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1.
BMC Pediatr ; 24(1): 525, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143528

RESUMO

BACKGROUND: Tubal mesosalpinx cysts are paratubal cysts, that account for approximately 10% of adnexal masses, and the presence of these cysts combined with adnexal torsion is a rare acute abdominal condition, with few cases reported in the literature. We reported two cases of adolescent tubal mesosalpinx cysts combined with adnexal torsion and reviewed the literature to help improve the diagnosis of the disease. CASE REPORTS: The first patient was an 11-year-old girl with left lower abdominal pain for 5 days and fever with nausea and vomiting for 3 days, who was found to have a cystic pelvic mass on preoperative imaging and was diagnosed intraoperatively and postoperatively on pathology as having a left tubal mesosalpinx cyst combined with adnexal torsion. The second patient was a 13-year-old girl with right lower abdominal pain for 16 h and a palpable mass in the lower and middle abdomen on examination, which was hard and tender to palpate. Preoperative imaging revealed a large cystic mass in the right adnexal region, and intraoperative and postoperative pathology revealed a right tubal mesosalpinx cyst combined with adnexal torsion. CONCLUSIONS: Tubal mesosalpinx cysts combined with adnexal torsion are rare causes of acute lower abdominal pain. Early diagnosis and timely surgery are necessary to ensure ovarian and tubal function. Accurate preoperative imaging diagnosis is challenging, and MRI is a beneficial supplement to ultrasound and CT examinations, providing more objective imaging information and reducing the incidence of adverse outcomes.


Assuntos
Anormalidade Torcional , Humanos , Feminino , Adolescente , Criança , Anormalidade Torcional/cirurgia , Anormalidade Torcional/complicações , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/diagnóstico , Cisto Parovariano/complicações , Cisto Parovariano/cirurgia , Cisto Parovariano/diagnóstico , Torção Ovariana/cirurgia , Torção Ovariana/complicações , Doenças dos Anexos/cirurgia , Doenças dos Anexos/complicações , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/diagnóstico
2.
Sci Rep ; 14(1): 19190, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160290

RESUMO

Sulfur deposition can result in an increase in the wall thickness of high-sulfur natural gas gathering pipelines, leading to issues like unstable pipeline flow. It is crucial to reveal the aggregation of sulfur particles at key locations of high-sulfur natural gas gathering pipelines to predict the location and amount of sulfur deposition in the pipelines. In this paper, the Euler-PBM (Population balance model) coupling is used to establish a numerical simulation model of gas-solid two-phase pipe flow accompanied by sulfur particle agglomeration in the pipe bends, focusing on the influence of sulfur particle volume fraction, pipe inclination angle and inlet flow velocity on sulfur particles agglomeration behavior. The results show that the sulfur particles have a significant agglomeration effect at the bend of the collecting pipeline, and the agglomeration growth occurs to different degrees throughout the bend, and the main area of sulfur particles agglomeration is near the top wall of the pipeline, followed by other areas near the wall of the pipeline. When the inlet volume fraction of sulfur particles was increased from 0.05 to 0.25%, and the inclination angle of the pipe was increased from 30° to 90°, the distribution range of sulfur particle size after agglomeration became wider, and the maximum size of sulfur particles was 187.56 µm, and the effect of sulfur particle agglomeration was enhanced; the inlet flow rate was increased from 3.0 to 9.0 m/s, and the reduction range of sulfur particle size after agglomeration was 5.68-9.87 µm. The maximum particle size of sulfur particles also decreased, and the effect of sulfur particle agglomeration was weakened.

