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2.
J Hazard Mater ; 471: 134344, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38678706

RESUMO

More information is needed to fully comprehend how acid mine drainage (AMD) affects the phototransformation of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in karst water and sewage-irrigated farmland soil with abundant carbonate rocks (CaCO3) due to increasing pollution of AMD formed from pyrite (FeS2). The results showed FeS2 accelerated the inactivation of ARB with an inactivation of 8.7 log. Notably, extracellular and intracellular ARGs and mobile genetic elements (MGEs) also experienced rapid degradation. Additionally, the pH of the solution buffered by CaCO3 significantly influenced the photo-inactivation of ARB. The Fe2+ in neutral solution was present in Fe(II) coordination with strong reducing potential and played a crucial role in generating •OH (7.0 µM), which caused severe damage to ARB, ARGs, and MGEs. The •OH induced by photo-Fenton of FeS2 posed pressure to ARB, promoting oxidative stress response and increasing generation of reactive oxygen species (ROS), ultimately damaging cell membranes, proteins and DNA. Moreover, FeS2 contributed to a decrease in MIC of ARB from 24 mg/L to 4 mg/L. These findings highlight the importance of AMD in influencing karst water and sewage-irrigated farmland soil ecosystems. They are also critical in advancing the utilization of FeS2 to inactivate pathogenic bacteria.


Assuntos
Carbonato de Cálcio , Ferro , Mineração , Sulfetos , Carbonato de Cálcio/química , Ferro/química , Sulfetos/química , Sequências Repetitivas Dispersas , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Bactérias/efeitos dos fármacos , Genes Bacterianos , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia
3.
Medicine (Baltimore) ; 103(17): e37980, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669362

RESUMO

The aim of this observational study was to investigate the effects of catechol-O-methyltransferase (COMT) and ATP-binding cassette transporter B1 (ABCB1) gene polymorphisms on the postoperative analgesic effect of sufentanil in Chinese Han pediatric patients with fractures. A total of 185 pediatric patients who underwent fracture surgery were included. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of COMT and ABCB1 genes. Sufentanil was used for postoperative analgesia. The pain level of the patients was evaluated using the face, legs, activity, cry, and consolability scale before surgery, during awakening, at 2, 6, 12, and 24 hours after surgery. The postoperative Ramsay sedation score, sufentanil consumption, and incidence of adverse reactions were also recorded. Pediatric patients with different genotypes of ABCB1 and COMT showed no statistically significant differences in general data such as age, gender, weight, height, surgical duration, and American Society of Anesthesiologists classification (P > .05). There were no statistically significant differences in sedation scores after surgery between different genotypes of ABCB1 and COMT (P > .05). Among patients with CC genotype in ABCB1, the pain scores and total consumption of sufentanil at awakening, 2 and 6 hours after surgery were higher compared to TT and CT genotypes (P < .05), while there were no statistically significant differences between TT and CT genotypes (P > .05). Among patients with AA genotype in COMT, the pain scores and total consumption of sufentanil at awakening, 2, 6, 12, and 24 hours after surgery were higher compared to AG and GG genotypes (P < .05), while there were no statistically significant differences between AG and GG genotypes (P > .05). There were no statistically significant differences in adverse reactions between different genotypes of ABCB1 and COMT (P > .05). The polymorphisms of COMT gene rs4680 and ABCB1 gene rs1045642 are associated with the analgesic effect and consumption of sufentanil in pediatric patients after fracture surgery.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Analgésicos Opioides , Catecol O-Metiltransferase , Fraturas Ósseas , Dor Pós-Operatória , Sufentanil , Humanos , Sufentanil/uso terapêutico , Sufentanil/administração & dosagem , Catecol O-Metiltransferase/genética , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/genética , Masculino , Feminino , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Criança , Fraturas Ósseas/cirurgia , Fraturas Ósseas/genética , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Genótipo , Pré-Escolar , Medição da Dor , Polimorfismo Genético , Adolescente , Polimorfismo de Nucleotídeo Único
4.
Can Respir J ; 2024: 5554886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584671

RESUMO

Objective: To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods: First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor ß, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results: APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.


