RESUMO
The competition between on-site electronic correlation and local crystal field stands out as a captivating topic in research. However, its physical ramifications often get overshadowed by influences of strong periodic potential and orbital hybridization. The present study reveals this competition may become more pronounced or even dominant in two-dimensional systems, driven by the combined effects of dimensional confinement and orbital anisotropy. This leads to electronic orbital reconstruction in certain perovskite superlattices or thin films. To explore the emerging physics, we investigate the interfacial orbital disorder-order transition with an effective Hamiltonian and how to modulate this transition through strains.
RESUMO
The efficacy of phoxim in treating bacterial sepsis in silver carp is significant, yet its underlying mechanism remains elusive. This study aimed to establish a model of Aeromonas veronii infection in silver carp and subsequently treat the infected fish with 10 µg/L phoxim. Kidney and intestine samples from silver carp were collected for transcriptome analysis and assessment of intestinal microbial composition, with the aim of elucidating the mechanism underlying the efficacy of phoxim in treating bacterial sepsis in silver carp. The results of transcriptome and intestinal microbial composition analysis of silver carp kidney indicated that A. veronii infection could up-regulate the expression of il1ß, il6, nos2, ctsl, casp3 et al., which means, signifying that the kidney of silver carp would undergo inflammation, induce apoptosis, and alter the composition of intestinal microorganisms. Phoxim immersion might enhance the energy metabolism of silver carp and change its intestinal microbial composition, potentially elevating the antibacterial infection resistance of silver carp. These findings may contribute to an understanding of how phoxim can effectively treat bacterial sepsis in silver carp.
Assuntos
Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Compostos Organotiofosforados , Animais , Carpas/imunologia , Doenças dos Peixes/imunologia , Compostos Organotiofosforados/farmacologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Aeromonas veronii/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: Carotid atherosclerosis is associated with an elevated risk of stroke in patients with chronic kidney disease. However, the molecular basis for the incidence of carotid atherosclerosis in patients with CKD is poorly understood. Here, we investigated whether circulating miR-423-5p is a crucial link between CKD and carotid atherosclerosis. METHODS AND RESULTS: We recruited 375 participants for a cross-sectional study to examine the occurrence of carotid plaque and plaque thicknesses. Levels of miR-423-5p were determined by qPCR analysis. We found that non-dialysis CKD patients had higher circulating exosomal and plasma miR-423-5p levels, and dialysis-dependent patients had lower miR-423-5p levels than non-dialysis CKD patients. After excluding for the influence of dialysis patients, linear regression analysis indicated that levels of circulating miR-423-5p are negatively correlated with eGFR (P < 0.001). Higher plasma miR-423-5p levels were associated with the incidence and severity of carotid plaques. In parallel, we constructed a murine model of CKD with a 5/6 nephrectomy protocol and performed RNA sequencing studies of aortic tissues. Consistent with these findings in CKD patients, circulating exosomal miR-423-5p levels in CKD mice were elevated. Furthermore, our RNA-seq studies indicated that the putative target genes of miR-423-5p were related to oxidative stress functions for aorta of CKD mice. CONCLUSION: Levels of miR-423-5p are associated with the presence and severity of carotid plaque in CKD. Data from our mouse model suggests that miR-423-5p likely influences gene expression programs related to oxidative stress in aorta of CKD mice.
Assuntos
Doenças das Artérias Carótidas , MicroRNAs , Placa Aterosclerótica , Insuficiência Renal Crônica , Humanos , Animais , Camundongos , Estudos Transversais , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/genética , MicroRNAs/metabolismoRESUMO
Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.
