersegmental pedicle screw fixation. RESULTS: Five patients were successfully operated without serious complications such as nerve and vascular injury. The average operation time was 109.00 ± 7.42 min, the interpretative average blood loss was 148.00 ± 31.14 ml, and the average fusion time was 11.20 ± 1.64 months. All patients were followed up for 2 years after surgery, and the visual analogue score (VAS) of low back pain and Oswestry disability index (ODI) scores were significantly improved compared with those before surgery, and the Henderson's evaluation were rated excellent or good. After the removal of the internal fixation, it was observed that temporary intersegmental fixation could repair the isthmus, reduce lumbar spondylolisthesis, and reconstruct the sagittal balance of the lumbosacral vertebrae while preserving lumbar motion and preventing intervertebral disc degeneration. Postoperative MRI indicated the Pfirrmann classification of the affected discs: 1 case from grade III to grade II, 3 cases from grade II to grade I, and 1 case remained grade II. CONCLUSIONS: Buck technique supplemented by temporary intersegmental pedicle screw fixation is a highly applicable and effective method for the treatment of adolescent lumbar spondylolysis. The isthmic fusion is accurate, and temporary intersegmental fixation can effectively prevent disc degeneration and reconstruct the sagittal balance of lumbosacral vertebra.


Assuntos
Vértebras Lombares , Parafusos Pediculares , Espondilólise , Humanos , Espondilólise/cirurgia , Espondilólise/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Adolescente , Masculino , Feminino , Adulto Jovem , Adulto , Resultado do Tratamento , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Seguimentos , Dor Lombar/cirurgia , Dor Lombar/etiologia
9.
J Dairy Sci ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851580

RESUMO

Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing specific and environmentally friendly inhibitors is a challenging endeavor. To identify a natural and effective methane inhibitor that specifically targets methyl-coenzyme M reductase, molecular docking technology was employed to screen a library of phytogenic compounds. A total of 52 candidate compounds were obtained through molecular docking technique. Rosmarinic acid (RA) was one of the compounds that could traverse a narrow channel and bind to the active sites of methyl-coenzyme M reductase, with a calculated binding free energy of -9.355 kcal/mol. Furthermore, the effects of rosmarinic acid supplementation on methane production, rumen fermentation, and the microorganism's community in dairy cows were investigated through in vitro rumen fermentation simulations according to a random design. Supplementation of RA resulted in a 15% decrease in methane production compared with the control. In addition, RA increased the molar proportion of acetate and propionate, whereas the sum of acetate and butyrate divided by propionate was decreased. At the bacterial level, the relative abundance of Rikenellaceae RC9 gut group, Christensenellaceae R7 group, Candidatus Saccharimonas, Desulfovibrio, and Lachnospiraceae FE2018 group decreased with RA supplementation. Conversely, the addition of RA significantly increased the relative abundance of DNF00809 (a genus from Eggerthellaceae), Denitrobacterium, an unclassified genus from Eggerthellaceae, an unclassified genus from Bacteroidales, and an unclassified genus from Atopobiaceae. At the archaeal level, the relative abundance of Methanobrevibacter decreased, while that of Methanosphaera increased with the RA supplementation. These findings suggested that RA has the potential to be used as a novel natural additive for inhibiting ruminal methane production.

10.
Alzheimers Dement ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934363

RESUMO

INTRODUCTION: Cognitive impairment is a core feature of Down syndrome (DS), and the underlying neurobiological mechanisms remain unclear. Translation dysregulation is linked to multiple neurological disorders characterized by cognitive impairments. Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) by its kinase eEF2K results in inhibition of general protein synthesis. METHODS: We used genetic and pharmacological methods to suppress eEF2K in two lines of DS mouse models. We further applied multiple approaches to evaluate the effects of eEF2K inhibition on DS pathophysiology. RESULTS: We found that eEF2K signaling was overactive in the brain of patients with DS and DS mouse models. Inhibition of eEF2 phosphorylation through suppression of eEF2K in DS model mice improved multiple aspects of DS-associated pathophysiology including de novo protein synthesis deficiency, synaptic morphological defects, long-term synaptic plasticity failure, and cognitive impairments. DISCUSSION: Our data suggested that eEF2K signaling dysregulation mediates DS-associated synaptic and cognitive impairments. HIGHLIGHTS: Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) is increased in the Down syndrome (DS) brain. Suppression of the eEF2 kinase (eEF2K) alleviates cognitive deficits in DS models. Suppression of eEF2K improves synaptic dysregulation in DS models. Cognitive and synaptic impairments in DS models are rescued by eEF2K inhibitors.