Assuntos
Ferroptose , Panax notoginseng , Fibrose Pulmonar , Animais , Camundongos , Fibrose Pulmonar/tratamento farmacológico , Ciclo-Oxigenase 2 , Colágeno , Receptores ErbB
5.
J Environ Manage ; 358: 120882, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38663080

RESUMO

This study offers an insightful and detailed examination of microplastic pollution in the Huixian karst wetland's groundwater, providing novel insights into the complex interplay of microplastic characteristics and their seasonal dynamics. We meticulously quantified microplastic concentrations, observing significant seasonal variation with values ranging from 4.9 to 13.4 n·L-1 in the wet season and 0.53-49.4 n·L-1 in the dry season. Our analysis pinpoints human activities and atmospheric deposition as key contributors to this contamination. A critical finding of our research is the pronounced disparity in microplastic levels between open wells and covered artesian wells, highlighting the vulnerability of open wells to higher pollution levels. Through correlation analysis, we unearthed the crucial influence of the karst region's unique hydrogeological characteristics on microplastic migration, distinctively different from non-karst areas. The karst terrain, characterized by its caves and subterranean rivers, facilitates the downward movement of microplastics from surface to groundwater, exacerbating pollution levels. Our investigation identifies agricultural runoff and domestic wastewater as primary pollution sources. These findings not only underscore the urgent need for environmental stewardship in karst regions but also provide a crucial foundation for formulating effective strategies to mitigate microplastic pollution in karst groundwater. The implications of this study extend beyond the Huixian karst wetland, offering a template for addressing microplastic pollution in similar ecosystems globally.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Microplásticos , Estações do Ano , Poluentes Químicos da Água , Áreas Alagadas , Água Subterrânea/química , Água Subterrânea/análise , Poluentes Químicos da Água/análise , Microplásticos/análise , Ecossistema
6.
PLoS Pathog ; 20(4): e1012138, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38640110

RESUMO

Proper transcription orchestrated by RNA polymerase II (RNPII) is crucial for cellular development, which is rely on the phosphorylation state of RNPII's carboxyl-terminal domain (CTD). Sporangia, developed from mycelia, are essential for the destructive oomycetes Phytophthora, remarkable transcriptional changes are observed during the morphological transition. However, how these changes are rapidly triggered and their relationship with the versatile RNPII-CTD phosphorylation remain enigmatic. Herein, we found that Phytophthora capsici undergone an elevation of Ser5-phosphorylation in its uncanonical heptapeptide repeats of RNPII-CTD during sporangia development, which subsequently changed the chromosomal occupation of RNPII and primarily activated transcription of certain genes. A cyclin-dependent kinase, PcCDK7, was highly induced and phosphorylated RNPII-CTD during this morphological transition. Mechanistically, a novel DCL1-dependent microRNA, pcamiR1, was found to be a feedback modulator for the precise phosphorylation of RNPII-CTD by complexing with PcAGO1 and regulating the accumulation of PcCDK7. Moreover, this study revealed that the pcamiR1-CDK7-RNPII regulatory module is evolutionarily conserved and the impairment of the balance between pcamiR1 and PcCDK7 could efficiently reduce growth and virulence of P. capsici. Collectively, this study uncovers a novel and evolutionary conserved mechanism of transcription regulation which could facilitate correct development and identifies pcamiR1 as a promising target for disease control.


Assuntos
MicroRNAs , Phytophthora , RNA Polimerase II , Transcrição Gênica , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Fosforilação , MicroRNAs/metabolismo , MicroRNAs/genética , Phytophthora/patogenicidade , Phytophthora/genética , Phytophthora/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/genética
7.
Mod Pathol ; 37(5): 100468, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460673