Assuntos
Autofagia , Degeneração do Disco Intervertebral , Nanopartículas , Ratos Sprague-Dawley , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Animais , Autofagia/efeitos dos fármacos , Nanopartículas/química , Ratos , Masculino , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Dor Lombar/tratamento farmacológico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sirolimo/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Núcleo Pulposo/metabolismo , Inflamação/tratamento farmacológico , Citocinas/metabolismo , Biomimética/métodos , Modelos Animais de Doenças , Fator de Crescimento Neural/metabolismo , Células RAW 264.7RESUMO
OBJECTIVES: To explore changes in cerebral blood flow (CBF) and white matter in hemodialysis patients. METHODS: Thirty-three hemodialysis patients who underwent two brain MRI at an interval of three years and 33 age- and sex-matched healthy controls (HC) underwent structural and arterial spin-labeling MRI examinations. Intergroup differences in CBF in the gray matter, white matter, and whole matter, and regional white matter hyperintensities (WMH) were analyzed. Based on the changes in CBF between the baseline and follow-up groups, the hemodialysis patients were divided into two subgroups: an increased CBF group and a decreased CBF group. Differences in CBF and WMH between the subgroups and HC were analyzed. RESULTS: Patients undergoing hemodialysis exhibited increased cerebral watershed (CW) WMH, deep WMH, and periventricular WMH (P < 0.01). The CBF of patients with decreased CBF was higher than that of HC at baseline (,P < 0.01) and lower than that of HC at follow-up (P < 0.01). Compared with the increased CBF group, obvious development of deep WMH was found in the decreased CBF group for the gray matter, white matter, and whole matter (P < 0.01). CONCLUSIONS: WMH in hemodialysis patients were distributed in the deep white matter, periventricular white matter and CW, and progressed with the extension of hemodialysis duration. CBF in hemodialysis patients could manifest as both increased and decreased, and WMH in patients with decreased CBF developed severely with prolongation of hemodialysis duration. ADVANCES IN KNOWLEDGE: These findings provide a basis for exploring neuropathological changes of hemodialysis patients.
Assuntos
Substância Branca , Humanos , Estudos Longitudinais , Substância Branca/diagnóstico por imagem , Circulação Cerebrovascular , Diálise Renal/efeitos adversos , Córtex CerebralRESUMO
BACKGROUND: Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. METHODS: In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. RESULTS: Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. CONCLUSION: lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.
Assuntos
Aldosterona , Estilo de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Aldosterona/sangue , Adulto , China/epidemiologia , Fatores Sexuais , Idoso , Obesidade/sangue , Obesidade/epidemiologia , Fatores de RiscoRESUMO
SIGNIFICANCE STATEMENT: Patients with end stage CKD often develop cognitive decline, but whether this is related to the underlying disease or to hemodialysis remains unclear. We performed three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping prospectively in 40 patients with stage 1-4 CKD, 47 nondialysis patients with stage 5 CKD, and 44 healthy controls. Our magnetic resonance imaging data demonstrate that changes in cerebral blood flow-susceptibility coupling might underlie this cognitive decline, perhaps in the hippocampus and thalamus. These results suggest that magnetic resonance imaging parameters are potential biomarkers of cognitive decline in patients with CKD. Moreover, our findings may lead to discovery of novel therapeutic targets to prevent cognitive decline in patients with CKD. BACKGROUND: Cerebral blood flow (CBF) and susceptibility values reflect vascular and iron metabolism, providing mechanistic insights into conditions of health and disease. Nondialysis patients with CKD show a cognitive decline, but the pathophysiological mechanisms underlying this remain unclear. METHODS: Three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping were prospectively performed in 40 patients with stage 1-4 CKD (CKD 1-4), 47 nondialysis patients with stage 5 CKD (CKD 5ND), and 44 healthy controls (HCs). Voxel-based global and regional analyses of CBF, susceptibility values, and vascular-susceptibility coupling were performed. Furthermore, the association between clinical performance and cerebral perfusion and iron deposition was analyzed. RESULTS: For CBF, patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than HCs. Patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than those with CKD 1-4. The susceptibility values in the hippocampus and thalamus were lower in patients with CKD 5ND than in HCs. Patients with CKD 5ND had higher susceptibility value in the caudate nucleus than those with CKD 1-4. More importantly, patients with CKD 5ND had lower CBF-susceptibility coupling than HCs. In addition, CBF and susceptibility values were significantly associated with clinical performance. CONCLUSIONS: Our findings demonstrate a new neuropathological mechanism in patients with CKD, which leads to regional changes in CBF-susceptibility coupling. These changes are related to cognitive decline, providing potential imaging markers for assessing clinical disability and cognitive decline in these patients.