11.
Int J Mol Sci ; 25(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38791216

RESUMO

The interplay patterns of amino acid residues are pivotal in determining the tertiary structure and flexibility of proteins, which in turn are intricately linked to their functionality and interactions with other molecules. Here, we introduce ARIP, a novel tool designed to identify contact residues within proteins. ARIP employs a modified version of the dr_sasa algorithm and an atomic overlap weighted algorithm to directly calculate the contact area and volume between atoms based on their van der Waals radius. It also allows for the selection of solvent radii, recognizing that not every atom in proteins can interact with water molecules. The solvent parameters were derived from the analysis of approximately 5000 protein and nucleic acid structures with water molecules determined using X-ray crystallography. One advantage of the modified algorithm is its capability to analyze multiple models within a single PDB file, making it suitable for molecular dynamic capture. The contact volume is symmetrically distributed between the interacting atoms, providing more informative results than contact area for the analysis of intra- and intermolecular interactions and the development of scoring functions. Furthermore, ARIP has been applied to four distinct cases: capturing key residue-residue contacts in NMR structures of P4HB, protein-drug binding of CYP17A1, protein-DNA binding of SPI1, and molecular dynamic simulations of BRD4.


Assuntos
Algoritmos , Simulação de Dinâmica Molecular , Proteínas , Software , Humanos , Cristalografia por Raios X/métodos , Ligação Proteica , Conformação Proteica , Proteínas/química , Solventes/química , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Água/química
12.
Anal Chem ; 96(19): 7669-7678, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38708542

RESUMO

Protein tyrosine kinase-7 (PTK7) has been reported as a vital participant in the Wnt signaling pathway, influencing tumorigenesis and metastasis. However, their specific roles in the mechanisms underlying cancer development and progression remain elusive. Here, using direct stochastic optical reconstruction microscopy (dSTORM) with aptamer-probe labeling, we first revealed that a weakening clustering distribution of PTK7 on the basal membranes happened as cellular migration increased during cancer progression. This correspondence was further supported by a diminished aggregated state of PTK7 caused by direct enhancement of cell migration. By comparing the alterations in PTK7 distribution with activation or inhibition of specific Wnt signaling pathway, we speculated that PTK7 could modulate cell migration by participating in the interplay between canonical Wnt (in MCF7 cells) and noncanonical Wnt signals (in MDA-MB-231 cells). Furthermore, we discovered that the spatial distribution morphology of PTK7 was also subject to the hydrolysis ability and activation state of the related hydrolase Matrix metallopeptidase14 (MMP14). This function-related specific assembly of PTK7 reveals a clear relationship between PTK7 and cancer. Meanwhile, potential molecular interactions predicted by the apparent assembly morphology can promote a deep understanding of the functional mechanism of PTK7 in cancer progress.


Assuntos
Receptores Proteína Tirosina Quinases , Humanos , Receptores Proteína Tirosina Quinases/metabolismo , Movimento Celular , Moléculas de Adesão Celular/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Neoplasias/metabolismo , Neoplasias/patologia , Metaloproteinase 14 da Matriz/metabolismo
13.
Neurobiol Aging ; 140: 116-121, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38763076

RESUMO

Synaptic dysfunction is highly correlated with cognitive impairments in Alzheimer's disease (AD), the most common dementia syndrome in the elderly. Long-term potentiation (LTP) and long-term depression (LTD) are two primary forms of synaptic plasticity with opposite direction of synaptic efficiency change. Both LTD and LTD are considered to mediate the cellular process of learning and memory. Substantial studies demonstrate AD-associated deficiency of both LTP and LTD. Meanwhile, the molecular signaling mechanisms underlying impairment of synaptic plasticity, particularly LTD, are poorly understood. By taking advantage of the novel transgenic mouse models recently developed in our lab, here we aimed to investigate the roles of AMP-activated protein kinase (AMPK), a central molecular senor that plays a critical role in maintaining cellular energy homeostasis, in regulation of LTD phenotypes in AD. We found that brain-specific suppression of the AMPKα1 isoform (but not AMPKα2 isoform) was able to alleviate mGluR-LTD deficits in APP/PS1 AD mouse model. Moreover, suppression of either AMPKα isoform failed to alleviate AD-related NMDAR-dependent LTD deficits. Taken together with our recent studies on roles of AMPK signaling in AD pathophysiology, the data indicate isoform-specific roles of AMPK in mediating AD-associated synaptic and cognitive impairments.