RESUMO

Soft tissue neoplasms, harboring fusions between EWSR1 and FUS with genes encoding CREB transcription factors family (ATF1, CREB1, and CREM), are an emerging heterogeneous group of mesenchymal tumors that differ significantly in morphology, immunophenotypes, and behavior. Recently, EWSR1/FUS::CREB fusions have been recognized to define a group of aggressive neoplasms of epithelioid morphology with multiple growth patterns and a striking predilection for mesothelial-lined cavities. These neoplasms presenting as a primary neoplasm of intra-abdominal visceral organs are rare, which could elicit a wide range of differential diagnoses because of their diverse morphologies and immunohistochemical profiles. We report 3 cases of intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions involving the kidney. This study included 2 female patients and 1 male patient, with age at presentation ranging from 17 to 61 years (mean: 32 years). All the patients underwent radical nephrectomy without adjunctive therapies. Grossly, the tumors were large, and all were solitary masses with sizes ranging from 5.6 to 30.0 cm (mean: 14.5 cm). Histologically, the neoplasms showed infiltrating and indistinct borders and were composed predominantly of monomorphic round-to-epithelioid cells with variable amounts of pale-to-clear cytoplasm, arranged in cords, nests, and sheets and embedded in a sclerotic hyalinized stroma with variable lymphoid cuffing either intermixed or at the periphery. Notably, a hemangiopericytomatous growth pattern was commonly seen. Nuclear atypia was mild, and mitotic activity was scarce. Immunohistochemically, all 3 cases were at least focally positive for epithelial membrane antigen and keratin AE1/AE3, with 2 tumors showing focal MUC4 expression and 1 case displaying diffuse CD34 and focal CAIX positivity. Targeted RNA sequencing identified EWSR1::CREM fusion in 2 cases and EWSR1::ATF1 fusion in 1 case. Subsequent fluorescence in situ hybridization analysis confirmed the RNA sequencing results. On follow-up, 1 patient developed multiple spinal bone metastases 5 months after the surgery while the other 2 patients were free of disease 9 and 120 months after diagnosis, respectively. Our findings demonstrate that intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions may rarely occur primarily in the kidney and should be included in the differential diagnosis of primary renal epithelioid mesenchymal neoplasms.

8.
Sci Bull (Beijing) ; 69(8): 1071-1080, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38302332

RESUMO

The commercialization of lithium-sulfur (Li-S) batteries has been hindered by the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs). Herein, we reported a viologen-based ionic conjugated mesoporous polymer (TpV-Cl), which acts as the cathode host for modifying Li-S batteries. The viologen component serves as a reversible electron conveyer, leading to a comprehensive enhancement in the adsorption of polysulfides and improved conversion rate of polysulfides during the electrochemical process. As a result, the S@TpV-PS cathode exhibits outstanding cycling performance, achieving 300 cycles at 2.0 C (1 C = 1675 mA g-1) with low decay rate of 0.032% per cycle. Even at a high sulfur loading of 4.0 mg cm-2, S@TpV-PS shows excellent cycling stability with a Coulombic efficiency of up to 98%. These results highlight the significant potential of S@TpV-PS in developing high-performance Li-S batteries.

9.
Biomed Pharmacother ; 172: 116270, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364737

RESUMO

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Humanos , Fibrose Pulmonar/tratamento farmacológico , Peroxidação de Lipídeos , Estresse Oxidativo , Células Epiteliais Alveolares , Ferro
10.
Proc Natl Acad Sci U S A ; 121(10): e2309957121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38422022

RESUMO

Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway.


Assuntos
Linfoma de Células B , Proteínas Repressoras , Animais , Camundongos , Hipóxia/metabolismo , Oxigenases de Função Mista/metabolismo , Proteínas Repressoras/metabolismo , Microambiente Tumoral
11.
mBio ; 15(3): e0317723, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38294217

RESUMO

Multi-fungicide resistance (MFR) is a serious environmental problem, which results in the excessive use of fungicides. Fitness penalty, as a common phenomenon in MFR, can partially counteract the issue of resistance due to the weakened vigor of MFR pathogens. Their underlying mechanism and relationship remain unexplained. By Oxford Nanopore Technologies sequencing and dot blot, we found that N6-methyloxyadenine (6mA) modification, the dominate epigenetic marker in Phytophthora capsici, was significantly altered after MFR emerged. Among the differently methylated genes, PcGSTZ1 could efficiently detoxify SYP-14288, a novel uncoupler, through complexing the fungicide with glutathione and induce MFR. Interestingly, PcGSTZ1 overexpression was induced by elevated 6mA levels and chromatin accessibility to its genomic loci. Moreover, the overexpression led to reactive oxygen species burst and ferroptosis in SYP-14288-resistant mutants, which enhanced the resistance and induced fitness penalty in P. capsici through triggering low energy shock adaptive response. Furthermore, this study revealed that the 6mA-PcGSTZ1-ferroptosis axis could mediate intergenerational resistance memory transmission and enabled adaptive advantage to P. capsici. In conclusion, the findings provide new insights into the biological role of 6mA as well as the mechanisms underlying the trade-off between MFR and fitness. These could also benefit disease control through the blockade of the epigenetic axis to resensitize resistant isolates.IMPORTANCEN6-methyloxyadenine (6mA) modification on DNA is correlated with tolerance under different stress in prokaryotes. However, the role of 6mA in eukaryotes remains poorly understood. Our current study reveals that DNA adenine methyltransferase 1 (DAMT1)-mediated 6mA modification at the upstream region of GST zeta 1 (GSTZ1) is elevated in the resistant strain. This elevation promotes the detoxification uncoupler and induces multifungicide resistance (MFR). Moreover, the overexpression led to reactive oxygen species burst and ferroptosis in SYP-14288-resistant mutants, which enhanced the resistance and induced fitness penalty in Phytophthora capsici through triggering low energy shock adaptive response. Furthermore, this study revealed that the 6mA-PcGSTZ1-ferroptosis axis could mediate intergenerational resistance memory transmission and enabled adaptive advantage to P. capsici. Overall, our findings uncover an innovative mechanism underlying 6mA modification in regulating PcGSTZ1 transcription and the ferroptosis pathway in P. capsici.