Assuntos
Disfunção Cognitiva , Insuficiência Renal Crônica , Humanos , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/etiologia , Marcadores de Spin , Hipocampo/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , FerroRESUMO
BACKGROUND: The association between surgical treatment of mitral regurgitation (MR) and renal function is not sufficiently well-known. We tried to evaluate renal function before and after the procedure of surgical mitral valve repair (SMVR) in degenerative severe MR. METHODS: Patients with primary severe (4+) MR and normal left ventricular ejection fraction (LVEF) that underwent SMVR, examined by a cutting-edge 3-dimensional (3D) echocardiographic probe were enrolled in this study. We took three CKD-EPI equations to measure estimated glomerular filtration rate (eGFR) before SMVR and shortly before patients discharge. A total of 40 patients with baseline lower mean eGFR were evaluated. RESULTS: Measurements substantiated statistically significant improvements in eGFR (p < 0.001), multivariable linear regression modeling indicating prominent associations between increase in eGFR and decrease of MR (p = 0.003), decline of pulmonary arterial systolic pressure (p = 0.018), as well as increment of forward stroke volume (p = 0.02), in spite of LVEF reduction, left ventricular global longitudinal strain worsening and left atrial ejection fraction impairment. CONCLUSIONS: Renal function improves after SMVR in patients with degenerative significant MR and preserved LVEF, regardless of cardiac functional worsening.
Assuntos
Ecocardiografia Tridimensional , Taxa de Filtração Glomerular , Insuficiência da Valva Mitral , Valva Mitral , Humanos , Feminino , Masculino , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Ecocardiografia Tridimensional/métodos , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Valva Mitral/fisiopatologia , Resultado do Tratamento , Rim/diagnóstico por imagem , Rim/fisiopatologia , Rim/cirurgia , Idoso , Volume Sistólico/fisiologiaRESUMO
Pre-fermentation treatment has an important impact on the color, aroma, taste, and other characteristics of fruit wine. To discover suitable pre-treatment techniques and conditions that yield strawberry wine of excellent quality, the influences of juice fermentation, pulp maceration, thermovinification, and enzymatic hydrolysis pre-treatments on the basic chemical composition, color, antioxidant capacity, and volatile organic compounds in strawberry wines were investigated. The results showed that the color, antioxidant properties, and volatile aroma of strawberry wines fermented with juice were different from those with pulp. Strawberry wines fermented from juice after 50 °C maceration had more desirable qualities, such as less methanol content (72.43 ± 2.14 mg/L) compared with pulp-fermented wines (88.16 ± 7.52 mg/L) and enzymatic maceration wines (136.72 ± 11.5 mg/L); higher total phenolic content (21.78%) and total flavonoid content (13.02%); enhanced DPPH (17.36%) and ABTS (27.55%) free radical scavenging activities; richer essential terpenoids and fatty acid ethyl esters, such as linalool (11.28%), ethyl hexanoate (14.41%), ethyl octanoate (17.12%), ethyl decanoate (32.49%), and ethyl 9-decenoate (60.64%); pleasant floral and fruity notes compared with juice-fermented wines macerated at normal temperatures; and a lighter color. Overall, juice thermovinification at 50 °C is a potential pre-treatment technique to enhance the nutrition and aroma of strawberry wine.
Assuntos
Antioxidantes , Fermentação , Fragaria , Compostos Orgânicos Voláteis , Vinho , Vinho/análise , Compostos Orgânicos Voláteis/análise , Fragaria/química , Antioxidantes/análise , Antioxidantes/química , Odorantes/análise , Fenóis/análise , Flavonoides/análise , Frutas/química , CorRESUMO
OBJECTIVE: To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation. METHODS: This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024. The ureteral stent with thread group, in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation. On the 9th day after the operation, the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed. The ureteral stent could be removed along with the suture. As to the cystoscope group, a ureteral stent was routinely placed during kidney transplantation, and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation. The pain scores [numerical rating scale (NRS)-11] during catheter removal and the incidence of urinary tract infections were observed and compared between the two groups. t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups, and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups. P < 0.05 was considered statistically significant. RESULTS: As of March 2024, all the recipients were followed up for an average of 6 months (3 to 12 months) postoperatively. A total of 46 kidney transplantation patients were included, with 21 in the ureteral stent with thread group and 25 in the cystoscope group. There were no statistically significant differences between the two groups in age distribution, male-to-female ratio, and deceased versus live donor grafts. Three months after renal transplantation, there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group (P=0.007). No significant urinary fistula, wound infection, or ureteral stenosis occurred in either group. No stent-related complications, stent migration, or stone formation were observed. The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4, respectively, with no statistically significant difference (t=0.29, P=0.773). However, the pain scores during ureteral stent removal were 4.9±1.6 and 3.0±1.0 in the two groups, respectively, with a statistically significant diffe-rence (t=5.017, P < 0.001). The total costs of indwelling and removing ureteral stents in the cystoscopy group and the ureteral stent with thread group were 6 452.0 (5 539.5, 6 452.0) yuan and 3 225.0 (3 225.0, 3 225.0) yuan, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Compared with the conventional transplanted kidney ureteral stent, the self-discharge ureteral stent technique with sutures is simpler, has a shorter ureteral stent inlay time, reduces the symptoms of bladder spasms, significantly reduces the cost of catheterization, and has fewer postoperative urinary system complications. It is a worthy improved surgical method to be promoted.