Assuntos
Proteínas Quinases Ativadas por AMP , Doença de Alzheimer , Modelos Animais de Doenças , Depressão Sináptica de Longo Prazo , Camundongos Transgênicos , Animais , Doença de Alzheimer/fisiopatologia , Proteínas Quinases Ativadas por AMP/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Neurônios/fisiologia , Neurônios/metabolismo , Plasticidade Neuronal
14.
J Oral Pathol Med ; 53(6): 366-375, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763759

RESUMO

BACKGROUND: Angiopoietin-like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin-like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear. METHODS: Using well-characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia-derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin-like 4-induced head and neck squamous cell carcinoma tumorigenesis. RESULTS: We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin-like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia-inducible factor-1 in this effect. Interestingly, amphiregulin and angiopoietin-like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin-induced activation of cell proliferation was dependent on angiopoietin-like 4. Although both p38 mitogen-activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin-like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin-like 4 promoted the secretion of interleukin 11 (IL-11), interleukin 12 (IL-12), interleukin-1 alpha (IL-1α), vascular endothelial growth factor, platelet-derived growth factor (PDGF), and tumour necrosis factor alpha (TNF-α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis. CONCLUSION: Our results demonstrate that angiopoietin-like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms.


Assuntos
Anfirregulina , Proteína 4 Semelhante a Angiopoietina , Movimento Celular , Proliferação de Células , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno , Humanos , Anfirregulina/farmacologia , Anfirregulina/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Movimento Celular/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Proteína 4 Semelhante a Angiopoietina/metabolismo , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Transdução de Sinais , Queratinócitos/metabolismo , Queratinócitos/efeitos dos fármacos , Receptores ErbB/metabolismo
15.
JMIR Public Health Surveill ; 10: e47626, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748469

RESUMO

BACKGROUND: Beyond the direct effect of COVID-19 infection on young people, the wider impact of the pandemic on other infectious diseases remains unknown. OBJECTIVE: This study aims to assess changes in the incidence and mortality of 42 notifiable infectious diseases during the pandemic among children and adolescents in China, compared with prepandemic levels. METHODS: The Notifiable Infectious Disease Surveillance System of China was used to detect new cases and fatalities among individuals aged 5-22 years across 42 notifiable infectious diseases spanning from 2018 to 2021. These infectious diseases were categorized into 5 groups: respiratory, gastrointestinal and enterovirus, sexually transmitted and blood-borne, zoonotic, and vector-borne diseases. Each year (2018-2021) was segmented into 4 phases: phase 1 (January 1-22), phase 2 (January 23-April 7), phase 3 (April 8-August 31), and phase 4 (September 1-December 31) according to the varying intensities of pandemic restrictive measures in 2020. Generalized linear models were applied to assess the change in the incidence and mortality within each disease category, using 2018 and 2019 as the reference. RESULTS: A total of 4,898,260 incident cases and 3701 deaths were included. The overall incidence of notifiable infectious diseases decreased sharply during the first year of the COVID-19 pandemic (2020) compared with prepandemic levels (2018 and 2019), and then rebounded in 2021, particularly in South China. Across the past 4 years, the number of deaths steadily decreased. The incidence of diseases rebounded differentially by the pandemic phase. For instance, although seasonal influenza dominated respiratory diseases in 2019, it showed a substantial decline during the pandemic (percent change in phase 2 2020: 0.21, 95% CI 0.09-0.50), which persisted until 2021 (percent change in phase 4 2021: 1.02, 95% CI 0.74-1.41). The incidence of gastrointestinal and enterovirus diseases decreased by 33.6% during 2020 but rebounded by 56.9% in 2021, mainly driven by hand, foot, and mouth disease (percent change in phase 3 2021: 1.28, 95% CI 1.17-1.41) and infectious diarrhea (percent change in phase 3 2020: 1.22, 95% CI 1.17-1.28). Sexually transmitted and blood-borne diseases were restrained during the first year of 2021 but rebounded quickly in 2021, mainly driven by syphilis (percent change in phase 3 2020: 1.31, 95% CI 1.23-1.40) and gonorrhea (percent change in phase 3 2020: 1.10, 95% CI 1.05-1.16). Zoonotic diseases were not dampened by the pandemic but continued to increase across the study period, mainly due to brucellosis (percent change in phase 2 2020: 0.94, 95% CI 0.75-1.16). Vector-borne diseases showed a continuous decline during 2020, dominated by hemorrhagic fever (percent change in phase 2 2020: 0.68, 95% CI 0.53-0.87), but rebounded in 2021. CONCLUSIONS: The COVID-19 pandemic was associated with a marked decline in notifiable infectious diseases in Chinese children and adolescents. These effects were not sustained, with evidence of a rebound to prepandemic levels by late 2021. To effectively address the postpandemic resurgence of infectious diseases in children and adolescents, it will be essential to maintain disease surveillance and strengthen the implementation of various initiatives. These include extending immunization programs, prioritizing the management of sexually transmitted infections, continuing feasible nonpharmaceutical intervention projects, and effectively managing imported infections.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Adolescente , Criança , Pré-Escolar , Adulto Jovem , Incidência , Masculino , Doenças Transmissíveis/epidemiologia , Feminino , Pandemias , Notificação de Doenças/estatística & dados numéricos
16.
Biochar ; 6(1): 52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799721