Assuntos
Ferroptose , Fungicidas Industriais , Fungicidas Industriais/farmacologia , Espécies Reativas de Oxigênio , Genoma , DNA
12.
Heliyon ; 10(1): e22742, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192835

RESUMO

Background: Continuous light exposure increases sympathetic excitation in rats, leading to hypertension, left ventricular hypertrophy, and fibrosis. This study was aimed to investigate whether continuous light exposure causes destabilization of vital signs and gut microbiota (GM) in Sprague Dawley (SD) rats and whether clonidine hydrochloride (CH), a central sympathetic depressant drug, could prevent these changes. Methods: Eight-week-old male SD rats were divided into three groups with different interventions for 14 weeks: control group (CG), 2-mL pure water gavaged daily while on a normal 12-h light/dark cycle; continuous illumination group (CI), 2-mL pure water gavaged daily while receiving continuous exposure to light (300 lx); and drug administration group (DA), CH (10 µg/kg) gavaged daily while receiving continuous exposure to light (300 lx). Results: The results showed that blood pressure, heart rate, and body weight were significantly higher in the CI group than in the CG and DA groups (P < 0.05). Moreover, the Shannon index was higher in the DA group than in the CI group (P = 0.012). The beta diversity index in the CG group was significantly higher in the CI group (P = 0.039). The pairwise comparison results of the linear discriminant analysis effect size showed that Oscillospirales were enriched in the DA group, whereas the Prevotellaceae lineage (family level) > Prevotella (genus level) > Prevotellaceae_bacterium (species level) were enriched in the CI group. The Muribaculaceae family was more abundant in the CG group than in the CI group. Conclusion: Sympathetic nerve inhibition restored the abnormal vital signs and GM changes under continuous light exposure.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38190065

RESUMO

The multitube design in the shell-and-tube type latent heat thermal energy storage (LHTES) system has received intensive attention due to its promising benefits in enhancing heat storage efficiency. In this paper, single and multi-tube shell LHTES systems were experimentally investigated. First, this study experimentally compared the thermal characteristics between a multiple-tube heat exchanger (MTHX) and a single-tube heat exchanger (STHX). The STHX's geometrical parameters coincided with a virtual cylindrical domain in the MTHX, being similar to the single-tube model formulated by simplifying the numerical solution to investigate the MTHX. The experimental data was then used to validate the simplified numerical model commonly used in the literature that converted the multi-tube problem to a single-tube model by formulating a virtual cylindrical domain for each tube in the MTHX system. The results showed that there was a noticeable difference in the thermal characteristics between the actual STHX and the virtual cylindrical STHX domain in the MTHX system. The comparison indicated that the simplified numerical model could not accurately reflect the thermal performance of the MTHX system. An experimental study or three-dimensional numerical modelling was required for the thermal analysis of the multi-tube problems. Second, the effect of tube number in the MTHX was experimentally investigated. It was found that an increase in tube number boosted both charging and discharging rates without inhibiting the natural convection. The five-tube configuration decreased the total charging and discharging duration by 50% compared to the two-tube one. Finally, the effect of heat transfer fluid (HTF) operating parameters on the system performance was evaluated on the five-tube MTHX system. The results revealed that the adoption of higher HTF temperature considerably improved the charging performance. The charging time decreased by up to 41% with the HTF temperature increasing from 70 to 80 °C. Meanwhile, a variation in the HTF flow rate from 5 to 20 L/min showed a more pronounced influence on charging than on discharging due to the different dominant heat transfer mechanisms.

14.
Adv Sci (Weinh) ; 11(7): e2305468, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064170

RESUMO

Hypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re-epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu-TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu-TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5-fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co-delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu-TSs not only promote macrophage phenotype-switching to inhibit inflammation by interleukin-related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen-related pathways. Therefore, TA/Fu-TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype-switching and anti-fibrosis effect.