Assuntos
Transplante de Rim , Stents , Ureter , Humanos , Transplante de Rim/efeitos adversos , Stents/efeitos adversos , Ureter/cirurgia , Estudos Prospectivos , Feminino , Masculino , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Suturas , Pessoa de Meia-IdadeRESUMO
Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of respiratory disease in patients and can cause respiratory distress and other symptoms in severe cases. Pneumolysin (PLY) is a pore-forming toxin that induces host tissue injury and inflammatory responses. Sortase A (SrtA), a catalytic enzyme that anchors surface-associated virulence factors, is critical for S. pneumoniae virulence. Here, we found that the active ingredient of the Chinese herb Scutellaria baicalensis, wogonin, simultaneously inhibited the haemolytic activity of PLY and SrtA activity. Consequently, wogonin decreased PLY-mediated cell damage and reduced SrtA-mediated biofilm formation by S. pneumoniae. Furthermore, our data indicated that wogonin did not affect PLY expression but directly altered its oligomerization, leading to reduced activity. Furthermore, the analysis of a mouse pneumonia model further revealed that wogonin reduced mortality in mice infected with S. pneumoniae laboratory strain D39 and S. pneumoniae clinical isolate E1, reduced the number of colony-forming units in infected mice and decreased the W/D ratio and levels of the inflammatory factors TNF-α, IL-6 and IL-1ß in the lungs of infected mice. Thus, wogonin reduces S. pneumoniae pathogenicity by inhibiting the dual targets PLY and SrtA, providing a treatment option for S. pneumoniae infection.
Assuntos
Proteínas de Bactérias , Streptococcus pneumoniae , Animais , Camundongos , Virulência , Proteínas de Bactérias/metabolismoRESUMO
BACKGROUND: Among digestive tract tumours, pancreatic ductal adenocarcinoma (PDAC) shows the highest mortality trend. Moreover, although PDAC metastasis remains a leading cause of cancer-related deaths, the biological mechanism is poorly understood. Recent evidence demonstrates that circular RNAs (circRNAs) play important roles in PDAC progression. METHODS: Differentially expressed circRNAs in normal and PDAC tissues were screened via bioinformatics analysis. Sanger sequencing, RNase R and actinomycin D assays were performed to confirm the loop structure of circEIF3I. In vitro and in vivo functional experiments were conducted to assess the role of circEIF3I in PDAC. MS2-tagged RNA affinity purification, mass spectrometry, RNA immunoprecipitation, RNA pull-down assay, fluorescence in situ hybridization, immunofluorescence and RNA-protein interaction simulation and analysis were performed to identify circEIF3I-interacting proteins. The effects of circEIF3I on the interactions of SMAD3 with TGFßRI or AP2A1 were measured through co-immunoprecipitation and western blotting. RESULTS: A microarray data analysis showed that circEIF3I was highly expressed in PDAC cells and correlated with TNM stage and poor prognosis. Functional experiments in vitro and in vivo revealed that circEIF3I accelerated PDAC cells migration, invasion and metastasis by increasing MMPs expression and activity. Mechanistic research indicated that circEIF3I binds to the MH2 domain of SMAD3 and increases SMAD3 phosphorylation by strengthening the interactions between SMAD3 and TGFßRI on early endosomes. Moreover, AP2A1 binds with circEIF3I directly and promotes circEIF3I-bound SMAD3 recruitment to TGFßRI on early endosomes. Finally, we found that circEif3i exerts biological functions in mice similar to those of circEIF3I in humans PDAC. CONCLUSIONS: Our study reveals that circEIF3I promotes pancreatic cancer progression. circEIF3I is a molecular scaffold that interacts with SMAD3 and AP2A1 to form a ternary complex, that facilitates the recruitment of SMAD3 to early endosomes and then activates the TGF-ß signalling pathway. Hence, circEIF3I is a potential prognostic biomarker and therapeutic target in PDAC.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/genética , Endossomos , Hibridização in Situ Fluorescente , Neoplasias Pancreáticas/genética , RNA Circular , Proteína Smad3/genética , Fator de Crescimento Transformador beta , Neoplasias PancreáticasRESUMO