3.
Bone Res ; 12(1): 38, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961077

RESUMO

Bone marrow adipocytes (BMAds) affect bone homeostasis, but the mechanism remains unclear. Here, we showed that exercise inhibited PCNA clamp-associated factor (PCLAF) secretion from the bone marrow macrophages to inhibit BMAds senescence and thus alleviated skeletal aging. The genetic deletion of PCLAF in macrophages inhibited BMAds senescence and delayed skeletal aging. In contrast, the transplantation of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2 receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence and subsequently spread senescence among osteogenic and osteoclastic cells. Of note, we developed a PCLAF-neutralizing antibody and showed its therapeutic effects on skeletal health in old mice. Together, these findings identify PCLAF as an inducer of BMAds senescence and provide a promising way to treat age-related osteoporosis.


Assuntos
Adipócitos , Envelhecimento , Senescência Celular , Animais , Adipócitos/metabolismo , Senescência Celular/fisiologia , Camundongos , Envelhecimento/fisiologia , Camundongos Endogâmicos C57BL , Células da Medula Óssea/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Masculino , Osteogênese/fisiologia , Transdução de Sinais , Macrófagos/metabolismo
4.
Arab J Gastroenterol ; 25(2): 150-159, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38719664

RESUMO

BACKGROUND AND STUDY AIMS: The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes. PATIENTS/MATERIAL AND METHODS: mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database. RESULTS: Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC. CONCLUSION: NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.


Assuntos
Neoplasias Colorretais , Células Matadoras Naturais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Células Matadoras Naturais/imunologia , Prognóstico , Mutação , Taxa de Sobrevida , Análise de Sobrevida , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Perfilação da Expressão Gênica/métodos
5.
Small ; : e2310865, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678537

RESUMO

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

6.
Sci Total Environ ; 930: 172702, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38657810

RESUMO

Exogenous Si mitigates the mobility and bioavailability of Cd in the soil, thereby alleviating its phytotoxicity. This study focused on specific Si-induced immobilisation effects within the rhizosphere (S1), near-rhizosphere (S2), and far-rhizosphere (S3) zones. Based on the rhizobox experiment, we found that applying Si significantly elevated soil pH, and the variation amplitudes in the S3 soil exceeded those in the S1 and S2 soils. Si-induced changes in the rhizosphere also included enhanced dissolved organic carbon and diminished soil Eh, particularly in the Si400 treatment. Meanwhile, the introduction of Si greatly enhanced the Fe2+ and Mn2+ concentrations in the S1 soil, but reduced them in the S2 soil. The rhizosphere effect of Si which enriched Fe2+ and Mn2+ subsequently promoted the formation of Fe and Mn oxides/hydro-oxides near the rice roots. Consequently, the addition of Si significantly reduced the available Cd concentrations in S1, surpassing the reductions in S2 and S3. Moreover, Si-treated rice exhibited increased Fe plaque generation and fixation on soil Cd, resulting in decreased Cd concentrations in rice tissues, accompanied by reduced Cd translocation from roots to shoots and shoots to grains. Structural equation modelling further highlighted that Si is essential in Cd availability in S1 and Fe plaque development, ultimately mitigating Cd accumulation in rice. Si-treated rice also exhibited higher biomass and grain yield than those of control groups. These findings provide valuable insights into Si-based strategies for addressing the Cd contamination of agricultural soils.


Assuntos
Cádmio , Oryza , Rizosfera , Silício , Poluentes do Solo , Solo , Cádmio/análise , Poluentes do Solo/análise , Solo/química , Disponibilidade Biológica , Raízes de Plantas , Fertilizantes
7.
Cell Death Dis ; 15(4): 271, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632264

RESUMO

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Exossomos , Células-Tronco Mesenquimais , Humanos , Exossomos/metabolismo , Complicações do Diabetes/metabolismo , Comunicação Celular , Células-Tronco Mesenquimais/metabolismo , Resultado do Tratamento , Diabetes Mellitus/metabolismo
8.
J Mater Chem B ; 12(13): 3240-3248, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38437473