RESUMO

While many studies have examined the role of biochar in carbon (C) accrual in short-term scale, few have explored the decadal scale influences of biochar on non-biochar C, e.g., native soil organic C (SOC) and added substrate. To address this knowledge gap, soils were collected from decade-old biochar field trials located in the United Kingdom (Cambisol) and China (Fluvisol), with each site having had three application rates (25-30, 50-60 and 75-100 Mg ha-1) of biochar plus an unamended Control, applied once in 2009. We assessed physicochemical and microbial properties associated with sucrose (representing the rhizodeposits) mineralization and the priming effect (PE) on native SOC. Here, we showed both soils amended with biochar at the middle application rate (50 Mg ha-1 biochar in Cambisol and 60 Mg ha-1 biochar in Fluvisol) resulted in greater substrate mineralization. The enhanced accessibility and availability of sucrose to microorganisms, particularly fast-growing bacterial genera like Arenimonas, Spingomonas, and Paenibacillus (r-strategists belonging to the Proteobacteria and Firmicutes phyla, respectively), can be attributed to the improved physicochemical properties of the soil, including pH, porosity, and pore connectivity, as revealed by synchrotron-based micro-CT. Random forest analysis also confirmed the contribution of the microbial diversity and physical properties such as porosity on sucrose mineralization. Biochar at the middle application rate, however, resulted in the lowest PE (0.3 and 0.4 mg of CO2-C g soil-1 in Cambisol and Fluvisol, respectively) after 53 days of incubation. This result might be associated with the fact that the biochar promoted large aggregates formation, which enclosed native SOC in soil macro-aggregates (2-0.25 mm). Our study revealed a diverging pattern between substrate mineralization and SOC priming linked to the biochar application rate. This suggests distinct mechanisms, biophysical and physicochemical, driving the mineralization of non-biochar carbon in a field where biochar was applied a decade before. Supplementary Information: The online version contains supplementary material available at 10.1007/s42773-024-00327-0.

17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(5): 593-597, 2024 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-38752247

RESUMO

Objective: To investigate the accuracy of positioning perforator of medial sural artery with three-dimensional ultrasound technique guided by a wide band linear matrix array volume transducer probe before operation, and the effectiveness of the flap design based on this in repairing the dorsal foot wounds. Methods: Between January 2019 and December 2022, 30 patients with skin and soft tissue defects of the dorsal foot were treated. There were 19 males and 11 females, with an average age of 43.9 years (range, 22-63 years). There were 12 cases of traffic accident injury, 15 cases of heavy crushing injury, and 3 cases of machine injury. The time from injury to hospitalization was 1-8 hours (mean, 3.5 hours). The wounds in size of 5 cm×3 cm to 17 cm×5 cm were thorough debrided and covered with vacuum sealing drainage dressing. Then the wounds were repaired with the medial sural artery perforator flaps after no obvious infection observed. To obtain the complete three-dimensional image, the number and position of the medial sural artery perforator branches and the position of the main blood vessels in the muscle were detected and recorded by wide band linear matrix array volume transducer probe before operation. Suitable perforating branches were selected to design the flap and guide the flap incision on this basis. The size of the perforating flap ranged from 6 cm×4 cm to 18 cm×6 cm. The sensitivity and positive predictive value were calculated by comparing preoperative exploration with intraoperative observation of perforating branches, so as to evaluate the positioning accuracy of three-dimensional ultrasound technique. The donor sites were sutured directly in 25 cases and repaired with free skin grafting in 5 cases. Results: The 60 perforating branches of medial sural artery were found before operation and 58 during operation in 30 patients. Among them, pre- and intra-operative perforations were consistent with 56. The sensitivity was 93.3% and positive predictive value was 96.6%. The intramuscular position and route of the main blood vessels were basically consistent with the pre- and intra-operative observation. All flaps survived and wounds healed by first intention. All incisions at the donor sites healed by first intention, and all skin grafts survived. All patients were follow up 9-24 months (mean, 14.7 months). The appearance, color, and texture of the flaps were good, and no obvious effect on wearing shoes and walking. At last follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind score ranged from 80 to 92, with an average of 87.5. The patient satisfaction was excellent in 29 cases and good in 1 case. Conclusion: The three-dimensional ultrasound technique guided by the wide band linear matrix array volume transducer probe can accurately locate the perforating branch of the medial sural artery, and the three-dimensional imaging is more intuitive, which can be used to guide the design and incision of the medial sural artery perforator flap.