Mixing in microfluidic channels is dominated by diffusion owing to the absence of chaotic flow. However, high-efficiency microscale mixing over short distances is desired for the development of lab-on-chip systems. Here, enhanced mixing in microchannels achieved using magnetic nonspherical particles (MNSPs), is reported. Benefiting from the nonspherical shape of the MNSPs, secondary vortices exhibiting cyclical characteristics appear in microchannels when the MNSPs rotate under an external magnetic field. Increasing the rotation rate enlarges the secondary vortices, expanding the mixing zone and enhancing the mixing, resulting in a mixing efficiency exceeding 0.9 at Re of 0.069-0.69. Complementary micro-particle image velocimetry (µPIV) for flow field analysis clarifies the mixing mechanism. In addition, a chaotic vortex area is generated in the presence of two MNSPs, which shortens the distance required for achieving an appropriate mixing efficiency. This study demonstrates the potential of employing MNSPs as efficient mixers in lab-on-chip devices.
RESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by rapid progression and poor prognosis. Understanding the genetic mechanisms that affect cancer properties and reprogram tumor immune microenvironment will develop new strategies to maximize the benefits for cancer therapies. METHODS: Gene signatures and biological processes associated with advanced cancer and unfavorable outcome were profiled using bulk RNA sequencing and spatial transcriptome sequencing, Caprin-1 was identified as an oncogenesis to expedite pancreatic cancer growth by activating autophagy. The mechanism of Caprin-1 inducing autophagy activation was further explored in vitro and in vivo. In addition, higher level of Caprin-1 was found to manipulate immune responses and inflammatory-related pathways. The immune profiles associated with increased levels of Caprin-1 were identified in human PDAC samples. The roles of CD4+T cells, CD8+T cells and tumor associated macrophages (TAMs) on clinical outcomes prediction were investigated. RESULTS: Caprin-1 was significantly upregulated in advanced PDAC and correlated with poor prognosis. Caprin-1 interacted with both ULK1 and STK38, and manipulated ULK1 phosphorylation which activated autophagy and exerted pro-tumorigenic phenotypes. Additionally, the infiltrated CD4+T cells and tumor associated macrophages (TAMs) were increased in Caprin-1High tissues. The extensive CD4+T cells determined poor clinical outcome in Caprin-1high patients, arguing that highly expressed Caprin-1 may assist cancer cells to escape from immune surveillance. CONCLUSIONS: Our findings establish causal links between the upregulated expression of Caprin-1 and autophagy activation, which may manipulate immune responses in PDAC development. Our study provides insights into considering Caprin-1 as potential therapeutic target for PDAC treatment.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Autofagia/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Imunidade , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases , Microambiente TumoralRESUMO
In 2020, Changchun Observatory developed a 280 mm wide-field optical telescope array to improve surveillance of space debris in the geosynchronous belt. There are many advantages including a wide field of view, the ability to observe a large area of sky and high reliability. However, the wide field of view causes a significant number of background stars to appear in the image when photographing space objects, making it difficult to detect them. This research focuses on the precise detection of GEO space objects from images taken by this telescope array in order to position them in large quantities. Our work further investigates the motion feature of an object, namely that the object can be seen as being in a uniform linear motion for a brief length of time. Based on this feature, the belt can be divided into a number of smaller areas and the telescope array scans each smaller area one at a time from east to west. To detect objects in the subarea, a combination of image differencing with trajectory association is used. The image differencing algorithm is used to remove most stars and screen out suspected objects in the image. Next, the trajectory association algorithm is employed to further filter out the real objects among the suspected ones, and the trajectories attributed to the same object are linked. The feasibility and accuracy of the approach were verified by the experiment results. The accuracy rate of trajectory association exceeds 90% and on average, more than 580 space objects can be detected per observation night. Since the J2000.0 equatorial system can accurately describe the apparent position of an object, the object can be detected by using this coordinate system as opposed to the pixel coordinate system.