RESUMO

Proteolysis targeting chimeras (PROTACs) is a promising strategy for cancer therapy. However, the always-on bioactivity of PROTACs may lead to non-target toxicity, which restricts their antitumor performance. Here, we developed an X-ray radiation responsive PROTAC nanomicelle (RCNprotac) by covalently conjugating a reported small molecule PROTAC (MZ1) to hydrophilic PEG via a diselenide bond-containing carbon chain, which then self-assembled into a 141.80 ± 5.66 nm nanomicelle. The RCNprotac displayed no bioactivity during circulation due to the occupation of the hydroxyl group on the E3 ubiquitin ligand component and could effectively accumulate at the tumor site owing to the enhanced permeability and retention effect. Upon exposure to X-ray radiation, the radiation-sensitive diselenide bonds were broken to specifically release MZ1 for tumor BRD4 protein degradation. Furthermore, the reduction in the BRD4 protein level could increase the tumor's sensitivity to radiation. RCNprotac showed a synergistic enhancement of antitumor effects both in vitro and in vivo. We believe that this X-ray-responsive PROTAC nanomicelle could provide a new strategy for the X-ray-activated spatiotemporally controlled protein degradation and for the BRD4 proteolysis enhanced tumor radiosensitivity.


Assuntos
Nanopartículas , Neoplasias , Humanos , Proteólise , Proteínas Nucleares/metabolismo , Fatores de Transcrição , Neoplasias/patologia , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/metabolismo
9.
J Colloid Interface Sci ; 660: 716-725, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38271807

RESUMO

Although solar steam generation is promising for seawater desalination, it is less effective in purifying wastewater with both salt/heavy metal ions and organic contaminants. It is thus imperative to develop multifunctional integrated solar-driven water purification systems with high solar-thermal evaporation and photocatalytic degradation efficiencies. Herein, a lamellar reduced graphene oxide (L-RGO) foam with the vertical lamellar structure is fabricated by bidirectional-freezing, lyophilization, and slight chemical reduction for water purification. The unique vertical lamellar structure not only accelerates upward transport of water for facilitating water evaporation but also endows the L-RGO foam with superb high elasticity for tuning the interlayer distance and varying interactions between the oxygen-containing groups and water molecules to adjust water energy state. As a result, the L-RGO foam achieves a superb water evaporation rate of 2.40 kg m-2 h-1 along with an energy efficiency of 95.3 % under the compressive strain of 44.7 % under 1-sun irradiation. Equally importantly, the decoration of L-RGO foam with polypyrrole is capable of efficiently degrading organic pollutants while retaining high solar steam generation performances, exhibiting great potential in the comprehensive treatment of various water sources for relieving freshwater crisis.

10.
Bone Res ; 12(1): 6, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38267422

RESUMO

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.


Assuntos
Calosidades , Fraturas Ósseas , Idoso , Humanos , Animais , Camundongos , Consolidação da Fratura , Senescência Celular , Envelhecimento , Macrófagos , Células-Tronco
11.
Environ Res ; 245: 118024, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38151151

RESUMO

River systems are important recipients of environmental plastic pollution and have become key pathways for the transfer of mismanaged waste from the land to the ocean. Understanding the sources and fate of plastic debris, including plastic litter (>5 mm) and microplastics (MPs) (<5 mm), entering different riverine systems is essential to mitigate the ongoing environmental plastic pollution crisis. We comprehensively investigated the plastic pollution in the catchments of two rivers in the Yangtze River basin: an urban river, the Suzhou section of the Beijing-Hangzhou Grand Canal (SZ); and a pristine rural river, the Jingmen section of the Hanjiang River (JM). The abundance of plastic pollutants in SZ was significantly higher than in JM: 0.430 ± 0.450 items/m3 and 0.003 ± 0.003 items/m3 of plastic litter in the water; 23.47 ± 25.53 n/m3 and 2.78 ± 1.55 n/m3 MPs in the water; and 218.82 ± 77.40 items/kg and 5.30 ± 1.99 items/kg of MPs in the sediment, respectively. Plastic litter and MPs were closely correlated in abundance and polymer composition. Overall, the polymer type, shape and color of MPs were dominant by polypropylene (42.5%), fragment (60.4%) and transparent (40.0%), respectively. Source tracing analysis revealed that packaging, shipping, and wastewater were the primary sources of plastic pollutants. The mantel analysis indicated that socio-economic and geospatial factors play crucial roles in driving the hotspot formation of plastic pollution in river networks. The composition of the MP communities differed significantly between the sediments and the overlying water. The urban riverbed sediments had a more pronounced pollutant 'sink' effect compared with the pristine rivers. These findings suggested that the modification of natural streams during urbanization may influence the transport and fate of plastic pollutants in them. Our results offer pivotal insights into effective preventive measures.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Plásticos , Rios , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Microplásticos , Água
12.
ACS Omega ; 8(30): 27761-27775, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37546639