Assuntos
Cicatriz Hipertrófica , Humanos , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patologia , Nanogéis/uso terapêutico , Fibrose , Fenótipo , Triancinolona Acetonida/uso terapêutico , Fluoruracila/uso terapêutico , Inflamação , Macrófagos/metabolismo
15.
Br J Pharmacol ; 181(5): 681-697, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37653584

RESUMO

BACKGROUND AND PURPOSE: Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR-dependent autophagy. EXPERIMENTAL APPROACH: The symptoms of dextran sulfate sodium (DSS)-induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild-type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS-induced AhRs and autophagic Becn1 was investigated using a dual-luciferase reporter system and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction assay. Caco-2 cells were used to investigate inflammatory responses and AhR-dependent autophagy. KEY RESULTS: APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS. CONCLUSIONS AND IMPLICATIONS: APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.


Assuntos
Colite , Receptores de Hidrocarboneto Arílico , Animais , Humanos , Camundongos , Autofagia , Células CACO-2 , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação , Camundongos Endogâmicos C57BL , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Receptores de Hidrocarboneto Arílico/genética
16.
Plant Dis ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037199

RESUMO

Artemisia capillaris (Asteraceae) is an annual herb found in ˃10 provinces in China. It is cultivated on ˃670 ha, with annual production around 2,500 tons. Its shoot is used in traditional Chinese medicine (Liu et al. 2021). From April to May 2023, Sclerotinia rot symptoms were seen at the Institute of Medicinal Plant Development (40.04°N, 116.28°E), Beijing, China. Disease incidence was up to 10% in the field through investigation of 300 plants. Initial symptoms were irregular tan-brown lesions (0.5 to 5.0 mm) that expended to circumferential necrosis on the roots and basal stem, aerial mycelia and sclerotia were developed on them. The leaves and stem tips were withered and droopy in severe cases. Twelve symptomatic primary roots of 12 plants from two sites were cut into 5 × 5 mm pieces, surface sterilized with 75% ethanol for 30 s and 5% NaClO for 60 s, rinsed with distilled water for three times, dried with sterile filter paper, put on potato dextrose agar (PDA), and incubated at 25°C in the dark for 2 days. Two Sclerotinia-like isolates were obtained using the hyphaltip method. White aerial mycelia were sparse and appressed for isolate YC1-3 and dense for isolate YC1-7. After incubated at 25°C in the dark for 15 days, 10 to 25 sclerotia were developed near the colony margin. Sclerotia of isolate YC1-3 were 1.0 to 3.9 × 1.2 to 4.5 (mean 1.8 × 2.2) mm (n = 60), ovoid or arc-shaped. Sclerotia of isolate YC1-7 were 1.5 to 3.4 × 2.7 to 9.2 (mean 2.3 × 4.3) mm (n = 60), ovoid, dumbbell shaped or curved. The isolates were identified as Sclerotinia sclerotiorum based on morphology (Maas 1998). To further identify the pathogens, molecular identification was performed with isolates YC1-3 and YC1-7. DNA of the two isolates were extracted by the cetyltrimethylammonium bromide (CTAB) method. Polymerase chain reaction was performed with primers ITS1/ITS4 for the internal transcribed spacer (ITS) region (Choi et al. 2020; White et al. 1990) and primers G3PDHfor/G3PDHrev for the glyceraldehyde 3-phosphate dehydrogenase (G3PDH) gene (Garfinkel. 2021). BLAST search analysis revealed that the ITS sequence (GenBank OR229758 and OR229762) was ≥99% similar to S. sclerotiorum (MN099281, MZ379265, KX781301, etc.), and the G3PDH sequence (OR778388 and OR761975) was too (MZ493894, JQ036048, OQ790148, etc.). Phylogenetic trees were computed with ITS and G3PDH sequences using the Maximum Likelihood in MEGA 11. Nine two-month-old seedlings of A. capillaris were used to test pathogenicity. The epidermis layer of each primary root was slightly wounded (2 × 2 mm, 1 mm deep) using a sterile dissecting blade. Three plants were inoculated with mycelial plugs (5 mm in diameter) of YC1-3 and YC1-7 that cultured on PDA for 7 days. Control plants were inoculated with sterile PDA plugs. All seedlings were then incubated at 25oC and 90% relative humidity. After isolate YC1-7 inoculation 3 days and isolate YC1-3 inoculation 5 days, inoculated roots had symptoms like those in the field, controls had no symptoms. S. sclerotiorum was consistently re-isolated from diseased roots, fulfilling Koch's postulates. Diseases caused by S. sclerotiorum have been reported threatens several important economical crops (Marin and Peres 2020; Guan et al. 2022). To our knowledge, this is the first report of S. sclerotiorum causes Sclerotinia rot on A. capillaris. To avoid of significant economic losses, it is urgent to establish an effective disease-management strategy.