RESUMO
This study was conducted to investigate if lncRNA TEX41 could have effects on SCC. The aim was to confirm that TEX41 could promote SCC progression by up-regulating Atg5 via miR-153-3p. TEX41, miR-153-3p, and Atg5 mRNA expression were examined by qRT-PCR. Western blot was used to examine Atg5 protein expression. CCK-8 assay and transwell assay were used to examine SCC cell proliferation and migration. Dual-luciferase reporter assay was used to forecast the binding site of miR-153-3p with Atg5 or TEX41. TEX41 expression was enhanced in SCC tissues and cells. TEX41 knockdown could reduce the SCC cell proliferation and migration. There was a binding site between TEX41 and miR-153-3p, and TEX41 negatively adjusted miR-153-3p in SCC cells. Atg5 was bonded with miR-153-3p, which was adjusted by TEX41. Our study revealed that TEX41 expression was increased in SCC cell lines and tissues. TEX41 could aggravate SCC progression through adjusting the miR-153-3p/Atg5 axis, providing a key target for SCC.
Assuntos
Carcinoma de Células Escamosas , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Renal ischemia-reperfusion injury (IRI) is one reason for renal transplantation failure. Recent studies have shown that mitochondrial dynamics is closely related to IRI, and that inhibition or reversal of mitochondrial division protects organs against IRI. Optic atrophy protein 1 (OPA1), an important factor in mitochondrial fusion, has been shown to be upregulated by sodium-glucose cotransporter 2 inhibitor (SGLT2i). Also, the antiinflammatory effects of SGLT2i have been demonstrated in renal cells. Thus, we hypothesized that empagliflozin could prevent IRI through inhibiting mitochondrial division and reducing inflammation. METHODS: Using hematoxylin-eosin staining, enzyme linked immunosorbent assay (ELISA), flow cytometry, immunofluorescent staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining, real-time PCR, RNA-sequencing, and western blot, we analyzed renal tubular tissue from in vivo and in vitro experiments. RESULTS: Through animal experiments and sequencing analysis, we first confirmed the protection against IRI and the regulation of mitochondrial dynamics-related factors and inflammatory factors by empagliflozin pretreatment. Then, through hypoxia/reoxygenation (H/R) cellular experiments, we confirmed that empagliflozin could inhibit mitochondrial shortening and division and upregulate OPA1 in human renal tubular epithelial cell line (HK-2) cells. Subsequently, we knocked down OPA1, and mitochondrial division and shortening were observed, which could be alleviated by empagliflozin treatment. Combined with the previous results, we concluded that OPA1 downregulation leads to mitochondrial division and shortening, and empagliflozin can alleviate the condition by upregulating OPA1. We further explored the pathway through which empagliflozin functions. Related studies have shown the activation of AMPK pathway by empagliflozin and the close correlation between the AMPK pathway and OPA1. In our study, we blocked the AMPK pathway, and OPA1 upregulation by empagliflozin was not observed, thus demonstrating the dependence of empagliflozin on the AMPK pathway. CONCLUSION: The results indicated that empagliflozin could prevent or alleviate renal IRI through antiinflammatory effects and the AMPK-OPA1 pathway. Ischemia-reperfusion injury is an inevitable challenge in organ transplantation. It is necessary to develop a new therapeutic strategy for IRI prevention in addition to refining the transplantation process. In this study, we confirmed the preventive and protective effects of empagliflozin in renal ischemia-reperfusion injury. Based on these findings, empagliflozin is promising to be a preventive agent for renal ischemia-reperfusion injury and can be applied for preemptive administration in kidney transplantation.