RESUMO

Crude oil pipeline transportation is usually a closed process under a certain depth of burial, and the condition of oil in the pipeline changes with the continuous decline of temperature during the transportation process. The safety and energy consumption of pipeline transportation are closely related to the accurate prediction of oil temperature. It is a popular technique to use the thermally affected region to overcome the problem of an unclosed calculation domain caused by the semi-infinite soil around the pipeline. However, there is no clear and unified guidance on the thermally affected region at present, and improper region size may lead to a loss of the accuracy of the pipeline system. Therefore, our study answers two questions about the optimal form of the thermally affected region and its economic scope of application. The coupled solution of heat transfer and flow in a tridimensional numerical model is carried out, and the thermodynamic influences of the geometric shape and range of the thermally affected region on the buried pipeline system are investigated. The results show that the rectangular region is more suitable for the modeling of buried oil pipelines, and a region with 16 m width and 9 m height is recommended for the conventional case.

13.
J Med Microbiol ; 72(8)2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37624368

RESUMO

Background. Local recurrence and distant metastasis are the main causes of death in patients with cancer. Only considering species abundance changes when identifying markers of recurrence and metastasis in patients hinders finding solutions.Hypothesis. Consideration of microbial abundance changes and microbial interactions facilitates the identification of microbial markers of tumour recurrence and metastasis.Aim. This study aims to simultaneously consider microbial abundance changes and microbial interactions to identify microbial markers of recurrence and metastasis in multiple cancer types.Method. One thousand one hundred and six non-RM (patients without recurrence and metastasis within 3 years after initial surgery) tissue samples and 912 RM (patients with recurrence or metastasis within 3 years after initial surgery) tissue samples representing 11 cancer types were collected from The Cancer Genome Atlas (TCGA).Results. Tumour tissue bacterial composition differed significantly among 11 cancers. Among them, the tissue microbiome of four cancers, head and neck squamous cell carcinoma (HNSC), lung squamous cell carcinoma (LUSC), stomach adenocarcinoma (STAD) and uterine corpus endometrial carcinoma (UCEC), showed relatively good performance in predicting recurrence and metastasis in patients, with areas under the receiver operating characteristic curve (AUCs) of 0.78, 0.74, 0.91 and 0.93, respectively. Considering both species abundance changes and microbial interactions for the four cancers, a combination of nine genera (Niastella, Schlesneria, Thioalkalivibrio, Phaeobacter, Sphaerotilus, Thiomonas, Lawsonia, Actinobacillus and Spiroplasma) performed best in predicting patient survival.Conclusion. Taken together, our results imply that comprehensive consideration of microbial abundance changes and microbial interactions is helpful for mining bacterial markers that carry prognostic information.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Gástricas , Humanos , Recidiva Local de Neoplasia , Interações Microbianas , Biomarcadores
14.
Sci Total Environ ; 902: 166152, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37567296