17.
Sci Rep ; 13(1): 22435, 2023 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-38105291

RESUMO

Since November 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the worldwide pandemic of the coronavirus disease 2019 (COVID-19), the impact of which is huge to the lives of world populations. Many studies suggested that such situation will continue due to the endless mutations in SARS-CoV-2 genome that result in complexity of the efforts for the control of SARS-CoV-2, since the special enrichment of nucleotide substitution C>U in SARS-CoV-2 sequences were discovered mainly due to the editing by human host factors APOBEC3 genes. The observation of SARS-CoV-2 variants Beta (B.1.351) and Omicron (B.1.1.529) firstly spreading in South Africa promoted us to hypothesize that genetic variants of APOBEC3 special in African populations may be attributed to the higher mutation rate of SARS-CoV-2 variants in Africa. Current study was conducted to search for functional variants of APOBEC3 genes associate with COVID-19 hospitalization in African population. By integrating data from the 1000 Genomes Project, Genotype-Tissue Expression (GTEx), and Host Genetics Initiative (HGI) of COVID-19, we identified potential functional SNPs close to APOBEC3 genes that are associated with COVID-19 hospitalization in African but not with other populations. Our study provides new insights on the potential contribution of APOBEC3 genes on the evolution of SARS-CoV-2 mutations in African population, but further replication is needed to confirm our results.


Assuntos
Desaminases APOBEC , COVID-19 , Humanos , COVID-19/genética , Mutação , SARS-CoV-2/genética , África do Sul/epidemiologia , Desaminases APOBEC/genética , Gravidade do Paciente
18.
BMC Ophthalmol ; 23(1): 516, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114950

RESUMO

BACKGROUND: Here we described a new threading technique for the universal fixation of any posterior chamber intraocular lens (IOL). METHODS: Twenty-seven eyes of 27 patients whose surgery done by Surgeon A with the needle-guided method or the suture needle retrograde threading (SNRT) method for intrascleral IOL fixation were enrolled in the first group. Thirty-four eyes of 34 patients whose surgery done by Surgeon A, Surgeon B or Surgeon C with the SNRT method for intrascleral IOL fixation were grouped into three sub-groups by surgeon. Information regarding age, sex, best-available visual acuity (BCVA), intraocular pressure (IOP), past ophthalmological history, threading time (from puncturing to externalizing suture) and complications during and after the surgery were gathered. RESULTS: The analysis showed that the threading time was less in the SNRT group than needle-guided group by Surgeon A. There was one eye with suture needle slipping from the guide needle when guiding out of the eye. The threading procedure was completed one time without suture ruptures or loop slippage in the SNRT group operated by Surgeon A. And using the SNRT method, Surgeon A, Surgeon B, and Surgeon C did not show any significant difference in threading time. No complications (e.g., vitreous hemorrhage, hyphemia, retinal detachment, suprachoroidal hemorrhage, or hypotony) were observed during surgery or postoperatively in all cases. No leakage occurred at the site of the puncture after the operation. CONCLUSIONS: The described technique appears to be a safe, simple, easy-to-learn, and universal surgical method, which is suitable for various types of IOLs.


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/métodos , Esclera/cirurgia , Olho Artificial , Técnicas de Sutura , Suturas , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
19.
bioRxiv ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37961566

RESUMO

Surviving in a constantly changing environment requires not only the ability to select actions, but also the flexibility to stop and switch actions when necessary. Extensive research has been devoted to understanding how the brain switches actions, yet the computations underlying switching and how it relates to selecting and stopping processes remain elusive. A central question is whether switching is an extension of the stopping process or involves different mechanisms. To address this question, we modeled action regulation tasks with a neurocomputational theory and evaluated its predictions on individuals performing reaches in a dynamic environment. Our findings suggest that, unlike stopping, switching does not necessitate a proactive pause mechanism to delay movement onset. However, switching engages a pause mechanism after movement onset, if the new target location is unknown prior to switch signal. These findings offer a new understanding of the action-switching computations, opening new avenues for future neurophysiological investigations.

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