Assuntos
Dinâmica Mitocondrial , Traumatismo por Reperfusão , Animais , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Rim , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Apoptose , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/farmacologiaRESUMO
BACKGROUND: Obesity, especially visceral obesity, plays an important role in the progression of cardiovascular disease (CVD). The body roundness index (BRI) is a new measure of obesity that is considered to reflect visceral obesity more comprehensively than other measures. This study aims to evaluate the relationship between BRI and CVD risk in hypertensive patients with obstructive sleep apnea (OSA) and explore its superiority in predicting CVD. METHODS: The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD. The area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess which measures of obesity had the best predictive value for CVD risk. RESULTS: During a median follow-up period of 6.8 years, 324 participants suffered a CVD event. After multivariable adjustment, compared with the reference group (the first tertile), the HRs (95% CI) of CVD were 1.25 (95% CI, 0.93-1.70) and 1.74 (95% CI, 1.30-2.33) for subjects in the tertile 2 and tertile 3 groups, respectively. Compared with other measurement indicators, BRI has the highest predictive value for CVD risk [AUC: 0.627, 95% CI: 0.593-0.661]. The addition of the BRI to the fully adjusted multivariate model improved the predictive power for CVD, which was validated in the continuous NRI and the IDI (all P < .05). CONCLUSIONS: BRI was significantly associated with the risk of CVD in hypertensive patients with OSA. Furthermore, BRI may improve CVD risk prediction in hypertensive patients with OSA.
Assuntos
Doenças Cardiovasculares , Hipertensão , Apneia Obstrutiva do Sono , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Obesidade Abdominal , Valor Preditivo dos Testes , Hipertensão/complicações , Obesidade/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Fatores de RiscoRESUMO
The effective retention of anaerobic ammonia oxidizing (anammox) bacteria and its high sensitivity to toxic substances and oxygen posed a major challenge to the application of partial nitrification combined with anammox (PN/A) in mature landfill leachate treatment, although it is a promising and efficient nitrogen removal process. In this study, a single-stage PN/A process based on expanded granular sludge bed was proposed to treat the mature landfill leachate. During the last phase, when the NH+ 4-N concentration of mature landfill leachate in influent was 1150.0 mg/L, the nitrogen removal efficiency (NRE) was 83.64% with 1.07 kg N/(m3·d) nitrogen removal rate (NRR). The activity of anammox bacteria (AnAOB) and ammonia oxidizing bacteria (AOB) was 9.21 ± 0.22 mg N/(gVSS·h) and 14.34 ± 0.65 mg N/(gVSS·h), respectively. The bacteria produced a high amount of tightly bound extracellular polymeric substance (TB-EPS) i.e., 4071.79 mg/(g·VSS). This helped to create granular sludge and provided favorable spatial conditions for the distribution of functional bacteria that were adapted to different environments. Due to the efficient retention of functional bacteria by the granular sludge, the relative abundance of Ca.Brocadia and Ca.Kuneneia was 1.71% and 0.31%, respectively. Redundancy analysis (RDA) and microbial correlation network diagram showed that the relative abundance of Ca. Kuenenia, Nitrosomonas and Truepera had a stronger positive correlation with the increase of the proportion of mature landfill leachate added to the influent. Overall, the PN/A process based on granular sludge provides an effective method for autotrophic biological nitrogen removal from mature landfill leachate.
Assuntos
Amônia , Poluentes Químicos da Água , Desnitrificação , Poluentes Químicos da Água/metabolismo , Esgotos , Nitrogênio/metabolismo , Oxidação Anaeróbia da Amônia , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Reatores Biológicos/microbiologia , Oxirredução , Nitrificação , Bactérias/metabolismoRESUMO
Salicylic acid (SA) is a pivotal hormone required for the development of resistance to many pathogens in plants. As an SA receptor, NPR1(Nonexpressor of Pathogenesis-Related Genes 1) plays a key regulatory role in the plant immune response. The function of NPR1 is dependent on the alteration of its oligomer-to-monomer. Research in recent years has proven that NPRs perceive SA and regulate the expression of downstream defense genes, but the mechanism of NPR1 oligomer-to-monomer conversion remains unclear. In this paper, we mainly studied the oligomerization of NPR1. By mutation experiments on some residues in the BTB domain involved in protein interactions, we found that the residue His80 plays a key role in the oligomerization of NPR1. We also found that NPR1, interacting with zinc ions at a ratio close to 1:1, was independent of the residue His80. These findings may help us to understand the conformational conversion of NPR1.