RESUMO

Marine microplastic (MP) pollution represents a global environmental issue that has ignited considerable apprehension within the international community. Seagrass beds, which serve as nearshore marine ecosystems, have emerged as focal points of plastic and MP contamination due to the pronounced density of anthropogenic activities and the hydrological mitigating effects of submerged vegetation. Nevertheless, our comprehension of MPs within seagrass ecosystems remains constrained. In this study, we employed bibliometric analyses and comprehensive data exploration to summarize the historical progression of the development, pivotal areas of interest, and research deficiencies, followed by proposing future research directions for MP pollution in seagrass beds. The 37 selected papers were sourced from the Web of Science Core Collection scientific database as of December 31st, 2022. Based on the current evaluation, MPs are ubiquitously discovered within seagrass canopies, sediments, and marine organisms, while less than 15 % of seagrass species worldwide have been investigated. Moreover, methodological inconsistencies in sampling, processing and visualization between studies hindered the fusion and comparison of data. MPs in upper sediments and seagrass blades were the most widely investigated, with an average abundance of 263.4 ± 309.2 n/kg and 0.09 ± 0.03 n/blade. In all environmental compartments, the prevalent forms of MPs comprise fibrous and fragmented particles, encompassing the dominant polymers such as polypropylene, polyethylene and polyethylene terephthalate. However, the source of MPs in seagrass beds based on MP characteristics and local hydrodynamics has not been comprehensively analyzed in previous studies. The evidence for MPs acting as pollutants and contaminant carries impacting the growth and decline of seagrass is also weak. Currently, the precise implications of MPs on submerged vegetation, organisms, and the broader seagrass ecosystem remain inconclusive. However, considering the persistent accumulation of MPs, it is imperative to explore the ecological hazards they may pose within the foreseeable future.


Assuntos
Microplásticos , Poluentes Químicos da Água , Ecossistema , Plásticos , Monitoramento Ambiental , Poluentes Químicos da Água/análise
15.
Adv Sci (Weinh) ; 10(26): e2301763, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37395388

RESUMO

Osteoarthritis is a degenerative disease characterized by abnormal neurovascularization at the osteochondral junctions, the regulatory mechanisms of which remain poorly understood. In the present study, a murine osteoarthritic model with augmented neurovascularization at the osteochondral junction is used to examine this under-evaluated facet of degenerative joint dysfunction. Increased extracellular RNA (exRNA) content is identified in neurovascularized osteoarthritic joints. It is found that the amount of exRNA is positively correlated with the extent of neurovascularization and the expression of vascular endothelial growth factor (VEGF). In vitro binding assay and molecular docking demonstrate that synthetic RNAs bind to VEGF via electrostatic interactions. The RNA-VEGF complex promotes the migration and function of endothelial progenitor cells and trigeminal ganglion cells. The use of VEGF and VEGFR2 inhibitors significantly inhibits the amplification of the RNA-VEGF complex. Disruption of the RNA-VEGF complex by RNase and polyethyleneimine reduces its in vitro activities, as well as prevents excessive neurovascularization and osteochondral deterioration in vivo. The results of the present study suggest that exRNAs may be potential targets for regulating nerve and blood vessel ingrowth under physiological and pathological joint conditions.


Assuntos
Osteoartrite , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Simulação de Acoplamento Molecular , Osteoartrite/metabolismo , RNA/genética
16.
Cell Death Dis ; 14(6): 385, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37385994