Assuntos
Traumatismos do Pé , Imageamento Tridimensional , Retalho Perfurante , Lesões dos Tecidos Moles , Ultrassonografia , Humanos , Masculino , Adulto , Feminino , Retalho Perfurante/irrigação sanguínea , Pessoa de Meia-Idade , Traumatismos do Pé/cirurgia , Ultrassonografia/métodos , Lesões dos Tecidos Moles/cirurgia , Lesões dos Tecidos Moles/diagnóstico por imagem , Adulto Jovem , Procedimentos de Cirurgia Plástica/métodos , Fíbula/irrigação sanguínea , Artérias , Cicatrização , Transplante de Pele/métodos
18.
Aesthetic Plast Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760536

RESUMO

BACKGROUND: Autologous fat grafting is a common treatment for tear trough deformities. This procedure involves a potential complication of fat nodule formation, leading to abnormal bulging of the lower eyelid. However, limited information exists about this complication, and an effective treatment is lacking. The present study aimed to present a novel surgical approach for the removal of fat nodules caused by autologous fat grafting in the tear trough. METHODS: This retrospective study included 33 patients who underwent surgery for the removal of fat nodules formed after autologous fat grafting. The procedure was performed using a conjunctival approach, allowing exposure and removal of all fat nodules in the anterior septal space, with the method adapted according to the severity of the deformity. RESULTS: A total of 66 eyelids were treated surgically, including 30 (45.45%) with mild nodular deformity, 23 (34.85%) with moderate nodular deformity, and 13 (10.70%) with severe nodular deformity. A second surgical procedure was required on 3 eyelids (4.56%). The main complications of the surgery were conjunctival congestion (21.21%), and localized depression (18.18%), bruising (12.12%). Among the patients, 29 (87.88%) were satisfied and 4 (12.12%) were dissatisfied with the treatment results. CONCLUSION: Conjunctival approach surgery is an effective method of removing fat nodules formed after autologous fat grafting in the tear trough, with good results and high levels of patient satisfaction. This approach enables the effective management of a common complication of autologous fat grafting and may enable the wider application of autologous fat grafting in the periorbital region. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

20.
J Hazard Mater ; 473: 134713, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38788570

RESUMO

Energy consumption structure has been adjusted worldwide as a measure to reduce CO2 emission and mitigate air pollution. The "Coal to Gas" transition in mainland China has successfully controlled air pollution in recent decades, but its impacts on the environment beyond air quality improvement remain unknown. With 210Pb dating, this study chronicled profiles of eight anthropogenic metal(loid)s in sediment core from 14 waterscape parks across the Ring Road Network of Beijing, China. Six sediment cores were dated showing a timing coupling of metal(loid) loadings with annual coal consumption during the increasing period before 2000. Two downwind sediment cores in downtown Beijing presented such couplings in both increasing and descending periods for coal consumption before and after 2000, respectively, close to the tipping point observed in 2002 for primary energy consumption efficiency. Evidence from stable Pb isotope composition and exceedances of Cu loadings against sediment quality guidelines of China and the USA suggest that vehicular sources have been dominating metal(loid) loadings in sedimentation in these waterscape parks after the "Coal to Gas" transition. These findings would be helpful in identifying environmental impact patterns resulting from shifts in energy consumption structure and dominance of emission sources thereafter.

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