RESUMO

Tau hyperphosphorylation in hippocampal neurons has an important pathogenetic role in the development of diabetic cognitive dysfunction. N6-methyladenosine (m6A) methylation is the most common modification of eukaryotic mRNA and is involved in regulating diverse biological processes. However, the role of m6A alteration in tau hyperphosphorylation of hippocampus neurons has not been reported. We found lower ALKBH5 expression in the hippocampus of diabetic rats and in HN-h cells with high-glucose intervention, accompanied by tau hyperphosphorylation. ALKBH5 overexpression significantly reversed tau hyperphosphorylation in high-glucose-stimulated HN-h cells. Furthermore, we found and confirmed by m6A-mRNA epitope transcriptome microarray and transcriptome RNA sequencing coupled with methylated RNA immunoprecipitation that ALKBH5 regulates the m6A modification of Dgkh mRNA. High glucose inhibited the demethylation modification of Dgkh by ALKBH5, resulting in decreases in Dgkh mRNA and protein levels. Overexpression of Dgkh reversed tau hyperphosphorylation in HN-h cells after high-glucose stimulation. Overexpression of Dgkh by adenovirus suspension injection into the bilateral hippocampus of diabetic rats significantly ameliorated tau hyperphosphorylation and diabetic cognitive dysfunction. In addition, ALKBH5 targeted Dgkh to activate PKC-α, leading to tau hyperphosphorylation under high-glucose conditions. The results of this study reveal that high glucose suppresses the demethylation modification of Dgkh by ALKBH5, which downregulates Dgkh and leads to tau hyperphosphorylation through activation of PKC-α in hippocampal neurons. These findings may indicate a new mechanism and a novel therapeutic target for diabetic cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Animais , Ratos , Neurônios , RNA Mensageiro , Disfunção Cognitiva/genética , Hipocampo , Desmetilação , Glucose
17.
ACS Appl Mater Interfaces ; 15(22): 27120-27129, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37248165

RESUMO

Although significant advances have been achieved in developing solar-driven water evaporators for seawater desalination, there is still room for simultaneously enhancing water evaporation efficiency, salt resistance, and utilization of solar energy. Herein, for the first time, we demonstrate a highly efficient three-dimensional (3D) mirror-assisted and concave pyramid-shaped solar-thermal water evaporation system for high-yield and long-term desalination of seawater and brine water, which consists of a 3D concave pyramid-shaped solar-thermal architecture on the basis of polypyrrole-coated nonwoven fabrics (PCNFs), a 3D mirror array, a self-floating polystyrene foam layer, and a tail-like PCNF for upward transport of water. The 3D concave pyramid-shaped solar-thermal architecture enables multiple solar light reflections to absorb more solar energy, while the 3D mirror-assisted solar light enhancement design can activate the solar-thermal energy conversion of the back side of the concave pyramid-shaped PCNF architecture to improve the solar-thermal energy conversion efficiency. Crucially, selective accumulation of the precipitated salts on the back side of the concave pyramid-shaped architecture is realized, ensuring a favorable salt-resistant feature. The 3D mirror-assisted and concave pyramid-shaped solar-driven water evaporation system achieves a record high water evaporation rate of 4.75 kg m-2 h-1 under 1-sun irradiation only and exhibits long-term desalination stability even when evaporating high-salinity brine waters, demonstrating its great applicability and reliability for high-yield solar-driven desalination of seawater and high-salinity brine water.

18.
Comput Biol Med ; 159: 106873, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37105115

RESUMO

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) technologies allow us to interrogate the state of an individual cell within its microenvironment. However, prior to sequencing, cells should be dissociated first, making it difficult to obtain their spatial information. Since the spatial distribution of cells is critical in a few circumstances such as cancer immunotherapy, we present MLSpatial, a novel computational method to learn the relationship between gene expression patterns and spatial locations of cells, and then predict cell-to-cell distance distribution based on scRNA-seq data alone. RESULTS: We collected the drosophila embryo dataset, which contains both the fluorescence in situ hybridization (FISH) data and single cell RNA-seq (scRNA-seq) data of drosophila embryo. The FISH data provided the spatial position of 3039 cells and the expression of 84 genes for each cell. The scRNA-seq data contains the expressions of 8924 genes in 1297 high-quality cells with cell location unknown. For a comparison, we also collected the MERFISH data of 645 osteosarcoma cells with cell location and the expression status of 10,050 genes known. For each data, the cells were randomly divided into a training set and a test set, in the ratio of 7:3. The cell-to-cell distances our model extracted had a higher correspondence (i.e., correlation coefficient 0.99) with those of the real situation than those of existing methods in the FISH data of drosophila embryo. However, in the osteosarcoma data, our model captured the spatial relationship between cells, with a correlation of 0.514 to that of the real situation. We also applied the model trained using the FISH data of drosophila embryo into the single cell data of drosophila embryo, for which the real location of cells are unknown. The reconstructed pseudo drosophila embryo and the real embryo (as shown by the FISH data) had a high similarity in the spatial distribution of gene expression. CONCLUSION: MLSpatial can accurately restore the relative position of cells from scRNA-seq data; however, the performance depends on the type of cells. The trained model might be useful in reconstructing the spatial distributions of single cells with only scRNA-seq data, provided that the scRNA-seq data and the FISH data are under similar background (i.e., the same tissue with similar disease background).


Assuntos
Perfilação da Expressão Gênica , Software , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodos , Hibridização in Situ Fluorescente , Análise da Expressão Gênica de Célula Única , Análise de Célula Única/métodos , Aprendizado de Máquina
19.
EMBO J ; 42(9): e111762, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36943004

RESUMO

Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age-related bone loss. As an important posttranscriptional regulatory pathway, alternative splicing (AS) regulates the diversity of gene expression and has been linked to induction of cellular senescence. However, the role of splicing factors in BMSCs during aging remains poorly defined. Herein, we found that the expression of the splicing factor Y-box binding protein 1 (YBX1) in BMSCs decreased with aging in mice and humans. YBX1 deficiency resulted in mis-splicing in genes linked to BMSC osteogenic differentiation and senescence, such as Fn1, Nrp2, Sirt2, Sp7, and Spp1, thus contributing to BMSC senescence and differentiation shift during aging. Deletion of Ybx1 in BMSCs accelerated bone loss in mice, while its overexpression stimulated bone formation. Finally, we identified a small compound, sciadopitysin, which attenuated the degradation of YBX1 and bone loss in old mice. Our study demonstrated that YBX1 governs cell fate of BMSCs via fine control of RNA splicing and provides a potential therapeutic target for age-related osteoporosis.


Assuntos
Células-Tronco Mesenquimais , Osteoporose , Humanos , Camundongos , Animais , Osteogênese/genética , Envelhecimento/metabolismo , Senescência Celular , Diferenciação Celular/genética , Osteoporose/metabolismo , Células da Medula Óssea , Proteína 1 de Ligação a Y-Box/metabolismo
20.
Sci Total Environ ; 858(Pt 1): 159769, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36309272

RESUMO

Environmental problems caused by microplastics (MPs) are attracting global attention. The ecological risks of bacteria attached to MPs have not been studied in detail under low temperature conditions. Here, MPs in surface water were sampled in winter from the Changjiang (or Yangtze) River Estuary. The physical and chemical characteristics of the MPs were identified, and the diversity and species composition of bacteria on the surface water MPs were analyzed. Phenotypic prediction analysis was used to analyze the potential risk of bacteria in the biofilm on the surfaces of MPs. The main chemical composition in the MPs in the surface water were PP (polypropylene), PE (polyethylene), PS (polystyrene) and other light weight MPs. Sampling sites played a decisive role in the bacterial species composition. The potential plastic-degrading bacterium Acinetobacter and the potential pathogenic bacterium Pseudomonas showed significant differences across different sampling sites. Microbial communities on the surfaces of MPs in winter were not significantly different from planktonic bacteria in the water body. Phenotypic prediction results showed that bacteria on the surface of MPs had a marked capacity to form biofilms, but a low pathogenicity risk. Based on the results of biodiversity analysis and phenotypic prediction, the potential ecological risk of bacteria in biofilms on MP surfaces is lower at low temperatures. In addition, the numerical simulation results show that the possibility of bacteria attached to MPs from the Changjiang River entering the Pacific Ocean in winter is small. MPs attached bacteria in the Changjiang estuary have low ecological risk to the estuary and the Pacific Ocean in winter.


Assuntos
Microbiota , Poluentes Químicos da Água , Microplásticos , Plásticos , Água/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Estuários , Bactérias
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